Journal article
Rare mutations in RINT1 predispose carriers to breast and lynch syndrome-Spectrum cancers
DJ Park, K Tao, F Le Calvez-Kelm, T Nguyen-Dumont, N Robinot, F Hammet, F Odefrey, H Tsimiklis, ZL Teo, LB Thingholm, EL Young, C Voegele, A Lonie, BJ Pope, TC Roane, R Bell, H Hu, undefined Shankaracharya, CD Huff, J Ellis Show all
Cancer Discovery | Published : 2014
Abstract
Approximately half of the familial aggregation of breast cancer remains unexplained. A multiple-case breast cancer family exome-sequencing study identified three likely pathogenic mutations in RINT1 (NM_021930.4) not present in public sequencing databases: RINT1 c.343C>T (p.Q115X), c.1132_1134del (p.M378del), and c.1207G>T (p.D403Y). On the basis of this finding, a population-based case-control mutation-screening study was conducted that identified 29 carriers of rare (minor allele frequency < 0.5%), likely pathogenic variants: 23 in 1,313 early-onset breast cancer cases and six in 1,123 frequency-matched controls [OR, 3.24; 95% confi- dence interval (CI), 1.29-8.17; P = 0.013]. RINT1 mutati..
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Funding Acknowledgements
The Australian BCFR (ABCFR; 1992-1995) was supported by the Australian National Health and Medical Research Council (NHMRC), the New South Wales Cancer Council, and the Victorian Health Promotion Foundation (Australia). The authors thank Margaret McCredie for her key role in the establishment and leadership of the ABCFR in Sydney, Australia, and the families who donated their time, information, and biospecimens. The Genetic Epidemiology Laboratory at the University of Melbourne has also received generous support from B. Hovey and Dr. R. W. Brown, to whom the authors are most grateful. The authors also thank G. Keough for assistance with article preparation. The work of the BCFR centers [BCFR-AU (ABCFS), BCFR-NC, BCFR-NY, BCFR-ON, BCFR-PA (FCCC), and BCFR-UT] was supported by grant UM1 CA164920 from the National Cancer Institute. The work of BCFR-ON was additionally supported by the Canadian Institutes of Health Research "CIHR Team in Familial Risks of Breast Cancer" program. The authors thank Heather Thorne, Eveline Niedermayr, all the research nurses and staff of the Kathleen Cuningham Foundation Consortium for research into Familial Breast Cancer (kConFab), and the heads and staff of the Family Cancer Clinics and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704, and 454508) for their contributions to this resource, and the many families who contribute to kConFab. kConFab has been supported by grants from the National Breast Cancer Foundation (Australia), the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, the Cancer Foundation of Western Australia, and the NIH (via U01 CA69638).