Risk of colorectal cancer associated with BRCA1 and/or BRCA2 mutation carriers: systematic review and meta-analysis

Abstract

Background Carriers of the BRCA1 and/or BRCA2 mutation incur a lifetime risk of up to 85 per cent for breast cancer, and between 20 and 40 per cent for ovarian cancer. Efforts to estimate the lifetime risk of developing colorectal cancer for BRCA mutation carriers have produced conflicting results. Consequently, there are no formal guidelines regarding the need for bowel screening for individuals with BRCA1 and/or BRCA2 mutations. This systematic review and meta‐analysis determined the risk of colorectal cancer associated with BRCA carrier mutations. Methods The primary outcome was incidence of colorectal cancer in BRCA mutation carriers. Secondary outcomes were the incidence in BRCA1 and BRCA2 carriers, Ashkenazi Jews, and age‐ and sex‐matched cohorts. Results Eleven studies were included in the review, with an overall population of 14 252 and 4831 colorectal cancers identified. Nine studies were included in the meta‐analysis. There was no increase in colorectal cancer among patients carrying a BRCA mutation (odds ratio 1·03, 95 per cent c.i. 0·80 to 1·32; P = 0·82). After adjustment for Ashkenazi heritage, and age and sex estimates, there was no increased odds of developing colorectal cancer (with no heterogeneity, I2 = 0 per cent). Conclusion BRCA1 and/or BRCA2 mutation carriers are not at a higher risk of colorectal cancer.

Dominantly Inherited Hereditary Nonpolyposis Colorectal Cancer Not Caused by MMR Genes

“…Two of the most frequently altered non-CRC hereditary cancer genes found in CRC patients are BRCA1 and BRCA2 ; however, the debate about whether those actually increase the risk of CRC is still ongoing [ 61 , 103 , 104 , 105 , 106 , 107 , 108 ]. A recent meta-analysis, together with familial/early onset CRC case-control data, indicate that BRCA1 and BRCA2 pathogenic variants do not increase the risk to CRC [ 109 , 110 ]. Contrarily, another meta-analysis suggests that pathogenic variants in BRCA1 increase CRC risk (OR = 1.56) but not in BRCA2 [ 111 ].…”

Case Report: Coinheritance of Germline Mutations in APC and BRCA1 in Colorectal Cancer

“…The cumulative breast cancer risk and ovarian cancer risk for mutation carriers are 5 times and 10-20 times higher than that for non-carriers (11), respectively. However, investigations on whether BRCA1/2 mutations increase lifetime risk of developing colorectal cancer have yielded conflicting results (12)(13)(14)(15).…”

WNT4 secreted by tumor tissues promotes tumor progression in colorectal cancer by activation of the Wnt/β-catenin signalling pathway

“…Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide [ 1 ], and evolves as a result of the accumulation of genetic and epigenetic events [ 2 ]. Data evaluated by the International Agency for Research on Cancer (IARC) indicated that about 1.8 million new cases of CRC were diagnosed and over 860,000 CRC patients died worldwide in 2018, which account for about 10% of all cancers and 9% of all cancer-related deaths, respectively [ 3 ].…”