Molecular Cancer Epidemiology

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Lab Head: Dr Amanda Spurdle

Summary of Research Projects in the Laboratory The Molecular Cancer Epidemiology Laboratory covers a range of projects with the themes of cancer epidemiology and molecular pathology. The projects include studies of breast and ovarian cancer, endometrial cancer, colon cancer and prostate cancer.

STUDIES OF BREAST, OVARIAN AND PROSTATE CANCER

a) BRCA1 and BRCA2 variants of unclassified pathogenic potential A considerable proportion of cancer-affected women from multiple-case "high-risk" breast cancer families carry mutations in the BRCA1 and BRCA2 genes, with the proportion ranging from 30-80% of families depending on selection criteria and source population. Although the classification of truncating mutations with respect to predicted pathogenicity is usually straightforward, it can sometimes be difficult to predict whether BRCA1 and BRCA2 amino acid substitution and splice site region variants are likely to be disease-associated simply by looking at the position and nature of the sequence change. Even when such variants are identified in affected women belonging to breast cancer syndrome families, it is not always possible to decide whether the sequence variant is cancer predisposing. Consequently, it is not possible to offer standard genetic counselling for these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these "unclassified sequence variants" will be directly useful with regard to the clinical management of these women and their families and will help develop an understanding of how different domains of these genes contribute to their role as cancer susceptibility genes. A collaborative research project has recently been undertaken to classify BRCA1 or BRCA2 variants of unknown pathogenicity. We are making use of Australian high-risk families ascertained via family cancer clinics as part of the Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) study, and identified as carrying such variants of unclassified pathogenic potential. The research study involves tracking the association between disease and presence of the potential mutation within families, and by assessing the effect of the potential mutation on gene/protein function using a variety of laboratory assays. An extEnsive list of collaborators is detailed below.

b) Breast and Ovarian Cancer Predisposition Genes Another focus of research in the laboratory is on the identification of genes involved in predisposition to breast cancer occurring at the population level. The majority of women presenting with breast cancer do not belong to multiple-case "high-risk" families, such as those carrying pathogenic BRCA1 or BRCA2 mutations. However, having even a single affected relative is the single biggest risk factor for cancer, indicating that genes are likely to play a role in the predisposition to cancer at the population level. Candidate cancer predisposition genetic variants with subtle functional effects, such as coding length polymorphisms, amino acid substitutions, or promoter region conserved motif variants, are candidate markers for association studies investigating the role of low-risk genes in breast cancer susceptibility. By definition, these "low-risk" genes would only slightly elevate the risk of cancer in individual women, but given the relatively high frequency of the disease-causing variants, they would account for a high attributable risk of cancer in the general population. In collaboration with A/Prof Chenevix-Trench at the QIMR, we have been carrying out ongoing association studies investigating the association with breast cancer of genetic variants of candidate genes. These studies have been making using of resources from the Australian Breast Cancer Family Study (ABCFS; Principle investigator Prof John Hopper), a large population-based case-control-family study conducted in Melbourne and Sydney, encompassing the Australian node of the NIH-funded Co-operative Family Registry for Breast Cancer Studies CFRBCS), and familial breast cancer cases recruited through kConFaB. The breast cancer risk associated with candidate genetic variants is investigated following standard case-control approaches, and significant associations are pursued by analysis of risk within families of cases. Analyses include assessment of the effects of endogenous and exogenous exposures on the risk of cancer conferred by variants. We are also involved in a collaborative effort with other researchers at the QIMR (A/Prof Chenevix-Trench, Dr Penelope Webb), to identify low-risk ovarian cancer predisposition genes, following similar approaches.

