Common Breast Cancer-Predisposition Alleles Are Associated with Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Antoniou, Antonis C.; Spurdle, Amanda B.; Sinilnikova, Olga M.; Healey, Sue; Pooley, Karen A.; Schmutzler, Rita K.; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Arnold, Norbert; Hofmann, Wera; Sutter, Christian; Niederacher, Dieter; Deissler, Helmut; Caldés, Trinidad; Kämpjärvi, Kati; Nevanlinna, Heli; Simard, Jacques; Beesley, Jonathan; Chen, Xiaoqing; Neuhausen, Susan L.; Rebbeck, Timothy R.; Wagner, Theresa; Lynch, Henry T.; Isaacs, Claudine; Weitzel, Jeffrey N.; Ganz, Patricia A.; Daly, Mary B.; Tomlinson, Gail E.; Olopade, Olufunmilayo I.; Blum, Joanne L.; Couch, Fergus J.; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Mônica; Radice, Paolo; Szabo, Csilla I.; Pereira, Lutécia; Greene, Mark H.; Rennert, Gad; Lejbkowicz, Flavio; Barnett‐Griness, Ofra; Andrulis, Irene L.; Özçelik, Hilmi; Gerdes, Anne–Marie; Caligo, Maria A.; Laitman, Yael; Kaufman, Bella; Milgrom, Roni; Friedman, Eitan; Domchek, Susan M.; Nathanson, Katherine L.; Osorio, Ana; Llort, Gemma; Milne, Roger L.; Benı́tez, Javier; Hamann, Ute; Hogervorst, Frans B.L.; Manders, Peggy; Ligtenberg, Marjolijn J. L.; Ouweland, Ans M.W. van den; Peock, Susan; Cook, Margaret; Platte, Radka; Evans, D. Gareth; Eeles, Rosalind; Pichert, Gabriella; Chu, Carol; Eccles, Diana; Davidson, Rosemarie; Douglas, Fiona; Godwin, Andrew K.; Barjhoux, Laure; Mazoyer, Sylvie; Sobol, Hagay; Bourdon, Violaine; Eisinger, François; Chompret, Agnès; Capoulade, Corinne; Paillerets, Brigitte Bressac-de; Lenoir, Gilbert; Gauthier‐Villars, Marion; Houdayer, Claude; Stoppa‐Lyonnet, Dominique; Chenevix-Trench, Georgia; Easton, Douglas F.

doi:10.1016/j.ajhg.2008.02.008

Cited by 242 publications

(194 citation statements)

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“…Multi-center, multi-national studies recently showed that such SNPs either did not modify the risk of breast cancer in BRCA1/2 mutation carriers or only modestly (eg, RR 1.1-1.3). 28,29 Xu et al analyzed the utility of the 14 SNPs associated with prostate cancer risk. 30 By themselves, the SNPs were not particularly helpful for identifying men who would go on to develop prostate cancer, as we have noted in our present study.…”

Section: Discussionmentioning

confidence: 99%

Prospective comparison of family medical history with personal genome screening for risk assessment of common cancers

2012

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Family history-based risk assessment (FHRA) is a genetic tool for identifying those at risk of disease. Genome-wide association studies have shown that single nucleotide polymorphisms (SNP) are statistically associated with low-to moderate-level risks of diseases. There has been limited study of complementarity for these two assessment methods. We sought to compare cancer risk categorizations from FHRA and from Navigenics Personal Genome Screening (PGS). We compared FHRA with PGS for breast (22 females), prostate (22 males), and colon cancer (44 males and females) assessed by kappa (j) statistic. We also assessed each participant's hereditary risk based on clinical criteria and/or gene-test results. Both FHRA and PGS placed 59%, 68% and 44% of participants into the same risk categories for breast, prostate, and colon cancer, respectively. Overall, however, there was little concordance in FHRA versus PGS for all three cancer risks (jo0.2). FHRA assigned 22 with hereditary risk compared with PGS, which identified one as high risk (Po0.0001). We assessed nine with hereditary colorectal cancer risk, five with germline mutations, but none were classified as PGS high risk (P¼0.0001). FHRA and PGS may be complementary tools for cancer risk assessment. However, evaluation of family history remains the standard to evaluate an individual's cancer risk until further research.

