Cancer

CARCINOGENS

1) Infectious Pathogens 2) Chemicals 3) Radiation

Transformation & Progression

Self-sufficiency in growth signals Insensitivity to growth-inhibiting signals Evasion of apoptosis Defects in DNA repair: "Spell checker" Limitless replicative potential: Telomerase Angiogenesis Invasive ability Metastatic ability

Malignant Tumors (Cancer)

Examples: Leiomyosarcoma Chondrosarcoma Osteosarcoma Liposarcoma Teratoma

Cancer EpidemiologyHistorical Perspective

1775 British surgeon, Percival Pott reported probably the first description of occupational carcinogenesis in the form of scrotum cancer among chimney sweeps. due to exposure to soot. 1700s: tobacco and cancer Reports of cancer risks associated with tobacco in the 18th century included snuff taking and nasal cancer, reported by Hill in 1761, and pipe smoking and lip cancer by von Soemmering in 1795.

Tight corsets and cancer

1842 Rigoni-Stern, Italian physician, observed that married women in the city were getting cervical cancer, but nuns in nearby convents weren't. He also observed that nuns had higher rates of breast cancer, and suggested that the nuns' corsets were too tight

Global Burden

A Leading cause of morbidity and mortality worldwide Annual incidence estimated at 10 million Accounted for around 7.9 million deaths in 2009 > 70% of all cancer deaths occur in low and middle-income countries By 2030, cases and deaths will increase by 69% and 72% respectively

Cancer Deaths in Developing Versus Developed Nations, Men, 2007

Among men living in developing nations, the total number of deaths due to either liver cancer or stomach cancer was more than 3.5 times higher than in developed nations reflecting high rates of infection by liver viruses (HBV and HCV) and stomach bacteria (Helicobacter Pylorus) plus contamination of food supplies by molds that produce highly carcinogenic aflatoxins. Deaths from colorectal cancer or prostate cancer, however, occurred more frequently in developed nations partly due to intake of diets high in fat and calories and low in fiber, fruits and vegetables. Lung cancer and other cancers arising from tobacco smoking caused the most male deaths in all populations.

Cancer Deaths in Developing Versus Developed Nations, Females, 2007

Among women living in developing nations, cancer of the uterine cervix caused the greatest number of deaths, principally due to lack of screening for premalignant dysplastic lesions of the cervical mucosa. Breast cancer was the leading cause of cancer death in developed nations and ranked second in developing nations.

Cancer Deaths in the US

Approximately 1.5 million new cases of invasive cancer are diagnosed annually in the United States. In 2007, more than 565,000 persons died from cancer. LUNG CANCER IS THE LEADING CAUSE OF CANCER DEATHS IN BOTH MEN AND WOMEN. Cancer mortality and incidence rates vary considerably by race and by gender. Men have about 30% higher cancer death rates than women. African American men have the highest death rates from cancers of the lung and bronchus, prostate, and colon and rectum compared to any of the other racial or ethnic groups in the United States.

Environmental vs. racial factors

Breast cancer incidence rates have historically been 4-7 times higher in the United States than in China or Japan When Chinese, Japanese, or Filipino women migrate to the United States, breast cancer risk rises over several generations and approaches that among U.S. Whites. Foreign-born Asians have some of the lowest breast cancer rates in the world, but their risk increases quickly when they adopt a Western diet and lifestyle.

Cancer

Cancer is a disease that affects around one-third of the human population, irrespective of nationality or ethnic origins. There are many types of cancer, but they all have one thing in common - they begin as rebel or mutant cells.

Cancer Mortality in U.S. Women, 1930-2007

Cancers of the lung and bronchus, breast, and colon and rectum account for more than half of all cancer deaths among U.S. women. Lung cancer surpassed breast cancer as the leading cause of cancer death in women in 1987. Since 1950, lung cancer mortality among women has increased by more than 600% and now accounts for about 25% of all female cancer deaths. Breast cancer mortality remained remarkably constant throughout the 20th century but appears to be slightly declining in recent years. Mortality rates from cervical cancer and stomach cancer declined dramatically during 1930-2011. Colorectal cancer mortality among has gradually declined since the 1950s (American Cancer Society, 2011).

