Cancer Prevention

Bhaskaran, 2014 This was a very large population based study where they had 5.24 million participants and it was in sent in the UK and what they did was review charts so they had these electronic medical records they review charts for anyone that was age 16 or older and what they found was that BMI was associated with ___________ cancers that they looked at but that the effect of the BMI varies substantially by site so of those 22 cancers 17 of them you could say that BMI increase your risk for 17 of those of those cancers but how much of an effect that being BMI had an increased risk dependent on the type of cancer so the impact of BMI on ______________ was different than the effect of BMI on lung cancer for example so we can generally say though that increased BMI increases our risk for overall cancer but there is a stronger association between BMI and specific cancers so if you're interested in looking at that i think that's a good study to look at

17 of the 22 breast cancer

According to the DiSebastiano et al article, when did the scientific evidence linking diet and cancer start to emerge?

1980s

If you gain weight or have a higher BMI what do you do about it. do you just sit around and kind of wait to get cancer or can you do anything about it so this study which was the nurses health study shows that with weight loss you can reduce your relative risk for cancer and their support for weight loss of as little as ______ kilograms can decrease the relative risk for cancer particularly breast cancer in these individuals so if you have gained weight or you have a higher BMI it does not mean that you're destined to develop cancer weight loss is also been shown to be beneficial

2 to 5

The BMI range which is recommended as the most chemoprotective is:

21-23

American Cancer Society Guidelines

-Eat a variety of healthful foods, with an emphasis on plant sources -Eat five or more servings of a variety of vegetables and fruits each day -Choose whole grains in preference to processed (refined) grains and sugars -Limit consumption of processed red meats -Choose foods that maintain a healthy weight -Adults should engage in 30 min of moderate to vigorous physical activity 5 or more/day per week -Maintain a healthy weight throughout life -If you drink alcoholic beverages, limit consumption.

6 key properties

-They disregard the external and internal signals that regulate cell proliferation -They tend to avoid suicide by apoptosis -They circumvent programmed limitations to proliferation, escaping replicative senescence and avoiding differentiation -They are genetically unstable -They escape from their home tissues(are invasive) -They survive and proliferate in foreign sites (they metastasize)

breast cancer is another one that we're getting a lot of research on in terms of alcohol more than 100 epidemiological studies have looked at the Association between alcohol consumption and the risk of breast cancer in women and they have consistently found an increased risk of breast cancer associated with increased you know alcohol intake so one of these meta analysis that really has showed this effect they looked at 53 studies which you know coming together was about 58,000 women with breast cancer and that showed that women who drank more than 45 grams of alcohol today per day which is about 3 drinks had a ____ times risk of developing breast cancer as non drinkers and so that was categorized as like a modestly increased risk so there is an increased risk of breast cancer is higher across all levels of alcohol intake so for every ___ grams of alcohol consumed per day which is slightly less of 1 drink the research has found that there is a small increase in risk of breast cancer. colorectal cancer too has been correlated with alcohol consumption it's a modestly increased risk of cancers of the colon and the rectum but just something to keep in mind

1 1/2 10

there were an estimated ______________ new cases of cancer reported in 2020 and an estimated ______________ deaths in 2020 from cancer alone and these numbers are pretty significant. In men, they have a _________ lifetime risk in women have a ___________ lifetime risk of developing cancer

1.8 million 610,000 one in two one in three

colon cancer is one of the most common malignancies in the United States and accounts yearly for about ___% of all cancer deaths the incidence of colon cancer are higher in western in the western world but they are rapidly increasing in developing countries and it's predicted that half the western population will develop at least one colorectal tumor by the age of ___ I mean that's like pretty startling to me by the age of 70 about half of the western world will have some sort of colorectal cancer

11 70

this particular study shows that there is a multivariate relative risk of breast cancer by BMI in the pooling project of perspective cohort studies now this study is a bit more interesting because we start to see an increased relative risk of breast cancer with a BMI that we would classify as normal 21 to 23 but from here the relative risk then starts to increase as the BMI goes up through a BMI of ____ so it looks as though the highest relative risk occurs within that BMI of 27 to 29 and that it doesn't show the same linear relationship that we have seen previously but one of the limitations of this study was that included so many fewer people in that higher BMI group then the previous studies

29

So what the research tells us is that the more alcohol a person drinks particularly the more alcohol a person drinks overtime regularly overtime the higher their risk of developing an alcohol associated cancer so an estimated ____% of all cancer deaths in the United States are alcohol related so the research really does show us that there is a clear Association between alcohol consumption and then head and neck cancers esophageal cancer liver cancer breast in colorectal cancer

3.5

_____% of cancers can be prevented and then there's some estimates they say that ____% of cancers can be prevented. 50% of all cancers can be prevented by ___________ and that's part of what we're going to talk about today now .when you look at cancer and how many individuals and families it affects that 50% is a lot of people right and there's some estimates that _____ plays such an important role in cancer prevention that accounts for about 30% of total cancer mortality so really about 1/3 of all cancer deaths could be prevented simply by making some dietary modifications and I know that sounds so it's so simplified to say it like that but that's really what the data shows us

30 50 lifestyle diet

Ordet Results: Found is that the individuals who did develop breast cancer what they found in that group was that there was a ________% risk reduction in the salad vegetable group so this was the group that consumed the raw vegetables the fruits in the olive oil what they also found was was that those individuals with a BMI less than ___ who were in that salad vegetable group had an even greater reduction so being in the salad vegetable group was protective then having your BMI less than 25 seemed to be even more protective and I think they had I think there's a _____% greater risk reduction in the lower BMI salad veggie group there was really no significant reduction in any of the other groups and what they attributed to the risk reduction was the fact that the salad group had a diet that was high in and biologically active

30 to 35 25 50

these individuals were first coming over to the US, they adapted to more of a western diet and what you see is that by the ____________ their risk of stomach cancer was similar to that of the United States right because they've changed their diet and they've decreased some of their consumption of you know some of the foods that are can be somewhat protective so that their wines their saki some of the other foods that are associated with that increased risk of stomach cancer so just to point out you know when you see immigrants their rates start to mimic by that 3rd generation especially start a minute mimic their rates of cancer in their host country.