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Section: Discussionmentioning

confidence: 99%

Prospective comparison of family medical history with personal genome screening for risk assessment of common cancers

2012

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“…The Consortium of Investigators of Modifiers of BRCA1/2 has recently evaluated whether variants in FGFR2 (rs2981582), TNRC9 (rs3803662) and MAP3K1 (rs889312) are associated with the risk of BC in over 10 000 BRCA1 and BRCA2 mutation carriers from 23 studies (Antoniou et al, 2008). The evidence of association with SNP rs889312 in MAP3K1 was weaker and was restricted to BRCA2 mutation carriers, however, this SNP was not associated with an increased risk in BRCA1 carriers.…”

Section: Map3k1mentioning

confidence: 99%

Breast cancer genome-wide association studies: there is strength in numbers

et al. 2011

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Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-specific protein 1 (LSP1). The most strongly associated SNP was in intron 2 of the FGFR2 gene that is amplified and overexpressed in 5-10% of BC. rs3803662 of TNRC9 gene has been shown to be the SNP with the strongest association with BC, in particular, this polymorphism seems to be correlated with bone metastases and estrogen receptor positivity. Relevant data indicate that SNP rs889312 in MAP3K1 is correlated with BC susceptibility only in BRCA2 mutation carriers, but is not associated with an increased risk in BRCA1 carriers. Finally, different SNPs in LSP1 and H19 and in minor genes probably were associated with BC risk. New susceptibility allelic variants associated with BC risk were recently discovered including potential causative genes involved in regulation of cell cycle, apoptosis, metabolism and mitochondrial functions. In conclusion, the identification of disease susceptibility loci may lead to a better understanding of the biological mechanism for BC to improve prevention, early detection and treatment.

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“…Reasons for variation may include different mutations in the same gene (allelic variation) [5,[7][8][9], the effect of modifying genes [10][11][12], and non-genetic modifiers [13]. Several studies have indicated that the penetrance of BRCA1 and BRCA2 mutations has increased in recent generations [14][15][16], which supports the concept that non-genetic risk factors, of which the prevalence has increased, also affect the risk.…”

Section: Introductionmentioning

confidence: 99%

Body weight and risk of breast cancer in BRCA1/2 mutation carriers

Manders

Pijpe²,

Hooning

et al. 2010

Breast Cancer Res Treat

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Obesity is an established risk factor for postmenopausal breast cancer in the general population. However, it is still unclear whether this association also exists in BRCA1/2 mutation carriers. We investigated the association between self-reported anthropometric measures and breast cancer risk in a nationwide retrospective cohort study, including 719 BRCA1/2 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. All time-varying Cox proportional hazards analyses were stratified by menopausal status. For premenopausal breast cancer, no statistically significant associations were observed for any of the anthropometric measures. The association between body mass index (BMI) at age 18 and premenopausal breast cancer risk suggested a trend of decreasing risk with increasing BMI 123Breast Cancer Res Treat (2011) 126:193-202 DOI 10.1007/s10549-010-1120 5 kg or more, and a relative adult weight gain of 20% or more were all non-significantly associated with a 50-60% increased risk of postmenopausal breast cancer [HR = 1.46 (0.86-2.51), HR = 1.56 (95% CI = 0.85-2.87), and HR = 1.60 (95% CI = 0.97-2.63), respectively], when compared with having a healthy or stable weight. No associations for body weight or BMI at age 18 were observed. In conclusion, menopausal status seemed to modify the association between body weight and breast cancer risk among BRCA1/2 carriers. We observed no clear association between body weight and premenopausal breast cancer, while overweight and weight gain increased postmenopausal breast cancer risk. Carriers may reduce their risk of postmenopausal breast cancer by maintaining a healthy body weight throughout life.

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Common Breast Cancer-Predisposition Alleles Are Associated with Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Cited by 242 publications

References 20 publications

Prospective comparison of family medical history with personal genome screening for risk assessment of common cancers

Prospective comparison of family medical history with personal genome screening for risk assessment of common cancers

Breast cancer genome-wide association studies: there is strength in numbers

Body weight and risk of breast cancer in BRCA1/2 mutation carriers

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