CYP2A6 genetic polymorphism is associated with decreased susceptibility to squamous cell lung cancer in Japanese smokers

Hiroki Hosono, Masaki Kumondai, Tomio Arai, Haruhiko Sugimura, Takamitsu Sasaki, Noriyasu Hirasawa, Masahiro Hiratsuka

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Cytochrome P450 2A6 (CYP2A6) is an enzyme involved in the metabolism of tobacco carcinogens, which are important risk factors in lung cancer. We and others have previously reported that CYP2A6∗4, a whole-gene deletion polymorphism, is associated with lower risk of lung cancer than the wild-type allele. However, the genotyping method used in these previous studies considered only the CYP2A6∗4 allele; this lead to insufficient classification of the CYP2A6 genotype, thereby underestimating the frequencies of the deficient alleles. In this study, CYP2A6 genotypes of Japanese smokers (110 individuals with squamous cell lung cancer (SQCC) and 132 sex-matched cancer-free controls) were determined using a sequencing-based approach to determine CYP2A6 haplotypes. The risk of SQCC was evaluated using the activity score (AS) system to predict CYP2A6 phenotype from its genotype. The risk of developing SQCC was significantly lower in the poor metabolizers assigned as AS 0.5 (adjusted odds ratio [OR] = 0.13, 95% CI = 0.04-0.45, P = 0.001) and AS 0 (adjusted OR = 0.15, 95% CI = 0.03-0.82, P = 0.028) than in the extensive metabolizers assigned as AS 2.0. In conclusion, CYP2A6 genetic polymorphisms may play important roles in the development of SQCC in Japanese smokers.

Original languageEnglish
Pages (from-to)263-268
Number of pages6
JournalDrug metabolism and pharmacokinetics
Volume30
Issue number4
DOIs
Publication statusPublished - 2015 Aug 6

Keywords

  • Activity score
  • CYP2A6
  • Genetic polymorphism
  • Smoker
  • Squamous cell lung cancer

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'CYP2A6 genetic polymorphism is associated with decreased susceptibility to squamous cell lung cancer in Japanese smokers'. Together they form a unique fingerprint.

Cite this