Risk Factors and Genetics

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Breast Cancer Survivors

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Breast cancer risk factors are related to prolonged exposure to estrogen. This is seen in women with early menarche and late menopause, older high estrogen dose oral contraceptives, and nulliparity. The highest risk involves a personal history of breast cancer or lobular carcinoma in situ. Family history in a premenopausal first degree relative is also an important risk factor.

Familial breast cancer has been associated with certain genes. The two main genes are BRCA I and BRCA II.1 BRCA I is found on chromosome 17 and is also associated with an increased risk of colon, ovarian, and prostate cancer. BRCA I is thought to function as a tumor suppressor gene in DNA repair. BRCA II, located on chromosome 13, is associated with male breast cancer. BRCA II is also thought to function as a tumor suppressor gene. Both of the above genes are inherited in an autosomal dominant pattern with incomplete penetrance. Prophylactic bilateral mastectomy has been shown to decrease breast cancer in women with the previous listed mutations in early studies.2 Other syndromes have increased risk of breast cancer include Li-Fraumini syndrome and p53 mutations. The most common abnormally expressed gene in any breast cancer is p53 on chromosome 17. The risk of breast cancer is especially increased with exposure to radiation. Male breast cancer is increased in BRCA II and in Klinefelter's syndrome with gynecomastia.

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