XRCC1基因多态性的单倍型分析与甲状腺癌风险

Haplotype analysis of XRCC1 gene polymorphisms and the risk of thyroid carcinoma.

作者信息

Bashir Kashif, Sarwar Romana, Fatima Shazia, Saeed Soma, Mahjabeen Ishrat, Akhtar Kayani Mahmood

机构信息

Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS Institute of Information Technology (CIIT), Park Road Chak Shahzad, Islamabad, Pakistan.

出版信息

J BUON. 2018 Jan-Feb;23(1):234-243.

DOI:

PMID:29552790

Abstract

PURPOSE

Variants in DNA repair genes may alter the repair mechanisms that make the persons vulnerable to DNA damage. These polymorphic variants in the DNA repair pathway genes, such as XRCC1, have been associated with susceptibility of several types of cancer including thyroid cancer. This study was designed to explore the link between XRCC1 polymorphisms and modulation of thyroid cancer risk.

METHODS

Our study consisted of 456 thyroid cancer patients and 400 controls. For XRCC1 polymorphisms analyses, three single nucleotide polymorphisms (SNPs) (rs25489, rs25487 and 1799782) were selected and genotyped by ARMS-PCR.

RESULTS

The homozygous mutant (AA) of rs25489 SNP showed highly significant association with thyroid cancer risk (OR=0.17; 95% CI=0.10-0.31; p=0.0001). In the rs25487 polymorphism all genotypes showed no significantly increased risk of thyroid cancer in patients compared to controls (p>0.05). In the rs1799782 of XRCC1 gene, the homozygous mutant (TT) significantly decreased the risk of thyroid cancer (OR=0.71; 95% CI=0.50-1.01; p=0.05). Eight haplotypes were generated for three selected SNPs (rs25489, rs25487 and rs1799782) of XRCC1 gene among thyroid cases and controls. The haplotype GAT (OR=1.69; 95% CI=1.25- 2.30; p=0.0005) and GGC (OR=2.75; 95% CI=2.11-3.58; p=1.29e-014) showed highly significant association with increased risk of thyroid cancer. The haplotypes AAC (OR=0.31; 95% CI=0.17-0.57; p=6.68e-005), AAT (OR= 0.51; 95% CI=0.34-0.78; p=0.001), AGT (OR=0.46; 95%CI=0.29- 0.71; p=0.0003) and GGT (OR=0.80; 95% CI=0.64-0.98; p=0.03) had significant reducing effect in thyroid cancer patients.

CONCLUSIONS

XRCC1 Arg280His and Arg194Trp were associated with thyroid cancer in Pakistani population. These genetic markers may provide an insight into the disease pathogenesis and help open novel therapeutic strategies for thyroid cancer.

摘要

目的

DNA修复基因中的变异可能会改变修复机制，使个体易受DNA损伤。DNA修复途径基因中的这些多态性变异，如XRCC1，与包括甲状腺癌在内的几种癌症的易感性有关。本研究旨在探讨XRCC1基因多态性与甲状腺癌风险调节之间的联系。

方法

我们的研究包括456例甲状腺癌患者和400例对照。对于XRCC1基因多态性分析，选择了三个单核苷酸多态性（SNP）（rs25489、rs25487和1799782），并通过扩增阻滞突变系统聚合酶链反应（ARMS-PCR）进行基因分型。

结果

rs25489 SNP的纯合突变体（AA）与甲状腺癌风险高度相关（OR = 0.17；95%可信区间 = 0.10 - 0.31；p = 0.0001）。在rs25487多态性中，与对照相比，所有基因型在患者中均未显示出甲状腺癌风险显著增加（p > 0.05）。在XRCC1基因的rs1799782中，纯合突变体（TT）显著降低了甲状腺癌风险（OR = 0.71；95%可信区间 = 0.50 - 1.01；p = 0.05）。在甲状腺病例和对照中，为XRCC1基因的三个选定SNP（rs25489、rs25487和rs1799782）生成了八种单倍型。单倍型GAT（OR = 1.69；95%可信区间 = 1.25 - 2.30；p = 0.0005）和GGC（OR = 2.75；95%可信区间 = 2.11 - 3.58；p = 1.29×10⁻¹⁴）与甲状腺癌风险增加高度相关。单倍型AAC（OR = 0.31；95%可信区间 = 0.17 - 0.57；p = 6.68×10⁻⁰⁵）、AAT（OR = 0.５1；95%可信区间 = 0.34 - 0.78；p = 0.001）、AGT（OR = 0.46；95%可信区间 = 0.29 - 0.71；p = 0.0003）和GGT（OR = 0.80；95%可信区间 = 0.64 - 0.98；p = 0.03）对甲状腺癌患者有显著的降低作用。