3rd generation

if you look just at the statistics of BMI greater than ____ increases the cancer risk by 52% in men and 62% in women and the cancers that are specifically correlated with the amount of body weight are __________ so there are a lot that are associated with an increased risk with increased risk of cancer with higher BMI's so not only is obesity an established risk factor for several cancers, it can lead to poor treatment outcomes as well and a worsened prognosis and increased cancer related mortality. so not only is your risk for developing it in the 1st place is higher when you have a higher BMI your disease outcomes are not as good either so weight status is correlated with an increased of developing cancer but so is adult weight gain so if you have been like a normal weight your entire life but you gain weight at any stage in adulthood your risk for cancer will increase as with many chronic diseases weight status is important but so is weight distribution right and weight distribution particularly ___________ is a strong predictor of certain cancers specifically of colon cancer

40 endometrium cancers breast cancer kidney Gallbladder esophageal cancer: rectal liver hematological malignancies in pancreatic cancers visceral adiposity

so in the 90s there was this theory that high fruit vegetable intake could reduce cancer risk by as much as ____% based on some of these case controlled studies so based on all of that information that came out in 1991 the American Cancer Institute they started a __________ program. the initiation of that program coincided with the start of a large perspective cohort study which showed that there was an Association between increased fruit and vegetable intake and reductions in risk then we had the world Cancer Research fund that was looking at this very carefully as well so they came out with a report in 1998 and then they came out with a report in 2007. so this world Cancer Research fund and the American Institute of Cancer reviewed a lot of the different studies that have been done and then they found among other things but what else that there really wasn't _______________ with increasing fruit and vegetable consumption so we based on these studies we came out with this whole campaign and this 2007 study came out said OK there's some maybe benefits there but there wasn't a significant risk reduction so for that review they actually looked at 17 large cohort studies and of these 17 studies they found that only 11 of them showed a decreased risk of cancer and only three out of those 11 found that they were actually statistically significant so again it was interesting because there really wasn't as strong of a support for increased fruit and vegetable intake without actually looking at these large cohort studies but it's because of that five a day campaign that in our mind that's where the first thing that we jump to is like what can we do to help to reduce risk for cancer in eat lots of fruits and vegetables.

50 5 a day a significant risk reduction

for head and neck cancer, alcohol consumption is a major risk factor for in particular for cancers of the oral cavity of the pharynx so the throat and then also of the larynx or researches and is that people who consume ___ or more grams of alcohol per day which is approximately 3 1/2 or more drinks per day have at least _________ times a greater risk of developing these specific cancers than non drinkers now if you act tobacco to the mix then the risk for head and neck cancer grows even substantially higher I also mentioned you know the correlation between alcohol and esophageal cancer alcohol consumption is a major risk factor for a particular type of esophageal cancer this _________________ so I mean you see that direct link there too with liver cancer that's a very obvious connection alcohol consumption is an independent risk factor four and a primary cause of liver cancer

50 two to three squamous cell carcinoma

worldwide there are approximately _____________ deaths that can be attributed to cancer

7.4 million

Excessive alcohol intake is associated with which type(s) of cancer?

Head and Neck Liver Esophageal Breast Colorectal

so research has shown time and time again that there is a linear relationship between _______________ so as BMI goes up so does cancer risk. oftentimes weight as a function of dietary intake rate particularly as it relates to higher fat intakes and lower fruit and vegetable intake this is generally associated with a _______ BMI but BMI independent of dietary specifics is a contributive factor in increasing cancer risk right but why so poor diet quality leading to higher BMI perhaps or is it the higher at adiposity that leads to more ____________ which are inflammatory in nature right increasing the risk it's hard to say but regardless of what it is we know that the amount of weight or somebody's weight status BMI is an independent risk factor for cancer

BMI and cancer risk higher adipokines

_____________________ also have a greater increased risk of cancer compared to other ethnic groups. although that is changing slightly with other ethnicities not quite catching up but unfortunately they are gaining some momentum. but i think what is perhaps more disturbing is the fact that about _________ of every 500,000 cancer deaths is related to ________________. so this is just one of the reasons why it's important to look at lifestyle in the relationship of cancer to lifestyle so that we can prevent it or at least significantly reduce cancer by making some of these lifestyle changes.

Caucasians and African Americans 1/3rd lifestyle

Based on the Key (2020) article, which of the following is identified as a carcinogenic food?

Chinese-style salted fish

Vitamin D deficiency has most readily been associated with which of the following types of cancer?

Colorectal

you have this oxidative stress which causes then direct _____ damage right and that promotes then this tumor brother cancer progression OK so just very fast if we start with obesity again you can see how this cascade works obesity leads to inflammation right it's not going through it leads to inflammation you have hormonal balances altered gene expression

DNA

we know that cancer results from uninhibited or uncontrolled cells that have had damage to their _______ but what is the mechanism behind this or what happens first. I want to point out that a __________ mutation is not enough to cause cancer. at any person's lifetime every single gene undergoes ______________ of mutations So what that means is that if a single mutation were enough to convert a typical healthy cell into a cancer cell that proliferates without restraint we would not be viable organisms right so every cell that ____________ does not result in cancer

DNA single thousands mutates

In the Emenaker et al (2018) article, we learn that several inconsistencies exist across the diet-cancer prevention scientific literature. Select one of the categories under which some of these inconsistencies fall:

Differences in study design

So what we know is that there have been elevated levels of _______ found in breast cancer cells ovarian tumors prostate tumors and in precancerous lesions as well in the colon the stomach the esophagus and even the oral cavities. so it appears that an increase in FA SN is necessary for proliferation and survival you know which are then necessary for malignancies to occur rate so since FA SN is over expressed in adipose tissue researchers have essentially theorized that the fatty acids that are formed from the FAS an enzyme provide fatty acid sources to that cancer now on the flip side when FAS N is manipulated to be inhibited researchers have found an _____________ effect specifically in breast cancer cells and in prostate cells

FASN antiproliferative

T or F: Populations who consume a diet rich in animal fats have a direct decrease in cancer incidence.

False

Which of the following nutrients has been strongly associated with increased risk of colon cancer?

