Ch 14 - Physical Activity, Fitness, and Cancer

Plausible mechanisms for reduced cancer risk with physical activity

-modulation of reproductive hormone levels -decrease in body weight and adiposity -change in levels of insulin-like growth factors and their binding proteins -decrease in inflammation -decrease in intestinal transit time -enhanced immune function

What is the median relative risk across all studies comparing most active with least active men is?

0.9. This median value is close to a relative risk of 1.0, which indicates no difference in prostate cancer incidence rates between active and inactive men

There are three major epidemiologic study designs:

1) randomized clinical trial 2) cohort study 3) case-control study

The large body of evidence that accumulated led to two cancer agencies to make recommendations specifically targeting physical activity as a cancer preventive measure for the first time in?

2002

On average, the studies have indicated that people who are physically active have a...

30% lower risk of developing lung cancer than those who are sedentary

Cancer

A chronic disease that is multifactorial in its etiology, with contributions from both environmental factors (not only factors such as radiation but also smoking, physical inactivity, diet, viruses, etc.) and genetic factors. The disease arises when excessive, uncontrolled, and purposeless proliferation of cells occurs in the absence of physiological stimuli. These cells invade the surrounding tissues and spread by means of the lymphatics and blood vessels to give rise to secondary cancers, or metastases.

Confounding

A phenomenon that may exist in the data from epidemiologic studies and cloud the interpretation of findings. As an example, say we compare the rates of colon cancer that develop among a group of athletes and among a group of sedentary persons. We find that the rates are lower among the athletes compared with the sedentary group. Can we conclude that physical activity lowers the risk of developing colon cancer? If we look more closely at the groups, we might find, perhaps that the athletes are much younger than the sedentary group. Cancer rates also increase with age. Thus, the lower rates of colon cancer that we see among the athletes may have nothing to do with physical activity but instead reflect the fact that the athletes are younger. This phenomenon is termed confounding. Statistical adjustment can be made in data analyses to factor in the age differences. If we perform this adjustment and continue to observe lower colon cancer rates among the athletes, it is reasonable to conclude that physical activity is associated with lower colon cancer rates, provided that there are no other confounders.

Randomized clinical trial (RCT)

A type of epidemiologic study design in which participants are grouped on the basis of the investigator-assigned exposure of interest, in this case, physical activity. For example, among a group of eligible participants, investigators may randomly assign them to exercise at three levels: no activity, moderate activity, and vigorous activity. These participants are then followed over time to assess the outcome of interest, such as change in abdominal fat. This is often considered the "gold standard" of epidemiologic study designs. However, because of the cost and issues regarding compliance with an assigned activity level, it may not always be feasible, or even desirable, to conduct RCTs.

Although some researchers have reported lower rectal cancer rates among active individuals, the data on the whole do not support any relationship between physical activity and rectal cancer risk.

Across all studies, the median relative risk when comparing most active to least active participants is 1.0. That is, on average, the data indicate that the rates of rectal cancer among most and least active persons are the same.

What is the major factor of why RCTS may not always be feasible or even desirable?

Because RCTs are by far the most expensive study design

In case control studies, participants with cancer are referred to as cases. A comparison group of participants without colon cancer is needed; they are referred to as controls.

Both groups are assessed for their physical activity in the past, and case participants are assessed for physical activity that occurred before the onset of cancer. The prevalence of different levels of physical activity in the two groups is then assessed. This allows the investigators to determine whether people with colon cancer have a lower prevalence of physical activity compared with control participants (i.e., are case participants less active?).

The most common sites of new cancers occurring in men in 2010 were expected to be

Breast, lung, colorectum, uterus, and thyroid

The data supporting a role oh physical activity in lowering lung cancer rates are promising, a major concern, given that the findings are derived from cohort and case-control studies, is confounding by?

Cigarette smoking. As discussed previously, physically active persons tend to be health conscious and thus are less likely to smoke cigarettes, a major risk for lung cancer.

Data suggests an inverse relationship between physical activity and endometrial cancer risk,

Consistent with the hypothesis that physical activity can lower estrogen levels, which are related to increased risk of this cancer.

It has been proposed that physical activity speeds up transit time within the colon,

Decreasing exposure to carcinogens, cocarcinogens, or promoters in the fecal stream. Although some studies have shown faster transit time among physically active persons, not all studies have supported this finding.

Data are clearest in support of physical activity or fitness as a means of preventing colon and breast cancers. It also appears reasonably clear that physical activity or fitness does not influence rectal cancer rates.

For prostate cancer, the data have been equivocal, whereas for lung and endometrial cancers, there are suggestive, although not definitive, data to support inverse associations.