c) Genetic Modifiers of Risk in BRCA1 and BRCA2 Mutation Carriers BRCA1 and BRCA2 families demonstrate variable expression with respect to age at onset, bilaterality, pathology, risk of ovarian cancer, risk of male breast cancer, and risk of other cancers. The penetrance of breast cancer in BRCA1 and BRCA2 mutation carriers is reported to be in the order of 80%-90% from studies on multiple-case families, but considerably lower at 40%-56% population-based studies. Although there is evidence for genotype- phenotype correlation with respect to mutation position within both BRCA1 and BRCA2, it is clear that differences in phenotype occur between individuals carrying the same mutation, and even between mutation-carrying individuals of the same family. These findings suggest that other genetic or environmental factors modify the expression of disease-causing BRCA1 or BRCA2 mutations. Research efforts include a project aiming to identify genes that modify the risk of cancer associated with the known high-risk BRCA1 and BRCA2 breast cancer predisposition genes. This involves screening carriers of BRCA1 and BRCA2 mutations for common genetic variants which may only slightly alter the function of the encoded protein, and assessing the association of variants with age at onset of disease, breast cancer in particular. Candidate genes include those considered candidate low-risk cancer predisposition genes as described above, and also genes encoding proteins that interact directly with BRCA1 or BRCA2. This is a collaborative study, and includes samples contributed by the Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) study, the ABCFS/CFRBCS, the Australian Jewish Breast Cancer Study (AJBCS; PI Prof John Hopper), and the British EMBRACE study (PI Dr Douglas Easton), and more recently as part of a large international consortium CIMBA (Consortium of Investigators or Modifiers of BRCA1 and BRCA2). Analytical methods are continually being refined in collaboration with Dr Easton (Cambridge) and Dr David Duffy (QIMR).

d) Ovarian Cancer Survival Genes Ovarian cancer is the 7th most common cancer in Australian women, with a lifetime risk of ovarian cancer of 1 in 108. Treatment outcomes are often poor, even in specialized gynaecologic oncology centres, with ~50% 5-year survival after diagnosis of invasive cancer. Ovarian cancer is considered to be a hormone-dependent cancer. Well-established risk factors for ovarian cancer include age and infertility, however family history is the single biggest risk factor, suggesting that at least some of the hormonal aetiology of this disease is driven by underlying genetic differences in hormone synthesis and response. We have been investigating the association between ovarian cancer survival and variation in genes acting in hormonal and other pathways. Specifically, in collaboration with researchers at QIMR (Dr Penny Webb, Dr Christina Nagle) and Queensland University of Technology (Dr Mary-Anne Kedda, Dr Ying Dong, A/Prof Judith Clements), we are studying the association between ovarian cancer outcome and kallikrein gene variants that are likely to alter expression or functional relevance of the kallikrein protein product. Kallikreins are considered good candidates for modifiers of survival, since these hormone-regulated protein-degrading enzymes involved in extracellular matrix degradation, facilitating tissue remodelling and affecting cell migration. There is strong evidence that kallikreins may be part of an enzymatic cascade pathway which is activated in aggressive forms of hormone-dependent cancers. Gene and/or protein expression levels of numerous kallikreins has been reported to be associated with progression-free and overall survival of ovarian cancer in multivariate models adjusting for other known prognostic factors, indicating that there will be additional prognostic value from prediction of expression levels of kallikrein genes. The study involves identification and characterization of likely functional polymorphisms within 5' putative promoter regions of selected kallikrein genes, use of functional assays to assess if such polymorphisms alter gene expression, and assessment of the association of selected polymorphisms with ovarian cancer survival and tumour prognostic features.

e) Prostate Cancer Predisposition and Prognosis In collaboration with researchers at the Queensland University of Technology (Dr Mary-Anne Kedda, Dr Ying Dong, A/Prof Judith Clements, Prof Beth Newman), we are conducting a complementary study to that on ovarian cancer survival, assessing the role of kallikrein polymorphisms in prostate cancer predisposition and progression.

