Page 69 Complete Your CE Test Online - Click Here deaths from CRC; a lot of nurses took more than 14 aspirin tablets per week for longer than ten years [285]. A 2016 publication by Cao et al. showed a more modest reduction in CRC incidence with lower-dose aspirin use as well as a small reduction in other GI cancers, when aspirin was taken for at least six years [61]. However, the USPSTF did find evidence of significant harms to aspirin use, including dose-related incidence of gastrointestinal bleeding and hemorrhagic stroke. They reported on one meta-analysis (of 16 randomized controlled trials) that looked at GI complications, and found an odds ratio of 5.36 for perforations, ulcers, and bleeding with the use of NSAIDs. Studies that looked at NSAIDs for other purposes have also found an increase in acute renal failure in those over 65, and elevations in blood pressure. These complications might be more pronounced in the older adult population, which is the group that most stands to benefit from CRC prophylaxis [285]. The USPSTF specifically recommends against using aspirin and NSAIDs for only colorectal cancer prevention in people who are at average risk of CRC [285]. However, in late 2015, the USPSTF released a draft guideline which recommends prophylactic aspirin for adults in adults aged 50 to 59 years old who are at a ten percent or greater risk of CVD over a ten-year period, which also offers CRC risk reduction to those same people. Adults age 60 to 69 can take aspirin if they meet the same CVD risk criteria and still do not have an increased risk of bleeding, assuming that they have a life expectancy of at least ten years. The USPSTF reported insufficient evidence to balance risks and benefits of adults younger than 50 or older than 69 [286]. Of note, the American Cancer Society has no recommendations at this time for use of NSAIDs or aspirin for people at average risk of CRC. It is interesting that the U.S. Food and Drug Administration approved the NSAID celecoxib for reducing polyps in people with familial adenomatous polyposis (FAP). This drug may cause less GI bleeding than other NSAIDs, but it might also increase heart attack and stroke risk [20]. Of course, the risk-benefit ratio is different in people with FAP because of their extremely high risk of CRC. Breast cancer risk reduction for women at high risk Women known to have significantly increased breast cancer risk can use chemoprevention in the form of tamoxifen (for premenopausal women) or raloxifene (for postmenopausal women), which have both been FDA-approved for this purpose. Studies show an overall relative risk reduction of about 38% for this preventive measure. This means that woman with an 8% risk of breast cancer in the next five years (which is pretty high) would see their absolute risk cut to about 5% with this drug treatment. But healthy women at age 60 would have about a 1.7% chance of breast cancer over the next five years, and a 38% risk reduction would drop their absolute risk to about 1.05%. The absolute benefit is clearly much less for women at average risk of breast cancer [34]. Tamoxifen only decreased estrogen receptor- positive cancer and DCIS, but the effect lasted for 16 years after starting tamoxifen (11 years after finishing the 5-year course). These drugs also have risks, which is another reason they are not recommended for general use in breast cancer prevention. Tamoxifen can cause symptoms of menopause and slightly increase the risk of cancer of the uterus, and both drugs can rarely cause blood clots (DVT or pulmonary embolus). Women who are pregnant, breastfeeding, at high risk of blood clots, or taking estrogen should not take either drug for breast cancer prevention. Women who smoke or are obese, hypertensive, or diabetic are at increased risk of blood clots. Tamoxifen should not be used in women who have had uterine cancer or precancerous lesions (atypical hyperplasia) of the uterus [34]. Aromatase inhibitors have shown that they can also reduce breast cancer risk in postmenopausal women at increased breast cancer risk, but have not been approved for that purpose as of 2016 [141]. Prophylactic bilateral mastectomy can also reduce risk in women with strong family histories of breast cancer [141]. Premenopausal women with BRCA gene mutations who undergo prophylactic oophorectomy have lower breast cancer incidence. Oophorectomy or ovarian ablation is linked to decreased breast cancer incidence in normal premenopausal women and in women with increased breast cancer risk resulting from thoracic irradiation [141]. Carcinogen exposure People are generally interested in reducing their exposure to carcinogenic substances whenever possible. In fact, the state of California passed a law (Proposition 65, also called the Safe Drinking Water and Toxic Enforcement Act of 1986) that set up its own registry and labeling requirements for products that contain or possibly contain carcinogens or that might cause reproductive toxicity. Unfortunately, the labels do not say what or how much is in the product, or the likelihood of exposure with normal use, so it is not especially helpful to most people who want to make judicious decisions about exposure (unless they have enough time to contact each manufacturer, learn what is in the product, and then find information on the target substance) [16]. Workplace exposures: Regulations have been put in place in the U.S. to reduce exposures to known carcinogens in the workplace, and to allow workers to find out about substances at work that may be carcinogenic or toxic in other ways. Table 5: Cancers associated with various occupations or occupational exposure. Adapted from: Agency for Toxic Substances and Disease Registry, CDC: Chemicals, Cancer and You, 2009 [1]. Cancer Substances or processes Lung Arsenic, asbestos, cadmium, coke oven fumes, chromium compounds, coal gasification, nickel refining, foundry substances, radon, soot, tars, oils, silica. Bladder Aluminum production, rubber industry, leather industry, 4-aminobiphenyl, benzidine. Nasal cavity and sinuses Formaldehyde, isopropyl alcohol manufacture, mustard gas, nickel refining, leather dust, wood dust. Larynx Asbestos, isopropyl alcohol, mustard gas. Pharynx Formaldehyde, mustard gas. Mesothelioma Asbestos. Lymphatic and hematopoietic Benzene, ethylene oxide, herbicides, x-radiation system. Skin Arsenic, coal tars, mineral oils, sunlight. Soft tissue sarcoma Chlorophenols, chlorophenoxyl herbicides. Liver Arsenic, vinyl chloride. Lip Sunlight.