Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for <i>BRCA1</i> and <i>BRCA2</i> Mutation Carriers: Implications for Risk Prediction

Antoniou, Antonis C.; Beesley, Jonathan; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Neuhausen, Susan L.; Ding, Yuan Chun; Rebbeck, Timothy R.; Weitzel, Jeffrey N.; Lynch, Henry T.; Isaacs, Claudine; Ganz, Patricia A.; Tomlinson, Gail E.; Olopade, Olufunmilayo I.; Couch, Fergus J.; Wang, Xianshu; Lindor, Noralane M.; Pankratz, V. Shane; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Barile, Mônica; Viel, Alessandra; Allavena, Anna; Dall’Olio, Valentina; Peterlongo, Paolo; Szabo, Csilla I.; Zikán, Michal; Claes, Kathleen; Poppe, Bruce; Foretová, Lenka; Phuong, L.; Greene, Mark H.; Rennert, Gad; Lejbkowicz, Flavio; Glendon, Gord; Özçelik, Hilmi; Andrulis, Irene L.; Thomassen, Mads; Gerdes, Anne–Marie; Sunde, Lone; Crüger, Dorthe Gylling; Jensen, Uffe Birk; Caligo, Maria A.; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Dubrovsky, Maya; Cohen, Shimrit; Borg, Åke; Jernström, Helena; Lindblom, Annika; Rantala, Johanna; Stenmark-Askmalm, Marie; Melin, Beatrice; Nathanson, Katherine L.; Domchek, Susan M.; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Osorio, Ana; Lasa, Adriana; Durán, Mercedes; Tejada, María-Isabel; Godino, Javier; Benı́tez, Javier; Hamann, Ute; Kriege, Mieke; Hoogerbrugge, Nicoline; Luijt, Rob B. van der; Asperen, Christi J. van; Devilee, Peter; Meijers-Heijboer, E.J.; Blok, Marinus J.; Aalfs, Cora M.; Hogervorst, Frans B.L.; Rookus, Matti A.; Cook, Margaret; Oliver, Clare; Frost, Debra; Conroy, Don; Evans, D. Gareth; Lalloo, Fiona; Pichert, Gabriella; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Paterson, Joan; Hodgson, Shirley; Morrison, Patrick J.; Porteous, Mary; Walker, Lisa; Kennedy, Michael J.; Dorkins, Huw; Peock, Susan; Godwin, Andrew K.; Stoppa‐Lyonnet, Dominique; Pauw, Antoine de; Mazoyer, Sylvie; Bonadona, Valérie; Lasset, Christine; Dreyfus, Hélène; Leroux, Dominique; Hardouin, Agnès; Berthet, Pascaline; Faivre, Laurence; Loustalot, Catherine; Noguchi, Tetsuro; Sobol, Hagay; Rouleau, Étienne; Noguès, Catherine; Frénay, Marc; Vénat-Bouvet, Laurence; Hopper, John L.; Daly, Mary B.; Terry, Mary Beth; John, Esther M.; Buys, Saundra S.; Yassin, Yosuf; Miron, Alexander; Goldgar, David E.; Singer, Christian F.; Dressler, Anne Catharina; Gschwantler‐Kaulich, Daphne; Pfeiler, Georg; Hansen, Thomas van Overeem; Jnson, Lars; Agnarsson, Bjarni A.; Kirchhoff, Tomas; Offit, Kenneth; Devlin, Vincent J.; Dutra-Clarke, Ana; Piedmonte, Marion; Rodriguez, Gustavo C.; Wakeley, Katie; Boggess, John F.; Basil, Jack; Schwartz, Peter E.; Blank, Stephanie V.; Toland, Amanda E.; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny N.; Tihomirova, Laima; Blanco, Ignacio; Lázaro, Conxi; Ramus, Susan J.; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Lochmann, Magdalena; Arnold, Norbert; Heidemann, Simone; Varon-Mateeva, Raymonda; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Dorothea; Preisler-Adams, Sabine; Kast, Karin; Schönbuchner, Ines; Caldés, Trinidad; Hoya, Miguel de la; Aittomäki, Kristiina; Nevanlinna, Heli; Simard, Jacques; Spurdle, Amanda B.; Holland, Helene; Chen, Xiaoqing; Platte, Radka; Chenevix-Trench, Georgia; Easton, Douglas F.

doi:10.1158/0008-5472.can-10-1907

Cited by 177 publications

(170 citation statements)

References 24 publications

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“…The association patterns in BRCA1 and BRCA2 mutation carriers follow closely the associations in the general population once stratified by tumour ER status [41]. However, it is yet unclear how the SNPs are associated with ER-positive or ER-negative breast cancer for BRCA1 and BRCA2 mutation carriers.…”

Section: Future Challengessupporting

confidence: 52%

“…Taken together with the already observed differences in the risk of developing breast cancer by the known SNP profiles [41], they suggest that as more modifiers of risk are identified, much greater improvements in profiling of mutation carriers can be achieved. However, in the context of genetic counselling, it is important to consider how the associations of the already identified SNPs vary with family history of breast or ovarian cancer.…”

Section: Future Challengesmentioning

confidence: 66%

“…Analysis of the interactions between pairs of nine of the modifying loci identified so far indicated that the combined effects on the breast cancer risk for BRCA1 and BRCA2 mutation carriers were consistent with a multiplicative model [41,49,50]. Under this model, and including only the FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7 ⁄ NEK10 and 5p12 loci, it was estimated that the hazard ratios for the combined effect of the SNPs on BRCA2 breast cancer risk can vary from one for those who were homozygous for the protective allele at all loci to 5.75 for those who were homozygous for the risk allele at all loci.…”

