XRCC1 632 as a Candidate for Cancer Predisposition via a Complex Interaction with Genetic Variants of Base Excision Repair and Double Strand Break Repair Genes

Abstract

Aim: The DNA repair system safeguards integrity of DNA. Genetic alterations force the improper repair which in conjugation with other factors ultimately results in carcinogenesis. Materials&methods: PCR-restriction fragment length polymorphism was used for genotyping, which was followed by statistical analysis using logistic regression analysis, multifactor dimensionality reduction and classification and regression analysis tree, elaborating the association with lung cancer subjects. Results: Combination of XRCC1 632 and OGG1326 showcased a high risk of eightfold (odds ratio: 7.92; 95% CI: 2.68–23.4; p = 0.0002; false discovery rate (FDR) p = 0.002). Similarly, XRCC1 632 and MUTYH 324 (odds ratio: 5.07; 95% CI: 2.6–9.67; p < 0.0001; FDRp = 0.002) had a high risk. Multifactor dimensionality reduction analysis revealed five factor model as the best model with prediction error of 0.37 (p = 0.02). Conclusion: There was a clear indication that high order interactions were major role players in the study.

Keywords::

• base excision repair
• classification and regression tree analysis
• cross validation consistency
• DNA
• lung cancer
• multidimensionality reduction
• odds ratio
• single nucleotide polymorphism
• susceptibility

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fon-2019-0297

Acknowledgments

We would like to express our gratitude to all the subjects and their families who participated in this current study. The authors have no conflicts of interest to declare.

Financial&competing interests disclosure

This work was supported by grant from the Indian Council of Medical Research, New Delhi, India. (grant number 5/13/126/2011/NCD-III). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by grant from the Indian Council of Medical Research, New Delhi, India. (grant number 5/13/126/2011/NCD-III). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.