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Grant Details

Grant Number: 5R01CA122756-04 Interpret this number
Primary Investigator: Cai, Qiuyin
Organization: Vanderbilt University
Project Title: Cell Cycle/Apoptosis Gene Variants and Breast Cancer Risk
Fiscal Year: 2011
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Abstract

DESCRIPTION (provided by applicant): It is well established that genetic factors play a major role in breast tumorigenesis. However, the known breast cancer susceptibility genes account for only a minority of breast cancer cases in the general population. Cumulative evidence from in vitro and animal studies suggests that the genes involved in the cell-cycle control and apoptosis pathways may be related to breast cancer. The cell-cycle control and apoptosis pathways function as an integrated molecular network, and perturbations in one pathway can have profound consequences on the other. In this application, we propose to investigate genetic variations of major genes involved in the cell- cycle control and apoptosis pathways in relation to breast cancer risk. The proposed study will use data and biological samples collected from the Shanghai Breast Cancer Study (SBCS, R01CA64277). Genetic polymorphisms in 25 candidate genes in the cell-cycle control and apoptosis pathways will initially be evaluated using both the genotype- and haplotype- approaches in 1,250 cases and 1,250 controls recruited from 1996 to 1998. Promising associations identified in the initial phase will be re-evaluated in a second set of subjects (1,850 cases and 1,850 controls) recruited from 2002 to 2005. This two-phase study design will effectively balance both Type I and Type 2 statistical errors and provide credible results towards our understanding of the etiology of breast cancer. We will use the multifactor-dimensionality reduction (MDR) statistical method to investigate any gene-gene interaction in relation to breast cancer risk. We will investigate interaction between genetic polymorphisms with endogenous estrogen exposure related factors in relation to breast cancer risk. We will evaluate whether genetic polymorphisms may be associated with the risk of specific subtypes of breast cancer. We will also conduct in vitro experiments to evaluate the function of genetic variations to further confirm the biological relevance of the association. With its large size and strong methodology, the SBCS provides a great opportunity to investigate gene-gene and gene-environment interactions in relation to breast cancer risk. The findings from the proposed study are likely to significantly advance our knowledge of the etiology of breast cancer and will be valuable for identifying high risk women for the primary and secondary prevention of breast cancer. We propose to investigate genetic variations of major genes involved in the cell-cycle control and apoptosis pathways in relation to breast cancer risk. The findings from the proposed study are likely to significantly advance our knowledge of the etiology of breast cancer and will be valuable for identifying high risk women for the primary and secondary prevention of breast cancer.

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Publications

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.
Authors: Spracklen C.N. , Chen P. , Kim Y.J. , Wang X. , Cai H. , Li S. , Long J. , Wu Y. , Wang Y.X. , Takeuchi F. , et al. .
Source: Human molecular genetics, 2017-05-01; 26(9), p. 1770-1784.
PMID: 28334899
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Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.
Authors: Wen W. , Shu X.O. , Guo X. , Cai Q. , Long J. , Bolla M.K. , Michailidou K. , Dennis J. , Wang Q. , Gao Y.T. , et al. .
Source: Breast cancer research : BCR, 2016-12-08; 18(1), p. 124.
EPub date: 2016-12-08.
PMID: 27931260
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Age at menarche and age at natural menopause in East Asian women: a genome-wide association study.
Authors: Shi J. , Zhang B. , Choi J.Y. , Gao Y.T. , Li H. , Lu W. , Long J. , Kang D. , Xiang Y.B. , Wen W. , et al. .
Source: Age (Dordrecht, Netherlands), 2016 Dec; 38(5-6), p. 513-523.
EPub date: 2016-09-14.
PMID: 27629107
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Associations of the Transforming Growth Factor β/Smad Pathway, Body Mass Index, and Physical Activity With Breast Cancer Outcomes: Results From the Shanghai Breast Cancer Study.
Authors: Su Y. , Cai H. , Zheng Y. , Qiu Q. , Lu W. , Shu X.O. , Cai Q. .
Source: American journal of epidemiology, 2016-10-01; 184(7), p. 501-509.
EPub date: 2016-09-19.
