Risk of ovarian cancer and inherited variants in relapse-associated genes

Abraham Peedicayil, Robert A. Vierkant, Lynn C. Hartmann, Brooke L. Fridley, Zachary S. Fredericksen, Kristin L. White, Elaine A. Elliott, Catherine M. Phelan, Ya Yu Tsai, Andrew Berchuck, Edwin S. Iversen, Fergus J. Couch, Prema Peethamabaran, Melissa C. Larson, Kimberly R. Kalli, Matthew L. Kosel, Vijayalakshmi Shridhar, David N. Rider, Mark Liebow, Julie M. CunninghamJoellen M. Schildkraut, Thomas A. Sellers, Ellen L. Goode

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Background: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk. Methods and Findings: Women with and without invasive ovarian cancer (749 cases, 1,041 controls) were genotyped at 136 single nucleotide polymorphisms (SNPs) within 13 candidate genes. Risk was estimated for each SNP and for overall variation within each gene. At the gene-level, variation within MSL1 (male-specific lethal-1 homolog) was associated with risk of serous cancer (p = 0.03); haplotypes within PRPF31 (PRP31 pre-mRNA processing factor 31 homolog) were associated with risk of invasive disease (p = 0.03). MSL1 rs7211770 was associated with decreased risk of serous disease (OR 0.81, 95% CI 0.66-0.98; p = 0.03). SNPs in MFSD7, BTN3A3, ZNF200, PTPRS, and CCND1A were inversely associated with risk (p<0.05), and there was increased risk at HEXIM1 rs1053578 (p = 0.04, OR 1.40, 95% CI 1.02-1.91). Conclusions: Tumor studies can reveal novel genes worthy of follow-up for cancer susceptibility. Here, we found that inherited markers in the gene encoding MSL1, part of a complex that modifies the histone H4, may decrease risk of invasive serous ovarian cancer.

Original languageEnglish (US)
Article numbere8884
JournalPloS one
Volume5
Issue number1
DOIs
StatePublished - Jan 27 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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