BRCA1 and BRCA2 Gene Mutations and Colorectal Cancer Risk: Systematic Review and Meta-analysis

Mok Oh, Ali McBride, Seongseok Yun, Sandipan Bhattacharjee, Marion K Slack, Jennifer R. Martin, Joanne M Jeter, Ivo L Abraham

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Investigations of the associations with colorectal cancer have yielded conflicting results. The aim of our study was to synthesize the research on colorectal cancer risks in BRCA mutation carriers by means of a systematic review and quantitatively by means of meta-analyses overall and in subgroups of BRCA mutation carriers. Methods: We searched PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios (ORs) were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type (BRCA1 or BRCA2), cancer type (colorectal or colon cancer), study design (age-sex-adjusted or crude), and ascertainment method (ascertained or inferred genotyping). The associations were evaluated using random-effect models. All statistical tests were two-sided. Results: Eighteen studies were included in the systematic review: five cohort studies with ascertained BRCA mutation, six cohort studies involving pedigree analysis, five case-control studies, and two kin-cohort studies. Of these, 14 were used in the meta-analysis, which revealed a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (OR = 1.24, 95% confidence interval (CI) = 1.02 to 1.51, P = .03). In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR = 1.49, 95% CI = 1.19 to 1.85, P < .001), but BRCA2 was not (OR = 1.10, 95% CI = 0.77 to 1.58, P = .61). In subgroup meta-analyses of studies reporting estimates adjusted for age and sex, an increased risk of colorectal cancer for BRCA1 (OR = 1.56, 95% CI = 1.23 to 1.98, P < .001), but not for BRCA2 (OR = 1.09, 95% CI = 0.75 to 1.58, P = .66) was observed. Analyses stratified by ascertainment method found no association between BRCA mutation and colorectal cancer risk. Conclusion: The meta-analysis results provide clinicians and health-care regulatory agencies with evidence of the increased risk of colorectal cancer in BRCA1 mutation carriers, but not in BRCA2.

Original languageEnglish (US)
Pages (from-to)1178-1189
Number of pages12
JournalJournal of the National Cancer Institute
Volume110
Issue number11
DOIs
StatePublished - Nov 1 2018

Fingerprint

BRCA2 Gene
BRCA1 Gene
Meta-Analysis
Colorectal Neoplasms
Mutation
Odds Ratio
Confidence Intervals
Cohort Studies
Pedigree
PubMed
MEDLINE
Colonic Neoplasms
Case-Control Studies
Delivery of Health Care

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

BRCA1 and BRCA2 Gene Mutations and Colorectal Cancer Risk : Systematic Review and Meta-analysis. / Oh, Mok; McBride, Ali; Yun, Seongseok; Bhattacharjee, Sandipan; Slack, Marion K; Martin, Jennifer R.; Jeter, Joanne M; Abraham, Ivo L.

In: Journal of the National Cancer Institute, Vol. 110, No. 11, 01.11.2018, p. 1178-1189.

Research output: Contribution to journalArticle

@article{cdf7b97409f64e25ae76345c53b13399,
title = "BRCA1 and BRCA2 Gene Mutations and Colorectal Cancer Risk: Systematic Review and Meta-analysis",
abstract = "Background: Investigations of the associations with colorectal cancer have yielded conflicting results. The aim of our study was to synthesize the research on colorectal cancer risks in BRCA mutation carriers by means of a systematic review and quantitatively by means of meta-analyses overall and in subgroups of BRCA mutation carriers. Methods: We searched PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios (ORs) were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type (BRCA1 or BRCA2), cancer type (colorectal or colon cancer), study design (age-sex-adjusted or crude), and ascertainment method (ascertained or inferred genotyping). The associations were evaluated using random-effect models. All statistical tests were two-sided. Results: Eighteen studies were included in the systematic review: five cohort studies with ascertained BRCA mutation, six cohort studies involving pedigree analysis, five case-control studies, and two kin-cohort studies. Of these, 14 were used in the meta-analysis, which revealed a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (OR = 1.24, 95{\%} confidence interval (CI) = 1.02 to 1.51, P = .03). In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR = 1.49, 95{\%} CI = 1.19 to 1.85, P < .001), but BRCA2 was not (OR = 1.10, 95{\%} CI = 0.77 to 1.58, P = .61). In subgroup meta-analyses of studies reporting estimates adjusted for age and sex, an increased risk of colorectal cancer for BRCA1 (OR = 1.56, 95{\%} CI = 1.23 to 1.98, P < .001), but not for BRCA2 (OR = 1.09, 95{\%} CI = 0.75 to 1.58, P = .66) was observed. Analyses stratified by ascertainment method found no association between BRCA mutation and colorectal cancer risk. Conclusion: The meta-analysis results provide clinicians and health-care regulatory agencies with evidence of the increased risk of colorectal cancer in BRCA1 mutation carriers, but not in BRCA2.",
author = "Mok Oh and Ali McBride and Seongseok Yun and Sandipan Bhattacharjee and Slack, {Marion K} and Martin, {Jennifer R.} and Jeter, {Joanne M} and Abraham, {Ivo L}",
year = "2018",
month = "11",
day = "1",
doi = "10.1093/jnci/djy148",
language = "English (US)",
volume = "110",
pages = "1178--1189",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - BRCA1 and BRCA2 Gene Mutations and Colorectal Cancer Risk