High consumption of red meat

we have also seen with an increase in this FAS inactivity is an increase in lipolytic enzymes like the ______________ like base this image GL pathway has been upregulated in many types of aggressive cancer cells so when the MGL is up regulated what we end up seeing is a release of ______________ into circulation then what happens is that these free fatty acids are available to generate lipid signaling molecules which are then thought to promote Genesis. now there's this other study that I looked at that found that cancer cells can access and use lipids from neighboring adipocyte stores So what they what they saw was there was a direct transfer of _________ from the adipocyte to the cancer cells what does that suggest it suggests that the cancer cells can directly use these transferred lipids as an ______________ which then promotes this tumor growth rate So what these mechanisms are really telling us is that cancer cells are able to utilize fatty acids that are present due to the obesity and that is just one possible link between adiposity and increased cancer risk cancer risk one possible sort of overarching mechanism

MGL or this monogylcerol free fatty acids lipids energy source

Some limitations of epidemiological research include

Significant labor and resource burden

World Cancer Research Fund

Report developed by a international panel of 21 experts 20 standardized systematic reviews conducted at 9 institutions in US, Europe 500,000 studies used in this meta-analysis With 7000 used in the final report. 5 year review process - "most comprehensive report on cancer and diet, physical activity, and weight" Criticism may come from the type of epidemiologic verses randomized control trials.

T or F: There is an increased risk of cancer with age.

True

so we know that alcohol increases the risk but how does it do that by metabolizing or breaking down ethanol in alcoholic drinks to _________ but what you need to know now is that we have this ethanol it's metabolize down to acetyl aldehyde which is a toxic chemical and is considered what they would call a probable human carcinogen so this acetyl aldehyde can damage both of ____ which we've talked about a lot now but also the ______ that are generating those reactive oxygen species right which can then themselves go ahead and damage the DNA you know by that oxidation and So what does that do that impairs the body's ability to breakdown and absorb then a variety of different nutrients that then may increase your risk for cancer so things like vitamin A you know the B vitamins like folic acid vitamin C vitamin D vitamin E all of these you know can are correlated with an increase risk of cancer

acetyl aldehyde DNA proteins

so high fiber diets in those smaller earlier studies had been linked to reduced colon cancer risk in some studies. so this 1999 nurses health study they found no link between dietary fiber and the prevalence of colon cancer. that study had almost 89 thousand women. the health professionals follow-up study was conducted in men and they had about 48,000 men and they found that dietary fiber had no clear link to the risk of colon cancer though it did have some protection against ___________ which are the benign polyps that are precursors of nearly all colon cancers. so while no direct link was seen with protective effect was seen with colon cancer it did seem to be there seemed to be a correlation between those adenomas later studies that came out also found that fiber was protective against those adenomas. which again they eventually turn into colon cancer but even though the studies are inconsistent there are definite benefits conferred with a high fiber diet maybe not directly linked to colon cancer but you know decrease risk of heart disease diverticulitis all of those things so if I were still good even though we haven't found that direct link or a very strong evidence of the direct link there is some research that suggestive of it but not any research that's very strongly correlated

adenomas

now what you also see happening is that the eicosanoids that are produced from the omega-3 fatty acids and the Omega six they can promote ____________ So what is angiogenesis? it is the _____________ and why is that important we need those new blood vessels in order for those tumors to grow. if there was no vascularization the tumors couldn't grow and they if they could grow they wouldn't be able to grow to be very large and they certainly wouldn't be able to differentiate and proliferate to any significant degree so you have these eicosanoids which essentially are these signaling molecules right so there are signaling that these abnormal cells need to be fed that is what triggers the angiogenesis so you get more oxygen and nutrients to those cells they start to divide they differentiate and then the tumor grows and progress

angiogenesis development of new blood vessels

we have to interpret information appropriately. you know that it was just a moderate modest risk reduction and we shouldn't be over zealous but really how can you go wrong with telling people eat more fruits and vegetables. which is really what they came to the conclusion right but in the concept that not all fruits and vegetables are created equal when you're looking at these different fruits and vegetables. we can look at the different ________________ that's what I have over here is like look at these different fruits and vegetables and then look at the antioxidant activity and there's enough research out there that shows that antioxidants are beneficial for cancer prevention as they related to decreasing free radicals and decreasing inflammation so by looking at this you know we can see that the red pepper broccoli carrot they have a lot more antioxidant activity than you know the cucumber which is at the lowest support just the point of this slide is to say that not all fruits and vegetables are equal in when they looked at these when they did these studies or looked had you did systematic reviews or meta analysis of these fruit and vegetables to these they were not differentiating between which fruits and vegetables people were eating they were just lumping them all into one category together

antioxidant activity

so most eicosanoids are produced by ___________________ which is a polyunsaturated fatty acid which is in Omega 6 fatty acid. in those all of those come from animal fats right but Some that are produced by omega-3 fatty acids. it appears though that the eicosanoids that are produced by the Omega 6 fatty acids are the ones that ____________ your risk for cancer more so even though omega-3 fatty acid derived eicosanoids can increase your risk it seems that Omega 6 fat derived eicosanoids are more harmful or more oncogenic. the Omega 6 derived eicosanoids also then can alter our DNA right and ultimately alter our gene expression which again then does what it increases cell proliferation and differentiation and ultimately results in tumor growth in cancer progression.

arachidonic acid increase

This figure is looking at cancer risk as it relates to mortality from uterine cancer so in this cohort we're seeing again as _____________ we see that the relative risk also increases so like the previous slide the risk increases as soon as the BMI enters at overweight category and there is that linear relationship but when we approach a BMI of greater than 40 we see a significant elevated risk for of mortality for uterine cancer specifically so you know when you get past 40 the risk starts to go up

body mass increases as BMI goes up

one of the strongest associations between fat intake has been made with _______________ in fact seems to be implicated in increased cancer risk more than other macro nutrients. and this Association is seen even immigrant populations who start to assimilate to a new country where their weights then mimic those of their new country due to lifestyle factors environment or oftentimes both so the Association between fat intake and mammory tumors specifically has been observed in animal studies and in human trials they already talked about this earlier but there is a strong correlation between national per capita fat consumption and breast cancer specifically and as is the case with much research there is some conflicting results so you know in in some of the larger I should say in the largest case control study that we've looked at that I looked at there really wasn't much of a difference between the group so diet plays a role in increasing risk when it comes to breast cancer we also see it work to protect against recurrence. when people follow a __________ diet you know we know that fat significantly effects energy intake two so by having a lower fat diet focused on maintaining a healthy BMI and decreasing weight gain during adulthood.

