In:
Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 11_Supplement ( 2014-11-01), p. B11-B11
Abstract:
To date, more than 100 single nucleotide polymorphisms (SNPs) have been found to be associated with breast cancer susceptibility in large genome-wide association studies (GWAS) conducted predominantly in women of European and Asian ancestries. To identify breast cancer susceptibility alleles in populations of African ancestry, we performed a GWAS in 3,686 subjects from Nigeria, Barbados and the United States (Baltimore, Chicago, Detroit, Philadelphia and the Southern Community Cohort Study), using the Illumina HumanOmni2.5 array. Using stringent quality control criteria, a total of 1,657 cases (777 with known estrogen receptor [ER] status) and 2,029 controls were successfully genotyped for 2,116,365 SNPs. Subsequently, imputation was conducted using reference panels from The 1000 Genomes Project and logistic regression models controlling age and global ancestry were applied to examine the association of 78 known breast cancer GWAS index SNPs and 44 iCOGS (Illumina iSelect genotyping array for Collaborative Oncological Gene-Environment Study) SNPs with breast cancer risk in our study population. Only 4 SNPs were statistically significant (unadjusted P & lt;0.01) associated with breast cancer in women of African descent: rs3112612 (16q12.1, P=0.0021), rs3817198 (11p15.5, P=0.0049), rs10069690 (5p15.33, P=0.0056), and rs1978503 (18q21.2, P=0.0066). Additional five SNPs were found to be associated with breast cancer at the unadjusted P & lt;0.05 significance level: rs458685 (12q21.3), rs361147 (4q31.3), rs4322600 (14q31.3), rs616488 (1p36.22), and rs17356907 (12q22). We also observed positive associations for ER-negative breast cancer: rs3817198 (11p15.5, P=0.0029), rs6762644 (3p26.1, P=0.0036), rs10069690 (5p15.33, P=0.0048), and rs3803662 (16q12.1, P=0.0050); and ER-positive breast cancer: rs12355688 (10q22.3, P=0.011), rs1978503 (18q21.2, P=0.020), rs3112612 (16q12.1, P=0.032), and rs4784227 (16q12.1, P=0.038). In conclusion, our observations highlight the necessity of validating previous breast cancer GWAS findings across diverse populations. Different environmental factors, allele frequencies and linkage disequilibrium patterns may influence the genetic risk profiles in different populations. Larger genetic studies in women of African ancestry hold promise to reveal additional risk variants for developing polygenic risk models for breast cancer susceptibility in this population. Citation Format: Yonglan Zheng, Dezheng Huo, Temidayo O. Ogundiran, Adeyinka G. Falusi, Oladosu Ojengbede, Clement Adebamowo, William J. Blot, Wei Zheng, Qiuyin Cai, Lisa B. Signorello, Katherine L. Nathanson, Susan M. Domchek, Timothy R. Rebbeck, Michael S. Simon, Anselm J.M. Hennis, Barbara Nemesure, Suh-Yuh Wu, Maria Cristina Leske, Stefan Ambs, Abayomi Odetunde, Imaria Anetor, Stella Akinleye, Qun Niu, Jing Zhang, Anna Pluzhnikov, Anuar Konkashbaev, Lin Chen, Eric R. Gamazon, Younghee Lee, Nancy J. Cox, Olufunmilayo O. Olopade. Replication of previously identified breast cancer susceptibility loci in a breast cancer case-control study on women of African ancestry. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B11. doi:10.1158/1538-7755.DISP13-B11
Type of Medium:
Online Resource
ISSN:
1055-9965
,
1538-7755
DOI:
10.1158/1538-7755.DISP13-B11
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036781-8
detail.hit.zdb_id:
1153420-5
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