STUDIES OF ENDOMETRIAL CANCER

Molecular Epidemiology of Endometrial Cancer Endometrial cancer is the most common invasive gynaecological cancer in Australian women, ranking 6th for incidence. Several histological subtypes are recognised and survival is poor for some of these. Although it is now clear that the aetiology of other gynaecologic cancers varies by subtype, few epidemiological studies have distinguished between different subtypes of endometrial cancer. Furthermore, very little is known regarding the role of germline genetic factors in endometrial cancer risk, except that an increased risk among relatives suggests a strong inherited component exists. A thorough examination of the genetic basis to disease within families has not been carried out, and the contribution from other lower-risk genes is unclear from studies to date. Our QIMR-based study group (including Drs Spurdle, Webb and Young) is conducting a large integrated, multidisciplinary study of endometrial cancer, the Australian National Endometrial Cancer Study. This large national population-based study of endometrial cancer involves recruitment of ~1500 incident cases of endometrial cancer, ~150 additional cases with rare histologies, ~1500 cancer-free controls, and selected relatives of cases that report a family history of cancer. There are several aims of this broad project. By evaluating risk factors separately for different subtypes, we aim to clarify existing and identify new modifiable risk factors, especially for the more aggressive subtypes. We are screening cases and controls for genetic polymorphisms in hormone pathways to assess the role of low-risk genetic variation in endometrial cancer aetiology, and will assess the interaction between environmental and low-risk genetic risk factors. We are examining the genetic basis to disease within multiple-case families by recording detailed family histories for all cases, and screening cases with a strong family history of endometrial and other cancers for mutations in the HNPCC (hereditary non-polyposis colon cancer syndrome) and PTEN genes. We are also establishing a biorepository and comprehensive epidemiological, molecular and clinical database for ongoing studies. This study will provide a better understanding of causal pathways leading to the different types of endometrial cancer, and identify potentially modifiable risk factors to assist development of prevention strategies in Australian women.

STUDIES OF COLORECTAL CANCER

Lynch syndrome is an autosomal dominant cancer syndrome, predisposing to colorectal and endometrial cancer predominantly, caused by mutations in mismatch repair (MMR) genes MLH1 and MSH2. MMR gene truncation mutations generally considered to be pathogenic can be identified in about half the families with suspected Lynch syndrome. However, >15% of Lynch syndrome families present with MMR gene sequence variants of uncertain clinical significance (UVs). Such UVs are well recognized to present a challenge in the clinical setting for genetic counselling, and thorough evaluation of their clinical significance would have direct clinical outcome for families concerned. In collaboration with Dr Youn at QIMR, we are testing the functional consequences of a panel of UVs in vitro, and comparing the efficiency of a variety of bioinformatic approaches in predicting the observed aberrations associated with each UV.

Staff

Labhead:	Dr Amanda Spurdle
Postdoc:	Dr Logan Walker
Research Assistants:	Ms Felicity Lose Mr Michael O'Brien Mr Peter Schultz
Scientific Technical Officer:	Mr Kaltin Ferguson
Graduate Student:	Ms Tracy O'Mara Mr Phillip Whiley

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Collaborators

Characterization of BRCA1 and BRCA2 variants of unclassified pathogenicity
Dr Melissa Brown, Prof Lakhani, University of Queensland
Dr Georgia Chenevix-Trench, QIMR
Dr Beric Henderson, University of New South Wales
Dr David Goldgar, University of Utah
Dr Sean Tavtigian, IARC, Lyon
Dr Fergus Couch, Mayo Clinic College of Medicine
Dr Sean Grimmond, Institute of Molecular Biosciences, Queensland

Case-control association studies to identify low-risk breast and ovarian cancer susceptibility genes
Drs Georgia Chenevix-Trench, and Penny Webb, QIMR
Prof John Hopper, University of Melbourne
Drs Douglas Easton, and Paul Pharoah, Cambridge University, UK
Breast Cancer Association Consortium (BCAC)

Genetic modifiers of BRCA1 and BRCA2 mutations
Dr Douglas Easton and Dr Antonis Antoniou, Cambridge University, UK
Consortium for Investigators of Modifiers of BRCA1/2 (CIMBA)

Kallikrein gene variation and function in hormone-dependent cancers
Drs Mary-Anne Kedda, Ying Dong, and Judith Clements, QUT
Drs Penny Webb and Christina Nagle, QIMR

