Abstract
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.
Keywords
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Article info
Publication history
Published online: December 27, 2022
Accepted:
December 7,
2022
Received:
July 8,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.