breast cancer low fat high fiber

we do have very strong epidemiological research that shows us that as fiber intake goes up cancer risk goes down but a lot of the recent studies don't really show as much of a protective effect of fiber as we once believed so this is an older study it's a 2000 study but it's a very it was a large study this 2007 Arizona polyp study and this was one of the earlier larger studies that did not show this positive protective relationship of fiber and it left people kind of kind of baffled as to why OK so if the research on fiber and colon cancer is inconclusive what can we do about colon cancer the research supports findings that ____________ are protective against colon cancer so then what are the causative agents like what do we know independent of fiber intake that can increase the risk of colon cancer there are red meats that are cooked at high temperatures alcohol and caffeine so even though fiber is not shown to be protective against colon cancer diets that are high in these in red meat highly cooked meats fat alcohol caffeine tend to be lower in cancer and those tend to be the dietary components that seemed to have an increased risk with colon cancer

calcium vitamin D folate antioxidants selenium garlic and even exercise

the world Cancer Research fund and its affiliates you know including the American Institute for Cancer Research they started compiling data in a comprehensive report which they started in 1998 that's when they issued their first report and then in 2007 they published their second report which is the most comprehensive report on _______________ up to that point so essentially you know what they do is they write these reports but what they do is conduct this huge standardized systematic review at institutions all around the world so this is what I have up here as a 2007 one they do that at night and institutions across the US in Europe but this third report that came out. they had sites all over the world there's a huge meta analysis for the 2007 report they analyzed 500,000 studies and then they distill them down to 7000 that were used in the final report now the world Cancer Research fund and its partners have completed a decade long effort to really objectively review an interpret all of this you know this rapidly expanding scientific literature on the diet and the nutrition and the physical activity and it's how they you know correlate to cancer and it's really intended to provide guidance to individuals for their personal goals to improve health as well as educating health care practitioners in evidence based interventions for their patients.

cancer diet physical activity and weight

What is cancer?

cancer is a disease that is caused by uncontrolled cell division right but not just any cells their abnormal cells right that are just dividing in an uncontrollable fashion so cancer is essentially the acceleration of uncontrolled growth of these neoplastic cells now generally any type of cancer is a result of some type of damage to the DNA or mutations in the DNA that can then result in more cells and ultimately can result in malignancy

____________________ studies where you're comparing two groups of people those who have the disease and those who don't have the disease and those that don't have the disease or what we would consider the _______________. so here you know you might be looking at female nurses who have lung cancer versus those who don't and here you try to see what was different among the groups that might have led one group to develop lung cancer while the other did not. and in this last type that I have listed here is _________________ where the goal is really just to find trends in the disease incidence and disease mortality instead of the larger overarching trends that we see with specific diseases

case control control group descriptive Epidemiology

the thought is that the insulin and IGF which are frequently high in overweight and obese individuals that they trigger a specific cascade which promotes _____________________ and this cascade then triggers leptin adino pectin inflammatory cytokines which then create an environment that can promote cancer development and growth so the bottom line here is that the link between obesity and cancer generation is complicated and it's a result of many different mechanisms and pathways that you know in in that staying within a healthy weight range and body composition can be protective against cancer.

cell growth and proliferation

_________________ are when you're looking at a particular outcome in groups of individuals who are very similar but they differ in certain characteristics so for example when you're looking at the rates of lung cancer among female nurses who smoked versus those who didn't right so you have this you have that there are all female nurses but then you they differ in the fact that one group smoked and one group did it.

cohort studies

likewise you know your fruits are the same way ____________ are superior to pineapple grapefruit and orange if you're just looking at antioxidant activity but how the nutrients in these then started to interact with maybe some of the other dietary components it's hard to say and that's why are the results are inconsistent in hard to interpret

cranberry and apple

what makes cancer such a difficult disease to tackle is the fact that cancer itself is caused by an interaction of ____________________ risk factors. right now going back to what I said earlier if ___% of all cancers can be prevented what does that tell us it tells us logically that we can assume that the _______________ plays a huge role and of those environmental factors we as a profession are most concerned with ______________________ and then to some degree physical activity right. So what research tells us is that food nutrition obesity physical activity all have an influence on various processes they can increase or decrease our risk for cancer. we also know that you know it's a leading does cause of death like I mentioned earlier and it's expected to increase again because of our increasing ________________.

dietary genetic and environmental 50 environment food nutrition obesity lifespan

the more important and most important in my opinion function of their report World Cancer Research Fund is that they provide summary recommendations to help guide governments and a vast array of public health organizations around the globe including WHO and what they're trying to do is to help them optimize their strategies and policies regarding agriculture and food production with the goal of what with the goal ultimately to ensure universal access to health promoting _______________ and thereby reducing that burden of cancer and other disease processes through the life cycle

dietary patterns

Sieri, 2004 Now this is also an older study but it started to give us some good information about the relationship between diet and breast cancer specifically so in 2004 C republished this ordet cohort and it was a large study of about 9000 women and it went on for about 9 1/2 years and it was designed to look at the incidence of breast cancer as it relates to dietary intake. So what they did was randomized their participants into four different types of ____________ so you had a salad and vegetable group that a raw fruits and vegetables and had monounsaturated fats, then there was the western diet group that had red meat potatoes eggs and then saturated fats like butter there's, the canteen dia group which would be most similar to that their native diets consisting of like pasta and tomatoes, and a more traditional Italian diet because the study was performed in Italy and this this was called the canteen protocol and then finally the last group was randomized into what they called the prudent group which consumed vegetables raise potato fish and wine. and what they found after 9 1/2 years was at _____ of the 9000 women did develop breast cancer and they used that then to take those individuals and stratify them into risk groups based on the number of cancer you know in the incidence of cancer in those women.

