PARP1 genetic variants modulate gene expression and cervical cancer susceptibility in a North Indian case-control study.

BACKGROUND: Poly (ADP-ribose) polymerase 1 (PARP1) is a nuclear protein involved in the DNA repair pathway. The aim of this investigation was to assess the association of PARP1 polymorphisms with PARP1 expression and cervical cancer susceptibility in North Indian women. METHODS AND RESULTS: This was a case-control study comprised of 141 cervical cancer patients and 147 healthy controls. The PCR-RFLP was performed for genotypic distribution. The qRT-PCR and immunohistochemistry were performed to check PARP1 gene and protein expression, respectively. The homozygous CC (rs1136410) in the genotype model was found to be significant (P = 0.002); however, the interval of the odds ratio was wide, thereby leading to an unstable association. In the additive model, the association was significant, but the odds ratio was less than 2, whereas the dominant model was significantly correlated with cervical cancer with a high odds ratio (P = 0.002; OR = 2.34). The heterozygous CT (rs7527192) was associated with cervical cancer in the genotype model (OR = 2.37). The dominant and additive models were also significantly associated with cervical cancer, conferring a 2.71 and 2.36 times higher risk. The gene and protein expression of PARP1 was higher in cervical cancer patients. There was an association of CC genotype (rs1136410) and PARP1 expression as per the Kruskal-Wallis test, but no such association was found in rs7527192 polymorphism. CONCLUSIONS: The findings suggest that rs7527192 may be associated with cervical cancer susceptibility in this cohort, and rs1136410 influences the PARP1 expression; however, independent validation in larger, multiethnic, and functionally characterized cohorts with HPV adjustment is required.