Glutathione S-Transferase Polymorphism Interactions with Smoking Status and HPV Infection in Cervical Cancer Risk: An Evidence-Based Meta-Analysis

Shuai Zhen,Chen-Ming Hu,Li-Hong Bian,William B Coleman

doi:10.1371/journal.pone.0083497

Shuai Zhen, Chen-Ming Hu + Show 2 more

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https://doi.org/10.1371/journal.pone.0083497

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Abstract

BackgroundHuman papillomavirus (HPV) infection is considered the major cause of cervical cancer (CC), but a number of infected women do not develop invasive lesions, suggesting the role of genetic susceptibility and environmental co-factors for cancer outbreak. Glutathione S- transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens.MethodsMEDLINE, EMBASE, and Cochrane databases were searched. All studies evaluating the association between GSTM1 polymorphisms and cervical cancer were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-or random-effects model.ResultsA total of 23 case-control studies were included in the meta-analysis. The overall result showed that the association between GSTM1 null genotype and risk for cervical cancer was statistically significant (OR = 1.56; 95%CI, 1.39–1.75). Subgroup analyses were performed based on ethnicity, smoking and HPV infection. Our results showed that smokers with null GSTM1 genotype had higher risk of cervical cancer (OR = 2.27, 95%CI, 1.46–3.54). For the ethnicity stratification, significant increased risk of null GSTM1 genotype was found in Chinese and Indian population, but no increased risk in other population was found.Conclusionsthis meta-analysis provided strong evidence that the GSTM1 genotype is associated with CC development, especially in Chinese and Indian populations. Smoking and HPV infection modified the association between the null GSTM1 genotype and CC.

Highlights

Cervical cancer (CC) is the second most common gynecologic malignancy in the world and the seventh most frequent overall malignancy [1]
According to several epidemiological and biological studies, human papilloma virus (HPV) infection is the dominant etiological event in CC development; it is insufficient as a causal agent because this virus is detected at a certain frequency among women who are cytologically normal, and CC occurs in only a fraction of Human papillomavirus (HPV)-infected women
The results showed that smokers had an increased risk of CC (OR = 2.27; 95%confidence interval (CI), 1.46–3.54), while no significant increased risk was observed in non-smokers (Figure 5)

Summary

Introduction

Cervical cancer (CC) is the second most common gynecologic malignancy in the world and the seventh most frequent overall malignancy [1]. Additional features of the host, including an active sexual history, weakened immune function, and cigarette smoking, have been confirmed as risk factors for CC [2]. Among these factors, smoking is associated with a significantly increased risk, and its effects, which are enhanced by interaction with HPV infection [3] but appear to be independent of socioeconomic status and sexual behavior [4], are dosedependent [3]. Cigarette smoke carcinogens, polycyclic aromatic hydrocarbons (PAHs), and benzo(a)pyrene have been detected in the cervical mucus of smokers, while cigarette smoke carcinogen-specific DNA adducts (e.g. NNK) have been found in the cervical epithelial cells of cigarette smokers [5] These results suggest that tobacco smoking could increase the risk of tumor onset and viral infection persistence. Glutathione S- transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens

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