CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer

Purpose As risk-modiWers of alcohol and tobacco eVects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN). Methods A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion (AP) due to interaction and its 95% conWdence interval (CI). Results SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93 6.35) and OR = 6.47 (95%CI: 2.92 14.35) for 19 30 g/day and >30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88 6.41) and OR = 7.65 (95%CI: 4.20 13.90) for 1 25 and >25 packyears of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53 3.92). No diVerences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction emerged from gene gene and gene environment interaction analyses. An attributable proportion (AP) due to biological interaction of 0.65 (95%CI: 0.40 0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI: 0.10 0.72) resulted forever smokers with low fruit and vegetables consumption. Conclusions Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype.