The frequency of the predominant Jewish mutations in BRCA1 and BRCA2 in unselected Ashkenazi colorectal cancer patients

Chen‐Shtoyerman, Rakefet; Figer, Arié; Fidder, Herma H.; Rath, Peter; Yeremin, L.; Meir, S. Bar; Friedman, Eitan; Theodor, Livia

doi:10.1054/bjoc.2000.1598

Cited by 20 publications

(12 citation statements)

References 20 publications

(13 reference statements)

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“…The three founder mutations, BRCA1 187delAG, BRCA1 5385insC and BRCA2 617delT, have a combined prevalence exceeding 2 per cent in Ashkenazi Jews, so most research has been conducted in this population. The results of several studies concur with the present finding that BRCA1 and BRCA2 mutation carriers in this population do not have a higher than normal incidence of colorectal cancer. Mersch and colleagues studied the cancer risk associated with BRCA1 and BRCA2 mutations among the general population.…”

Section: Discussionsupporting

confidence: 91%

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

Cullinane

Creavin

OʼConnell

et al. 2020

British Journal of Surgery

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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.

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Section: Discussionsupporting

confidence: 91%

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

Cullinane

Creavin

OʼConnell

et al. 2020

British Journal of Surgery

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“…The prevalence of BRCA1 / 2 mutations in the general US population is estimated to be approximately 1 in 300–500 . In order to identify enough carriers for an accurate estimation of risk, most case–control studies have been restricted to populations where the prevalence is increased, such as Ashkenazi Jews and Poland . Results from specific populations with founder mutations cannot necessarily be generalized to the entire carrier population; if the risk of colon cancer differs for different mutations, then the results may not be generalizable to carriers of other mutations.…”

Section: What Is the Penetrance Of Brca1/2 Mutations For Colorectal Cmentioning

confidence: 99%

“…The approaches used in these studies included prospective cohort, retrospective cohort and kin‐cohort designs (summarized in Table ), association/case–control designs (Table ), and family‐based designs (Table ). In general, most of the positive results (relative risks of two to four) were derived from studies of high‐risk cancer families, whereas studies of unselected colon cancer patients generally found no significantly increased risks for either BRCA1 or BRCA2 . The validity of these studies must be assessed for precision and statistical power, which is determined in large part by the number of exposed cases identified (colon cases with mutations), and for bias, in order for conclusions to be made.…”

Section: What Is the Penetrance Of Brca1/2 Mutations For Colorectal Cmentioning

confidence: 99%

BRCA1 and BRCA2 mutations and the risk for colorectal cancer

et al. 2014

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Women who carry a BRCA1 or BRCA2 mutation are at high risk of breast and ovarian cancer, and may be at moderately increased risk of other cancer types. This review examines studies to date that have evaluated the risk of BRCA1 and BRCA2 mutations for colorectal cancer. Accurate knowledge of colorectal cancer risk in BRCA1/2 carriers is important, because colonoscopy screening can prevent colorectal cancer through the removal of adenomatous polyps. Most studies that have identified an increased risk for colorectal cancer in BRCA1/2 mutation carriers were in high-risk cancer families, while studies that found no association were conducted in specific populations and involved the analysis of founder mutations. A recent prospective study of 7015 women with a BRCA1 or BRCA2 mutation identified significant fivefold increased risk of colorectal cancer among BRCA1 mutation carriers younger than 50 years [standardized incidence ratio (SIR): 4.8; 95% CI: 2.2-9], but not in women with a BRCA2 mutation or in older women. Based on this evidence, women with BRCA1 mutations should be counseled about their increased risk for early-onset colorectal cancer, and offered colonoscopy at 3- to 5-year intervals between the ages of 40 and 50 years, and should follow population guidelines thereafter.

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“…These authors argued that the higher incidence of colon cancer observed in some BRCA1 families may be attributed, at least in part, to misdiagnosed ovarian and rectal cancer [17]. Formal analysis showed no increased predisposition to colorectal cancer in BRCA1 mutation carriers [18].…”

Section: Inter-study Risk Variabilitymentioning

confidence: 99%