Tobacco carcinogen-metabolizing genes CYP1A1, GSTM1, and GSTT1 polymorphisms and their interaction with tobacco exposure influence the risk of head and neck cancer in Northeast Indian population.
Genetic polymorphisms in tobacco-metabolizing genes may modulate the risk of head and neck cancer (HNC). In Northeast India, head and neck cancers and tobacco consumption remains most prevalent. The aim of the study was to investigate the combined effect of cytochrome P450 1A1 (CYP1A1) T3801C, glutathione S-transferases (GSTs) genes polymorphisms and smoking and tobacco-betel quid chewing in the risk of HNC. The study included 420 subjects (180 cases and 240 controls) from Northeast Indian population. Polymorphisms of CYP1A1 T3801C and GST (M1 & T1) were studied by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR, respectively. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approach were applied for statistical analysis. LR analysis revealed that subjects carrying CYP1A1 TC/CC + GSTM1 null genotypes had 3.52-fold (P < 0.001) increase the risk of head and neck squamous cell carcinoma (HNSCC). Smokers carrying CYP1A1 TC/CC + GSTM1 null and CYP1A1 TC/CC + GSTT1 null genotypes showed significant association with HNC risk (odds ratio [OR] = 6.42; P < 0.001 and 3.86; P = 0.005, respectively). Similarly, tobacco-betel quid chewers carrying CYP1A1 TC/CC + GSTM1 null genotypes also had several fold increased risk of HNC (P < 0.001). In MDR analysis, the best model for HNSCC risk was the four-factor model of tobacco-betel quid chewing, smoking, CYP1A1 TC/CC, and GSTM1 null genotypes (testing balance accuracy [TBA] = 0.6292; cross-validation consistency [CVC] = 9/10 and P < 0.0001). These findings suggest that interaction of combined genotypes of carcinogen-metabolizing genes with environmental factors might modulate susceptibility of HNC in Northeast Indian population.
Molecular Medicine Laboratory, Department of Biotechnology, Assam University, Silchar, Assam, 788011, India.
Javed Hussain
JH
Choudhury
Seram Anil
SA
Singh
Sharbadeb
S
Kundu
Biswadeep
B
Choudhury
Fazlur R
FR
Talukdar
Shilpee
S
Srivasta
Ruhina S
RS
Laskar
Bishal
B
Dhar
Raima
R
Das
Shaheen
S
Laskar
Manish
M
Kumar
Wetetsho
W
Kapfo
Rosy
R
Mondal
Sankar Kumar
SK
Ghosh
D000328:Adult; D002273:Carcinogens / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000235:genetics / Q000473:pathology; D064424:Tobacco Use / Q000235:genetics / Q000473:pathology; D014026:Nicotiana
D002273:Carcinogens; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C569463:CYP1A1 protein, human; C413545:glutathione S-transferase T1