Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium†

Figueroa, Jonine D.; García-Closas, Montserrat; Humphreys, Manjeet K.; Platte, Radka; Hopper, John L.; Southey, Melissa C.; Apicella, Carmel; Hammet, Fleur; Schmidt, Marjanka K.; Broeks, Annegien; Tollenaar, Rob A.E.M.; Veer, Laura J. van’t; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Strick, Reiner; Peto, Julian; dos‐Santos‐Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Burwinkel, Barbara; Marmé, Federik; Schneeweiß, Andreas; Sohn, Christof; Bojesen, Stig E.; Flyger, Henrik; Nordestgaard, Børge G.; Benı́tez, Javier; Milne, Roger L.; Arias, José Ignacio; Zamora, M. Pilar; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Rahman, Nazneen; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Ko, Yon; Baisch, Christian; Fischer, Hand Peter; Hamann, Ute; Pesch, Beate; Rabstein, Sylvia; Harth, Volker; Chang‐Claude, Jenny; Hein, Rebecca; Wang-Gohrke, Shan; Dörk, Thilo; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Yuriy; Karstens, Johann H.; Bermisheva, Marina; Prokofieva, Darya; Gantcev, Shamil Hanafievich; Хуснутдинова, Э. К.; Lindblom, Annika; Margolin, Sara; Chenevix‐Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Bowtell, David D.; Chenevix-Trench, G.; deFazio, Anna; Gertig, Dorota M.; Green, A.; Webb, Penelope M.; Mannermaa, Arto; Kosma, Veli Matti; Soini, Ylermi; Kataja, Vesa; Lambrechts, Diether; Yesilyurt, Betül T.; Chrisiaens, Marie Rose; Peeters, Stéphanie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Mônica; Couch, Fergus J.; Lee, Adam M.; Diasio, Robert B.; Wang, Xianshu; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Maclean, Catriona; Offit, Ken; Robson, Mark E.; Vijai, Joseph; Gaudet, Mia M.; John, Esther M.; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Mulligan, Anna Marie; O’Malley, Frances P.; Brinton, Louise A.; Sherman, Mark E.; Lissowska, Jolanta; Chanock, Stephen J.; Hooning, Maartje J.; Martens, John W.M.; Ouweland, Ans M.W. van den; Collée, J. Margriet; Hall, Per; Czene, Kamila; Cox, Angela; Brock, Ian W.; Reed, Malcolm; Cross, Simon S.; Pharoah, Paul D.P.; Dunning, Alison M.; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Ahn, Sei Hyun; Jakubowska, Anna; Lubiński, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valérie; Brennan, Paul; McKay, James; Shen, Chen; Ding, Shian Ling; Hsu, Huan Ming; Yu, Jyh Cherng; Anton‐Culver, Hoda; Ziogas, Argyrios; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael E.; Orr, Nick; Trentham‐Dietz, Amy; Egan, Kathleen M.; Newcomb, Polly A.; Titus-Ernstoff, Linda; Easton, Doug; Spurdle, Amanda B.

doi:10.1093/hmg/ddr368

Cited by 68 publications

(49 citation statements)

References 27 publications

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“…27 These heterogeneities were supported by the associations of epidemiological and genetic factors including copy number, gene expression and genetic variants with distinct tumor subtypes. 24,[28][29][30] Consistently, our study provides evidence on the epidemiological heterogeneity within breast tumor subtypes, supporting that the well-known risk factors of breast cancer are more frequent in HR1 HER22 but not in the other subtypes.…”

Section: Discussionsupporting

confidence: 86%

Heterogeneity of epidemiological factors by breast tumor subtypes in Korean women: A case-case study

et al. 2014

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Breast cancer is heterogeneous in clinical behavior by subtypes; however, it is unclear how this heterogeneity is related to epidemiological factors. To evaluate the differences in epidemiological factors by breast tumor subtypes, we investigated the associations of epidemiological factors between tumor subtypes in Korean women. From the Seoul Breast Cancer Study, a total of 3,058 patients with breast cancer were included in the analyses. Tumor subtypes were classified based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses. The epidemiological factors of each subtype were compared through case-case analyses using multivariate a polytomous logistic regression model adjusted for age and recruiting centers. The distribution of the subtypes was as follows: 1,714 HR1 HER22 (56.0%), 414 HR1 HER21 (13.5%), 423 HR2 HER21 (13.9%) and 507 HR2 HER22 (16.6%) patients with breast cancer. There were significant differences in age, menopausal status, age at menarche, number of children, age at first full-term pregnancy (FFTP), duration of breastfeeding and duration of endogenous estrogen exposure between tumor subtypes (p < 0.05). Compared to HR1 HER22 patients, the other subtype patients showed more frequency in having more numbers of children and less frequency in having earlier menarche, later FFTP and longer endogenous estrogen exposure. Although HR2 HER21 patients were less obese, HR2 HER22 patients were younger and more obese. In conclusion, age, body mass index and reproductive factors were differentially associated with breast tumor subtypes suggesting a possible distinct etiology for tumor progression.Breast cancer is a heterogeneous disease in terms of clinical behavior. Breast tumors have been classified into intrinsic subtypes using gene expression patterns measured by microarrays.1-3 The intrinsic subtypes were explained as the clinicopathological definition based on the expression of estrogen and progesterone receptors (ER and PR), human epidermal growth factor receptor 2 (HER2) and For the basallike subtype of breast cancer, epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) were also used as surrogates.5 These tumor subtypes have shown significant differences in their clinical features. 2,3,6 Notwithstanding the clinical heterogeneity of the tumor subtype, the etiological heterogeneity has not been established.7 Through previous epidemiological studies, several reproductive factors, such as early menarche, late menopause and late age at first full-term pregnancy (FFTP), and family history have been established as risk factors of breast cancer, and obesity has been probable as protective or a risk factor of breast cancer depending on the menopausal status. [8][9][10] Furthermore, well-known risk factors of breast cancer have been associated with the ER-positive subtype rather than the ER-negative subtype.

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Section: Discussionsupporting

confidence: 86%

Heterogeneity of epidemiological factors by breast tumor subtypes in Korean women: A case-case study

et al. 2014

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“…Additionally, genome-wide association studies (GWAS) have identified breast cancer risk genes on this chromosome in several different population groups. Such GWAS [18], however, cannot evaluate the involvement of GM alleles, as these determinants are not included in the current genotyping platforms. To our knowledge, they are not being tagged by any SNPs that are included in the platforms.…”

Section: Discussionmentioning

confidence: 99%

Genetic markers of immunoglobulin G and susceptibility to breast cancer

Pandey

Kistner-Griffin

Iwasaki³

et al. 2012

Human Immunology

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“…Genome-wide association studies (GWAS) have identified common variants in RAD51B associated with female and male breast cancer [9][10][11] and a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer [12]. Here we present a novel germline RAD51B nonsense mutation in a family with cutaneous melanoma.…”

Section: Introductionmentioning

confidence: 90%

Germline RAD51B truncating mutation in a family with cutaneous melanoma

et al. 2015

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Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While this case report is consistent with melanoma being part of the RAD51B cancer spectrum further population-based screening of large case-control sample series will be needed to definitively establish if this is the case.

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Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium†

Cited by 68 publications

References 27 publications

Heterogeneity of epidemiological factors by breast tumor subtypes in Korean women: A case-case study

Heterogeneity of epidemiological factors by breast tumor subtypes in Korean women: A case-case study

Genetic markers of immunoglobulin G and susceptibility to breast cancer

Germline RAD51B truncating mutation in a family with cutaneous melanoma

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