Breast cancer is a rare disease in men.Germ-line mutations in BRCA2 and androgen receptor (AR) genes are thought to be responsible for a proportion of male breast cancer cases.
Although germline brca2 mutations may account for a small proportion of all OM cases, there may be additional loci that contribute to familial aggregation of OM and to the familial association between OM and breast cancer.
Besides these two likely deleterious mutations, eight rare variants of unknown significance, mostly in the BRCA2 gene, were detected in six of 32 (19%) early-onset breast cancer cases and in three of 17 (18%) site-specific breast cancer families, one containing a male breast cancer case.
In addition, multiple, germline BRCA2 missense mutations identified in breast cancer patients but of heretofore unknown biological/clinical consequence appear to disrupt PALB2 binding and disable BRCA2 HR/DSBR function.
In this report we present the results of mutational analysis of the BRCA2 coding sequences in 105 high-risk individuals affected with breast cancer and/or ovarian cancer and previously found to be negative for mutations of the BRCA1 coding sequence in our laboratory.
Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.
Some studies have shown that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer.
The entire coding regions of the two breast cancer susceptibility genes BRCA1 and BRCA2 from breast cancer patients from 40 Cypriot families with multiple cases of breast and ovarian cancer were sequenced.