Association of cytochrome p4502a variants with the life style and dietary habit induced gastric cancer

Background: Gastric malignancy constitutes the most common malignancy worldwide and continues to be an important contributor to the global burden of cancer. Gastric cancer is generally diagnosed in the advanced stages of the disease and exhibits an extremely poor prognosis, as patients with gastric cancer have unresectable, metastatic or recurrence. Methods: This case control type study was conducted in the department of General Surgery and Clinical Biochemistry, Sher e Kashmir Institute of Medical Sciences and SKIMS Medical College from June 2018 to September 2020 comprising of 82 cases of Gastric cancer. Data regarding socio-demographic characteristics like age, gender, place of residence, anthropometric measures, education and life style habits was collected from all cases. Qualitative and quantitative analysis of genomic DNA was done. Results: A total of 82cases were compared with 82 controls with male: female ratio of 2:1. The mean ages of cases and controls were 60.08 ±11.25years and 61.57 ±11.17years, respectively. In CYP2A6a genotype analysis, variant genotype, showed inverse but slightly insignificant association as compared to homozygous wild genotype (OR = 0.65; 95% CI = 0.42 – 1.06).CYP2A6a wild genotype showed an increased gastric cancer risk on limiting the analysis to smoking(OR = 2.66; 95% CI = 1.34 – 5.28).Positive history of any malignancy showed a stronger association with wild genotype carrying participants (OR = 8.87; 95% CI = 4.48 – 17.95) as compared to variant genotype (OR = 2.80; 95% CI = 1.15 – 7.75). In CYP2A6b genotype analysis, variant genotypes showed overall no change in the modification of gastric cancer risk (OR = 1.04;95% CI =0.67 – 1.60).CYP2A6bwild genotype harboring subjects showed a synergistically significant ESCC vulnerability in tobacco smokers (OR = 2.94; 95% CI = 1.25 – 6.91). However, with a family history of any malignancy, variant (OR = 8.21; 95% CI = 2.19 – 30.37) as well as wild (OR = 5.17; 95% CI = 2.76 – 9.66) genotype carrying subjects showed significantly a strong association towards gastric cancer development. Males turned out to be at higher risk than females on carrying a wild genotype (OR = 2.12; 95% CI = 1.00 – 4.78). Conclusions: The study suggests that polymorphism in major xenobiotic metabolizing enzyme CYP2A6, modify the gastric cancer risk.