Section: Common Alleles and Cancer Risks For Mutation Carriersmentioning

confidence: 78%

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Unravelling modifiers of breast and ovarian cancer risk forBRCA1andBRCA2mutation carriers: update on genetic modifiers

Barnes¹,

Antoniou²

2012

Journal of Internal Medicine

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Abstract. Barnes DR, Antoniou AC (Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK). Unravelling modifiers of breast and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: update on genetic modifiers (Review). J Intern Med 2012;271: 331-343.Pathogenic mutations in the tumour suppressor genes BRCA1 and BRCA2 confer increased risks for breast and ovarian cancer and account for approximately 15% of the excess familial risk of breast cancer amongst first-degree relatives of patients with breast cancer. There is considerable evidence indicating that these risks vary by other genetic and environmental factors clustering in families. In the past few years, based on the availability of genomewide association data and samples from large collaborative studies, several common alleles have been found to modify breast or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. These common alleles explain a small proportion of the genetic variability in breast or ovarian cancer risk for mutation carriers, suggesting more modifiers remain to be identified. We review the so far identified genetic modifiers of breast and ovarian cancer risk and consider the implications for risk prediction. BRCA1 and BRCA2 mutation carriers could be some of the first to benefit from clinical applications of common variants identified through genomewide association studies. However, to be able to provide more individualized risk estimates, it will be important to understand how the associations vary with different tumour characteristics and their interactions with other genetic and environmental modifiers.

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Section: Future Challengessupporting

confidence: 52%

Section: Future Challengesmentioning

confidence: 66%

Section: Common Alleles and Cancer Risks For Mutation Carriersmentioning

confidence: 78%

See 1 more Smart Citation

Unravelling modifiers of breast and ovarian cancer risk forBRCA1andBRCA2mutation carriers: update on genetic modifiers

Barnes¹,

Antoniou²

2012

Journal of Internal Medicine

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“…19,20 Only 125 individuals from 78 families (mean 1.6, range 1-6 family members) were available for consideration in this study and there may be some inflation of risks associated with the analysis of multiple members from the same family due to shared environmental factors or other genetic susceptibilities. However, there were no large families that skewed the allele frequencies.…”

Section: Discussionmentioning

confidence: 99%

Common variants modify the age of onset for basal cell carcinomas in Gorlin syndrome

et al. 2014

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Gorlin syndrome is an autosomal dominant disorder, characterized by multiple early-onset basal cell carcinomas (BCCs) and jaw keratocysts. Through association studies in cohorts of sporadic BCC, nine genetic variants have previously been identified to increase the risk of BCC. The nine SNPs were genotyped by Taqman allelic discrimination in 125 individuals with Gorlin syndrome. Kaplan-Meier survival curves and Cox proportional-Hazard regression analysis were applied to determine the association between genotypes and age of first BCC in individuals with Gorlin syndrome. The p.(Arg151Cys) variant in MC1R (rs1805007) was associated with an earlier median age of onset of BCC of 27 years (95% CI: 20-34) compared with 34 years (95% CI: 30-40) for wild-type individuals (hazard ratio (HR) ¼ 1.64, 95% CI: 1.04-2.58, P ¼ 0.034). The risk allele of the variant at the chromosome 5p15 locus encompassing TERT-CLPTM1L (rs401681) was also associated with an earlier median onset of BCC, 31 years (95% CI: 28-37) compared with 41 years (95% CI: 32-48, HR ¼ 1.44, 95% CI: 1.08-1.93, P ¼ 0.014). In individuals with a risk allele at either rs1805007 or rs401681 the median time to BCC was 31 years of age (95% CI: 28-34) compared with 44 years of age (95% CI: 38-53) in wild-type individuals (HR ¼ 2.48, 95% CI: 1.47-4.17, P ¼ 0.0002). Our findings may have implications for future personalized risk estimates and BCC screening strategies in individuals with Gorlin syndrome.

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“…Therefore, mutations that occur in DNA repair genes are strongly related with excessive cancer risks in human. Although great advancement has been made in the association studies of polymorphisms in repair genes and breast (Antoniou et al, 2010), colorectal ) and lung cancer (López-Cima et al, 2007), however, the research focus on liver cancer was infrequently published. Codon 399 in XRCC1 was investigated among Taiwanese population (Yu et al, 2003), and both positive association and dose-dependent relationship for early-onset HCC were observed.…”

Section: Genetic Variationmentioning

confidence: 99%

Genetic Factors, Viral Infection, Other Factors and Liver Cancer: An Update on Current Progress

Su¹,

Yan²,

Cai³

2013

Asian Pacific Journal of Cancer Prevention

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Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

Cited by 177 publications

References 24 publications

Unravelling modifiers of breast and ovarian cancer risk forBRCA1andBRCA2mutation carriers: update on genetic modifiers

Unravelling modifiers of breast and ovarian cancer risk forBRCA1andBRCA2mutation carriers: update on genetic modifiers

Common variants modify the age of onset for basal cell carcinomas in Gorlin syndrome

Genetic Factors, Viral Infection, Other Factors and Liver Cancer: An Update on Current Progress

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