title: 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 reduce cancer risk by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). This case-control study was aimed at determining associations between dietary ITCs, GSTs polymorphisms and risk habits (cigarette smoking, alcohol drinking and betel-quid chewing) with oral cancer in 115 cases and 116 controls. Information on dietary ITC intake from cruciferous vegetables was collected via a semi-quantitative food 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 performed to determine the association of ITC and GSTs polymorphism and risk of oral cancer. When dietary ITC was categorized into high (greater than/equal to median) and low (less than median) intake, there was no significant difference between cases and control group. Logistic regression yielding odd ratios resulted in no significant association 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 age of 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 drinking and 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 may be associated with the risk of oral cancer and modulate the age of disease onset.
authors.affiliation: Oral Cancer Research and Coordinating Centre (OCRCC), Kuala Lumpur, Malaysia.
authors.forename: Lee Peng
authors.initials: LP
authors.lastname: Karen-Ng
authors.forename: Jamaludin
authors.initials: J
authors.lastname: Marhazlinda
authors.forename: Zainal Arif Abdul
authors.initials: ZA
authors.lastname: Rahman
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Yang
authors.forename: Norma
authors.initials: N
authors.lastname: Jalil
authors.forename: Sok Ching
authors.initials: SC
authors.lastname: Cheong
authors.forename: Rosnah Binti
authors.initials: RB
authors.lastname: Zain
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects; D001114:Areca / Q000009:adverse effects; D001937:Brassica / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D017879:Isothiocyanates; C037152:isothiocyanic acid; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human