Molecular epidemiology of endometrial cancer
Drs Penny Webb and Joanne Young,QIMR
Dr Andreas Obermair, Royal Brisbane Hospital
Dr Michael Quinn, University of Melbourne
Dr Penelope Blomfield, Royal Hobart Hospital and University of Tasmania
Dr Colin Stewart, King Edward Hospital, Perth
Prof Judy Kirk, Westmead Hospital
ANECS collaborators from multiple site across Australia

Characterization of Mismatch Repair Gene variants of unclassified pathogenicity
Dr Joanne Young,QIMR
Dr Melissa Brown, University of Queensland
Dr David Goldgar, University of Utah
Dr Sean Tavtigian, IARC, Lyon
Dr Michael Woods, Memorial University of Newfoundland
Dr Mark Jenkins, University of Melbourne

Funding Support

ID 442970, National Health and Medical Research, 2007-2009. A.B. Spurdle, S.Grimmond, M.A.Brown, C.Clarke. Evaluation of unclassified variants of BRCA1 and BRCA2 using a multifactorial approach. $440,250.

ID 390130 National Health and Medical Research , 2006-2008. M-A Kedda, AB Spurdle, J Clements, B Newman. The role of kallikrein gene variants in prostate cancer: analysis of gene regulation and diagnostic/prognostic use. $470,380.

ID 496616. National Health and Medical Research 2008-2010. A.B. Spurdle, M.A.Brown, J. Young. Assessment of mismatch repair gene sequence variants for clinical relevance. A$453,750

ID 496615. The Cancer Council Queensland 2008-2009. A.B. Spurdle, J. Young, C Stewart Characterization of population-based endometrial cancer families: Redefinition of familial cancer syndromes. $160 000

Student Projects

Research projects are available within the Molecular Cancer Epidemiology Laboratory for Bsc Honours and PhD students interested in the genetic epidemiology of breast, ovarian, colorectal and endometrial cancer.

Key Publications

PUBLICATIONS - Dr Amanda Spurdle

Spurdle AB, Goodwin B, Hodgson E, Hopper JL, Chen X, Purdie DM, McCredie MRE, Giles, GG, Chenevix-Trench G, Liddle C (2002). The Cytochrome P450 3A4 5’ Nifedipine-specific Response Element Polymorphism has no Apparent Functional Significance and is not Associated with Risk of Breast or Ovarian Cancer in Australian Women. Pharmacogenetics. 12: 355-366.[pubmed abstract]

Spurdle AB, Hopper JL, Chen X, McCredie MRE, Giles GG, Newman B, Chenevix-Trench G (2002). The Prohibitin 3’ Untranslated Region Polymorphism is not Associated with Risk of Breast Cancer in Australian women. Lancet. 360: 925-926.[pubmed abstract]

Spurdle AB, Antoniou AC, Duffy D, Pandeya N, Kelemen L, Chen X, Peock S, Cook MR, Smith PL, Purdie DM, Newman B, Dite GS, Apicella C, Southey MC, Giles GG, Hopper JL, kConFaB, EMBRACE Study Collaborators, ABCFS, AJBCS, Chenevix-Trench G, Easton DF (2005). The Androgen Receptor CAG Repeat Polymorphism and Modification of Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. Breast Cancer Research. 7:R176-R183. [pubmed abstract]

Webb P, Hopper JL, Newman B, Chen X, Giles GG, Southey M, Chenevix-Trench, G, Spurdle AB (2005). Double Strand Break Repair Gene Polymorphisms and Risk of Breast or Ovarian Cancer. Cancer Epidemiol Biormarkers Prev. 14: 319-323. [pubmed abstract]

Chang J-H, Gertig DM, Chen X, Dite GS, Jenkins MA, Milne RL, Southey MC, McCredie MRE, Giles GG, Chenevix-Trench G, Hopper JL, Spurdle AB (2005). CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors: Australian Breast Cancer Family Study. Breast Cancer Res 7:R513-R521. [pubmed abstract]

