Journal article

Functional Polymorphisms in the TERT Promoter Are Associated with Risk of Serous Epithelial Ovarian and Breast Cancers

Jonathan Beesley, Hilda A Pickett, Sharon E Johnatty, Alison M Dunning, Xiaoqing Chen, Jun Li, Kyriaki Michailidou, Yi Lu, David N Rider, Rachel T Palmieri, Michael D Stutz, Diether Lambrechts, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Jenny Chang-Claude, Stefan Nickels, Alina Vrieling, Dieter Flesch-Janys, Shan Wang-Gohrke Show all

PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2011

Abstract

Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC). We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP) within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.

Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by U.S. Army Medical Research and Materiel Command


Awarded by National Health and Medical Research Council of Australia


Awarded by U.S. National Institutes of Health


Awarded by Cancer Research-UK


Awarded by Deutsche Krebshilfe e.V.


Awarded by Federal Ministry of Education and Research (BMBF) Germany


Awarded by Deutsche Krebshilfe e. V.


Awarded by state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm


Awarded by NHMRC



Awarded by Cancer Research UK


Awarded by Medical Research Council


Awarded by The Francis Crick Institute


Awarded by DIVISION OF CANCER CONTROL &POPULATION SCIENCE


Awarded by DIVISION OF CANCER PREVENTION AND CONTROL


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund. kConFaB is supported by the National Breast Cancer Foundation, the National Health and Medical Research Council of Australia, and the Cancer Councils of Queensland, New South Wales, Western Australia, South Australia, and Victoria. The Clinical Follow-up Study of kConFaB is funded by the National Health and Medical Research Council (NHMRC) of Australia (145684 and 288704). AOCS was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), the National Health and Medical Research Council of Australia (199600), and the Cancer Council Tasmania and Cancer Foundation of Western Australia. Tissues and samples were received from the Australian Breast Cancer Tissue Bank which is supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The tissues and samples are made available to researchers on a non-exclusive basis. The BEL study was supported by the Nationaal Kankerplan - actie 29. The HAW study is supported by the U.S. National Institutes of Health (R01 CA58598, N01-CN-55424, N01-PC-67001). SEARCH was supported by Cancer Research-UK grants [C1287/A10118, C490/A11021, C8197/A10123]. The MAYO study was supported by R01 CA122443 and P50 CA136939. The MARIE study was supported by the Deutsche Krebshilfe e.V., grant number 70-2892-BR I, the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the DNA extraction and genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany grant 01KH0402. The GESBC epidemiological study was supported by the Deutsche Krebshilfe e. V. [70492] and GESBC genotyping in part by the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm [P.685]. The OVAL-BC Study is supported by the British Columbia Workers Compensation Board and the Canadian Institutes for Health Research. The NJO study was funded by NIH-K07 CA095666, R01CA83918, and The Cancer Institute of New Jersey. The UKO study is supported by funding from Cancer Research UK, the Eve Appeal, and the OAK Foundation; some of this work was undertaken at UCLH/UCL which received some funding from the Department of Health's NIHR Biomedical Research Centre funding scheme. ACP study is funded by The Breast Cancer Research Trust, UK. JB, HAP, SEJ, MDS and RRR are supported by NHMRC project grant 1012023. DFE is a Principal Research Fellow of Cancer Research UK. SM is supported by an NHMRC career development award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.