Article: Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of Chinese, Japanese, and European ancestry
| Title | Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of Chinese, Japanese, and European ancestry | ||||||||||||||||||||||||||||||||||||||||
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| Authors | Cai, Q3 Wen, W3 Qu, S3 Li, G3 Egan, KM15 Chen, K22 Deming, SL3 Shen, H8 Shen, CY20 Gammon, MD21 Blot, WJ3 11 Matsuo, K6 Haiman, CA12 Khoo, US4 Iwasaki, M16 Santella, RM14 Zhang, L22 Fair, AM2 Hu, Z8 Wu, PE20 Signorello, LB3 11 TitusErnstoff, L17 Tajima, K6 Henderson, BE12 Chan, KYK4 Kasuga, Y5 Newcomb, PA7 13 Zheng, H22 Cui, Y2 Wang, F8 Shieh, YL20 Iwata, H6 Le Marchand, L10 Chan, SY4 Shrubsole, MJ3 TrenthamDietz, A7 9 Tsugane, S16 GarciaClosas, M1 Long, J3 Li, C3 Shi, J3 Huang, B3 Xiang, YB18 Gao, YT18 Lu, W19 Shu, XO3 Zheng, W3 | ||||||||||||||||||||||||||||||||||||||||
| Issue Date | 2011 | ||||||||||||||||||||||||||||||||||||||||
| Publisher | American Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/ | ||||||||||||||||||||||||||||||||||||||||
| Citation | Cancer Research, 2011, v. 71 n. 4, p. 1344-1355 [How to Cite?] DOI: http://dx.doi.org/10.1158/0008-5472.CAN-10-2733 | ||||||||||||||||||||||||||||||||||||||||
| Abstract | We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinesewomen [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10 -30], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10 -4], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r 2 = 0.91) and European-ancestry (r 2 = 0.83) populations, but not in Africans (r 2 = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. ©2011 AACR. | ||||||||||||||||||||||||||||||||||||||||
| ISSN | 0008-5472 2011 Impact Factor: 7.856 2011 SCImago Journal Rankings: 1.309 | ||||||||||||||||||||||||||||||||||||||||
| DOI | http://dx.doi.org/10.1158/0008-5472.CAN-10-2733 | ||||||||||||||||||||||||||||||||||||||||
| ISI Accession Number ID | WOS:000287352600017
Funding Information: This research was supported by US NIH grant R01CA124558. The genotyping assays conducted at Vanderbilt University were done at the Survey and Biospecimen Core, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA68485). Participating studies (Principal Investigator, grant support) of the consortium are as follows: the Shanghai Breast Cancer Study (W. Zheng, R01CA64277), the Nashville Breast Health Study (W. Zheng, R01CA100374), the Shanghai Breast Cancer Survival Study (X.O. Shu, R01CA118229), the Shanghai Endometrial Cancer Study (X.O. Shu, R01CA92585, contributed only controls to the consortium), the Tianjin Study (K. Chen, the National Natural Science Foundation of China Grant No. 30771844), the Nanjing Study (H. Shen, IRT0631, China), the Taiwan Biobank Study (C.-Y. Shen, DOH97-01), the Hong Kong Study (U.S. Khoo, Research Grant Council, Hong Kong SAR, China, HKU 7520/05M and 76730M), the Nagoya study (K. Tajima, Grants-in-Aid for Scientific Research on Priority Areas (17015052) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; H. Tanaka, Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, H20-002), the Multiethnic Cohort Study (B. E. Henderson, CA63464; L. Kolonel, CA54281; and C.A. Haiman, CA132839), the Nagano Breast Cancer Study [S. Tsugane, Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scientific Research on Priority Areas (17015049) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan], the Collaborative Breast Cancer Study including Massachusetts (K.M. Egan, R01CA47305), Wisconsin (P.A. Newcomb, R01 CA47147) and New Hampshire (L. Titus-Ernstoff, R01CA69664) centers, the Long Island Breast Cancer Study Project (M. D. Gammon, U01CA/ES66572; R.M. Santella, P30ES009089; J.A. Swenberg, P30ES010126), and the Southern Community Cohort Study (W.J. Blot, R01CA092447). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. | ||||||||||||||||||||||||||||||||||||||||
| PubMed Central ID | PMC3083305 | ||||||||||||||||||||||||||||||||||||||||
| References | References in Scopus | ||||||||||||||||||||||||||||||||||||||||
| Grants | Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility |
| dc.contributor.author | Cai, Q | ||||||||||||||||||||||||||||||||||||||||