To be certain that the inverse relationship between physical activity and lung cancer rates do not reflect confounding by smoking, a study could be conducted for not among never-smokers.

However, lung cancer occurs very infrequently among never-smokers which would make this a difficult study to conduct

The available evidence suggests that moderate levels of physical activity can enhance the immune system.

However, prolonged and intense exercise (e.g., running a marathon) may have the opposite effect, leading to a temporary period of immunosuppressive that lasts perhaps days to as long as two weeks

Early onset prostate cancer may be more likely influenced by genetic factors, with physical activity less important, and the opposite may be the case for prostate cancers occurring at older ages.

However, studies of physical activity and prostate cancer occurring at different ages have not provided clear evidence supporting this hypothesis

The most common fatal cancers occurring among U.S. men in 2010 were estimated to be:

In order of frequency, cancers of the lung, prostate, colorectum, pancreas, and liver

Elevated levels of inflammatory markers such as C-reactive protein (CRP) and decreased levels of anti-inflammatory markets such as adiponectin have been linked with?

Increased cancer risk (schottenfeld and beebe-dimmer 2006). Physical activity is associated with a reduced inflammatory state, and this also may be the result of decreased adiposity

Physical activity may reduce the risk of developing cancer by enhancing the?

Innate immune system, which is responsible for regulating susceptibility to cancer development

Physically inactive persons who take up physical activity may be more likely to lose abdominal fat. Obesity, in particular abdominal obesity, is associated with insulin resistance, hyperinsulinemia, hypertriglyceridemia, and higher levels of insulin-like growth factors.

Insulin and insulin-like growth factors have been implicated in the etiology of several cancers, such as breast, prostate, and colon cancers. Thus, this may represent a third pathway through which physical activity has the potential to influence cancer development.

What is one limitation of RCTs whether long or short term

Is the characteristics of participants being studied. The criteria for inclusion in a clinical trial tend to be strict; participants often need to be in good health to enter the study, must agree to be randomized to the different treatment (or intervention) groups, and must agree remain committed to the study protocol for the duration of the trial. This leads to selection of individuals who tend not to be representative of the population of interest to selection of individuals who tend not to be representative of the population of interest.

In 2007, 2.4 millions died in the U.S.; of these deaths, 25% were attributed to heart disease, and 23% more than half a million deaths were attributed to cancer.

Looked at in a different way, these data indicate that approximately one of every four deaths in 2007 was caused by cancer.

Among adult pre-and postmenopausal women, higher levels of physical activity have been correlated with?

Lower levels of estrogen and progesterone

That most common fatal occurring among U.S. women were expected to be cancers of the:

Lung, breast, colorectum, pancreas, and ovary

Girls who participate in physical activity and sport tend to be older at?

Menarche and are more likely to have cycles that are anovulatory. These effects can decrease breast cancer risk because later age at menarche is associated with lower breast cancer rates, whereas anovulatory cycles are associated with lower levels of estrogen.

Participants for the other study designs, described next, also may not be representative, the lack of representativeness generally is more pronounced for RCTs because?

Participants have to agree to be randomized to different treatment groups as opposed to merely being said observed for their usual habits.

Because risk factors for breast cancer in premenopausal women and postmenopausal women may be different, several studies have examined these groups separately.

Physical activity appears to have a somewhat larger effect for post-than for premenopausal women.

Globally, as well as in the states, cancer is the?

Second leading cause of death, after cardiovascular disease

Evidence for a role of physical activity in preventing cancer

The evidence for a role of physical activity in preventing certain cancers comes primarily from epidemiologic studies. The findings from such studies are supported by plausible biologic mechanisms

The most common sites of new cancers occurring in men in 2010 were expected to be, in order of frequency:

The prostate, lung, colorectum, bladder, and skin (melanoma)

Many studies have continues to show a lower risk of breast cancer among active women even after adjustment for other risk factors such as age, body mass index, alcohol intake, use of oral contraceptives and hormone therapy, reproductive variables (ages at menarche and menopause, menopausal status, parity, age at first birth, breastfeeding), benign breast disease, and family history of breast cancer

There have been no RCTs, the data that we have for breast cancer are unlikely to be confounded by risk factors associated with a physically active lifestyle.

Increased concentrations of sex hormones binding globulin have been observed in women who are physically active

These globulins bind to estrogens in the circulation, leading to lower concentrations of the free, active hormones. Such changes in estrogen levels with physical activity also can be expected to decrease the risk of developing endometrial cancer among physically active women, because higher levels of estrogen strongly predict higher rates of endometrial cancer.

A second major pathway through which physical activity may influence the risk of cancer is via its influence on?

Weight and adiposity. Because physical activity is associated with lower body weight and fat, it may reduce the risk of developing several obesity-related cancers