GSTM1, GSTT1, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population: different pattern of squamous cell carcinoma and adenocarcinoma

Abstract

Aim: To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (ADC) in a high risk area of northwest of France.

Methods: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP1A1*2C and GSTP1 exon 7 Val alleles, GSTM1*2/*2 and GSTT1*2/*2 null genotypes). A total of 79 esophageal cancer cases and 130 controls were recruited.

Results: GSTM1*2/*2 and CYP1A1*1A/*2C genotype frequencies were higher among squamous cell carcinomas at a level close to statistical significance (OR = 1.83, 95% CI 0.88-3.83, P = 0.11; OR = 3.03, 95% CI 0.93-9.90, P = 0.07, respectively). For GSTP1 polymorphism, no difference was found between controls and cases, whatever their histological status. Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference (OR = 13.31, 95% CI 1.66-106.92, P<0.01).

Conclusion: In SCC, our results are consistent with the strong association of this kind of tumour with tobacco exposure. In ADC, our results suggest 3 distinct hypotheses: (1) activation of exogenous procarcinogens, such as small halogenated compounds by GSTT1; (2) contribution of GSTT1 to the inflammatory response of esophageal mucosa, which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis; (3) higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.