X-Ray Repair Cross-Complementing Group 1(XRCC1) Genetic Polymorphisms and Thyroid Carcinoma Risk: a Meta-Analysis

Ke Qian,Wen-Jun Yi,Feng Xu,En-Xiang Zhou,Zhong-Hua Tang,Xian-Yu Chen,Kui-Jie Liu,Gan-Nong Chen

doi:10.7314/apjcp.2012.13.12.6385

Abstract

A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials.

Highlights

Thyroid cancer is of special concern in endocrinology because it accounts for more than 90% of all endocrine cancers and contributes to more than 50% of all deaths from endocrine cancers (Gilfillan, 2010; Aschebrook-Kilfoy et al, 2011)
Subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for X-ray repair cross complementing group 1 (XRCC1) Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism
Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials

Summary

Introduction

Thyroid cancer is of special concern in endocrinology because it accounts for more than 90% of all endocrine cancers and contributes to more than 50% of all deaths from endocrine cancers (Gilfillan, 2010; Aschebrook-Kilfoy et al, 2011). Exposure to ionizing radiation is the only well established risk factor for thyroid cancer, especially when it occurs in early stages of life (Papadopoulou et al, 2009). There are evidences that many gene polymorphisms including DNA repair genes influence on thyroid cancer susceptibility (Gudmundsson et al, 2012, Jendrzejewski et al, 2012). X-ray repair cross complementing group 1 (XRCC1), located on chromosome 19q13.2–13.3, with 33 kilobases in length, and encodes a scaffold protein involved in the repair of DNA single-strand break (SSB) formed by ionizing radiation and alkylation damage (Chou et al, 2008). The three SNPs have been reported to be associated with many types of cancer, such as lung cancer (Dai et al, 2012), gastric cancer (Chen et al, 2012), breast cancer (Huang et al, 2009) and leukemia (Wang et al, 2012)

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Conclusion