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| dc.contributor.author | Wen, W | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Qu, S | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Li, G | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Egan, KM | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Chen, K | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Deming, SL | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Shen, H | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Shen, CY | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Gammon, MD | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Blot, WJ | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Matsuo, K | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Haiman, CA | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Khoo, US | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Iwasaki, M | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Santella, RM | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Zhang, L | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Fair, AM | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Hu, Z | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Wu, PE | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Signorello, LB | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | TitusErnstoff, L | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Tajima, K | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Henderson, BE | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Chan, KYK | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Kasuga, Y | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Newcomb, PA | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Zheng, H | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Cui, Y | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Wang, F | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Shieh, YL | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Iwata, H | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Le Marchand, L | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Chan, SY | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Shrubsole, MJ | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | TrenthamDietz, A | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Tsugane, S | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | GarciaClosas, M | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Long, J | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Li, C | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Shi, J | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Huang, B | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Xiang, YB | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Gao, YT | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Lu, W | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Shu, XO | ||||||||||||||||||||||||||||||||||||||||
| dc.contributor.author | Zheng, W | ||||||||||||||||||||||||||||||||||||||||
| dc.date.accessioned | 2011-08-26T14:29:57Z | ||||||||||||||||||||||||||||||||||||||||
| dc.date.available | 2011-08-26T14:29:57Z | ||||||||||||||||||||||||||||||||||||||||
| dc.date.issued | 2011 | ||||||||||||||||||||||||||||||||||||||||
| dc.description.abstract | We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinesewomen [ORs (95% CI) = 1.30 (1.22-1.38) and 1.64 (1.50-1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10 -30], Japanese women [ORs (95% CI) = 1.31 (1.13-1.52) and 1.37 (1.06-1.76), P for trend = 2.51 × 10 -4], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99-1.16) and 1.18 (1.04-1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63-1.06) and 0.85 (0.65-1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r 2 = 0.91) and European-ancestry (r 2 = 0.83) populations, but not in Africans (r 2 = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. ©2011 AACR. | ||||||||||||||||||||||||||||||||||||||||
| dc.description.grant | Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility | ||||||||||||||||||||||||||||||||||||||||
| dc.description.grant | Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility | ||||||||||||||||||||||||||||||||||||||||
| dc.description.grantcode | 28077 | ||||||||||||||||||||||||||||||||||||||||
| dc.description.grantcode | 29671 | ||||||||||||||||||||||||||||||||||||||||
| dc.description.nature | link_to_OA_fulltext | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.citation | Cancer Research, 2011, v. 71 n. 4, p. 1344-1355 [How to Cite?] DOI: http://dx.doi.org/10.1158/0008-5472.CAN-10-2733 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.doi | http://dx.doi.org/10.1158/0008-5472.CAN-10-2733 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.eissn | 1538-7445 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.epage | 1355 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.hkuros | 191720 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.isi | WOS:000287352600017