Types of Cancer

Carcinoma - most common type of cancer. They are formed by epithelial cells, Sarcoma - form in bone and soft tissues, including muscle, fat, blood vessels, lymph vessels, and fibrous tissue Leukemia - begin in the blood-forming tissue of the bone marrow Lymphoma - begins in lymphocytes (T cells or B cells). Multiple Myeloma- begins in plasma cells Melanoma - cancer that begins in cells that become melanocytes, which are specialized cells that make melanin (the pigment that gives skin its color).

TUMOR SUPPRESSOR GENES

Genes which, when mutated, lose their normal ability to suppress cell growth TGF-β COLON NF-1,2 NEURAL TUMORS SMADs GI RB RETINOBLASTOMA P53 EVERYTHING!! WT-1 WILMS TUMOR BRCA-1,2 BREAST KLF6 PROSTATE etc

Infectious Pathogen Carcinogens

Human papilloma virus Cervical cancer Epstein-Barr Virus Nasopharyngeal cancer Hepatitis B virus HepatoCellular Carcinoma (Liver) Human herpes virus-8 Kaposi sarcoma Helicobacter Pylori (bacteria) == Gastric cancer Streptococcus bovis == Colorectal carcinoma Schistosomiasis hematobium == Bladder cancer

Somatic Mutation Theory of Cancer

In the Somatic Mutation Theory, carcinogenesis results from accumulation of two or more somatic mutations that favor neoplastic development (Knudson, 2001) Cancer arises from a single mutated cell that develops into a cancerous tumor with cell replication and accumulation of multiple DNA mutations over time.

Benign

Lipoma Fibroid (leiomyoma) Fibroadenoma (benign breast tumor) Pituitary adenoma etc Papilloma Adenoma Nevus

Metastasis

Metastatic cancer is a cancer that has spread from the part of the body where it started (the primary site) to other parts of the body. Breast cancer that spreads to and forms a metastatic tumor in the lung is metastatic breast cancer, not lung cancer When cancer cells break away from a tumor, they can travel to other areas of the body through the bloodstream the lymph system (which contains a collection of vessels that carry fluid and immune system cells). Direct Invasion

Global Cancer Deaths: Female

More than 3.3 million women died from cancer in the world population during 2007 (American Cancer Society, 2007). Breast cancer caused the most deaths (more than 465,000) followed closely by lung cancer (more than 376,000). Gastrointestinal cancers (i.e., stomach, liver, esophagus and pancreas) together accounted for about one million deaths. Malignancies of the genitourinary tract (i.e., uterine cervix and ovaries) caused another 450,000 deaths.

Global Cancer Deaths: Male

More than 4.3 million men died from cancer in the world during 2007 (ACS, 2007). More than one million men died from lung cancer and other malignancies of the respiratory tract Nearly two million died from malignancies of the gastrointestinal tract An additional 10% of male cancer deaths were caused by malignancies of the genitourinary tract (prostate, kidneys, bladder).

Theory of Cancer

More than a century ago, the famous German pathologist, Rudolph Virchow, suggested that chronic inflammation leads to cancer development by increasing uncontrolled cellular proliferation (Virchow, 1863; Balkwill and Mantovani, 2001).

Cancer Mortality among U.S. Men, 1930-2007

More than half of all cancer deaths in US men are due to cancers of the lung and bronchus, prostate, colon and rectum. While lung cancer mortality has declined slightly since about 1990, the male death rates from lung cancer are still more than double that of any other anatomic site. Prostate cancer surpassed colorectal cancer in 1987 as the second leading cause of cancer deaths in men. The mortality rates from both prostate cancer and colorectal cancer show evidence of a gradual decline in the past decade. Mortality rates from other malignancies have remained constant, except for stomach cancer rate which have declined dramatically beginning in about 1930 (American Cancer Society, 2011).

