期刊
PLOS GENETICS
卷 6, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1001016
关键词
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资金
- ACS/AOCS - National Health and Medical Research Council of Australia [199600]
- U. S. Army Medical Research and Materiel Command [DAMD17-01-1-0729, W81XWH-06-1-0220]
- Cancer Council Tasmania and Cancer Foundation of Western Australia
- Westmead Millennium Foundation
- Westmead Gynaecological Oncology
- Westmead Hospital, Westmead, NSW, Australia
- NIH [R01CA112523, RO1 CA87538]
- National Cancer Institute [R01CA095023, CA-58860, CA-92044, R01CA54419, P50CA105009]
- German Federal Ministry of Education and Research of Germany
- Programme of Clinical Biomedical Research [01 GB 9401]
- Medical Faculty of the University of Ulm [685]
- Lon V. Smith Foundation [LVS-39420]
- National Institutes of Health [R01-CA122443]
- National Cancer Institute, Department of Health and Human Services, USA
- US Public Health Service [R01-CA-58598]
- National Cancer Institute, NIH, Department of Health and Human Services [N01-CN-55424, N01-PC-67001]
- Cancer Research UK
- Department of Health's NIHR Biomedical Research Centres
- Oak Foundation
- OCAC
- MRC [G0801875] Funding Source: UKRI
- Cancer Research UK [11021] Funding Source: researchfish
- Cancer Research UK
- The Francis Crick Institute [10124] Funding Source: researchfish
- Medical Research Council [G0801875] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10119] Funding Source: researchfish
We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs-PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616-were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with P(per-allele)<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. P(per-allele)>= 0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (P(per-allele)=0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. OR(per-allele) 1.14 (1.04-1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus.
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