BRCA1 和 BRCA2 基因突变与结直肠癌风险：系统评价和荟萃分析。

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

机构信息

Department of Pharmacy Practice and Science, Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, University of Arizona, Tucson, AZ.

Department of Pharmacy Practice and Science, College of Pharmacy, Banner University Medical Center, University of Arizona Cancer Center, Tucson, AZ.

出版信息

J Natl Cancer Inst. 2018 Nov 1;110(11):1178-1189. doi: 10.1093/jnci/djy148.

DOI:10.1093/jnci/djy148

PMID:30380096

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.

摘要

背景

针对结直肠癌风险与 BRCA 基因突变之间关联的研究结果相互矛盾。本研究旨在通过系统综述和定量的荟萃分析，全面评估 BRCA 基因突变携带者结直肠癌风险，并按 BRCA 基因突变类型（BRCA1 或 BRCA2）、癌症类型（结直肠或结肠癌）、研究设计（年龄性别调整或原始）和确定方法（确定或推断的基因分型）进行亚组分析。我们检索了 PubMed/MEDLINE、Embase、Cochrane、Scopus 和 ProQuest Dissertation & Theses。使用未调整的优势比（OR）来推导结直肠癌风险的汇总估计值，总体和按突变类型（BRCA1 或 BRCA2）、癌症类型（结直肠或结肠癌）、研究设计（年龄性别调整或原始）和确定方法（确定或推断的基因分型）进行亚组分析。使用随机效应模型评估关联。所有统计检验均为双侧。

结果

本系统综述纳入了 18 项研究：5 项基于队列的研究，对 BRCA 基因突变进行了明确的确定；6 项涉及家系分析的队列研究；5 项病例对照研究；2 项亲缘队列研究。其中，14 项研究纳入荟萃分析，结果显示 BRCA 基因突变携带者结直肠癌风险显著增加（OR=1.24，95%置信区间（CI）=1.02 至 1.51，P=0.03）。按 BRCA 类型的亚组荟萃分析显示，BRCA1 突变与结直肠癌风险增加相关（OR=1.49，95%CI=1.19 至 1.85，P<0.001），而 BRCA2 则没有（OR=1.10，95%CI=0.77 至 1.58，P=0.61）。对报告经年龄和性别调整后的估计值的研究进行亚组荟萃分析，发现 BRCA1 （OR=1.56，95%CI=1.23 至 1.98，P<0.001）而非 BRCA2 （OR=1.09，95%CI=0.75 至 1.58，P=0.66）的突变与结直肠癌风险增加相关。按确定方法分层的分析未发现 BRCA 突变与结直肠癌风险之间存在关联。