Common risk variants for colorectal cancer: an evaluation of associations with age at cancer onset.
Common risk variants for colorectal cancer: an evaluation of associations with age at cancer onset.
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DOI：
10.1038/srep40644
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发表时间：
2017-01-13
影响因子：
4.6
通讯作者：
Oh JH
中科院分区：
文献类型：
--
作者：
Song N;Shin A;Park JW;Kim J;Oh JH
全基因组关联研究（GWAS）已在约40个位点确定了结直肠癌（CRC）的常见遗传风险变异。我们通过病例对照分析和病例对照分析，研究了这些风险变异与结直肠癌发病年龄的关系。本研究共纳入了来自韩国国家癌症中心进行的两项独立病例对照研究的1，962例CRC病例和2，668例对照。我们对33个GWAS鉴定的与CRC风险相关的单核苷酸多态性（SNP）进行了基因分型。在仅病例分析中，位于ZMIZ 1-AS 1基因10q22.3的SNP rs704017中的风险等位基因在年龄<50岁的CRC患者中的频率始终低于年龄≥50岁的CRC患者（优势比（OR）= 0.78，95%置信区间（CI）= 0.66-0.92，P = 2.7 × 10−3，在相加模型中），尽管这没有超过多重检验的阈值。在联合病例对照分析中，rs704017和CRC风险之间的关联方向因年龄组而异（优势模型中，<50岁：OR = 0.77，95% CI = 0.60-0.98，P = 0.03; ≥50岁：OR = 1.13，95% CI = 0.98-1.29，P = 0.09）;异质性（P异质性= 7.5 × 10−3）和交互作用（P交互作用= 7.8 × 10−3，在主导模型中）的p值具有统计学显著性。我们的研究结果表明，CRC易感性SNP rs704017对CRC的发病年龄具有遗传效应。
Common genetic risk variants for colorectal cancer (CRC) have been identified at approximately 40 loci by genome-wide association studies (GWAS). We investigated the association of these risk variants by age at onset of CRC using case-only and case-control analysis. A total of 1,962 CRC cases and 2,668 controls from two independent case-control studies conducted by Korea’s National Cancer Center were included in this study. We genotyped 33 GWAS-identified single-nucleotide polymorphisms (SNPs) associated with CRC risk. The risk allele in SNP rs704017, located at 10q22.3 in the ZMIZ1-AS1 gene, was consistently less frequent among CRC patients aged <50 years than among CRC patients aged ≥50 years in the case-only analysis (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.66–0.92, P = 2.7 × 10−3, in an additive model), although this did not surpass the threshold for multiple testing. The direction of associations between rs704017 and CRC risk differed by age group in the combined case-control analysis (<50 years: OR = 0.77, 95% CI = 0.60–0.98, P = 0.03 and ≥50 years: OR = 1.13, 95% CI = 0.98–1.29, P = 0.09, in a dominant model); the p-values for heterogeneity (Pheterogeneity = 7.5 × 10−3) and for interaction were statistically significant (Pinteraction = 7.8 × 10−3, in the dominant model). Our results suggest that the CRC susceptibility SNP rs704017 has a hereditary effect on onset age of CRC.