Role of BCL2 (ala43thr), CCND1 (G870A) and FAS (A-670G) polymorphisms in modulating the risk of developing esophageal cancer

Cancer Detect Prev. 2007;31(3):225-32. doi: 10.1016/j.cdp.2007.04.005. Epub 2007 Jun 11.

Abstract

Background: Perturbations in the cell cycle and apoptotic genes have been implicated in human malignancies. A study of BCL2 ala43thr, CCND1 G870A and FAS A-670G gene polymorphisms was undertaken to explore their role in influencing the susceptibility for development of esophageal cancer.

Methods: A total of 151 patients and age and gender matched 201 controls were investigated for BCL2 ala43thr, CCND1 G870A and FAS A-670G polymorphisms by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

Results: The ala43ala genotype of BCL2 anti-apoptotic gene was significantly associated with risk of developing esophageal cancer (OR 2.1, 95%CI=1.0-4.4, P=0.03), more so in males (OR 2.6, 95%CI=P=0.03). In CCND1 G870A polymorphism, the AA genotype was marginally associated with higher risk of esophageal cancer (OR 1.5, 95%CI=0.98-2.4, P=0.05). No significant differences in genotype frequencies of FAS A-670G polymorphism were seen between esophageal cancer patients and controls (P=0.32). Interaction of BCL2 ala43ala, CCND1 870AA and FAS -670AA genotypes did not increase the risk multiplicatively. Association with clinical characteristics showed BCL2 ala43ala genotype to be at increased risk for developing tumors in the middle third location (OR 2.3, 95%CI=1.0-5.3, P=0.03), while patients with CCND1 870AA genotypes were at higher risk for the development of cancer in the upper third location (OR 3.8, 95%CI=1.6-9, P=0.002). BCL2 ala43ala genotype did not modulate the cancer risk in tobacco users. However, patients with CCND1 870AA and FAS -670AA genotypes were associated with a significantly lower number of smoking and chewing pack-years, suggesting a dose-dependent interaction in the risk for esophageal cancer (P=0.005).

Conclusion: There appears to be an influence of BCL2 ala43ala and CCND1 870AA genotypes on esophageal cancer phenotype, particularly with regard to tumor location, which supports the theory of prevalence of site-specific genetic alterations. FAS A-670G was not associated with the risk of developing esophageal cancer. Gene-environment interaction analysis showed cancer susceptibility in CCND1 870AA and FAS -670AA genotype to be influenced by quantity of tobacco.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Cyclin D
  • Cyclins / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Prevalence
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Risk Factors
  • Smoking / adverse effects
  • Tobacco, Smokeless / adverse effects
  • fas Receptor / genetics*

Substances

  • Cyclin D
  • Cyclins
  • FAS protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor