BRCA1 mutations and colorectal cancer in Poland

Abstract

Evidence to date that germline mutations in the tumor suppressor gene BRCA1 increase the incidence of colorectal cancer is mixed, and both positive and negative results have been reported. To establish whether or not inherited variation in BRCA1 influences the risk of colorectal cancer, we genotyped 2,398 unselected patients with colorectal cancer and 4,570 controls from Poland for three BRCA1 founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.42% of unselected cases of colorectal cancer and in 0.48% of controls (OR = 0.8; P = 0.8). The mutation frequency was slightly higher (0.93%) in 321 cases who reported a family history of colon cancer in a first- or second-degree relative (OR = 1.9; P = 0.5). A BRCA1 mutation was also seen in excess (0.82%) in 851 cases who were diagnosed with colorectal cancer at age 60 or earlier (OR = 1.7; P = 0.3). The mean age at onset in carriers was 7 years younger than in non-carriers (57.0 years vs. 64.0) and the difference was significant (P = 0.05). This study suggests that BRCA1 mutations may be associated with early-onset of colorectal cancer.

Incidence of colorectal cancer in BRCA1 and BRCA2 mutation carriers: results from a follow-up study

“…In a recent study, 2398 unselected patients with colorectal cancer and 4570 controls from Poland were screened for three BRCA1 founder mutations (Suchy et al , 2010). A BRCA1 mutation was present in 0.42% of unselected cases of colorectal cancer and in 0.48% of controls (OR=0.8; P =0.8).…”

“…GLOBOCAN 2008 has used International Classification of Disease (ICD, 10th revision) coding system to classify the cancers according to the site of origin (Suchy et al , 2010). In the ICD, 10th revision, colorectal cancers are listed as ‘Colorectum (C18-21)' with the individual cancer sites coded as: C18.0-Cecum, C18.1-Appendix, C18.2-Ascending colon, C18.3-Hepatic flexure of colon, C18.4-Transverse colon, C18.5-Splenic flexure of colon, C18.6-Descending colon, C18.7-Sigmoid colon, C18.8-Overlapping lesion of colon, C18.9-Colon, NOS, C19.9-Rectosigmoid junction, C20.9-Rectum, NOS, C21.0-Anus, NOS, C21.1-Anal canal, C21.2-Cloacogenic zone, and C21.8-Overlapping lesion of rectum, anus, and anal canal.…”

The breast cancer susceptibility genes (BRCA) in breast and ovarian cancers

“…The lifetime risk of breast cancer in BRCA1- and BRCA2- mutation carriers is 45–80% (143, 144) and for ovarian cancer, the lifetime risk is 45–60% and 11–35% for BRCA1-and BRCA2 -mutation carriers, respectively(143–145). BRCA mutation carriers are also at risk for other malignancies such as fallopian tube cancer, melanoma, endometrial, pancreatic, prostate, and colorectal cancer (11, 146–150). Compared to nonhereditary breast cancer patients, nearly 80% of BRCA1- mutation carriers are diagnosed with breast cancer prior to menopause (146, 151–153).…”

Clinical Considerations ofBRCA1- andBRCA2-Mutation Carriers: A Review

“…Specifically, the increased risk of prostate cancer is associated with the BRCA1 4153delA and the C61G mutations [21]. A BRCA1 mutation has been shown to be associated with an increased risk of early onset colon cancer in a defined population but does not seem to increase the overall risk of colon cancer [22]. Patients with a BRCA2 mutation have an increased risk of prostate and pancreatic cancer [23–25].…”