Association of Genetic Variants of CYP2C19 and CYP2D6 with Esophageal Squamous Cell Carcinoma Risk in Northern India, Kashmir.

Genetic polymorphism in xenobiotic metabolizing enzymes (XMEs) is associated with various malignancies. However, the association of esophageal cancer with XMEs is mixed. The current study was aimed to explore the association of genetic polymorphisms of cytochrome(CYP) 2C19andCYP2D6genotypes with esophageal squamous cell carcinoma (ESCC) risk in Kashmir, India. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing methods were used for genotyping of 492 ESCC cases and equal number of individually matched controls. Conditional logistic regression models were used to assess odds ratios (ORs) and 95% confidence intervals. Increased ESCC risk was observed in subjects with variant genotypes ofCYP2C19(OR = 3.3) orCYP2D6(OR = 2.1) and risk was higher (OR = 4.6) in subjects who harbored both the genotypes. Almost same but higher risk turned when subjects were smokers and carried a variant genotype ofCYP2C19(OR = 4.4) orCYP2D6(OR = 4.7). Risk was appreciably increased in subjects who had family history of any cancer and also harbored a variant genotype of eitherCYP2C19(OR = 15.5) orCYP2D6(OR = 9.7). Subjects harboring a variant genotype ofCYP2D6showed an added risk when they used biomass as fuel (OR = 4.6). In conclusion, variant genotypes ofCYP2C19andCYP2D6are associated with an increased risk of ESCC. [ABSTRACT FROM PUBLISHER]