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

PLoS One. 2014 Oct 9;9(10):e106580. doi: 10.1371/journal.pone.0106580. eCollection 2014.

Abstract

Purpose: This study was conducted to explore the effects of genetic polymorphisms (CYP1B1*2 G355T, CYP1B1*3 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 CYP1B1*2 355T and CYP2E1*5 -1293C showed a higher risk for developing laryngeal cancer (for CYP1B1*2 355T, adjusted OR = 2.657, P <0.001; for CYP2E1*5 -1293C, adjusted OR = 1.938, P <0.001), while carriers of mutation allele CYP1B1*3 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 CYP1B1*2 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: CYP1B1*2 355T and CYP2E1*5 -1293C are associated with an increased laryngeal cancer risk, while CYP1B1*3 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 (CYP1B1*2 355T and CYP1B1*3 4326G) for promoting laryngeal cancer risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / genetics*
  • Alleles
  • Asian People / genetics*
  • Case-Control Studies
  • Cytochrome P-450 CYP1B1 / genetics*
  • Cytochrome P-450 CYP2E1 / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Haplotypes / genetics
  • Humans
  • Laryngeal Neoplasms / etiology
  • Laryngeal Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Risk
  • Risk Factors
  • Smoking / adverse effects
  • Smoking / genetics*

Substances

  • Cytochrome P-450 CYP2E1
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1

Grants and funding

This work is supported by the Science and Technology Foundation of Wenzhou City, Zhejiang Province, China (H20090025, URL: http://www.wzkj.gov.cn) and the Science and Technology Foundation of Health bureau of Zhejiang Province, China (2012ZB106, URL: http://zgj.zjtcm.net). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.