The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10-14 in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10-18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10-9 in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10-17 versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10-7, pheterogeneity = 5.1×10-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours. © 2012 Hein et al.
Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)
Hein, Rebecca; Maranian, Melanie; Hopper, John L.; Kapuscinski, Miroslaw K.; Southey, Melissa C.; Park, Daniel J.; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B. L.; Bueno de Mesquit, H. Bas; Muir, Kenneth R.; Lophatananon, Artitaya; Rattanamongkongul, Suthee; Puttawibul, Puttisak; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fletcher, Olivia; Johnson, Nichola; dos Santos Silva, Isabel; Peto, Julian; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Marmee, Frederick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Cordina Duverger, Emilie; Menegaux, Florence; Truong, Thérèse; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Zamora, M. Pilar; Benítez, Javier; Anton Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Clarke, Christina A.; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Rahman, Nazneen; Seal, Sheila; Turnbull, Clare; Renwick, Anthony; Meindl, Alfons; Schott, Sarah; Bartram, Claus R.; Schmutzler, Rita K.; Brauch, Hiltrud; Hamann, Ute; Ko, Yon Dschun; Wang Gohrke, Shan; Dörk, Thilo; Schürmann, Peter; Karstens, Johann H.; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Zalutsky, Iosif V.; Antonenkova, Natalia N.; Bermisheva, Marina; Prokovieva, Darya; Farahtdinova, Albina; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana; Chen, Xiaoqing; Beesley, Jonathan; Lambrechts, Diether; Zhao, Hui; Neven, Patrick; Wildiers, Hans; Nickels, Stefan; Flesch Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu; Fredericksen, Zachary; Giles, Graham G.; BAGLIETTO, LAURA ;Mclean, Catriona A.; Severi, Gianluca; Offit, Kenneth; Robson, Mark; Gaudet, Mia M.; Vijai, Joseph; Alnæs, Grethe Grenaker; Kristensen, Vessela; Børresen Dale, Anne Lise; John, Esther M.; Miron, Alexander; Winqvist, Robert; Pylkäs, Katri; Jukkola Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Figueroa, Jonine D.; García Closas, Montserrat; Lissowska, Jolanta; Sherman, Mark E.; Hooning, Maartje; Martens, John W. M.; Seynaeve, Caroline; Collée, Margriet; Hall, Per; Humpreys, Keith; Czene, Kamila; Liu, Jianjun; Cox, Angela; Brock, Ian W.; Cross, Simon S.; Reed, Malcolm W. R.; Ahmed, Shahana; Ghoussaini, Maya; Pharoah, Paul D.P.; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elzbieta; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Shen, Chen Yang; Yu, Jyh Cherng; Hsu, Huan Ming; Hou, Ming Feng; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Swerdlow, Anthony; Trentham Dietz, Amy; Newcomb, Polly A.; Titus, Linda; Egan, Kathleen M.; Chenevix Trench, Georgia; Antoniou, Antonis C.; Humphreys, Manjeet K.; Morrison, Jonathan; Chang Claude, Jenny; Easton, Douglas F.; Dunning, Alison M.
2012-01-01
Abstract
The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10-14 in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10-18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10-9 in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10-17 versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10-7, pheterogeneity = 5.1×10-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours. © 2012 Hein et al.
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Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande. La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.