Effects of SNPs (CYP1B1*2 G355T, CYP1B1*3 C4326G, and CYP2E1*5 G-1293C), smoking, and drinking on susceptibility to laryngeal cancer among Han Chinese.

PURPOSE

This study was conducted to explore the effects of genetic polymorphisms (CYP1B12 G355T, CYP1B13 C4326G, and CYP2E1*5 G-1293C) and environmental factors (smoking and drinking) on susceptibility to laryngeal cancer in a Han Chinese study group.

METHODS

This case-control study included 552 Han Chinese patients diagnosed with laryngeal cancer and 666 healthy control subjects of the same ethnicity, similar age, and gender. Genetic polymorphisms were examined using multi-PCR and Matrix Assisted Laser Desorption Ionization - Time of Flight (MALDI-TOF MS) methodology. The association of these genetic and environmental factors with susceptibility to laryngeal cancer was evaluated using a statistical approach.

RESULTS

The frequencies of all three polymorphisms in the patient cohort were significantly different from those in the control cohort. Compared to the control cohort, carriers of variant alleles of CYP1B12 355T and CYP2E15 -1293C showed a higher risk for developing laryngeal cancer (for CYP1B12 355T, adjusted OR = 2.657, P <0.001; for CYP2E15 -1293C, adjusted OR = 1.938, P <0.001), while carriers of mutation allele CYP1B13 4326G showed a lower risk (adjusted OR = 0.562, P <0.001). Joint effects of these polymorphisms were observed. When compared to haplotype G355C4326G-1293, haplotypes T355C4326G-1293 (adjusted OR = 1.809, P <0.001), G355C4326C-1293 (adjusted OR = 1.644, P = 0.044), and T355C4326C-1293 (adjusted OR = 3.104, P <0.001) were associated with a significantly higher laryngeal cancer risk. The adjusted ORs for non-smokers, non-drinkers, smokers, and drinkers with the GT/TT genotype at CYP1B12 G355T were 2.190 (P = 0.006), 2.008 (P = 0.001), 5.875 (P <0.001), and 4.518 (P <0.001), respectively.

CONCLUSIONS

CYP1B12 355T and CYP2E15 -1293C are associated with an increased laryngeal cancer risk, while CYP1B13 4326G is associated with a decreased risk. These polymorphisms showed joint effects on laryngeal cancer risk. Smoking and drinking showed collaborative effects with two high risk alleles (CYP1B12 355T and CYP1B1*3 4326G) for promoting laryngeal cancer risk.