TURKISH JOURNAL OF ONCOLOGY 2025 , Vol 40 , Num 4
CYP2A6 and CYP2A13 Genetic Variants are Associated with Decreased Risk of Esophageal Squamous Cell Carcinoma- A Case-control Study Based Assessment
Gulzar Ahmad BHAT1,Nasir Ab SHEIKH2,Gowhar RASHID2,Farooq A GANIE3,Tariq Rasool MALIK4,Mudassar SYED5,Nazir A DAR1
1Multidisciplinary Research Unit, Sher-i-Kashmir Institute of Medical Sciences Srinagar, India
2Department of Clinical Biochemistry, University of Kashmir, Srinagar-India
3Department of Cardio Vascular and Thoracic Surgery, Sher-i-Kashmir Institute of Medical Sciences Srinagar, India
4Department of Radiation Oncology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar-India
5Department of Biochemistry, Sher-i-Kashmir Institute of Medical Sciences, Srinagar-India DOI : 10.5505/tjo.2025.4648 OBJECTIVE
Xenobiotic metabolising enzymes (XMEs) play an important role in carcinogenesis. However, in the case of oesophagal cancer, the association of XMEs in general and Phase-1 XMEs in particular remained largely inconclusive. The current study aimed to explore the association of the genetic variants of cytochrome P450 (CYP) 2A6 and CYP2A13 with oesophagal squamous cell carcinoma (ESCC) and the potential effects of environmental factors on such association.

METHODS
The genetic variants of CYP2A6 and CYP2A13 genes were investigated by polymerase chain reaction- restriction fragment length polymorphism, allele-specific PCR and sequencing methods in 492 histopathologically confirmed ESCC cases and an equal number of matched controls. Gene-gene and gene-environment interactions were calculated by logistic regression analysis.

RESULTS
Inverse association was found between the variant genotypes of CYP2A6 (OR=0.6; 95% CI, 0.4-0.9) and CYP2A13 (OR=0.5; 95% CI, 0.31-0.8) with ESCC risk. Individually, the inverse association of variant genotypes of the three studied CYP2A6 genes was retained when harboured by a participant in combination with CYP2A13 variant genotype (OR=0.3; 95%CI, 0.1-0.8). Participants who were smokers, consumed alkaline beverage, had used biomass fuel for cooking, lived in adobe houses and had a positive family history of cancer showed a strong ESCC risk when harbouring homozygous wild genotypes of CYP2A6 and CYP2A13. Among the different gene environmental interactions, only CYP2A6b (OR=1.5; 95%CI, 1.1-2.0; Pinteraction=0.018), and CYP2A13 (OR=1.4; 95%CI, 1.1-2.0; Pinteraction=0.021) genotypes showed statistically significant interactions with smoking.

CONCLUSION
Normal genotypes of CYP2A6 and CYP2A13 considerably increase ESCC risk in subjects who also had exposure to environmental risk factors. Keywords : Cytochrome P450 gene variants; gene-environment interaction; Kashmi; oesophagal squamous cell carcinoma