dietary patterns 207

Key properties: what you might also see in cancer Genesis and promotion is the fact that these cells avoid _________ and escape ___________. so in normal cells what happens is that cells mature and differentiate into non dividing terminal cells but in cancer cells instead of differentiating into these mature but terminal cells they often stay as _____ cells and they continue to replicate so then you can see why that would be a problem. normal cells also enter into what is called this replicative senescence, which is thought to be a tumor _________ mechanism where cells enter a permanent arrest of growth and altered function after a finite set number of division. so once they divide a set number of times then they go into this replicative senescence where they don't start to grow anymore. they don't multiply anymore. and this is something that's sort of built into that normal cell. so in essence there's only a set number of times that a normal cell can divide but that's not the case when it comes to cancer cells. in cancer cells we don't see this mechanism working so these cells don't go into this sort of repressed state.

differentiation replicative senescence stem suppressive

we have studies that are saying fruits and vegetables are protective right then we have studies that are coming out saying OK hold on not so fast fruits and veggies are good for you but they may not really reduce your risk for cancer, and then you have more studies coming out and saying never mind maybe fruits and vegetables are good after all maybe the earlier studies weren't looking at dose dependency so you know we had the five a day campaign but then the research said OK you need at least _____ servings to have an effect OK So what are we to make of all of this why isn't the human evidence more compelling why do you think why do you think more of these studies aren't showing a statistically significant difference so think about that for a moment

eight

____________________ research helps us to identify disease frequency so it's like a quantifiable way to describe the occurrence of a disease. it allows us to understand disease ________________ like who is it that gets the disease and where is this disease occurring and when is it occurring. and importantly it helps us in trying to answer the why of disease occurrence in distribution. so Epidemiology is a basic science of public health or really the foundational science of public health.

epidemiological distribution

so part of it right is that these studies don't take into account that not all fruits and vegetables are created __________ they all have different nutrients different antioxidants right these studies are also not accounting for the fact that there are a variety of dietary components that might affect cancer risk so when we're studying fruit and vegetable consumption it's not all that the participants are consuming right so these studies are not looking at how other components might interact with each other to create in effect So what do we know about the general diet of individuals who tend to consume a lot of fruits and vegetables those people that tend to just generally consume a lot of fruits and vegetables they tend to follow a healthier diet than those who don't consume a lot of fruits and vegetables right that's another factor that we need to consider why all these results are not as consistent or significant so like the epic trial

equally

why do we see this protective effect everyone is differences in hormones right including __________________ also breast density matters . now estrogen can be a driver of breast cancer but there are different levels and sources of __________ before and after menopause so before menopause the primary source of estrogen comes from the ________ and some is produced by adipose tissue so the thought is that the estrogen that's produced by the fatty tissue might actually help to ___________ the amount of estrogen that's produced by the ovaries so that small amount of estrogen that's produced by the fat tissue before menopause may help tell the ovaries that they can produce less estrogen and also they may help regulate other hormones or growth factors but after menopause women that have that ________ adipose tissue tend to have higher estrogen levels than those women in the same stage of menopause with lower adiposity

estrogen growth factors estrogen ovaries downregulate higher

some of the Association between adiposity and cancer risk may be able to be explained by the simple fact right that the state of obesity results in excess storage of ____. you know there are many many possible mechanisms. why we think this might why we might see this increased risk so we know that obesity is characterized by excess fat storage right and there's some evidence that cancer cells are able to utilize lipids there is evidence that when we have obese individuals we see an upregulation of _______________ or this FA SN this enzyme makes endogenous fatty acids which are then repackaged into structural lipids which are required for cell division

fat fatty acid synthase

a diet that is high in ________ overall can increase their risk for cancer and there's a couple of different reasons for this or couple different thoughts or theories around this. one is that the meat displaces some of the cancer ________ foods. if you have a diet that's really high in meat then you're less likely to be eating high amounts of fruits and vegetables and whole grains just because of the displacement that occurs. meats are also sources of _________ and specific fatty acids that have been linked to increase risk for cancer. although the mechanism by which this happens is not that well defined. I try to find some good research that explained why we see that risk and I really couldn't find good answer to that and then red meats are source of ___________ which is also been shown to increase the risk by promoting oxidative damage.

meat preventing fatty acids heme iron

Mechanism through which obesity may drive this cancer pathogenesis is through converting the __________ that we consume through a diet that would be high in fat enter these pro tumorigenic signaling lipids so there are lipids which actually have signaling properties. so the thought is that the signaling lipids that become pro tumorigenic can then signal other cells to start that ___________ process there have been studies that have shown that you know like why like I just talked about that the aggressive cancer cells that are you know that up regulate the medial that they are then incorporated into these oncogenic signaling lipids which in turn drives cancer pathogenicity so of course we can all guess right the link between _______________ adiposity in cancer right we know that adipocyte's induce a low grade chronic metabolically linked inflammatory state right which is different than the traditional inflammation and as we talked about a lot last semester that is due to cytokines in more specifically it's due to those adipokines right causing the state of inflammation which increases cancer risk so the major players in this are all the ones that we've heard of before right the tumor necrosis factor Alpha or TNF a interleukin 6PL1 left in all of these.

fatty acids oncogenic inflammation

so each ______ point increase in BMI after menopause is associated with a 12% increase relative risk but each five point increase in BMI before menopause confers protection. so we see an ___% decrease relative risk of breast cancer prior to menopause for every five point increase in BMI. I want to point out that breast cancer risk again I want to point this out starts to increase in a BMI range of ______ right and that's within the normal range so that's pretty significant and when you look at general cancer prevention guidelines for BMI they recommend keeping our BMI within that 21 to 23 range but what is the actual optimal BMI range for breast cancer prevention it's a BMI of _______

five 8 21 to 23 20 to 22

Specific studies to show how some of the evidence based guidelines for cancer prevention have originated so when we talk about cancer prevention what is one of the first dietary strategies that pops into your head ,I always think of high ____________________ as being sort of the first line of defense when it comes to preventing cancer. and we aren't the only ones to make that connection we as in the United States have done has done a pretty good job of communicating that particular message to the public. this idea that fruits and vegetables can be protective against cancer is something that's pretty widely accepted and known so there is a significant body of evidence that shows that there is a reduction in cancer occurrences as fruit and vegetable intake increases and again we've tried to get that message out pretty strongly.

