Melbourne School of Population and Global Health - Research Publications

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    Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk
    Gaudet, MM ; Kuchenbaecker, KB ; Vijai, J ; Klein, RJ ; Kirchhoff, T ; McGuffog, L ; Barrowdale, D ; Dunning, AM ; Lee, A ; Dennis, J ; Healey, S ; Dicks, E ; Soucy, P ; Sinilnikova, O ; Pankratz, VS ; Wang, X ; Eldridge, RC ; Tessier, DC ; Vincent, D ; Bacot, F ; Hogervorst, FBL ; Peock, S ; Stoppa-Lyonnet, D ; Peterlongo, P ; Schmutzler, RK ; Nathanson, KL ; Piedmonte, M ; Singer, CF ; Thomassen, M ; Hansen, TVO ; Neuhausen, SL ; Blanco, I ; Greene, MH ; Garber, J ; Weitzel, JN ; Andrulis, IL ; Goldgar, DE ; D'Andrea, E ; Caldes, T ; Nevanlinna, H ; Osorio, A ; van Rensburg, EJ ; Arason, A ; Rennert, G ; van den Ouweland, AMW ; van der Hout, AH ; Kets, CM ; Aalfs, CM ; Wijnen, JT ; Ausems, MGEM ; Frost, D ; Ellis, S ; Fineberg, E ; Platte, R ; Evans, DG ; Jacobs, C ; Adlard, J ; Tischkowitz, M ; Porteous, ME ; Damiola, F ; Golmard, L ; Barjhoux, L ; Longy, M ; Belotti, M ; Ferrer, SF ; Mazoyer, S ; Spurdle, AB ; Manoukian, S ; Barile, M ; Genuardi, M ; Arnold, N ; Meindl, A ; Sutter, C ; Wappenschmidt, B ; Domchek, SM ; Pfeiler, G ; Friedman, E ; Jensen, UB ; Robson, M ; Shah, S ; Lazaro, C ; Mai, PL ; Benitez, J ; Southey, MC ; Schmidt, MK ; Fasching, PA ; Peto, J ; Humphreys, MK ; Wang, Q ; Michailidou, K ; Sawyer, EJ ; Burwinkel, B ; Guenel, P ; Bojesen, SE ; Milne, RL ; Brenner, H ; Lochmann, M ; Aittomaki, K ; Doerk, T ; Margolin, S ; Mannermaa, A ; Lambrechts, D ; Chang-Claude, J ; Radice, P ; Giles, GG ; Haiman, CA ; Winqvist, R ; Devillee, P ; Garcia-Closas, M ; Schoof, N ; Hooning, MJ ; Cox, A ; Pharoah, PDP ; Jakubowska, A ; Orr, N ; Gonzalez-Neira, A ; Pita, G ; Rosario Alonso, M ; Hall, P ; Couch, FJ ; Simard, J ; Altshuler, D ; Easton, DF ; Chenevix-Trench, G ; Antoniou, AC ; Offit, K ; Hunter, KW (PUBLIC LIBRARY SCIENCE, 2013-03)
    Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9 × 10(-8)). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer.
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    Australian Twin Registry: 30 Years of Progress
    Hopper, JL ; Foley, DL ; White, PA ; Pollaers, V (CAMBRIDGE UNIV PRESS, 2013-02)
    The Australian Twin Registry (ATR) is a national volunteer resource of twin pairs and higher-order multiples willing to consider participating in health, medical, and scientific research. The vision of the ATR is 'to realize the full potential of research involving twins to improve the health and well-being of all Australians'. The ATR has been funded continuously by the National Health and Medical Council for more than 30 years. Its core functions entail the recruitment and retention of twin members, the maintenance of an up-to-date database containing members' contact details and baseline information, and the promotion and provision of open access to researchers from all institutes in Australia, and their collaborators, in a fair and equitable manner. The ATR is administered by The University of Melbourne, which acts as custodian. Since the late 1970s the ATR has enrolled more than 40,000 twin pairs of all zygosities and facilitated more than 500 studies that have produced at least 700 peer-reviewed publications from classical twin studies, co-twin control studies, within-pair comparisons, twin family studies, longitudinal twin studies, randomized controlled trials, and epigenetics studies, as well as studies of issues specific to twins. New initiatives include: a Health and Life Style Questionnaire; data collection, management, and archiving using a secure online software program (The Ark); and the International Network of Twin Registries. The ATR's expertise and 30 years of experience in providing services to national and international twin studies has made it an important resource for research across a broad range of disciplines.