T2 - Systematic Review and Meta-analysis

AU - Oh, Mok

AU - McBride, Ali

AU - Yun, Seongseok

AU - Bhattacharjee, Sandipan

AU - Slack, Marion K

AU - Martin, Jennifer R.

AU - Jeter, Joanne M

AU - Abraham, Ivo L

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: Investigations of the associations with colorectal cancer have yielded conflicting results. The aim of our study was to synthesize the research on colorectal cancer risks in BRCA mutation carriers by means of a systematic review and quantitatively by means of meta-analyses overall and in subgroups of BRCA mutation carriers. Methods: We searched PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios (ORs) were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type (BRCA1 or BRCA2), cancer type (colorectal or colon cancer), study design (age-sex-adjusted or crude), and ascertainment method (ascertained or inferred genotyping). The associations were evaluated using random-effect models. All statistical tests were two-sided. Results: Eighteen studies were included in the systematic review: five cohort studies with ascertained BRCA mutation, six cohort studies involving pedigree analysis, five case-control studies, and two kin-cohort studies. Of these, 14 were used in the meta-analysis, which revealed a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (OR = 1.24, 95% confidence interval (CI) = 1.02 to 1.51, P = .03). In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR = 1.49, 95% CI = 1.19 to 1.85, P < .001), but BRCA2 was not (OR = 1.10, 95% CI = 0.77 to 1.58, P = .61). In subgroup meta-analyses of studies reporting estimates adjusted for age and sex, an increased risk of colorectal cancer for BRCA1 (OR = 1.56, 95% CI = 1.23 to 1.98, P < .001), but not for BRCA2 (OR = 1.09, 95% CI = 0.75 to 1.58, P = .66) was observed. Analyses stratified by ascertainment method found no association between BRCA mutation and colorectal cancer risk. Conclusion: The meta-analysis results provide clinicians and health-care regulatory agencies with evidence of the increased risk of colorectal cancer in BRCA1 mutation carriers, but not in BRCA2.

AB - Background: Investigations of the associations with colorectal cancer have yielded conflicting results. The aim of our study was to synthesize the research on colorectal cancer risks in BRCA mutation carriers by means of a systematic review and quantitatively by means of meta-analyses overall and in subgroups of BRCA mutation carriers. Methods: We searched PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios (ORs) were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type (BRCA1 or BRCA2), cancer type (colorectal or colon cancer), study design (age-sex-adjusted or crude), and ascertainment method (ascertained or inferred genotyping). The associations were evaluated using random-effect models. All statistical tests were two-sided. Results: Eighteen studies were included in the systematic review: five cohort studies with ascertained BRCA mutation, six cohort studies involving pedigree analysis, five case-control studies, and two kin-cohort studies. Of these, 14 were used in the meta-analysis, which revealed a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (OR = 1.24, 95% confidence interval (CI) = 1.02 to 1.51, P = .03). In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR = 1.49, 95% CI = 1.19 to 1.85, P < .001), but BRCA2 was not (OR = 1.10, 95% CI = 0.77 to 1.58, P = .61). In subgroup meta-analyses of studies reporting estimates adjusted for age and sex, an increased risk of colorectal cancer for BRCA1 (OR = 1.56, 95% CI = 1.23 to 1.98, P < .001), but not for BRCA2 (OR = 1.09, 95% CI = 0.75 to 1.58, P = .66) was observed. Analyses stratified by ascertainment method found no association between BRCA mutation and colorectal cancer risk. Conclusion: The meta-analysis results provide clinicians and health-care regulatory agencies with evidence of the increased risk of colorectal cancer in BRCA1 mutation carriers, but not in BRCA2.

UR - http://www.scopus.com/inward/record.url?scp=85056579323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056579323&partnerID=8YFLogxK

U2 - 10.1093/jnci/djy148

DO - 10.1093/jnci/djy148

M3 - Article

C2 - 30380096

AN - SCOPUS:85056579323

VL - 110

SP - 1178

EP - 1189

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 11

ER -