HPV seropositivity joints with susceptibility loci identified in GWASs at apoptosis associated genes to increase the risk of Esophageal Squamous Cell Carcinoma (ESCC).

Ju Yang,Qian Jiang,Xianglin Yuan,Wen Li,Xiangning Fu,Huanlei Wu,Huihua Xiong,Zhaozhen Qi,Zhongxing Liao,Sheng Wei,Guangyuan Hu

doi:10.1186/1471-2407-14-501

Abstract

BackgroundWe previously showed that human papillomavirus (HPV) serostatus was not an independent risk factor for esophageal squamous cell carcinoma(ESCC) in nonsmokers and nondrinkers; however, HPV increased the risk in smokers.MethodsHere we investigated possible interactions between HPV16 serostatus and three susceptibility loci identified in GWASs at apoptosis associated genes with regard to risk of ESCC in a case–control study of 313 patients with ESCC and 314 healthy controls. The loci (CHK2 rs738722, C12orf51 rs2074356, and PLCE1 rs2274223) were genotyped, and the presence or absence of HPV16 in serum was measured by ELISA. Multivariable logistic regression was used to evaluate possible interactions of HPV16 serostatus and the three loci on the risk of ESCC.ResultsA significant interaction was found between HPV16 serology and rs2074356 (P = 0.005, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11–1.77) or rs2274223 (P < 0.001, OR 1.53, 95% CI 1.23–1.91), but not for rs738722. For rs2074356, risk of ESCC was increased substantially in smokers (P < 0.001, OR 8.25, 95% CI 3.84–17.71) and drinkers (OR4.04, P = 0.001, 95% CI 1.79–9.10) who carried risk alleles (TT or TC genotype) and were HPV16-seropositive. Similar results were observed for rs2274223 in smokers (P < 0.001, OR6.06, 95% CI 2.85–12.88) and drinkers (P < 0.001, OR 5.43, 95% CI 2.51–11.76), but not for rs738722.ConclusionConsistent with the previous study, loci at rs2074356 and rs2274223 could increase the risk of ESCC, furthermore, there were significant interactions between HPV sero-status and the susceptibility loci on the risk of ESCC. This effect could be modified obviously by smoking and drinking.

Highlights

We previously showed that human papillomavirus (HPV) serostatus was not an independent risk factor for esophageal squamous cell carcinoma(ESCC) in nonsmokers and nondrinkers; HPV increased the risk in smokers
HPV infection combined with smoking and drinking could increase the risk of ESCC [9], only a fraction of ESCCs are associated with HPV infection, implying that other genetic factors can modify the association between HPV infection and the risk of ESCC
We found that genotypes at rs2274223 and rs2074356 contributed to the risk of ESCC independently of HPV16 seropositivity, as had been found in previous genomewide association studies; we found that rs738722 did not contribute to the risk of ESCC

Summary

Introduction

We previously showed that human papillomavirus (HPV) serostatus was not an independent risk factor for esophageal squamous cell carcinoma(ESCC) in nonsmokers and nondrinkers; HPV increased the risk in smokers. In high-risk areas such as northern Iran, Central Asian countries, and north central China, esophageal squamous cell carcinoma (SCC). HPV infection is a risk factor for the development of several types of tumors, HPV16 and HPV18 infection and cervical cancer [6]. HPV16 was reported to be an important infectious factor in the high incidence of esophageal cancer in China [7]. HPV infection combined with smoking and drinking could increase the risk of ESCC [9], only a fraction of ESCCs are associated with HPV infection, implying that other genetic factors can modify the association between HPV infection and the risk of ESCC

Methods

Results

Conclusion