评估汉族人群中8种多态性与癌症易感性的关联。

Evaluating the Association of Eight Polymorphisms with Cancer Susceptibility in a Han Chinese Population.

作者信息

Dong Ying, Chen Jing, Chen Zhiqiang, Tian Chaoyong, Lu Huaisheng, Ruan Jigang, Yang Wenjun

机构信息

Medical Oncology Department of General Hospital, Ningxia Medical University, Yinchuan, Ningxia, China; Key Laboratory of Ningxia Reproduction and Heredity, Ningxia Medical University, Yinchuan, Ningxia, China.

Key Laboratory of Ningxia Reproduction and Heredity, Ningxia Medical University, Yinchuan, Ningxia, China.

出版信息

PLoS One. 2015 Jul 15;10(7):e0132797. doi: 10.1371/journal.pone.0132797. eCollection 2015.

Abstract

BACKGROUND

The identification of susceptibility genes for specific types of cancer can provide necessary information for the complete characterization of cancer syndromes. Eight single nucleotide polymorphisms (SNPs), rs465498, rs17728461, rs4488809, rs753955, rs13361707, rs9841504, rs2274223, and rs13042395, were reported by genome wide association studies (GWASs) to be closely related to the susceptibility of lung cancer (LC), gastric cancer (GC) or esophageal cancer (EC) in Han population from northern or southern China. However, Chinese Han people from different geographic areas may have different genetic backgrounds. This study aims to assess the genetic associations of the eight SNPs mentioned above with three cancers risk in a Han population from northwest China.

METHODS

A total of 186 cancer-free controls and 436 cases with non-small cell lung cancer (NSCLC) (159 cases), non-cardia GC (167 cases) or EC (110 cases) were enrolled in this study. Chi-square test and polytomous logistic regression analyses were used to estimate the association between eight cancer-related SNPs and three cancers in a Han Chinese population from northwest China. The logistic regression results were adjusted for confounding factors and Benjamini and Hochberg False Discovery Rate (FDR) method was used to adjust the multiple hypothesis tests. Association analyses by cigarette smoking or alcohol drinking status were analyzed by crossover analyses.

RESULTS

One of the eight SNPs, rs17728461 was associated with NSCLC susceptibility (in a heterozygous model, OR = 0.44, 95% CI = 0.27-0.72, p = 0.001). Two SNPs, rs753955 and rs13042395, were associated with the risk of non-cardia GC in different genetic models (p < 0.05). No SNPs were associated with EC. The crossover analyses showed that the rs13042395 CT genotype, combined with cigarette smoking or alcohol drinking, could further increase the risk for non-cardia GC (p < 0.05).

CONCLUSIONS

These results indicated that rs17728461 may be specifically associated with the risk of NSCLC. rs753955 and rs13042395 were specifically associated with susceptibility to non-cardia GC in Ningxia Han Chinese. Susceptibility-associated polymorphisms in the northwestern Han Chinese were not very consistent with those in the northern Han Chinese or southern Han Chinese. The validation of these findings with a functional evaluation and a larger population is still required.

摘要

背景

特定类型癌症易感性基因的鉴定可为癌症综合征的全面特征描述提供必要信息。全基因组关联研究(GWAS)报告称,8个单核苷酸多态性(SNP),即rs465498、rs17728461、rs4488809、rs753955、rs13361707、rs9841504、rs2274223和rs13042395,与中国北方或南方汉族人群的肺癌(LC)、胃癌(GC)或食管癌(EC)易感性密切相关。然而,来自不同地理区域的中国汉族人群可能具有不同的遗传背景。本研究旨在评估上述8个SNP与中国西北汉族人群三种癌症风险的遗传关联。

方法

本研究共纳入186名无癌对照者和436例非小细胞肺癌(NSCLC)(159例)、非贲门GC(167例)或EC(110例)患者。采用卡方检验和多分类逻辑回归分析来估计8个癌症相关SNP与中国西北汉族人群三种癌症之间的关联。逻辑回归结果针对混杂因素进行了调整,并使用Benjamini和Hochberg错误发现率(FDR)方法对多重假设检验进行了调整。通过交叉分析对吸烟或饮酒状态进行关联分析。

结果

8个SNP中的rs17728461与NSCLC易感性相关(杂合子模型中,OR = 0.44,95%CI = 0.27 - 0.72,p = 0.001)。2个SNP,rs753955和rs13042395,在不同遗传模型中与非贲门GC风险相关(p < 0.05)。没有SNP与EC相关。交叉分析表明,rs13042395 CT基因型与吸烟或饮酒相结合,可进一步增加非贲门GC的风险(p < 0.05)。

结论

这些结果表明,rs17728461可能与NSCLC风险特异性相关。rs753955和rs13042395与宁夏汉族非贲门GC易感性特异性相关。中国西北汉族人群中与易感性相关的多态性与中国北方汉族或南方汉族人群中的多态性不太一致。仍需要通过功能评估和更大规模人群对这些发现进行验证。

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