Journal article

Is RNASEL:p.Glu265*a modifier of early-onset breast cancer risk for carriers of high-risk mutations?

Tu Nguyen-Dumont, Zhi L Teo, Fleur Hammet, Alexis Roberge, Maryam Mahmoodi, Helen Tsimiklis, Daniel J Park, Bernard J Pope, Andrew Lonie, Miroslav K Kapuscinski, Khalid Mahmood, David E Goldgar, Graham G Giles, Ingrid Winship, John L Hopper, Melissa C Southey



BACKGROUND: Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. METHODS: In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. RESULTS: RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Au..

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Awarded by USA National Cancer Institute

Awarded by NHMRC

Awarded by USA National Institute of Health

Awarded by Victorian Life Sciences Computation Initiative grant


Funding Acknowledgements

The ABCFR is the Australian site of the Breast Cancer Family Registry, and this work was supported by grant UM1 CA164920 from the USA National Cancer Institute. The content of the manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products or organisations imply endorsement by the USA Government or the BCFR. The Australian Breast Cancer Family Registry was also supported by the Australian National Health and Medical Research Council (NHMRC), the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium (VBCRC).This work was supported by the NHMRC (APP1025145), the USA National Institute of Health (RO1CA155767), the VBCRC and by a Victorian Life Sciences Computation Initiative grant (number VR0182) on its Peak Computing Facility, an initiative of the Victorian Government. TN-D is a National Breast Cancer Foundation (Australia) Career Development Fellow. ZLT was supported by Postgraduate Scholarships provided by the Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne and the NHMRC (Dora Lush Postgraduate Fellowship). AR was supported by a Bourse de Mobilite from Region Rhone-Alpes, France. JLH is a NHMRC Senior Principal Research Fellow and a VBCRC Group Leader. MCS is an NHMRC Senior Research Fellow and a VBCRC Group Leader. The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.