Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Nat Genet. 2010 Mar;42(3):224-8. doi: 10.1038/ng.522. Epub 2010 Jan 24.
We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.
我们对来自 12 项前瞻性队列研究和 8 项病例对照研究的 3851 名胰腺癌患者（病例）和 3934 名无影响对照者进行了全基因组关联研究。基于针对基因型趋势效应的逻辑回归模型，该模型调整了研究、年龄、性别、自我描述的祖先和五个主要成分，我们确定了位于染色体 13q22.1、1q32.1 和 5p15.33 上的三个位置的 8 个 SNP。两个相关 SNP，rs9543325（P = 3.27 x 10(-11)，每等位基因优势比（OR）1.26，95%置信区间（CI）1.18-1.35）和 rs9564966（P = 5.86 x 10(-8)，每等位基因 OR 1.21，95% CI 1.13-1.30），映射到染色体 13q22.1 上的非基因区域。1q32.1 上的五个 SNP 映射到 NR5A2，最强信号位于 rs3790844（P = 2.45 x 10(-10)，每等位基因 OR 0.77，95% CI 0.71-0.84）。单个 SNP rs401681（P = 3.66 x 10(-7)，每等位基因 OR 1.19，95% CI 1.11-1.27）映射到 5p15.33 上的 CLPTM1L-TERT 基因座，该基因座与多种癌症有关。我们的研究已经确定了胰腺癌的常见易感基因座，需要进一步的研究。
