Dataset Information

Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

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.

SUBMITTER: Hein R

PROVIDER: S-EPMC3413660 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

Hein Rebecca R Maranian Melanie M Hopper John L JL Kapuscinski Miroslaw K MK Southey Melissa C MC Park Daniel J DJ Schmidt Marjanka K MK Broeks Annegien A Hogervorst Frans B L FB Bueno-de-Mesquita H Bas HB Muir Kenneth R KR Lophatananon Artitaya A Rattanamongkongul Suthee S Puttawibul Puttisak P Fasching Peter A PA Hein Alexander A Ekici Arif B AB Beckmann Matthias W MW Fletcher Olivia O Johnson Nichola N dos Santos Silva Isabel I Peto Julian J Sawyer Elinor E Tomlinson Ian I Kerin Michael M Miller Nicola N Marmee Frederick F Schneeweiss Andreas A Sohn Christof C Burwinkel Barbara B Guénel Pascal P Cordina-Duverger Emilie E Menegaux Florence F Truong Thérèse T Bojesen Stig E SE Nordestgaard Børge G BG Flyger Henrik H Milne Roger L RL Perez Jose Ignacio Arias JI Zamora M Pilar MP Benítez Javier J Anton-Culver Hoda H Ziogas Argyrios A Bernstein Leslie L Clarke Christina A CA Brenner Hermann H Müller Heiko H Arndt Volker V Stegmaier Christa C Rahman Nazneen N Seal Sheila S Turnbull Clare C Renwick Anthony A Meindl Alfons A Schott Sarah S Bartram Claus R CR Schmutzler Rita K RK Brauch Hiltrud H Hamann Ute U Ko Yon-Dschun YD Wang-Gohrke Shan S Dörk Thilo T Schürmann Peter P Karstens Johann H JH Hillemanns Peter P Nevanlinna Heli H Heikkinen Tuomas T Aittomäki Kristiina K Blomqvist Carl C Bogdanova Natalia V NV Zalutsky Iosif V IV Antonenkova Natalia N NN Bermisheva Marina M Prokovieva Darya D Farahtdinova Albina A Khusnutdinova Elza E Lindblom Annika A Margolin Sara S Mannermaa Arto A Kataja Vesa V Kosma Veli-Matti VM Hartikainen Jaana J Chen Xiaoqing X Beesley Jonathan J Lambrechts Diether D Zhao Hui H Neven Patrick P Wildiers Hans H Nickels Stefan S Flesch-Janys Dieter D Radice Paolo P Peterlongo Paolo P Manoukian Siranoush S Barile Monica M Couch Fergus J FJ Olson Janet E JE Wang Xianshu X Fredericksen Zachary Z Giles Graham G GG Baglietto Laura L McLean Catriona A CA Severi Gianluca G Offit Kenneth K Robson Mark M Gaudet Mia M MM Vijai Joseph J Alnæs Grethe Grenaker GG Kristensen Vessela V Børresen-Dale Anne-Lise AL John Esther M EM Miron Alexander A Winqvist Robert R Pylkäs Katri K Jukkola-Vuorinen Arja A Grip Mervi M Andrulis Irene L IL Knight Julia A JA Glendon Gord G Mulligan Anna Marie AM Figueroa Jonine D JD García-Closas Montserrat M Lissowska Jolanta J Sherman Mark E ME Hooning Maartje M Martens John W M JW Seynaeve Caroline C Collée Margriet M Hall Per P Humpreys Keith K Czene Kamila K Liu Jianjun J Cox Angela A Brock Ian W IW Cross Simon S SS Reed Malcolm W R MW Ahmed Shahana S Ghoussaini Maya M Pharoah Paul D P PD Kang Daehee D Yoo Keun-Young KY Noh Dong-Young DY Jakubowska Anna A Jaworska Katarzyna K Durda Katarzyna K Złowocka Elżbieta E Sangrajrang Suleeporn S Gaborieau Valerie V Brennan Paul P McKay James J Shen Chen-Yang CY Yu Jyh-Cherng JC Hsu Huan-Ming HM Hou Ming-Feng MF Orr Nick N Schoemaker Minouk M Ashworth Alan A Swerdlow Anthony A Trentham-Dietz Amy A Newcomb Polly A PA Titus Linda L Egan Kathleen M KM Chenevix-Trench Georgia G Antoniou Antonis C AC Humphreys Manjeet K MK Morrison Jonathan J Chang-Claude Jenny J Easton Douglas F DF Dunning Alison M AM

PloS one 20120807 8

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 collabora ...[more]

PMID: 22879957

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Project description:BackgroundBlack men are more likely to die of prostate cancer (PCa) compared with white men. Factors ranging from genetics to neighborhood environment contribute to these disparities. However, unlike genetics, agnostic investigations that identify candidate variables from large-scale data, and that allow for empiric investigations into differential associations between neighborhood and PCa by race/ethnicity, to the authors' knowledge have not been well explored. Thus, herein, the authors built on their previously developed, empiric neighborhood-wide association study (NWAS) in white men and conducted a NWAS in black men to determine whether findings differed by race.MethodsPennsylvania Cancer Registry data were linked to US Census data. For the NWAS in non-Hispanic black men, the authors evaluated the association between 14,663 neighborhood census variables and advanced PCa (11 high-stage and/or high-grade cases and 8632 low-stage and/or low-grade cases), adjusting for age, diagnosis year, spatial correlation, and multiple testing. Odds ratios and 95% credible intervals were reported. Replication of NWAS findings across black and white races was assessed using Bayesian mixed effects models.ResultsFive variables related to housing (3 variables), education (1 variable), and employment and/or transportation (1 variable) were found to be significantly associated with advanced PCa in black men compared with 17 socioeconomic variables (mostly related to poverty and/or income) in white men. The top hit in black men was related to crowding in renter-occupied housing (odds ratio, 1.10; 95% credible interval, 1.001-1.12). Nine of 22 NWAS hits (4 of 5 hits in black men) were replicated across racial/ethnic groups.ConclusionsDifferent neighborhood variables, or "candidates," were identified across race-specific NWASs. These findings and empiric approaches warrant additional study and may inform PCa racial disparities, particularly future gene-environment studies aimed at identifying patients and/or communities at risk of advanced PCa.

Dataset Information

Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

Publications

Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

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