Funding Information: This research was supported by US NIH grant R01CA124558. The genotyping assays conducted at Vanderbilt University were done at the Survey and Biospecimen Core, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA68485). Participating studies (Principal Investigator, grant support) of the consortium are as follows: the Shanghai Breast Cancer Study (W. Zheng, R01CA64277), the Nashville Breast Health Study (W. Zheng, R01CA100374), the Shanghai Breast Cancer Survival Study (X.O. Shu, R01CA118229), the Shanghai Endometrial Cancer Study (X.O. Shu, R01CA92585, contributed only controls to the consortium), the Tianjin Study (K. Chen, the National Natural Science Foundation of China Grant No. 30771844), the Nanjing Study (H. Shen, IRT0631, China), the Taiwan Biobank Study (C.-Y. Shen, DOH97-01), the Hong Kong Study (U.S. Khoo, Research Grant Council, Hong Kong SAR, China, HKU 7520/05M and 76730M), the Nagoya study (K. Tajima, Grants-in-Aid for Scientific Research on Priority Areas (17015052) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; H. Tanaka, Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, H20-002), the Multiethnic Cohort Study (B. E. Henderson, CA63464; L. Kolonel, CA54281; and C.A. Haiman, CA132839), the Nagano Breast Cancer Study [S. Tsugane, Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scientific Research on Priority Areas (17015049) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan], the Collaborative Breast Cancer Study including Massachusetts (K.M. Egan, R01CA47305), Wisconsin (P.A. Newcomb, R01 CA47147) and New Hampshire (L. Titus-Ernstoff, R01CA69664) centers, the Long Island Breast Cancer Study Project (M. D. Gammon, U01CA/ES66572; R.M. Santella, P30ES009089; J.A. Swenberg, P30ES010126), and the Southern Community Cohort Study (W.J. Blot, R01CA092447). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.issn | 0008-5472 2011 Impact Factor: 7.856 2011 SCImago Journal Rankings: 1.309 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.issue | 4 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.pmcid | PMC3083305 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.pmid | 21303983 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.scopus | eid_2-s2.0-79951841312 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.spage | 1344 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/137635 | ||||||||||||||||||||||||||||||||||||||||
| dc.identifier.volume | 71 | ||||||||||||||||||||||||||||||||||||||||
| dc.language | eng | ||||||||||||||||||||||||||||||||||||||||
| dc.publisher | American Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/ | ||||||||||||||||||||||||||||||||||||||||
| dc.publisher.place | United States | ||||||||||||||||||||||||||||||||||||||||
| dc.relation.ispartof | Cancer Research | ||||||||||||||||||||||||||||||||||||||||
| dc.relation.references | References in Scopus | ||||||||||||||||||||||||||||||||||||||||
| dc.subject.mesh | Asian Continental Ancestry Group - genetics | ||||||||||||||||||||||||||||||||||||||||
| dc.subject.mesh | Breast Neoplasms - epidemiology - ethnology - genetics | ||||||||||||||||||||||||||||||||||||||||
| dc.subject.mesh | Carcinoma - epidemiology - ethnology - genetics | ||||||||||||||||||||||||||||||||||||||||
| dc.subject.mesh | Chromosomes, Human, Pair 6 - genetics | ||||||||||||||||||||||||||||||||||||||||
| dc.subject.mesh | European Continental Ancestry Group - genetics | ||||||||||||||||||||||||||||||||||||||||
| dc.title | Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of Chinese, Japanese, and European ancestry | ||||||||||||||||||||||||||||||||||||||||
| dc.type | Article |
- National Cancer Institute
- Meharry Medical College
- Vanderbilt Ingram Cancer Center
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- Nagano Matsushiro General Hospital
- Aichi Cancer Center Hospital and Research Institute
- Paul P. Carbone Comprehensive Cancer Center
- Nanjing Medical University
- University of Wisconsin Madison
- University of Hawaii at Manoa
- International Epidemiology Institute
- Keck School of Medicine of USC
- Fred Hutchinson Cancer Research Center
- Columbia University Medical Center
- H. Lee Moffitt Cancer Center and Research Institute
- National Cancer Center Tokyo
- Norris Cotton Cancer Center
- null
- Shanghai Center for Disease Control and Prevention
- Institute of Biomedical Sciences Academia Sinica Taiwan
- The University of North Carolina at Chapel Hill
- Tianjin Medical University

