Association of single nucleotide polymorphisms in glycosylation genes with risk of epithelial ovarian cancer

Thomas A. Sellers, Yifan Huang, Julie Cunningham, Ellen L. Goode, Rebecca Sutphen, Robert A. Vierkant, Linda E. Kelemen, Zachary S. Fredericksen, Mark Liebow, V. Shane Pankratz, Lynn C. Hartmann, Jeff Myer, Edwin S. Iversen, Joellen M. Schildkraut, Catherine Phelan

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Studies suggest that underglycosylation of the cell membrane mucin MUC1 may be associated with epithelial ovarian cancer. We identified 26 genes involved in glycosylation and examined 93 single nucleotide polymorphisms (SNP) with a minor allele frequency of ≥0.05 in relation to incident ovarian cancer. Cases were ascertained at the Mayo Clinic, Rochester, MN (n = 396) or a 48-county region in North Carolina (Duke University; n = 534). Ovarian cancer-free controls (n = 1,037) were frequency matched to the cases on age, race, and residence. Subjects were interviewed to obtain data on risk factors and a sample of blood for DNA and genotyped using the Illumina GoldenGate assay. We excluded subjects and individual SNPs with genotype call rates of <90%. Data were analyzed using logistic regression, with adjustment for age and residence. We fitted dominant, log additive, and recessive genetic models. Among Caucasians, nine SNPs in eight genes were associated with risk at P < 0.05 under at least one genetic model before adjusting for multiple testing. A SNP in GALNT1 (rs17647532) was the only one that remained statistically significant after Bonferroni adjustment for multiple testing but was not statistically significant in Hardy-Weinberg equilibrium among controls. Haplotype analyses revealed a global association of GALNT1 with risk (P = 0.038, under a recessive genetic model), which largely reflected a decreased risk of one haplotype (0.10 frequency; odds ratio, 0.07; P = 0.01) compared with the most common haplotype (0.39 frequency). These results suggest that genetic polymorphisms in the glycoslyation process may be novel risk factors for ovarian cancer.

Original languageEnglish (US)
Pages (from-to)397-404
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2008

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Fingerprint Dive into the research topics of 'Association of single nucleotide polymorphisms in glycosylation genes with risk of epithelial ovarian cancer'. Together they form a unique fingerprint.

  • Cite this

    Sellers, T. A., Huang, Y., Cunningham, J., Goode, E. L., Sutphen, R., Vierkant, R. A., Kelemen, L. E., Fredericksen, Z. S., Liebow, M., Pankratz, V. S., Hartmann, L. C., Myer, J., Iversen, E. S., Schildkraut, J. M., & Phelan, C. (2008). Association of single nucleotide polymorphisms in glycosylation genes with risk of epithelial ovarian cancer. Cancer Epidemiology Biomarkers and Prevention, 17(2), 397-404. https://doi.org/10.1158/1055-9965.EPI-07-0565