Genetic susceptibility to multiple primary neoplasms in the upper aero-digestive tract: genotype score and phenotype correlation

Cancer Lett. 2013 May 10;332(1):46-54. doi: 10.1016/j.canlet.2013.01.017. Epub 2013 Jan 21.

Abstract

Early detection and treatment of head and neck cancer has led to increased patient survival. However such patients are at a high risk for multiple primary neoplasm(s) (MPN). In order to study the genetic susceptibility to MPN, 22 candidate SNPs were genotyped based on which a distinctive Genotype Score was created using Additive, Dominant and Recessive models. Using lymphoblastoid cell lines (LCLs) generated from these individuals, the Genotype Score was correlated with carcinogen sensitivity in vitro. LCLs from MPN patients exhibited significantly higher Genotype Score and showed resistance to genotoxic agents compared to matched controls. This report demonstrates quantitative assessment of cumulative effect of gene polymorphisms and its correlation with carcinogen sensitivity for predicting susceptibility to MPN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / toxicity*
  • Apoptosis / drug effects
  • Carcinogens / toxicity*
  • Case-Control Studies
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Transformed
  • Cell Line, Tumor
  • DNA Damage
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene-Environment Interaction
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Logistic Models
  • Lymphocytes / drug effects*
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Models, Genetic
  • Mutagenicity Tests
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors

Substances

  • Carcinogens
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide