1. Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).
- Author
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Hein R, Maranian M, Hopper JL, Kapuscinski MK, Southey MC, Park DJ, Schmidt MK, Broeks A, Hogervorst FB, Bueno-de-Mesquita HB, Muir KR, Lophatananon A, Rattanamongkongul S, Puttawibul P, Fasching PA, Hein A, Ekici AB, Beckmann MW, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Sawyer E, Tomlinson I, Kerin M, Miller N, Marmee F, Schneeweiss A, Sohn C, Burwinkel B, Guénel P, Cordina-Duverger E, Menegaux F, Truong T, Bojesen SE, Nordestgaard BG, Flyger H, Milne RL, Perez JI, Zamora MP, Benítez J, Anton-Culver H, Ziogas A, Bernstein L, Clarke CA, Brenner H, Müller H, Arndt V, Stegmaier C, Rahman N, Seal S, Turnbull C, Renwick A, Meindl A, Schott S, Bartram CR, Schmutzler RK, Brauch H, Hamann U, Ko YD, Wang-Gohrke S, Dörk T, Schürmann P, Karstens JH, Hillemanns P, Nevanlinna H, Heikkinen T, Aittomäki K, Blomqvist C, Bogdanova NV, Zalutsky IV, Antonenkova NN, Bermisheva M, Prokovieva D, Farahtdinova A, Khusnutdinova E, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen J, Chen X, Beesley J, Lambrechts D, Zhao H, Neven P, Wildiers H, Nickels S, Flesch-Janys D, Radice P, Peterlongo P, Manoukian S, Barile M, Couch FJ, Olson JE, Wang X, Fredericksen Z, Giles GG, Baglietto L, McLean CA, Severi G, Offit K, Robson M, Gaudet MM, Vijai J, Alnæs GG, Kristensen V, Børresen-Dale AL, John EM, Miron A, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Figueroa JD, García-Closas M, Lissowska J, Sherman ME, Hooning M, Martens JW, Seynaeve C, Collée M, Hall P, Humpreys K, Czene K, Liu J, Cox A, Brock IW, Cross SS, Reed MW, Ahmed S, Ghoussaini M, Pharoah PD, Kang D, Yoo KY, Noh DY, Jakubowska A, Jaworska K, Durda K, Złowocka E, Sangrajrang S, Gaborieau V, Brennan P, McKay J, Shen CY, Yu JC, Hsu HM, Hou MF, Orr N, Schoemaker M, Ashworth A, Swerdlow A, Trentham-Dietz A, Newcomb PA, Titus L, Egan KM, Chenevix-Trench G, Antoniou AC, Humphreys MK, Morrison J, Chang-Claude J, Easton DF, and Dunning AM
- Subjects
- Asia, Europe, Female, Haplotypes genetics, Humans, Linkage Disequilibrium genetics, Receptors, Estrogen genetics, Risk Factors, Breast Neoplasms genetics, Chromosomes, Human, Pair 6 genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
- 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), p(heterogeneity) = 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.
- Published
- 2012
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