Base excision repair pathway: PARP1 genotypes as modulators of therapy response in cervical cancer patients

Abstract

Context: Genetic polymorphisms in genes of the base excision repair (BER) pathway appear to modulate the therapy response of cancer patients. PARP1 protein recognizes the DNA strand damage and facilitates the subsequent recruitment of BER proteins. Few studies have reported an association between PARP1 Val762Ala polymorphism (rs1136410) and cancer therapy response.

Objective: The purpose of our study was to determine whether PARP1 Val762Ala polymorphism have prognostic value in patients with cervical cancer.

Materials and methods: Two hundred and sixty adult patients, with histologically confirmed cervical cancer, at FIGO-stages IB2-IVA, primarily treated with concurrent chemotherapy (cisplatin) and radiotherapy. Overall survival (OS) and disease-free survival (DFS) were the primary end points of the analysis. The PARP1 Val762Ala genetic variants were analyzed by allelic discrimination by real-time PCR.

Results: We observed that peri- and postmenopausal women carrying the C-allele present a statistically significant lower OS and DFS (log-rank test, p = 0.008 and p = 0.006, respectively) among those with early stage cervical cancer. Cox regression analysis confirmed these results, after adjustment for other prognostic factors (for OS: HR, 3.70; 95%CI, 1.32–10.38; p = 0.013 and for DFS: HR, 3.97; 95%CI, 1.59–9.93; p = 0.003).

Conclusions: This is the first study evaluating the effect of PARP1 Val762Ala polymorphism in treatment response in cervical cancer patients. PARP1 genotypes may contribute as an independent prognostic factor in cervical cancer, being useful in predicting the clinical outcome.

keywords:

• Cervical cancer
• DNA adducts/repair mechanisms
• genetic polymorphisms
• PARP1
• prognosis

Acknowledgements

The authors thank the Liga Portuguesa Contra o Cancro-Centro Regional do Norte (Portuguese League against Cancer).

Disclosure statement

The authors declare no conflicts of interest.

Funding information

This work was supported in part by Project Number CI-IPOP-22-2015 from the Research Center the Portuguese Institute of Oncology of Porto, Portugal. The individual grant for Doctoral degree of the second author was supported by the Minister of Science and Education – FCT (Fundação para a Ciência e Tecnologia: SFRH/BD/98536/2013).