Gene–environment interaction and susceptibility in head and neck cancer patients and in their first‐degree relatives: a study of N ortheast I ndian population

Background The environmental and genetic factors are known to be associated with head and neck squamous cell carcinoma ( HNSCC ). Here, we investigated the GSTM 1 and GSTT 1 polymorphisms and tobacco uses in patients and in their first‐degree relatives to evaluate susceptibility toward HNSCC . Further, we explored high‐risk interaction between genetic and environmental risk factors. Subjects and methods Genotyping of GSTM 1 and GSTT 1 was performed in 170 patients, 300 first‐degree relatives of patients and 300 controls using multiplex PCR . Multifactor dimensionality reduction ( MDR ) and logistic regression approach were applied for statistical analysis. Results Analysis revealed that GSTM 1 and GSTT 1 null genotype frequencies were significantly higher in patients (adjusted odds ratio ( OR ) = 2.18; P  <   0.001 and OR  = 1.61; P  =   0.031, respectively). Also, the GSTM 1 and GSTT 1 null genotype frequencies were significantly higher in first‐degree relatives of patients compared with controls ( P  =   0.004 and P  =   0.041, respectively). In MDR analysis, the best model for HNSCC risk was four‐factors model of tobacco, betel quid chewing, smoking and GSTM 1 null genotypes (cross‐validation consistency = 10/10 and P  <   0.0001), whereas in interaction entropy graphs, tobacco chewing and GSTM 1 null genotype further showed strongest synergistic interaction. Conclusion GSTM 1 and GSTT 1 null genotypes may act as markers to determine the genetic susceptibility in HNSCC patients and in their first‐degree relatives. Furthermore, tobacco chewing and GSTM 1 null genotype interaction identified as the strongest gene‐environment model to predict HNSCC .