PMID: 27651382
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Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci.
Authors: Han M.R. , Long J. , Choi J.Y. , Low S.K. , Kweon S.S. , Zheng Y. , Cai Q. , Shi J. , Guo X. , Matsuo K. , et al. .
Source: Human molecular genetics, 2016-08-01; 25(15), p. 3361-3371.
EPub date: 2016-06-27.
PMID: 27354352
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Evaluation of potential regulatory function of breast cancer risk locus at 6q25.1.
Authors: Sun Y. , Ye C. , Guo X. , Wen W. , Long J. , Gao Y.T. , Shu X.O. , Zheng W. , Cai Q. .
Source: Carcinogenesis, 2016 Feb; 37(2), p. 163-168.
EPub date: 2015-12-08.
PMID: 26645718
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference.
Authors: Wen W. , Kato N. , Hwang J.Y. , Guo X. , Tabara Y. , Li H. , Dorajoo R. , Yang X. , Tsai F.J. , Li S. , et al. .
Source: Scientific reports, 2016-01-20; 6, p. 17958.
EPub date: 2016-01-20.
PMID: 26785701
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Increased pSmad2 expression and cytoplasmic predominant presence of TGF-βRII in breast cancer tissue are associated with poor prognosis: results from the Shanghai Breast Cancer Study.
Authors: Qiu Q. , Su Y. , Zheng Y. , Cai H. , Wu S. , Lu W. , Zheng W. , Shu X.O. , Cai Q. .
Source: Breast cancer research and treatment, 2015 Jan; 149(2), p. 467-77.
EPub date: 2014-12-27.
PMID: 25542272
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Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.
Authors: Hwang J.Y. , Sim X. , Wu Y. , Liang J. , Tabara Y. , Hu C. , Hara K. , Tam C.H. , Cai Q. , Zhao Q. , et al. .
Source: Diabetes, 2015 Jan; 64(1), p. 291-8.
EPub date: 2014-09-03.
PMID: 25187374
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Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1.
Authors: Cai Q. , Zhang B. , Sung H. , Low S.K. , Kweon S.S. , Lu W. , Shi J. , Long J. , Wen W. , Choi J.Y. , et al. .
Source: Nature genetics, 2014 Aug; 46(8), p. 886-90.
EPub date: 2014-07-20.
PMID: 25038754
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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.
Authors: Villegas R. , Williams S.M. , Gao Y.T. , Long J. , Shi J. , Cai H. , Li H. , Chen C.C. , Tai E.S. , AGEN-T2D Consortium , et al. .
Source: Annals of human genetics, 2014 Jan; 78(1), p. 23-32.
PMID: 24359475
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New breast cancer risk variant discovered at 10q25 in East Asian women.
Authors: Shi J. , Sung H. , Zhang B. , Lu W. , Choi J.Y. , Xiang Y.B. , Kim M.K. , Iwasaki M. , Long J. , Ji B.T. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2013 Jul; 22(7), p. 1297-303.
EPub date: 2013-05-15.
PMID: 23677579
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Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls.
Authors: Zheng W. , Zhang B. , Cai Q. , Sung H. , Michailidou K. , Shi J. , Choi J.Y. , Long J. , Dennis J. , Humphreys M.K. , et al. .
Source: Human molecular genetics, 2013-06-15; 22(12), p. 2539-50.
EPub date: 2013-03-27.
PMID: 23535825
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A common deletion in the APOBEC3 genes and breast cancer risk.
Authors: Long J. , Delahanty R.J. , Li G. , Gao Y.T. , Lu W. , Cai Q. , Xiang Y.B. , Li C. , Ji B.T. , Zheng Y. , et al. .
Source: Journal of the National Cancer Institute, 2013-04-17; 105(8), p. 573-9.
EPub date: 2013-02-14.
PMID: 23411593
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Meta-analysis identifies common variants associated with body mass index in east Asians.
Authors: Wen W. , Cho Y.S. , Zheng W. , Dorajoo R. , Kato N. , Qi L. , Chen C.H. , Delahanty R.J. , Okada Y. , Tabara Y. , et al. .
