Interaction among susceptibility genotypes of PARP1 SNPs in thyroid Carcinoma

Abstract

Polymorphisms in DNA repair genes may alter the repair mechanism which makes the person susceptible to DNA damage. Polymorphic variants in these DNA repair pathway genes such as Poly (ADP-ribose) polymerase- 1 (PARP1) have been associated with susceptibility of several types of cancer including thyroid. Many studies have been published on PARP1 gene polymorphisms and carcinogenesis with inconsistent results. The present study was designed to explore the link between the PARP1 polymorphisms and thyroid cancer risk. This case-control study was comprised of 456 thyroid cancer patients and 400 healthy controls. Three SNPs of PARP1 gene; rs1136410, rs1805414 and rs1805404 were analyzed using ARMS-PCR. The combined genotype and haplotype analysis were performed using haploview software 4.2. Major allele homozygote (CC) of rs1136410 and combined genotype (TT+TC) of rs180414 showed a significant association with thyroid cancer risk (OR = 1.30; 95% CI 0.99–1.77; P = 0.05) and (OR = 0.43; 95% CI = 0.27–0.67; P = 0.03). Histological subtype analysis showed the significant association of selected PARP1 SNPs with papillary, follicular and anaplastic subtypes in thyroid cancer patients. Haplotype analysis showed that TCT (p = 0.01), CTT (p = 0.02) and CTC (p = 0.03) were significantly higher in controls when compared to cases. However, TTC (p = 0.05) and TCC (p = 0.01) haplotype frequency was significantly higher in cases compared to controls. Global haplotype analysis showed that there was an overall significant difference between cases and controls (p = 0.001). Identification of these genetic risk markers may provide evidence for exploring insight into mechanisms of pathogenesis and subsequently aid in developing novel therapeutic strategies for thyroid cancer.