TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population

Yanli Li,Zuo-Feng Zhang,Lina Mu,Rungui Niu,Baoxing Zhao,Jiawei Li,Christina R Crabtree-Ide,Li Liu,Jianping Shi,Lin Cai,Jia Su,Shen-Chih Chang,Shunzhang Yu,Xiaoyou Han

doi:10.1186/1471-2407-13-607

Abstract

BackgroundA pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interaction with environmental factors and risk of lung cancer.MethodsA case–control study was conducted in Taiyuan, China. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Multiplicative and additive interactions between TP53 SNPs and lifestyle factors were evaluated.ResultsVariant TP53 rs2078486 SNP was significantly associated with elevated lung cancer risk among smokers (OR: 1.70, 95% CI: 1.08 - 2.67) and individuals with high indoor air pollution exposure (OR: 1.51, 95% CI: 1.00-2.30). Significant or borderline significant multiplicative and additive interactions were found between TP53 rs2078486 polymorphism with smoking and indoor air pollution exposure. The variant genotype of TP53 SNP rs1042522 significantly increased lung cancer risk in the total population (OR: 1.57, 95% CI: 1.11-2.21), but there was no evidence of heterogeneity among individuals with different lifestyle factors.ConclusionsThis study confirmed that TP53 rs2078486 SNP is potentially a novel TP53 SNP that may affect lung cancer risk. Our study also suggested potential synergetic effects of TP53 rs2078486 SNP with smoking and indoor air pollution exposure on lung cancer risk.

Highlights

A pathway-based genotyping analysis suggested rs2078486 was a novel TP53 single-nucleotide polymorphisms (SNPs), but very few studies replicate this association
No significant associations with lung cancer risk were found for TP53 rs2078486 SNP, despite a tendency towards an elevated lung cancer risk associated with the variant genotype
A significantly increased lung cancer risk was observed among individuals with the homozygous variant genotype (CC) of TP53 SNP rs1042522, compared with the homozygous wild type (GG)

Summary

Introduction

A pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interaction with environmental factors and risk of lung cancer. Lung cancer is one of the most common cancers and is a leading cause of cancer death in China. Lung cancer mortality increased 465% during the past 30 years and now is the leading cancer death cause in China [2]. Smoking is regarded as the most important risk factor for lung cancer, and indoor air pollution from cooking. Several functional TP53 SNPs have been reported to be associated with risk of developing different human cancers, including lung cancer [7,8,9]

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