Molecular Basis of Cancer

NON-lethal genetic damage A tumor is formed by the clonal expansion of a single precursor cell (monoclonal) Carcinogenesis is a multistep process

Neoplasia

Neoplasia is new, uncontrolled growth of cells that is not under physiologic control. A "tumor" or "mass lesion" is simply a "growth" or "enlargement" The term "cancer" implies malignancy, but neoplasms can be sub classified as either benign or malignant.

CHEMICAL CARCINOGENS:INITIATORS

Nitrosamine and amides (tar, nitrites) Vinyl chloride angiosarcoma Nickel Chromium Insecticides Fungicides PolyChlorinated Biphenyls (PCBs) Natural Plant and Microbial Products Aflatoxin B1 Hepatomas Griseofulvin Antifungal Cycasin from cycads Safrole from sassafras Betel nuts Oral SCC

Screening exams

Pap test and human papillomavirus (HPV) testing starting at age 21 repeat every 3 yrs Yearly mammograms starting at age 40 Colonoscopy, sigmoidoscopy, and high-sensitivity fecal occult blood tests (FOBTs) beginning at age 50 Regular breast self-exams Clinical breast exams every 3 yrs PSA test starting from 45-50 yrs Skin exams Immunizations

GROWTH SUPPRESSOR GENES

Problems of GROWTH SUPPRESSION, result in GROWTH being UN-regulated. Cancer cells - immortal cells

PREVENTIVE MEASURES to Reduce Cancer Risk.

Stay away from tobacco. Get to and stay at a healthy weight. Get moving with regular physical activity. Eat healthy with plenty of fruits and vegetables. Limit how much alcohol you drink (if you drink at all). Protect your skin. Know yourself, your family history, and your risks. Get regular check-ups and cancer screening tests.

Risk Factors for Cancer

Sun exposure Melanomas 6x incidence New Zealand vs. Iceland Blacks have low incidence of melanoma, so do normally pigmented areas like areolae on white people Smoking and alcohol abuse Body mass Overweight = 50% increase in cancer Environmental vs. racial factors Japanese immigrants to USA Viral exposure Human papilloma virus (HPV) and cervical cancer Hepatitis B virus (HBV) and liver cancer (Africa, Asia) Epstein-Barr Virus (EBV) and lymphoma

Epigenetic Theory of Cancer

The Epigenetic Theory proposes that cancer develops due to activation or deactivation of certain genes that impact upon mechanisms of cell survival and cell division, but in the absence of mutations that alter the DNA sequence (Verma, Maruvada and Srivastara, 2003; Momparler, 2003) . ....alter the conformation of the DNA and determine whether genes, e.g., tumor suppressor genes, are expressed or suppressed.

Cancer Deaths Globally

The metastatic spread of cancer to vital organs of the body may result in massive tissue destruction, loss of life-sustaining functions and ultimately, the untimely death of the human host. Worldwide, cancer causes more than 7.7 million deaths per year, about 13% of the 60 million annual deaths from all causes. Across all age groups, cancer currently ranks second behind heart disease as a leading cause of global death (World Health Organization, 2010).

RADIATION CARCINOGENS

UV: BCC, SCC, MM IONIZING: photons and particulate Hematopoetic and Thyroid (90%/15yrs) tumors in fallout victims Radiation - X-rays and other procedures used in medicine (medical tests and therapies) Radioactive substances used in industry Nuclear power generators Radioactivity (e.g., radioactive fallout) from the production and detonation (primarily for testing purposes) of nuclear weapons.

Clinical Features of Cancer

Unexplained weight loss Fever - Less often, fever may be an early sign of cancer, such as blood cancers like leukemia or lymphoma. Fatigue Pain Unusual bleeding or discharge Change in bowel habits or bladder function Skin changes - These signs and symptoms include: Darker looking skin (hyperpigmentation) Yellowish skin and eyes (jaundice) Reddened skin (erythema) Itching (pruritis)