Combined Effects of Isothiocyanate Intake, Glutathione s-Transferase Polymorphisms and Risk Habits for Age of Oral Squamous Cell Carcinoma Development

Abstract

Dietary isothiocyanates (ITCs) found in cruciferous vegetables (Brassica spp.) has been reported to reducecancer risk by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). Thiscase-control study was aimed at determining associations between dietary ITCs, GSTs polymorphisms andrisk habits (cigarette smoking, alcohol drinking and betel-quid chewing) with oral cancer in 115 cases and 116controls. Information on dietary ITC intake from cruciferous vegetables was collected via a semi-quantitativefood frequency questionnaire (FFQ). Peripheral blood lymphocytes were obtained for genotyping of GSTM1,GSTT1 and GSTP1 using PCR multiplex and PCR-RFLP. Chi-square and logistic regression were performedto determine the association of ITC and GSTs polymorphism and risk of oral cancer. When dietary ITC wascategorized into high (greater than/equal to median) and low (less than median) intake, there was no significantdifference between cases and control group. Logistic regression yielding odd ratios resulted in no significantassociation between dietary ITC intake, GSTM1, GSTT1 or GSTP1 genotypes with oral cancer risk overall.However, GSTP1 wild-type genotype was associated with later disease onset in women above 55 years of age(p=0.017). Among the men above 45 years of age, there was clinical significant difference of 17 years in the ageof onset of oral cancer between GSTP1 wild-type + low ITC intake and GSTP1 polymorphism + high ITC intake(p=0.001). Similar conditions were also seen among men above 45 years of age with risk habits like drinkingand chewing as the earlier disease onset associated with GSTP1 polymorphism and high ITC intake (p<0.001).This study suggests that combination effects between dietary ITCs, GSTP1 polymorphism and risk habits maybe associated with the risk of oral cancer and modulate the age of disease onset.