Lovelock P, Healey S, Au W, Sum E, Wong EM, Tesoriero A, Brinkworth R, Bekessy A, Waring P, Roberts D, Jenkins M, Hopper JL, kConFab, Tavtigian S, Goldgar D, Lindeman G, Visvader J, Couch F, Henderson B, Southey M, Chenevix-Trench G, Spurdle AB, Brown M (2006). Genetic, functional and histopatholigical evaluation of two C-terminal BRCA1 missense variants. Journal Medical Genetics 43: 74-83. [pubmed abstract]

Pettigrew C, Wayte N, Lovelock PK, Tavtigian SV, Chenevix-Trench G, Spurdle AB, Brown MA (2005). Evolutionary conservation analysis increases the colocalization of predicted ESEs in the BRCA1 gene with missense sequence changes and in-frame deletions but not polymorphisms. Breast Cancer Res 7: R929-R939. [pubmed abstract]

Spurdle AB, Antoniou AC, Duffy D, Kelemen L, Holland H, Peock S, Cook MR, Smith PL, Struewing J, Durocher F, BCFR Collaborators, kConFab, EMBRACE Study Collaborators, ABCFS, AJBCS, Easton DF, Chenevix-Trench G (2006). The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev 15: 76-79. [pubmed abstract]

Chenevix-Trench G, Healey S, Lakhani S, Waring P, Cummings M, Brinkworth R, Deffenbaugh A, Burbridge LA, Bekessy A, Marsh A, Lovelock P, Wong M, Tesoriero A, Southey M, Hopper JL, Yannoukakos D, Brown M, kConFab, Easton D, Tavtigian SV, Jenkins M, Brown M, Goldgar D, Spurdle AB (2006). Genetic and histopathological evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. Cancer Research 66: 2019-2027. [pubmed abstract]

Lovelock P, Wong EM, Sprung C, Marsh A, Hobson K, French J, Southey M, kConFab Investigators, Sculley T, Pandeya N, Brown M, Chenevix-Trench G, McKay M, Spurdle AB (2006). Prediction of BRCA1 and BRCA2 mutation status using post-irradiation assays of lymphoblastoid cell lines is compromised by inter-cell line phenotypic variability. Breast Cancer Res Treat Oct 25 [Epub ahead of print] [pubmed abstract]

Nagle CN, Chenevix-Trench G, Spurdle AB, Webb PM (2007). The role of Glutathione-S-transferase polymorphisms in ovarian cancer survival. Eur J Cancer 43: 283-190. [pubmed abstract]

Lai J, Kedda M-A, Hinze K, Smith RLG, Yaxley J, Spurdle AB, Morris P, Harris J, Clements JAC (2006). PSA/KLK3 ARE promoter polymorphism alters androgen receptor binding and is associated with prostate cancer susceptibility. Carcinogenesis, 28(5):1032-9.[pubmed abstract]

Jaskowski L, Young J, Jackson L, Arnold S, Barker M, Walsh M, Buchanan D, Holma S, Mensink KA, Thibodeau SN, Jass J, Spurdle A (2006). Stability of BAT26 in Lynch Syndrome Tumours. Eur J Hum Genetics, Nov29 [Epub ahead of print].[pubmed abstract]

Nagle CN, Chenevix-Trench G, Webb PM, Spurdle AB (2006). Ovarian cancer survival and polymorphisms in hormone and DNA repair pathway genes. Cancer Lett, Dec 18 [Epub ahead of print][pubmed abstract]