fruit and vegetable intake

so now both Omega threes and Omega 6 derived eicosanoids affect tumor growth and progression but like I said Omega threes to a lesser degree so the Omega sixes are the ones that lead to the alter ________________ but the omega-3 fatty acids can affect this ____________ you can see they'll make a six is they promote angiogenesis they also call cause the alter gene expression cell proliferation in cancer growth The Omega threes also will in fact it will impact apoptosis so again what is apoptosis It's cell death right so in cancer one of the things that I talked about before is this balance right. so in cancer you have the loss of balance between ________________ and cells that should have died did not receive the signal to do so so it's thought that these omega-3 eicosanoids slow down apoptosis thus creating that imbalance right where you see the cancerous cells proliferate and differentiate an then you know that ultimately results in tumor growth in cancer progression but then you have that really reduced apoptosis so they're also not slowing so the cancer cells that are proliferating in growing are doing so at a faster rate than those cells that are dying and so you see how it plays at vital role in carcinogenesis

gene expression and angiogenesis apoptosis cell division and cell death

the Association between BMI and breast cancer risk has been looked at for you know for a while now and here's what we know first there seems to be a little bit of a paradox where you know a _______ BMI in pre menopausal women seems to be protective against breast cancer but increases the risk and those who are post menopausal so in other words a higher body weight or adiposity in younger women is linked to a lower risk of breast cancer

higher

we see a higher prevalence of you know what we would call or consider ____________________ cancers the ones that are sensitive to estrogens so cancer is like ___________________ but also things like stomach cancer and liver cancer as well. now when it comes to children you know again we most often think of those blood and bone marrow cancers right like the ______________________ but you also see brain tumors and solid tumors in the pediatric population as well sadly.

hormone positive prostate cancer breast cancer lung cancer colorectal cancers leukemias and lymphomas

now in addition to a high fat diet leading to obesity, dietary fatty acids can impact the synthesis of eicosanoids as well. so eicosanoids are lipids that in some ways behave like _____________ they're kind of like a localized hormone so they're essentially these short lived hormone like lipids that are derived from _________________. so they act as these signaling molecules in a variety of different cellular and hormonal pathways so hormones are often produced right in one part of the body but then they travel to work at other sites right but it goes in waves are produced mostly mainly where they're going to have an effect and they also breakdown fairly rapidly so they don't really travel very far either so it's so it's more of a localized effect that they have

hormones omega-3 and Omega 6 fatty acids

epidemiological research is really this study of ___________ diseases occur in different groups and then why are we seeing those results or in other words, it is the study of the distribution of ________________ in populations and the application of this study to control actual health problems or health outcomes.

how often diseases and other health related conditions

in the 2007 world Cancer Research fund report that they came out that they came out with and so these are really supporting their recommendations and why the recommendations were actually made. now when you look at this figure the relative risk is on the left and the use of hormones is on the right and this study was looking at post menopausal women so the hormones are referring to our estrogen replacement therapy hormones and then you have weight gain that's going across the bottom now take a look at sort of these pinkish purplish bars in the front row show women who have never used hormone replacement therapy now what I want you guys to take note of is that as these women gain weight there was an ________ in relative risk could see the risk start to increase with the highest relative risk being an individuals who had more weight right so you can start to see the that as your weight goes up so does your relative risk and that's really all I'm pointing out here so weight gain so not only is your weight status put you at increased risk weight gain in your adult years also puts you at an increased risk

increase

so in this particular study by Cali which was in 2003 they looked at a rather large cohort of individuals who are identified as having colorectal cancer and it's risk as it related to BMI so it's interesting to find out that you know our control group had a BMI of 18.5 to 24.9 and this represented a relative risk level 1 but even if we look at the BMI index of the overweight category the 25 to the 29.9 you can start to see an _____________ risk of colorectal cancer in that population So what we have is that here is that there is a linear relationship you know as BMI increases so does the relative risk so we have evidence that supports BMI as an independent risk factor for cancer and in this case specifically colorectal cancer that I just want to point out some of the different studies so you can see how consistently we've gotten these results even with some of this older data

increase

so in a healthy gut with enough fiber you have enough short chain fatty acids to mediate this macrophage recruitment you don't want these macrophages because they then can lead to _____________ and ultimately cancer so these short chain fatty acids you know help with that they also help manage the production of proinflammatory cytokines because we know right that there was a direct link between inflammation and cancer risk and then finally having the right amount of short chain fatty acids maintains the integrity of the gut making sure that the GI tract can really stand up to salt an injury from inflammation even though there are a lot of epidemiological studies that have shown an inverse relationship between fiber intake and colon cancer

inflammation

how dietary fats can create an oncogenic environment so the simplest relationship on this chart is the 1 between these high fat diet and obesity right so you consume a high fat diet that leads to obesity that leads to __________________ leads to hormonal imbalances which can then affect our gene expression by way of _____________ then you start to see those cells with the alter gene expression increase their rate of ___________________ because remember right cancer is an uninhibited growth of those mutated cells and then what ends up happening you end up with tumor growth and progression right.

inflammation altering our DNA proliferation and differentiation

the increased risk of cancer is projected to continue. so the increase is significant but I want to say it's not as as dramatic as it may appear on the surface. so a lot of times you hear statistics that say that cancer rates are going to continue to increase and this is true but this is also largely due to the fact that our ____________ is increasing. so as we age, our risk for cancer increases and so when you look at this graph you can see that the greatest increase is in the _______ individuals and this is related to the fact that there is a greater incidence of cancer in the elderly. so the population is getting older, people are living longer, so we start to see cancer rates continue to increase now when you look along the bottom of this graph. the individuals age less than 50, you don't really see an increase. it's you know kind more stabilized. there's a slight increase here compared to what is here but it's pretty stable and individuals less than 50 and the increases are really only evident after the age of ____.

lifespan older 65

____________ factors have been linked to cancer and this link is well established and widely accepted. we know that the BMI independent of dietary specifics is a contributor factor in increasing cancer risk. we also know that there is a relationship between the way we cook in processed food and cancer risk rate so it was really big news when the WHO categorized red and processed meats as causing cancer. it turned out that how we prepare the food also increases this risk or plays into this risk so specifically the research showed that red meat increase the risk for ____________ cancer as did the consumption of processed meat. a study was conducted by a group of international quote unquote nutritionists so I'm not sure if they were dietitians or not because they just called themselves nutritionists but they came to the conclusion you know through what appears to have been a systematic review and five smaller studies their conclusion was that they failed to find any certainty that eating red meat or processed meat causes cancer or diabetes or heart disease, so they want to step further to come up with ______________ and they stated that people did not need to reduce their red beat their red meat and processed meat consumption.

