Cancer Prevention Institute of California, Fremont, California, USA.
Gut. 2014 May;63(5):800-7. doi: 10.1136/gutjnl-2013-305189. Epub 2013 Aug 9.
Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer.
We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10(-4) was used to determine statistical significance of the associations.
Two correlated SNPs--rs10090154 and rs4242382--in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites.
This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.
全基因组关联研究已经确定了许多与广泛的癌症部位相关的单核苷酸多态性（SNP）。其中一些变体与多种癌症有关，表明一些癌症之间存在多效性效应和共同的生物学机制。我们假设以前与其他癌症相关的 SNP 可能还与结直肠癌有关。在一项大规模研究中，我们研究了之前与 18 种不同癌症相关的 171 个 SNP 与结直肠癌的相关性。
我们从三个联盟（人群基因组学和流行病学（PAGE）、结直肠癌遗传流行病学（GECCO）和结肠癌家族登记处（CCFR））中检查了 13338 例结直肠癌病例和 40967 例对照。针对年龄、性别、遗传祖先的主要成分以及/或相关的研究特定因素，对每个 SNP 与结直肠癌风险之间的关联进行了特定于研究的逻辑回归分析，结果进行了固定效应荟萃分析。使用 Bonferroni 校正的 p 值 2.92×10(-4) 来确定关联的统计学意义。
染色体 8q24 区域 1 中两个相关的 SNP--rs10090154 和 rs4242382--与前列腺癌易感性区域，与结直肠癌风险有统计学显著关联。与 rs4242382 观察到最显著的关联（荟萃分析 OR=1.12；95%CI 1.07 至 1.18；p=1.74×10(-5)），该 SNP 也在不同种族/族裔人群和解剖亚部位中表现出类似的关联。
这是第一个明确显示染色体 8q24 区域 1 为结直肠癌易感性区域的研究；因此，将结直肠癌添加到与 8q24 这一特定多癌症风险区域相关的癌症部位列表中。