Cox A, Dunning AM, Garcia-Closas M, Balasubramanian S, Reed MWR, Pooley KA, Scollen S, Ponder BAJ, Chanock S, Lissowka J, Brinton L, Southey MC, Hopper JL, McCredie MRE, Giles GG, Fletcher O, Johnson N, dos Santos Silva I, Gibson L, Bojeson SE, Nordestgaard BG, Axelsson CK, Torres D, Hamann U, Justenhoven C, Brauch H, Chang-Claud J, Kropp S, Risch A, Wnag-Gorke S, Schurmann P, Bogdanova N, Dork T, Fagerhol, R, Aaltonen K, Blomqvist C, Nevanlinna H, Seal S, The Breast Cancer Susceptibility Collaboration (UK), Stratton MR, Rahman N, Sangrajrang S, Hughes D, Odefrey F, Brennan P, Spurdle AB, Chenevix-Trench G, Beesley J, kConFaB, Mannermaa A, Hartikainen J, Kataja V, Kosma V-M, Couch FJ, Olson J, Goode EL, Broeks A, Schmidt MK, Hogervorst FBL, Van't Veer LJ, Kang D, Yoo K-Y, Noh D-Y, Ahn S-H, Wedren S, Hall P, Low Y-L, Liu J, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Sigurdon AJ, Stredrick DL, Alexander BH, Struewing JP, Pharoah PDP, Easton DF, on behalf of the Breast Cancer Association Consortium. (2007). corrigendum: A common coding variant in CASP8 is associated with breast cancer risk. Nature Genetics 39: 352-8. [pubmed abstract]

Spurdle AB, Chang, J-H. Byrnes GB, Chen X, Dite G, McCredie MRE, Giles GG, Southey MC, Chenevix-Trench G, Hopper JL (2007). A systematic approach to analyzing gene-gene interactions: Polymorphisms at the microsomal epoxide hydrolase EPHX and Glutathione S-Transferase GSTT1, GSTM1 and GSTP1 loci and breast cancer risk. Cancer Epidemiol Biomarkers Prev 16: 769-74.[pubmed abstract]

Easton DF, Pooley KA, Dunning AM, Pharoah DP, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Search collaborators, Haiman C, Kolonel L, Henderson B, Le Marchand L, Brennan P, Sangrajrang S, Gaborieau S, Godfrey F, Shen C-Y, Wu P-E, Wang H-C, Eccles D, Evans DG, Fletcher O, Peto J, Johnson N, Stratton MR, Rahman N, Chenevix-Trench G, Bojesen SE, Nordestgaard BG, Axelsson CK, Garcia-Closas M, Brinton L, Chanock S, Lissowska J, Nevanlinna H, Fagerholm R, Eerola H, Kang D, Yoo K-Y, Noh D-Y, Ahn S-H, Hunter DJ, Hankinson SE, Cox DG, Hall P, Wedren S, Liu JJ, Yen-Ling L, Bogdanova N, Schürmann P, Dörk T, Tollenaar RAEM, Jacobi CE, Klijn JGM, Devilee P, Sigurdson A, Doody MM, Alexander BH, Zhang J, Cox A, Brock IW, MacPherson G, Read MWR, Couch F, Goode E, Olson J, Meijers-Hiejboer H, Unterlinden A, Milne R, Ribas G, Gonzalez A, Benitez J, Hopper J, McCredie M, Southey M, Giles G, Schroen C, Justenhoven C, Brauch H, Hamann U, Ko Y-D, Spurdle AB, Beesley J, Chen X, kConFab, AOCS Management Group, Mannermaa A, Kosma V-M, Kataja V, Hartikainen J, Day NE, Cox DR, Ponder BAJ (2007). A genome-wide association study identifies multiple novel breast cancer susceptibility loci. Nature 447:1087-93. [pubmed abstract]

Lose F, Arnold J, Young, DB, Brown CJ, Mann GJ, Pupo GM, kConFaB, Khanna KK, Chenevix-Trench G, Spurdle AB (2007). BCoR-L1 variation and breast cancer. Breast Cancer Res 9: R54. [pubmed abstract]

Spurdle AB, Lakhani S, Healey S, Parry S, Deffenbaugh AM, Pruss D, Da Silva L, Brinkworth R, Hopper JL, kConFab Investigators, Brown MA, Babikyan D, Chenevix-Trench G, Tavtigian SV, Goldgar D (2008). Clinical classification of BRCA1 and BRCA2 DNA sequence variants: the value of cytokeratin profiles and evolutionary analysis. J Clin Oncol 26: 1657-1663. [pubmed abstract]

