Genetics of breast cancer: Contribution of BRCA1/2 genes alterations to hereditary predisposition

The term “hereditary cancer” refers to cancers associated with specific germ-line mutations in highly penetrant genes which are inherited as a Mendelian trait, whether through an oncogene, a tumor suppressor gene, or a DNA repair gene. Since the first association between germ-line mutations and hereditary predisposition for particular cancer types has been found in the mid of 90-ties, investigations pointed out a variety of tumor types with inherited predisposition to a high or moderate/low risk for development of disease (melanoma, gastric cancer, MEN I, MEN II, hereditary nonpolyposis colon cancer, etc) . Data that hereditary predisposition, recognized by family clustering, has been found for the arising number of cancer types, together with introducing of screening for the mutations in responsible genes, makes different insight into cancer prevention and management of patients with malignant disease. Breast cancer is the most frequent malignant tumor in females in Serbia. The incidence can be described with more than 4,000 newly diagnosed cases per year 5, . Unfortunately, incidence and mortality trends show permanent increment in the few last years. Breast cancer can occur as sporadic, familial and hereditary. The majority of breast cancers are recognized as sporadic in patients with no cancer history in the family. The incidence of sporadic breast cancer rises in women over 50 years old. Minorities of breast and/or ovarian cancer patients (up to 5% to 10%) have a striking family history, suggestive of Mendelian autosomal dominant inheritance. An additional 20% of breast cancer cases are considered as familial describing situation with at least two cancer cases in extended family. In hereditary form of disease one of the two alleles of the gene responsible for the disease is altered by germ-line mutation. The off-spring of the mutation carriers has 50% chance of inheriting a mutant allele from either parent. The most common variant of hereditary breast cancer (HBC) is the appearance of breast as well as ovarian cancer cases in the same family (HBOC). The disease can also occur as site-specific breast or ovarian cancer. Other tumor types such as pancreatic cancer, Fallopian tube carcinoma, melanoma or prostate cancer in men can be commonly present in families with hereditary breast cancer .