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Association of Promoter Polymorphisms in Xrcc2 Gene Involved in DNA Double Strand Break Repair and Increased Susceptibility to Thyroid Cancer Risk in Pakistani Population
Sarwar R, Bashir K, Saeed S, Mahjabeen I and Kayani MA
Introduction: The incidence of thyroid cancer (TC) has rapidly increased globally in recent decades. It is the most frequent endocrine malignancy which is fifth most common cancer in females. Double strand break repair (DSBR) pathway gene, X-Ray Repair Complementing Defective Repair in Chinese Hamster Cells 2 (XRCC2) has high rate of polymorphisms and may cause individual’s susceptibility towards carcinogenesis including thyroid cancer.
Objective: Main objective of present study is to find the association of hotspot promotor polymorphisms in XRCC2 gene with thyroid cancer risk.
Methods: In this study, we performed genetic association studies in 856 individuals (456 cases and 400 controls) for three promoter region SNPs of XRCC2 gene i.e., G4234C (rs3218384), G4088T (rs3218373) and G3063A (rs2040639). Genotyping was performed by amplification refractory mutation system (ARMS-PCR) followed by direct sequencing.
Results: We found association of G4234C with thyroid cancer risk in stage I and II (p>0.0004) cancer patients while no association was observed with other parameters. Significant increased risk of developing thyroid cancer risk was observed in patients for G4088T with variant heterozygote T/G (OR=1.65, 95% CI=1.20-2.24; p<0.001) and polymorphic homozygote G/G (OR=1.66, 95% CI=1.16-2.36; p=0.005) compared with healthy controls. For G3063A polymorphism, a significant difference in genotypes distributions was observed for heterozygous variant G/A (OR=2.11; 95% CI=1.52-2.94; p<0.0001) and A/A variant genotype (OR=2.02; 95% CI=1.37-2.97; p<0.0003). When stratified for different parameters, significant increased risk was observed in female patients, patients with age ≥ 42 years, smoking and stage I and II patients for G4088T and G3063A in comparison to controls.
Conclusion: Present study concluded that G4234C, G4088T and G3063A SNPs in XRCC2 gene may modify the risk of thyroid cancer development.