Lovelock PK, Spurdle AB, Mok M, Couch F, Henderson BR , Lakhani S, Healey S, Arnold S, Buchanan D, kConFab Investigators5, Deffenbaugh A, Goldgar D, Tavtigian SV, Chenevix-Trench G, Brown MA (2007). Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants? Breast Cancer Research Nov 26; 9(6):R82 [pubmed abstract]

Walsh MD, Cummings MC, Buchanan DB, Dambacher W, Arnold S, McKeone D, Byrnes R, Barker MA, Leggett BA, Gattas M, Jass JR, Spurdle AB, Young J, Obermair A (2008). Molecular, pathologic and clinical features of early-onset endometrial cancer: indications for genetic testing of presumptive Lynch syndrome cases. Clinical Cancer Research 14(6):1692-1700 [pubmed abstract]

Dowty JG, Lose F, Jenkins MA, Chang J-H, Chen X, Beesley J, Dite GS, Southey MC, Byrnes GB, Giles G.G, Tesoriero A, kConFaB, ABCFS, Hopper JL, Spurdle AB (2007). The Rad51D E233G variant and breast cancer risk: population-based and clinic-based family studies of Australasian women. Breast Cancer Res Treat, December 4 [Epub ahead of print] [pubmed abstract]

Walker LC, Waddell N, Ten Haaf A, kConFab Investigators, Grimmond S, Spurdle AB (2007). Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers. Breast Cancer Res Treat, December 20 [Epub ahead of print] [pubmed abstract]

Spurdle AB, Webb PM, ANECS collaborators (2008). Re: Excess of early onset multiple myeloma in endometrial cancer probands and their relatives suggests common susceptibility. [Letter to the editor]. Gynecol Oncol Jan 28 [Epub ahead of print].

Antoniou AA, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, Hofmann W, Sutter C, Niederacher D, Deissler H, Caldes T, Kämpjärvi K, Nevanlinna H, Simard J, Beesley J, Chen X, the Kathleen Cuningham Consortium for Research into Familial Breast Cancer, Neuhausen SL, Rebbeck TR, Wagner T, Lynch HT, Isaacs C, Weitzel J, Ganz PA, Daly MB, Tomlinson G, Olopade OI, Blum JL, Couch FJ, Peterlongo P, Manoukian S, Barile M, Radice P, Szabo CI, Mateus Pereira LH, Greene MH, Rennert G, Lejbkowicz F, Barnett-Griness O, Andrulis I, Ozcelik H, OCGN, Gerdes A-M, Caligo MA, Laitman Y, Kaufmann B, Milgrom R, Friedman E, SWE-BRCA, Domchek SM, Nathanson KL, Osorio A, Llort G, Milne RL, Benítez J, Hamann U, Hogervorst FBL, Manders P, Ligtenberg MJL, van den Ouweland AMW, The DNA-HEBON collaborators, Peock S, Cook M, Platte R, Evans DG, Eeles R, Pichert G, Chu C, Eccles D, Davidson R, Douglas F, EMBRACE, Godwin AK, Barjhoux L, Mazoyer S, Sobol H, Bourdon V, Eisinger F, Chompret A, Capoulade C, Bressac-de-Paillerets B, Lenoir GM, Gauthier-Villars M, Houdayer C, Stoppa-Lyonnet D, GEMO, Chenevix-Trench G, Easton DF on behalf of CIMBA (2008). Common breast cancer predisposition alleles modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genetics 82(4):937-948. [pubmed abstract]

Waddell N, Ten Haaf A, Marsh A, Johnson J, Walker L, kConFab Investigators, Gongora M, Brown M, Grover P, Girolami M, Grimmond S, Chenevix-Trench G and Spurdle AB. BRCA1 and BRCA2 Missense Variants of High and Low Clinical Significance Influence Lymphoblastoid Cell Line Post-Irradiation Gene Expression. PLoS Genetics, accepted March 2008

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