The Joint Effect of hOGG1, APE1, and ADPRT Polymorphisms and Cooking Oil Fumes on the Risk of Lung Adenocarcinoma in Chinese Non-Smoking Females

Xiaoxia Xue,Miao Yu,Yao Lu,Ying Yan,Baosen Zhou,Lu Yao,Zhihua Yin,Haibo Zhang,Yuxia Zhao,Zeshi Cui,Xuelian Li,Xiao-Ping Miao

doi:10.1371/journal.pone.0071157

Abstract

BackgroundThe human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and adenosine diphosphate ribosyl transferase (ADPRT) genes play an important role in the DNA base excision repair pathway. Single nucleotide polymorphisms (SNPs) in critical genes are suspected to be associated with the risk of lung cancer. This study aimed to identify the association between the polymorphisms of hOGG1 Ser326Cys, APE1 Asp148Glu, and ADPRT Val762Ala, and the risk of lung adenocarcinoma in the non-smoking female population, and investigated the interaction between genetic polymorphisms and environmental exposure in lung adenocarcinoma.MethodsWe performed a hospital-based case-control study, including 410 lung adenocarcinoma patients and 410 cancer-free hospital control subjects who were matched for age. Each case and control was interviewed to collect information by well-trained interviewers. A total of 10 ml of venous blood was collected for genotype testing. Three polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism technique.ResultsWe found that individuals who were homozygous for the variant hOGG1 326Cys/Cys showed a significantly increased risk of lung adenocarcinoma (OR = 1.54; 95% CI: 1.01–2.36; P = 0.045). When the combined effect of variant alleles was analyzed, we found an increased OR of 1.89 (95% CI: 1.24–2.88, P = 0.003) for lung adenocarcinoma individuals with more than one homozygous variant allele. In stratified analyses, we found that the OR for the gene-environment interaction between Ser/Cys and Cys/Cys genotypes of hOGG1 codon 326 and cooking oil fumes for the risk of lung adenocarcinoma was 1.37 (95% CI: 0.77–2.44; P = 0.279) and 2.79 (95% CI: 1.50–5.18; P = 0.001), respectively.ConclusionsThe hOGG1 Ser326Cys polymorphism might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, there is a significant gene-environment association between cooking oil fumes and hOGG1 326 Cys/Cys genotype in lung adenocarcinoma among female non-smokers.

Highlights

Lung cancer has become a major cause of cancer mortality worldwide, especially in China, and pathological studies have found that adenocarcinoma is the main form of lung cancer in the female population [1,2]
Using subjects with the human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser/Ser genotype as the reference group, homozygous carriers of the hOGG1 326Cys/Cys genotype had a 1.54-fold risk of lung adenocarcinoma compared with the homozygous wild genotypes
When patients homozygous for two or three gene variants were combined as one group, we found an increased odds ratio (OR) of 1.89 for lung adenocarcinoma individuals with more than one homozygous variant allele of hOGG1 326 Cys/Cys, apyrimidinic endonuclease 1 (APE1) 148Glu/Glu and adenosine diphosphate ribosyl transferase (ADPRT) 762Ala/Ala

Summary

Introduction

Lung cancer has become a major cause of cancer mortality worldwide, especially in China, and pathological studies have found that adenocarcinoma is the main form of lung cancer in the female population [1,2]. Lung cancer maybe caused mainly by the other factors in Chinese women, it is important to study the factors that affect female lung cancer, especially non-smoking females. Genetic variations in DNA repair genes are thought to affect DNA repair capacity and are suggested to be associated with a risk for lung cancer [6,7,8]. The human 8-oxoguanine DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and adenosine diphosphate ribosyl transferase (ADPRT) genes play an important role in the DNA base excision repair pathway. This study aimed to identify the association between the polymorphisms of hOGG1 Ser326Cys, APE1 Asp148Glu, and ADPRT Val762Ala, and the risk of lung adenocarcinoma in the non-smoking female population, and investigated the interaction between genetic polymorphisms and environmental exposure in lung adenocarcinoma

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