Association of XPC Polymorphisms with Cutaneous Malignant Melanoma Risk: Evidence from a Meta-Analysis.

Fatemeh Asadian,Seyed Alireza Emarati,Seyed Mohammadreza Niktabar,Jalal Sadeghizadeh-Yazdi,Elahe Akbarian,Hossein Neamatzadeh,Yaser Ghelmani,Shadi Kargar

doi:10.14712/18059694.2020.27

Abstract

A number of studies have reported that the xeroderma pigmentosum complementation group C (XPC) polymorphisms are associated with cutaneous malignant melanoma (CMM) susceptibility. But the results of those studies were inconsistent. Here, we performed a study to obtain a more conclusive result on the association of XPC polymorphisms with risk of CMM. The XPC Lys939Gln and Ala499Val polymorphisms were genotyped in 150 CMM cases and 150 controls by PCR-RFLP assay. Subsequently, all published relevant studies were identified through a comprehensive literature search in PubMed, Web of Science, and CNKI databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of correlation. There was no significant association between XPC Lys939Gln and Ala499Val polymorphisms and CMM risk in our population. A total of 15 case-control studies including ten studies with 5,990 cases and 7,697 controls on XPC Lys939Gln and five studies with 3,139 cases and 3,721 controls on XPC Ala499Val polymorphism were selected. Pooled data revealed that XPC Lys939Gln (C vs. A: OR = 1.108, 95% CI 1.008- 1.217; P = 0.033) and Ala499Val (C vs. A: OR = 0.918, 95% CI 0.850-0.992; p = 0.031; CC+CA vs. AA: OR = 0.904, 95% CI 0.819-0.997; p = 0.043) polymorphisms were significantly associated with an increased risk of CMM. Moreover, stratified analyses by ethnicity revealed that the XPC Ala499Val and Lys939Gln polymorphisms were significantly associated with risk of CMM in Caucasians and mixed populations, respectively. This meta-analysis result suggested that XPC Lys939Gln and Ala499Val polymorphisms were significantly associated with risk of CMM.

Highlights

MATERIALS AND METHODSCutaneous malignant melanoma (CMM) is an aggressive tumor of melanocytes in skin with rapidly increasing incidence causing a major public health problem [1]
All observed genotype frequencies of the xeroderma pigmentosum complementation group C (XPC) Lys939Gln and Ala499Val polymorphisms in the control group were in accordance with the Hardy-Weinberg equilibrium (HWE) (p = 0.492 and p = 0.698, respectively)
When all the eligible studies were pooled into the meta-analysis of XPC Ala499Val polymorphism was significantly increased risk of cutaneous malignant melanoma (CMM) was found under two genetic models i.e., allele (T vs. C: Odds ratios (ORs) = 0.918, 95% confidence intervals (CIs) 0.850-0.992; P = 0.031, Fig 2B) and dominant (TT+TC vs. CC: OR = 0.904, 95% CI 0.8190.997; P = 0.043)

Summary

Introduction

MATERIALS AND METHODSCutaneous malignant melanoma (CMM) is an aggressive tumor of melanocytes in skin with rapidly increasing incidence causing a major public health problem [1]. Selection Criteria The inclusion criteria of studies in the meta-analysis were defined as follows: 1) original and published data; 2) studies with case-control or cohort design; 3) evaluates the associations of XPC Lys939Gln and Ala499Val polymorphisms with CMM risk; 4) provides sufficient data for calculation of odds ratio (OR) with 95% confidence interval (CI).

Results

Conclusion