Chapter 12 Physical Activity, Cancer, and Immunity “FEAR IS THE CANCER” ― S I M O N H O LT, T H E D E V O U R I N G P-307 In the US cancer was predicted to kill about 570,000 in 2010—2nd only to CVD. About 1/3 of cancer deaths occurring each year are said to be attributable to poor diet and inactivity. 6 major cancers: breast, colon, lung, prostate, endometrial, and ovarian—all may have a relation to physical inactivity. Physical activity may particularly reduce breast and colon cancer—2 of the most prevalent and deadly cancers in the USA. Cancer is a family of related diseases that results from uncontrolled growth and spread of abnormal cells which usually becomes a tumor[tumor—Latin for ‘swelling’]—tumors can be benign or malignant—malignant tumors are called cancer. Greek physician Hippocrates coined the term for cancer in 4th century BC. Carcinoma is the Greek word for crab—to describe ulcer-forming tumors, presumably because tumor projections resembled the shape of a crab’s body and legs. Bernardino Ramazzini, the father of occupational medicine and early cancer epidemiologist, observed in the early 1700’s that sedentary workers had elevated risks of chronic disease, including cancer. Magnitude of the Problem: Cancer is a leading cause of morbidity and mortality in high income countries. In the US cancer is 2nd only to CVD in death causes. The financial burden is enormous-$263 bill from med costs. All cancers involve the malfunction of genes that control cell growth and division—only 5% of cancer is strongly hereditary—so primary and secondary prevention are priorities for public health. Almost half of men and over 1/3 of women in the US will develop some form of cancer during their lifetimes. Etiology of Cancer Cancer originates in 2 phases: initiation and promotion. Initiation: normal cells are changed into potentially cancerous cells by damage from mutational factors. Promotion: Tumor growth is stimulated by other agents, including naturally circulating endogenous hormones. P-310. Normally, cells grow, divide and die according to a systematic schedule. Telomeres; telomerase; oncogenes; tumor suppressor genes; carcinogens; metastasize. Cancers are named by their site of origin, even if they spread to another part of the body. In general, those arising from epithelial cells are called carcinoma while those coming from connective tissue are known as sarcoma. •Cancers are generally categorized according to 4 stages or as recurrent. •Stage I cancers are small, localized tumors that are usually curable. •Stage II and III cancers are advanced, localized tumors or have spread to local lymph nodes. •Stage IV cancers usually are inoperable or have metastasized. Epithelia are formed of cells that line the cavities in the body and also cover flat surfaces. Of the four major tissue types found in the human body (Figure 1), epithelial cells are by far the most prolific. Risk Factors: Smoking—lung cancer; excessive sun exposure—basal cell and squamous cell carcinoma. UV radiation (tanning) melanoma. Inactivity is an independent, and plausibly causal risk factor for some cancers. Physical activity & cancer: P-311 Colon & Rectal Cancer: Studies: P-315 Biological Plausibility: Lower risk of adenomas (polyps) among the physically active. Bowel transit time: physically active people have a shortened gastrointestinal transit time (peristalsis) which reduces the contact of potential carcinogens with the mucosal lining of the colon. Insulin resistance & obesity: people with colon cancer have higher than average rate of metabolic syndrome; Inflammation: Physical activity may reduce systemic inflammation alone or in combination with improved weight, composition or both; Also—changes in prostaglandin levels with exercise. Breast cancer: P-322. Next to skin cancer breast is 2nd among women. Most breast lumps are benign and result from fibrocystic changes in breast tissue. 1 in 8 (12%) is the chance of a woman developing invasive breast cancer—the chance that this will cause death is about 1 in 25 (3%). Carcinoma in Situ: When a cancer is confined to breast lobules and has not spread. Invasive Carcinoma: spreads in the breast and to other parts of the body. Between 5% to 10% and 27% of breast cancer cases are hereditary, and about half of the hereditary cases believed to result from mutations of the BRAC1 and BRAC2 genes which normally express proteins that inhibit abnormal cell reproduction. About 35% to 84% of women with inherited BRAC1 or BRAC2 mutations will develop breast cancer by the age of 70. P-325 Breast cancer risk factors: age, sex, family history, previous proliferative breast disease, previous breast irradiation, menstrual history, high socioeconomic status, oral contraceptive use, nulliparity (no children), hormone therapy, EtOH consumption, obesity & high-fat diets, environmental toxins and physical inactivity. More than 60 studies of physical activity and breast cancer incidence show a reduction in risk with higher levels of physical activity. P-333: Biological plausibility. In addition to enhancing immune function, physical activity may influence menstrual function and sex steroid hormones, reduction in blood levels of insulin-like growth factor as a result of negative energy balance, or indirect associations with lower body weight and thus lower levels of free estrogen—less inflammation. Sex hormones: Physical activity might protect against breast cancer by reducing the cumulative lifetime exposure to circulating ovarian hormones, especially estrogen, since higher levels of estrogen are associated with increased breast cancer risk. Menstrual function: Strenuous activity during adolescence may increase the age of menarche and is also associated with longer menstrual cycles. In general, a 20% reduction in breast cancer is observed for every year that menarche is delayed. Onset of menopause: It is also plausible that activity could be associated with an earlier age at menopause. Women who experience natural menopause before 45 are estimated to have half the risk of breast cancer of women whose natural menopause occurs after 55. Obesity also influences breast cancer risk. Lung cancer is the 2nd most commonly occurring cancer in the USA and the leading cause of cancer deaths for both men and women—it is the leading cause of cancer deaths worldwide. Higher levels of activity may be associated with lower lung cancer risk: P-335. Endometrial cancer is the most common gynecologic cancer and the 4th most commonly occurring cancer in women. Activity may lower the risk—in that activity is associated with a lower body weight and obesity increases the risk of this cancer. Rectal cancer: Little evidence to support whether activity lowers this risk of cancer. Prostate: Some evidence to support and some does not the relationship of activity and suppressing this cancer. Summary: Cancer is a major cause of mortality and morbidity in the USA and worldwide. A modifiable factor that can reduce the risk of developing cancer is physical activity—although this differs depending upon the type of cancer at hand.