期刊
HUMAN MOLECULAR GENETICS
卷 18, 期 12, 页码 2297-2304出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddp138
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资金
- Cancer Research UK
- Roswell Park Alliance
- Danish Cancer Society
- National Cancer Institute [CA71766, CA16056, RO1 CA61107, RO1 CA122443]
- Ovarian Cancer Research Fund.
- US Army Medical Research and Materiel Command [DAMD17-01-1-0729]
- Cancer Council Tasmania and Cancer Foundation of Western Australia (AOCS study),
- National Health and Medical Research Council of Australia [199600]
- US national Cancer Institute [R01 CA87538, R01 CA112523]
- German Federal Ministry of Education and Research of Germany, [01 GB 9401]
- state of Baden-Wurttemberg through Medical Faculty of the University of Ulm [P.685]
- US Public Health Service [R01-CA-58598]
- National Cancer Institute, NIH, Department of Health and Human Services [N01-CN-55424, N01-PC-35137, CA-58860, CA-92044]
- OAK Foundation
- Department of Health's NIHR Biomedical Research Centre
- MRC [G0801875] Funding Source: UKRI
- Cancer Research UK [11022, 10118, 19275] Funding Source: researchfish
- Medical Research Council [G0801875] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10119] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.
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