Association of NAT-2 Gene Polymorphisms Toward Lung Cancer Susceptibility and Prognosis in North Indian Patients Treated with Platinum-Based Chemotherapy

Abstract

Aim: The present study has been carried out to evaluate the association of the N-acetyl transferase 2 (NAT2) variants in North Indian lung cancer patients and healthy controls. Furthermore, we have also determined the effect of the polymorphic variants of the NAT2 gene on the clinical outcomes and overall survival among lung cancer (LC) subjects treated with platinum-based doublet chemotherapy. Methods: This case-control study comprised a total of 550 cases and 550 healthy controls. The genotyping was carried out using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and the statistical analysis was carried out using MedCalc. Results: There was a lack of any significant association for both 590G>A and 803A>G polymorphisms toward risk for LC, but 857G>A polymorphism exhibited a risk toward LC (p = 0.005). Whereas, variant alleles for the 481C>T polymorphism had a decreased risk for LC (p = 0.0003). Further, 857G>A polymorphism conferred a positive association between genotype and ADCC (p = 0.001) and 481C>T polymorphism had a decreased risk for SQCC (OR = 0.39, p = 0.0006) and SCLC (p = 0.001) subjects. The smokers carrying mutant genotype for the 481C>T polymorphism had a decreased risk toward LC (p < 0.0001) even in light (p = 0.002) as well as heavy smokers (p = 0.001). In case of females, 2.59-fold and 3.66-fold increased risk of LC development was observed in subjects with intermediate and slow acetylator for the 857G>A polymorphism. Whereas, in case of males this polymorphism depicts a reduced risk for LC. On the other hand, 803A>G depicted a 2.82-fold risk of LC in case of female subjects who were slow acetylators. Our study exhibits a significant difference in the overall haplotype distribution between cases and controls. In our study overall, (857G>A, 481C>T, 803A>G) was found to be best model, but was not significant using MDR. Considering the CART results 481C>T polymorphism came out to be the most significant factor in determining the LC risk. For the 803A>G polymorphism, a threefold odds of lymph node invasion were observed for mutant genotype, the recessive model exhibited an odds ratio of 2.8. 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy as the survival time for such patients was better. Conclusion: These results suggest that NAT2 variant genotype for 590G>A and 803A>G was not found to modulate risk toward LC, but 857G>A polymorphism exhibited a risk toward LC and 481C>T polymorphism had a decreased risk for LC. NAT2 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy and 481C>T came out to be significant factor using CART.

Keywords::

• association
• chemotherapy
• cisplatin
• lung cancer
• NAT2
• overall survival
• pack-years
• polymorphism
• smoking

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/pgs-2021-0080

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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

Ethical conduct of research

This work was conducted in accordance to the code of conduct for human research at the Thapar Institute of Engineering and Technology and approved by the Institutional Review Board of the University. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.