lifestyle colorectal guidelines

Link between _______________ is further strengthened when you look at the differences between and within countries overtime as well as immigrant studies that illustrate how individuals or their descendants eventually develop cancer at the _________ as those in their host country and that is really what I just want this slide to depict you on the previous slide I showed you how you know the people from Japan had lower morbidity and mortality but even with their decreased overall risk they had they had high rates of significantly high rates of gastric cancer

lifestyle and cancer same rate

how you're cooking it does make a difference. the amount and type of carcinogens that accumulate in cooked meats are dependent on the _______________________. so pan frying grilling barbecuing all have been shown to produce high levels of these mutagens with ____________ yielding higher mutagenic activity than grilling at a similar temperature. we see an increased risk in cancers like breast cancer and kidney cancer but how does this actually happen so the thought is that these hot this high temperature cooking that high temperature produces these _____________ or sometimes you'll see them referred to as HCA's and they produce these ______________ or the ages which arm eugenic meaning that they cause changes in the DNA that may increase the risk for cancer

meat type, the cooking method, and the temperature and the duration of cooking pan frying heterocyclic amines Poly cyclic aromatic hydrocarbons

The other thing is that not all people are the same so because we have so many people how they ____________ something how it interacts with other components of their life how their diet interplays with their lifestyle all play a role so when we're looking at _______________ studies we have to realize that they are associations they're not cause and effect so we can just do these general sweeping generalizations but we cannot say that their cause and effect

metabolize epidemiological

but insulin and insulin growth factor are really at the center of a lot of research as they relate to cancer so human observational studies have reported have reported increased cancer mortality in those with __________________ which could be due to the hyperinsulinemia or the elevated IGF rate. on the flip side those with low insulin IGF appear to be relatively _________________ from cancer development. also what research has shown us is that type 2 diabetics who get insulin therapy or drugs to stimulate insulin secretion have a significantly higher incidence of cancer than those who are type 2 or those that are on _______________ in fact you know when you look at the epidemiological studies have consistently associated metformin used with decreased cancer incidence in cancer related mortality and because of that metformin is being looked at as a potential anti cancer agent.

obesity and type 2 diabetes protected metformin

So the actual biological mechanisms underlying their relationship between obesity and cancer are complex and they're not that well understood they include __________________ there's a lot of things that affect cancer cell promotion and progression so even though the correlation between obesity and cancer is not new in fact when you look at the medical literature you can see that relationship going back many many decades you know the relationship between obesity in cancer it just wasn't very well understood until that cail article that first chart that the first graph that I showed you until then we just don't really quite understand what was happening that was really a landmark study and it was large so the results were quite meaningful

obesity related hormones growth factors modulation of energy balance calorie restriction multiple like signaling pathways inflammatory processes

so the mechanism by which dietary fats might exert these modulatory effect on like these modular effects I should say on cancer initiation and progression are not very well understood but the general thought thoughts are that they may include there know the impact that these fats have on _______________ and alteration of the hormonal metabolism modulation of cell signaling transduction pathways and the regulation of gene expression

oxidative stress

so these epidemiological studies are really critical to prevention because when the study results are valid they are directly applicable to _____________ as opposed to laboratory findings that we might have in animals which often cannot be just simply extrapolated to humans. that we tend to report animal results as if they are generalizable but they aren't. as we know I've talked a lot about the benefits of Epidemiology but there are some limitations that I want to point out to so most epidemiology is ________ so there aren't as many randomized control trials and we know those are the gold standard. the way things are measured in Epidemiology are subject to interpretation. we also have no way of knowing how long we need to measure something or how long an exposure needs to be to see the effects. so how long does someone need to consume an antioxidant rich food to see an effect or how long does somebody need to smoke with when there to increase their risk for lung cancer also the amount of effort and resources in these large scale epidemiological studies are that are required are quite significant

people observational

Epidemiology as a discipline has played a key role in cancer _______________. so over the past 60 or 70 years or so this epidemiological research has really helped to elucidate many __________________ when it comes to cancer specifically. so this research has Really helped us identify not only the risk factors for specific cancers but it also helped to estimate the proportion of cancer deaths that are attributable to those established risk factors. so when you wonder you know where these numbers or where this information comes is coming from it's coming from this epidemiological research.

prevention and control risk factors and preventive agents

so after menopause the ovaries are no longer the ___________________ of estrogen. instead most of the estrogen is coming from adipose tissue right because you're post menopausal so you're the main source of your estrogen now is the adipose tissue. so more adipose tissue then post menopausal means we have higher estrogen levels which can then increase the risk for breast cancer. so premenopausal the thought is that the ovaries are producing so much estrogen and if you have a lot of fat cells that are producing a smaller amount they will tell that will push the ovaries to produce less estrogen. it won't need to produce as much 'cause the fat cells are producing something so you have this amount of estrogen that you need but now what after menopause the ovaries are not producing at any estrogen right so all the estrogen that's floating around in your body is floating around that's being made by the fat cells so the more ________ you have the higher estrogen will be so it will be higher than you need because we don't need estrogen at that point or high rates of estrogen after menopause right so that's where you see that increase risk

primary source fat cells

so then we thought you know what do we do with this information and the thought was well you know fruits and vegetables can't hurt so keep pushing them for other benefits even if we don't see such a strong relationship between increased food vegetable intake and _________________. then in 2010 the epic study looked at fruit and vegetable intake and they did find you know particularly in increasing fruit consumption that there was a ______________ reduction in risk with increasing the number of fruit servings with vegetables there were only that that benefit was only significant in the _________ population. this epic trial was a very large study that was really hoping to find more of a positive Association between fruit and vegetable intake consumption and the reduced risk of cancer so the results were disappointing and they were modest at best i only go through that to say you know it's we feel like there's such a high association but the research isn't as strong

