gms | German Medical Science

Breast cancer is a rare disease in men. The incidence is 1 per cent of the incidence in women. Genetic risk factors for male breast cancer are poorly understood. Mutations in distinct genes are estimated to account for up to roughly 10% of male breast cancer cases (Table 1). High penetrance genes such as BRCA1 and BRCA2 account for only a small proportion of the disease. The cumulative breast cancer risk for male BRCA2 mutation carriers by the age of 80 years is estimated with 6,92%. Men with Klinefelter syndrome have one or more extra X chromosomes and have a 50-fold increased risk fort he development of breast cancer. A recent study reveals that longer CAG repeats in the androgen receptor (AR) gene are more common in men with breast cancer. Androgen hyposensitivity, caused by long CAG repeats, may increase the breast cancer risk. Suspected genetic factors include the cell-cycle checkpoint kinase (CHEK)2 protein truncating mutation 1100delC that has been shown to confer a 10-fold increase of breast cancer risk in men. The c.1-34T>C 5' promoter region polymorphism in cytochrome P450c17 (CYP17), a key enzyme in the biosynthesis of estrogen, has been associated with male breast cancer risk, hemochromatosis gene (HFE) mutations, the mismatch repair genes (hMSH2, hMLH1,hPMS1,hPMS2) and PTEN mutations (Cowden syndrome) are associated with male breast cancer. Cowden syndrome is an inherited hamartoma syndrome with a high risk of breast, thyroid and endometrial carcinomas and, some suggest, melanoma. The main epidemiologic risk factors for male breast cancer include disorders associated with relative hyperestrogenism as obesity, testicular dysfunction (e.g. orchiectomy, cryptorchidism, mumps orchitis), exposure to ionizing radiation and being the first-born child of a mother. Suspected epidemiologic risk factors include estrogen therapy (male-to-female transsexuals, prostate cancer), alcohol abuse, prostate cancer, gynecomastia, occupational exposures to electromagnetic fields, to polycyclic aromatic hydrocarbons and high temperatures.