Department of Population and Public Health Sciences and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain.
Cancer Epidemiol Biomarkers Prev. 2024 Mar 1;33(3):400-410. doi: 10.1158/1055-9965.EPI-23-0717.
High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations.
A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan.
Meta-analyses confirmed positive associations between increased consumption of red meat and processed meat with colorectal cancer risk [per quartile red meat OR = 1.30; 95% confidence interval (CI) = 1.21-1.41; processed meat OR = 1.40; 95% CI = 1.20-1.63]. Two significant genome-wide GxE interactions for red meat consumption were found. Joint GxE tests revealed the rs4871179 SNP in chromosome 8 (downstream of HAS2); greater than median of consumption ORs = 1.38 (95% CI = 1.29-1.46), 1.20 (95% CI = 1.12-1.27), and 1.07 (95% CI = 0.95-1.19) for CC, CG, and GG, respectively. The two-step EDGE method identified the rs35352860 SNP in chromosome 18 (SMAD7 intron); greater than median of consumption ORs = 1.18 (95% CI = 1.11-1.24), 1.35 (95% CI = 1.26-1.44), and 1.46 (95% CI = 1.26-1.69) for CC, CT, and TT, respectively.
We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer.
The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups.
大量摄入红肉和/或加工肉类是结直肠癌的既定风险因素。我们进行了一项全基因组基因-环境（GxE）交互作用分析，以确定可能改变这些关联的遗传变异。
本研究纳入了 27 项研究中 29842 例结直肠癌病例和 39635 例对照的欧洲裔 pooled 样本。通过对来自协变量标准化问卷的数据进行构建，确定了红肉和加工肉类摄入量的分位数。基于 Haplotype Reference Consortium 对基因分型芯片进行了 imputation。我们在全基因组扫描中采用了两步 EDGE 和 GxE 交互作用联合检验。
荟萃分析证实，增加红肉和加工肉类的摄入量与结直肠癌风险呈正相关[每四分位红肉 OR = 1.30；95%置信区间（CI）= 1.21-1.41；加工肉类 OR = 1.40；95% CI = 1.20-1.63]。发现了两个与红肉摄入量相关的具有统计学意义的全基因组 GxE 交互作用。联合 GxE 检验显示，位于染色体 8（HAS2 下游）的 rs4871179 单核苷酸多态性；大于中位数的消耗比值比（ORs）分别为 1.38（95%CI=1.29-1.46）、1.20（95%CI=1.12-1.27）和 1.07（95%CI=0.95-1.19），对于 CC、CG 和 GG 基因型。两步 EDGE 方法鉴定了位于染色体 18（SMAD7 内含子）的 rs35352860 单核苷酸多态性；大于中位数的消耗 ORs 分别为 1.18（95%CI=1.11-1.24）、1.35（95%CI=1.26-1.44）和 1.46（95%CI=1.26-1.69），对于 CC、CT 和 TT 基因型。
我们提出了两个新的生物标志物，支持肉类摄入与结直肠癌风险增加之间的关系。
报告的 GxE 相互作用可能解释了某些人群亚组结直肠癌风险增加的原因。