reduce risk for cancer small very modest female

now dietary Epidemiology has been highly successful in identifying the _______________ in many diseases right like think something like scurvy or pellagra or blindness or spina bifida. like we've been able to say OK it is this deficiency that's causing this syndrome and you know these are all conditions that we know are highly related to diet right. So what are cancer Epidemiology studies trying to accomplish they're really trying to describe the distribution of cancer as well as discover the _____________ that may be specific to each cancer or groups of cancer so you know for example a good example is the link that's been established between smoking and lung cancer rate so those studies that they did were very critical in identifying the causative agent

responsible agent determinants

this graph is looking at the morbidity and mortality from cancer when you compare it to the intake of animal fat per capita so in other words you know the intake of ________________ so they're looking at cancer morbidity mortality as it relates to fat saturated fat intake so this data is from a lot of different countries and as there is an increase in the intake of animal fat there's also a concomitant increase in the ______________. there is also an increase in the relative risk of morbidity in all cause mortality rate. and then at looking at specific countries you can start to identify populations that have higher fat intake and that because of this higher fat intake, they have higher rates of morbidity and mortality. and I'm just pointing out Japan here because they have one of the lowest animal fat intakes and they have one of the lower age adjusted morbidity and mortality rates because of that. then what about you know when you start to look at some of the you know the western countries on here what do you seek we see a higher fat per capita in a higher age adjusted morbidity and mortality rate so by using this population data and extrapolating the data you can begin to look at these relationships and _______________ helps us do that.

saturated fat cancer incidence Epidemiology

cancer is actually the ____________ leading cause of death in the United States in the adult population and is the _________ leading cause of death in children a lot of the childhood cancers

second fourth

what we need for cancer Genesis are ________________ that have to occur within the lineage of 1 cell so that single mutation doesn't do it you need you know multiple mutations within the lineages of that one cell to result in a cell's mutant enough that can turn into a cancer cell. so it seems based on the research at the development of cancer requires mutations in about ___ genes or more and there are ___ key properties for cancer development but I also want to point out is that we have a pretty intricate system in place to keep those damaged or mutated cells from taking over so every cell in the body has a number of very elaborate ________________ that can be deployed to fix this sort of damage so that normally these cells won't and can't divide uncontrollably. so while we think of cancer as the division of damaged cells essentially what it really is a failure of our repair mechanisms to work appropriately so then what happens we have these damaged cells that escape the protective mechanisms right that we have in place which then results in a _____________, which is just knew an abnormal growth of tissue and some part of the body.

several independent rare accidents 10 6 repair mechanisms neo plasm

from the impact of fiber obviously the impact that it has on the gut microbiota. we know that there are numerous diseases and conditions that are associated with disturbed gut microbiota. many of these health benefits that are derived from fiber can be attributed to the fermentation of dietary fiber into those________________ in the colon so the idea is that these high fiber diets increase and promote the transit of food stuff like through the intestine thereby limiting the amount of time that ______ are present within the intestine so essentially then you're increasing the rate at which toxins are excreted and also minimizing the time that the toxins can come into contact with the intestinal cells now also we have the short chain fatty acids right that are produced by the breakdown and the fermentation of the fiber so these short chain fatty acids exert a lot of influence on them on things like macrophage recruitment on these proinflammatory cytokines and the maintenance which is really important of that GI barrier right

short chain fatty acids toxins

Key properties: Cells have to disregard the external and internal ___________ that regulate cell proliferation. so there are homeostatic mechanisms in place that regulate the rate of proliferation and we generally have mechanisms in place to stop the proliferation but we also have mechanisms in place to balance that proliferation not just by preventing the proliferation from occurring in the 1st place so in normal adult tissues especially those at risk of cancer cells may proliferate continually but their numbers remained pretty steady because cell production is then balanced by cell _____________. A common DNA mutation is 1 in which this balancing mechanism is altered leading to cancer because that apoptosis is altered so specifically these cells tend to avoid _______ via apoptosis

signals apoptosis suicide

Key properties: these cancer cells also are genetically __________ so they have the ability to escape from their home tissues which is not the case with other cells like we don't see lung cells implanting themselves and growing in the in the liver. so we wouldn't see like a liver cell just go and transplant itself in the heart or in the lung. for example now tide to the fact that they can escape is the fact that they can then survive and proliferate in different tissues or in foreign sites so these liver cells can grow and thrive in the lung and then escape and thrive in the breast tissue for example so these six properties that I have listed here they are the requisite properties that a cancer cell possesses in order to survive and thrive

unstable

whether people with higher vitamin D intakes or higher blood levels of vitamin D have lower risks have been inconsistent I mean possibly because of the challenges that we talked about earlier and carrying out a lot of these dietary studies like for example a lot of these dietary studies don't account for the _______________ and level of vitamin D measured in the blood at a single point in time. as happens with many of these studies may not reflect a person's true vitamin D status right but the the cancers for which the most human data are available for colorectal breast prostate and pancreatic cancer and a number of epidemiological studies have shown that higher intake are blood levels of vitamin D are associated with a reduced risk of some of these cancers in very specifically with _____________________ but I will say that the results have been inconsistent and so right now the Association is weak and so why are we seeing some of these inconsistencies you know just because you know some of the supplementation that they've done in these research studies has been really small you know the ability of participants to take additional vitamin D on her own because that's really all there monitoring is what the what vitamin D there so there's just a lot of variability so there's a lot more research that needs to be done in fact there are a few large trials going on right now that are trying to look at this link

vitamin D intake made in this skin right from sunlight exposure colorectal cancer

The Who, the American Cancer society, many other health organizations do not agree with us so if you see this you need to see that the consensus does not agree with this and they really feel like these recommendations do not reflect current nutrition literature and you know from our perspective, I feel like this is what causes confusion right to the public. but it was their recommendations that were based on not a very strong study that caused everybody to say hold on not so fast so eating red meat and processed meat you know increases the risk for cancer but researchers also found that high meat cookery also can increase your risk for certain cancers. other research that found that high consumption of __________________ they also increase the risk for cancer specifically things like colorectal cancer pancreatic cancer prostate cancer. So what are the lower risk cooking methods _____________________. OK So what else do we know about the relationship between cancer and nutrition we know that deficiencies as well as excess is of certain nutrients right can increase the risk and lifestyle factors like physical activity, substance abuse which is a large factor and then viruses right HPV which increases the risk for _____________ cancer as we talked about last semester H pylori it's increased risk for gastric cancer

well-done fried or charred meats baking broiling crock pot cooking cervical