For breast cancer, the major risk factor is prolonged and unopposed exposure to estrogen. Well-established risk factors thus include early onset of menarche (before age 14), nulliparity, completion of first live birth after age 30, and delayed menopause.2 The incidence of breast cancer increases with age, doubling with every decade until menopause. Smoking, either directly or through second-hand exposure, has also been implicated as a possible risk factor.2'4'5 Women with a family history of breast cancer and those who carry germline mutations of BRCA1 or BRCA2 are also at high risk for developing breast cancer. For instance, women with one first-degree relative with a history of breast cancer have a 1.5-2.0 relative risk of developing the disease, but the risk is even further increased (relative risk approximately 20.0) if the first-degree relative had bilateral premenopausal onset of the cancer. Relative risk has been estimated at 4.0-6.0 if two first-degree relatives have had breast cancer. In addition, women carrying germline mutations for BRCA1 or BRCA2 have a 56-85% lifetime risk of developing breast cancer, much higher than the general population.6-8
For prostate cancer, the most important risk factor is also prolonged exposure to steroid hormones, i.e. androgens. Early castration or genetic defects blocking androgen synthesis essentially eliminate the risk of prostate cancer, while more subtle abnormalities, such as qualitative differences in the levels of circulating androgens or qualitative differences in androgen receptor function or related signal transduction pathways due to various genetic polymorphisms may also alter the risk of prostate cancer in certain subpopulations.9 For example, genetic variations of 5a-reducatase may create more productive enzymatic conversion of testosterone to dihydrotestosterone (DHT), which has been suggested as one mechanism of increased prostate cancer risk.10 Studies have looked at the potential role of vitamin D receptor (VDR) polymorphisms in prostate cancer risk, particularly in African American men.11 It has also been noted that Black men of college age have 13% higher serum free testosterone levels than White men of the same age.12 In addition, advancing age, race (African American) and positive family history also confer an increased risk for the development of prostate cancer.13 A single first-degree relative with prostate cancer increases the relative risk by a factor of 2.1-2.8, and having a first-degree and a second-degree relative with prostate cancer may increase the relative risk by as much as 4-6-fold when compared to the general population.14 The corresponding relative risks may be even higher in African Americans - in this population a history of two or more first-degree relatives with prostate cancer may increase the relative risk up to ten fold.15
The role of diet in cancer risk has been under intense scrutiny, especially given the strong association between high dietary fat intake and prostate cancer risk. Although the exact mechanism is unclear, high levels of fat intake may increase the bioavailability of steroid sex hormones, perhaps by interfering with their ability to bind to serum globulins.16 Conversely, vegetarian diets have been shown to lead to lower levels of circulating androgens and estrogens. Data also demonstrate a strong correlation between dietary fat and significantly different incidence rates of prostate cancer in Western vs. Eastern cultures.9 Several highly suggestive studies in animal and in vitro model systems also support an important role for dietary fat in the promotion and progression of prostate cancer. Dietary nutrients may also have a function in the development of prostate cancer; however, this is difficult to elucidate and is currently under study.
While body mass and various occupational exposures are currently being studied as putative risk factors, other risk factors, such as socioeconomic status, smoking and history of prostatitis or sexually transmitted diseases, probably play little if any role in prostate cancer development.9'13 Recent evidence has also failed to support vasectomy as a significant risk factor for prostate cancer, and any association between the two may simply be related to health care-seeking behavior.
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