Breast cancer
Breast cancer is classified under carcinoma: cancer that is derived from epithelial cells. The National Cancer Institute at NIH ranks breast cancer as the second most common cancer after prostate cancer, with an estimated 230 thousand new cases diagnosed in 2013 and almost 40,000 deaths. In the US, approximately one in eight women will develop breast cancer at some point in her life, the rate being just under 12%. Breast cancer does not only occur in women; men are also susceptible to breast cancer, although the rate of occurrence is much lower.
Approximately 5%–10% of breast cancers can be linked to gene mutations that are inherited from one of the parents. Mutations of the BRCA1 and BRCA2 are the most common. Women with BRCA1/2 mutations have up to 80% risk of developing breast cancer during their lifetime, and they are more likely to be diagnosed at a younger age (before menopause). This is explained previously in the heritable cancer section. An increased ovarian cancer risk is also associated with these genetic mutations. Mutations in BRCA1 or BRCA2 can be passed on from the mother or the father.
BRCA1/2
BRCA1 (BReast CAncer gene one) is located in chromosome 17q21, while BRCA2 (BReast CAncer gene two) is located in chromosome 13q12.3. These genes play a significant role in breast cancer because mutations in these two genes account for up to 10% of all breast cancer cases. Hundreds of cancer-associated mutations in BRCA1/2 have been documented, and they are not only specific to breast and ovarian cancer.
Both BRCA1 and BRCA2 are tumor suppressor genes and subclassified as caretakers. Tumor suppressor genes can be further classified into gatekeepers and caretakers. Gatekeepers are genes that are responsible for controlling inhibition of cell growth; they are the guardians of the cell cycle. Caretakers, as the name suggests, are genes that take care of genome stability. Genome instability can arise owing to mutations in DNA or rearrangements that occur in the chromosomal level. The caretaker genes protect the genome by maintaining and repairing DNA damages; they are involved in nucleotide excision repair, base excision repair, nonhomologous end joining recombination pathways, mismatch repair pathways, and telomere metabolism. BRCA1 is involved in both the nonhomologous end joining repair and homologous recombination, while BRCA2 is only involved in homologous recombination. BRCA1 and BRCA2 work with other important proteins to perform DNA repair, such as KU proteins that are involved in nonhomologous end joining and Rad51 proteins that are involved in homologous recombination (Figure 1).