Abstract: The association of single nucleotide polymorphisms in folate metabolism genes with hypermethylation patterns in smokers at high risk for lung cancer (2011 SACNAS National Conference)

Friday, October 28, 2011

Hall 1-2 (San Jose Convention Center)

Amanda Mackey, BS, BA , Chemical Engineering, University of New Mexico, Albuquerque, NM

Kristina Flores, PhD , Epidemiology, University of New Mexico, Albuquerque, NM

Stidley Christine, PhD , Epidemiology, University of New Mexico, Albuquerque, NM

Maria Picchi, BA, MPH , Lovelace Respiratory Research Institute, Albuquerque, NM

Tim Byers, MD, MPH , University of Colorado Denver, Denver, CO

Marianne Berwick, PhD, MPH , Epidemiology, University of New Mexico, Albuquerque, NM

Steven Belinsky, PhD , Lovelace Respiratory Research Institute, Albuquerque, NM

Shuguang Leng, MD, PhD , Lovelace Respiratory Research Institute, Albuquerque, NM

Folate metabolism is imperative for nucleotide synthesis and DNA methylation reactions. Consequently, interference of these important reactions via altered folate metabolism may contribute to the development of cancer. Promoter hypermethylation and single nucleotide polymorphisms (SNPs) are possible biomarkers for the early detection of lung cancer. This study examined the relationship between SNPs in folate metabolism genes with promoter hypermethylation patterns in sputum cell DNA. A 12 gene methylation panel was assessed on sputum DNA from 937 non-Hispanic white participants. SNPs in folate metabolism genes were analyzed from lymphocyte DNA using Illumina GoldenGate. Participants were stratified by gender, and outcomes were based on high or low methylation. Logistic regression was used to examine the relationship between SNPs and methylation. A SNP in the cystathionine-beta synthase (CBS) gene was found to be significantly associated with gene promoter hypermethylation after adjusting for multiple comparisons. Furthermore, an interaction between gender and the CBS SNP was found (p<0.0001). Males with the variant allele had an increased risk for high methylation (OR= 3.61; 95% CI: 1.71, 7.64); p<0.001), while females with the variant allele had a decreased risk for high methylation (OR = 0.64; 95% CI: 0.40, 1.00; p=0.05). Studies in the literature support a gender specific regulation of the CBS gene. A study by Vitvitsky et al. showed that CBS is regulated by testosterone in mice and humans. It could also be linked to sex-dependent differences in plasma homocysteine levels that, in turn, may be relevant for methylation reactions through folate metabolism.