Molecular Biology Reports

, Volume 39, Issue 8, pp 8335–8344 | Cite as

Meta-analysis of the association of CYP1A1 polymorphisms with gastric cancer susceptibility and interaction with tobacco smoking

  • Fujun Han
  • Xinsheng Wang
  • Xuhui Wang
  • Yongfeng Luo
  • Wei Li


The association of two cytochrome P4501A1 (CYP1A1) polymorphisms, m1 (T6235C transition) and m2 (A4889G transition), with gastric cancer risk is inconclusive. We conducted a meta-analysis of all available studies to evaluate the potential role of the polymorphisms and their interactions with tobacco smoking in gastric cancer susceptibility. Published literature from PubMed was retrieved by two investigators independently. Fourteen case–control studies with 2,032 gastric cancer cases and 5,099 controls were selected. A fixed effects model or a random-effects model was used to estimate the odds ratio (OR) for the CYP1A1 polymorphisms and the occurrence of gastric cancer. Significant associations between CYP1A1 m1 and m2 polymorphisms and gastric cancer susceptibility were not observed in all genetic models in the overall analyses. Subgroup analyses by ethnicity and source of controls did not reveal significant associations with gastric cancer risk. Stratification analysis by smoking status found that carriers of the heterozygous and homozygous m1 genotypes decreased the susceptibility of gastric cancer among ever-smokers (pooled OR = 0.56, 95 % CI 0.36–0.89, fixed effects). In contrast, the m2 genotypes (G/G and A/G) did not show any relevance to gastric cancer risk among the smoking population (pooled OR = 1.30, 95 % CI 0.84–2.00, fixed effects). Overall, we found that the CYP1A1 polymorphism itself, either m1 or m2, did not represent an independent genetic risk factor influencing gastric cancer. However, subgroup analyses suggest that carriers of the heterozygous and homozygous m1 genotype who are exposed to tobacco smoke have a significantly lower risk of developing gastric cancer. To explain the observed reduction of gastric cancer risk, we proposed a novel hypothesis of “observation bias”. This hypothesis is also applicable to explain the combined effects of other genetic polymorphisms and environmental factors on the risk of developing cancers, and the rationality of the hypothesis needs to be further investigated.


CYP1A1 Polymorphism Gastric cancer Smoking Meta-analysis rs4646903 T6235C A4889G rs1048943 CYP1A1*2A CYP1A1*2C 



Cytochrome P4501A1


Odds ratio


Confidence interval


Hardy–Weinberg equilibrium



Conflict of interest

We declare that we have no conflict of interest. There is no source of funding for each author, for the study, and for the manuscript preparation.


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Fujun Han
    • 1
    • 2
  • Xinsheng Wang
    • 3
  • Xuhui Wang
    • 4
  • Yongfeng Luo
    • 5
  • Wei Li
    • 1
  1. 1.Cancer CenterThe First Hospital of Jilin UniversityChangchunChina
  2. 2.School of Biochemistry, Medical SciencesUniversity of BristolBristolUK
  3. 3.Department of Cardre WardPeople’s Liberation Army No. 458 HospitalGuangzhouChina
  4. 4.Department of GynecologyJilin Tumour HospitalChangchunChina
  5. 5.Guangzhou Institute of Respiratory DiseaseFirst Affiliated Hospital of Guangzhou Medical CollegeGuangzhouChina

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