Association of haplotype and linkage disequilibrium of PARP1 polymorphisms rs1136410, rs1805405 and rs3219088 with gallbladder cancer.

BACKGROUND

Previously, we have reported that PARP1 rs1136410 is significantly associated with increased the risk of gallbladder cancer.

AIM: We aimed to investigate the association of PARP1 rs1805405 and rs3219088 polymorphisms with risk of GBC and also association of the haplotype and combined effect of PARP1 SNPs (rs1805405 G/A, rs3219088 G/T and rs1136410 A/G). We have also investigated the expression profile of PARP1 and its correlation with polymorphisms, clinical parameters and overall survival.

METHODS

PARP1 polymorphisms were genotyped by PCR-RFLP and the expression profile of PARP1 at mRNA level was analyzed by semi-quantitative PCR. Overall survival was analyzed using Kaplan-Meier plot and Cox-regression analysis.

RESULTS

Haplotype analysis of the PARP1 polymorphisms revealed that AGG, AAG and GGT haplotypes are significantly associated with decreased risk of GBC, while AAT, AGT, GGG and GAG haplotypes are significantly associated with increased risk of GBC. Patients with T1+T2 and treated with chemotherapy having risk genotypes of rs1805405 have decreased overall survival. Upregulation of PARP1 is significantly associated with longer overall survival in patients with GBC with different clinical parameters. SNPs rs1136410 and rs1805405 genotypes are significantly associated with PARP1 expression.

CONCLUSION

Haplotype analysis suggests that PARP1 may have a potential role in gallbladder carcinogenesis.