Breast cancer is the most common malignancy among women in many parts of the world. Genetic factors play an important role in the etiology of breast cancer. However, to date, only a few breast cancer susceptibility genes have been identified, and they explain only a very small fraction of breast cancer cases in the general population. A large number of candidate-gene studies have been conducted over the past 10 years. These studies, however, are clearly inadequate to fully uncover the genetic basis of breast cancer. With recent significant advances in high-throughput genotyping technologies, it has become feasible to conduct genome-wide association (GWA) studies to systematically evaluate genetic risk factors for breast cancer. The multi-phase GWA study proposed in this application will be built upon the resources established in two large, on-going studies funded by NCI, the Shanghai Breast Cancer Study (R01 CA64277) a population-based case-control study, and the Shanghai Women's Health Study (RO1 CA70867) a population-based prospective cohort study. Approximately 8,000 breast cancer cases and controls will be included in this proposed study. In the first phase of the study, we will conduct a GWA scan in 1,000 cases and 1,000 controls using the Illumina HumanHap550 BeadChip. We will then select the 10,600 most promising SNPs for a validation study in an independent sample of 1500 cases and 1500 controls. All promising SNPs will be further validated using data from 1000 cases and 2000 controls selected from the prospective Shanghai Women's Health Study. The parent projects of this newly-proposed study have been exceptionally well-conducted with a strong methodology. The feasibility and utility of the proposed study have been clearly demonstrated in our pilot study. The study is unique and has many unique features that facilitate a rigorous evaluation of breast cancer genetic factors. The results from the study will be valuable in identifying high risk women for primary and secondary prevention of breast cancer.

Public Health Relevance

Genetic factors and gene-environment interaction are believed to cause most breast cancers, yet only a small number of cases are explained by genetic factors identified thus far. The large epidemiologic study we propose will comprehensively evaluate genetic markers in relation to breast cancer risk. This study will generate valuable results for the identification of high-risk women for the primary and secondary prevention of breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA124558-05
Application #
8265665
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Martin, Damali
Project Start
2008-07-15
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$582,443
Indirect Cost
$203,001
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Cai, Qiuyin; Zhang, Ben; Sung, Hyuna et al. (2014) Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1. Nat Genet 46:886-90
Villegas, Raquel; Williams, Scott M; Gao, Yu-Tang et al. (2014) Genetic variation in the peroxisome proliferator-activated receptor (PPAR) and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) gene families and type 2 diabetes. Ann Hum Genet 78:23-32
Zhang, Ben; Jia, Wei-Hua; Matsuda, Koichi et al. (2014) Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk. Nat Genet 46:533-42
Wen, Wanqing; Zheng, Wei; Okada, Yukinori et al. (2014) Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Hum Mol Genet 23:5492-504
Zhang, Yanfeng; Long, Jirong; Lu, Wei et al. (2014) Rare coding variants and breast cancer risk: evaluation of susceptibility Loci identified in genome-wide association studies. Cancer Epidemiol Biomarkers Prev 23:622-8
Zhang, Ben; Jia, Wei-Hua; Matsuo, Keitaro et al. (2014) Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians. Int J Cancer 135:948-55
Shi, Jiajun; Sung, Hyuna; Zhang, Ben et al. (2013) New breast cancer risk variant discovered at 10q25 in East Asian women. Cancer Epidemiol Biomarkers Prev 22:1297-303
Jia, Wei-Hua; Zhang, Ben; Matsuo, Keitaro et al. (2013) Genome-wide association analyses in East Asians identify new susceptibility loci for colorectal cancer. Nat Genet 45:191-6
Delahanty, R J; Beeghly-Fadiel, A; Long, J R et al. (2013) Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women. Hum Reprod 28:1135-43
Shen, Chong; Delahanty, Ryan J; Gao, Yu-Tang et al. (2013) Evaluating GWAS-identified SNPs for age at natural menopause among chinese women. PLoS One 8:e58766

Showing the most recent 10 out of 37 publications