Gene-environment interactions associated with CYP1A1 MspI and GST polymorphisms and the risk of upper aerodigestive tract cancers in an Indian population.
OBJECTIVE
Genetic risk to tobacco related cancers are associated with polymorphisms in CYP1A1 and GST, which are involved in the metabolic activation and detoxification of carcinogens. The genetic variations in these drug-metabolizing enzymes may alter the susceptibility to UADT cancers triggered by environmental exposures. The hospital-based case-control study evaluated the impact of combined CYP1A1 MspI and GST (M1 & T1) polymorphisms among the individuals exposed to environmental risk factors as modulators in the risk of UADT cancers in Tamilians, a population of south India.


METHODS
The unrelated histopathologically confirmed 408 cases and 220 population-based controls matched by age and gender were genotyped for CYP1A1 MspI, GSTM1 and GSTT1 polymorphisms using PCR based methods. To investigate the potential gene-environment interactions, analyses were carried out stratifying by smoking and tobacco chewing status using SPSS software.


RESULTS
The combination of genes and environment interactions by stratified analyses revealed significant interactions among the habitual tobacco smokers (CYP1A1 MspI & GSTM1 null: OR 14.06; 95% CI 3.90-50.68, CYP1A1 MspI & GSTT1 null: OR 33.28; 95% CI 4.24-261.19) and tobacco chewers (CYP1A1 MspI & GSTM1 null: OR 20.51; 95% CI 6.77-62.13, CYP1A1 MspI & GSTT1 null: OR 79.35; 95% CI 10.40-605.55) on the multiplicative scale.


CONCLUSIONS
Our findings have indicated that the individuals polymorphic for CYP1A1 MspI either with GSTM1 null or with GSTT1 null genotypes revealed an increased risk for UADT cancers than that ascribed to a single susceptible gene among the tobacco users in the population [single gene risk among smokers and chewers, respectively, for CYP1A1 MspI (OR 6.43; 95% CI 3.69-11.21); (OR 10.24; 95% CI 5.95-17.60), GSTM1*0 (OR 3.77; 95% CI 1.94-7.37); (OR 7.97 95% CI 4.10-15.76) and GSTT1*0 (OR 6.95 95% CI 2.88-16.77); (OR 25.83 95% CI 7.78-85.76).
Sam
Soya Sisy
SS
Pharmacogenomics Laboratory, Department of Pharmacology, Jawaharlal Institute of Post-Graduate Medical Education and Research, Pondicherry 605006, India. soyasoya@rediffmail.com
Thomas
Vinod
V
Reddy
K S
KS
Surianarayanan
Gopalakrishnan
G
Chandrasekaran
Adithan
A
D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014030:Tobacco, Smokeless / Q000009:adverse effects*
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase