Association of polymorphisms in the Cyclin D1 and XPD genes and susceptibility to cancers of the upper aero-digestive tract

Shama Buch, Bing Zhu, Autumn Gaither Davis, Dominic Odom, Jill M. Siegfried, Jennifer R. Grandis, Marjorie Romkes

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

DNA repair enzyme genetic polymorphisms have been postulated to increase the risk of certain cancers in the presence of tobacco carcinogen exposures. The XPD protein is an important component of the TFIIH transcription factor complex. XPD genetic polymorphisms resulting in amino acids substitutions may lead to alterations in TFIIH helicase activity, resulting in repair and transcription defects. Cyclin D1 is a key regulatory protein for the transition of cells from the G1-S cell cycle phase. The CCND1 G870A polymorphism has been reported to enhance alternate splicing of a stable mRNA variant, which may result in the bypass of the G1/S cell cycle checkpoint. In this study, XPD G23591A (Asp312Asn) and A35931C (Lys751Gln) polymorphisms and the CCND1 G870A splice variant frequencies were determined in 273 upper aero-digestive tract cancer cases and 269 controls. The XPD Asp312Asn variant frequency was significantly different among cases and controls and conferred an odds ratio (OR) of 1.3 (95% CI 1.0-1.8). However, individuals with the CCND1 G870A and XPD Lys751Gln variants had higher age adjusted ORs of 3.2 (95% CI 2.2-4.6) and 2.2 (95% CI 1.5-3.2), respectively. Furthermore, a significant gene-gene interaction was observed among cases with at least two variant alleles for both CCND1 and XPD genes [OR 7.09 (95% CI 4.03-12.5)]. Smokers with a combination of at least one variant allele of both CCND1 and XPD genes also had an elevated risk as compared to nonsmokers. This is the first study to suggest an associative interaction between XPD and CCND1 genetic polymorphisms, tobacco exposure, and cancer risk.

Original languageEnglish (US)
Pages (from-to)222-228
Number of pages7
JournalMolecular Carcinogenesis
Volume42
Issue number4
DOIs
StatePublished - Apr 2005

Keywords

  • CCND1
  • DNA repair
  • Genetic epidemiology
  • Upper aero-digestive tract cancer
  • XPD

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