Source: Nature genetics, 2012-02-19; 44(3), p. 307-11.
EPub date: 2012-02-19.
PMID: 22344219
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Joint effect of genetic and lifestyle risk factors on type 2 diabetes risk among Chinese men and women.
Authors: Villegas R. , Delahanty R. , Gao Y.T. , Long J. , Williams S.M. , Xiang Y.B. , Cai H. , Li H.L. , Hu F. , Cai Q. , et al. .
Source: PloS one, 2012; 7(11), p. e49464.
EPub date: 2012-11-21.
PMID: 23185337
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Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer.
Authors: Long J. , Cai Q. , Sung H. , Shi J. , Zhang B. , Choi J.Y. , Wen W. , Delahanty R.J. , Lu W. , Gao Y.T. , et al. .
Source: PLoS genetics, 2012; 8(2), p. e1002532.
EPub date: 2012-02-23.
PMID: 22383897
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Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium.
Authors: Cai Q. , Long J. , Lu W. , Qu S. , Wen W. , Kang D. , Lee J.Y. , Chen K. , Shen H. , Shen C.Y. , et al. .
Source: Human molecular genetics, 2011-12-15; 20(24), p. 4991-9.
EPub date: 2011-09-09.
PMID: 21908515
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Peroxisome proliferator-activated receptor delta (PPARD) genetic variation and type 2 diabetes in middle-aged Chinese women.
Authors: Villegas R. , Williams S. , Gao Y. , Cai Q. , Li H. , Elasy T. , Cai H. , Edwards T. , Xiang Y.B. , Zheng W. , et al. .
Source: Annals of human genetics, 2011 Sep; 75(5), p. 621-9.
PMID: 21834910
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No evidence for association of the MDM2-309 T/G promoter polymorphism with prostate cancer outcomes.
Authors: Jaboin J.J. , Hwang M. , Perez C.A. , Cooper C. , Chen H. , Ye C. , Cai Q. , Wills M.L. , Lu B. .
Source: Urologic oncology, 2011 May-Jun; 29(3), p. 319-23.
EPub date: 2009-06-12.
PMID: 19523862
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Relation of FGFR2 genetic polymorphisms to the association between oral contraceptive use and the risk of breast cancer in Chinese women.
Authors: Xu W.H. , Shu X.O. , Long J. , Lu W. , Cai Q. , Zheng Y. , Xiang Y.B. , Dai Q. , Zhao G.M. , Gu K. , et al. .
Source: American journal of epidemiology, 2011-04-15; 173(8), p. 923-31.
EPub date: 2011-03-07.
PMID: 21382839
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The matrix metalloproteinase-7 polymorphism rs10895304 is associated with increased recurrence risk in patients with clinically localized prostate cancer.
Authors: Jaboin J.J. , Hwang M. , Lopater Z. , Chen H. , Ray G.L. , Perez C. , Cai Q. , Wills M.L. , Lu B. .
Source: International journal of radiation oncology, biology, physics, 2011-04-01; 79(5), p. 1330-5.
EPub date: 2010-06-03.
PMID: 20605361
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Genetic variation in VEGF family genes and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study.
Authors: Beeghly-Fadiel A. , Shu X.O. , Lu W. , Long J. , Cai Q. , Xiang Y.B. , Zheng Y. , Zhao Z. , Gu K. , Gao Y.T. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Jan; 20(1), p. 33-41.
EPub date: 2010-11-30.
PMID: 21119072
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Identification of new genetic risk variants for type 2 diabetes.
Authors: Shu X.O. , Long J. , Cai Q. , Qi L. , Xiang Y.B. , Cho Y.S. , Tai E.S. , Li X. , Lin X. , Chow W.H. , et al. .
Source: PLoS genetics, 2010-09-16; 6(9), p. e1001127.
EPub date: 2010-09-16.
PMID: 20862305
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Evaluation of breast cancer susceptibility loci in Chinese women.
Authors: Long J. , Shu X.O. , Cai Q. , Gao Y.T. , Zheng Y. , Li G. , Li C. , Gu K. , Wen W. , Xiang Y.B. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Sep; 19(9), p. 2357-65.
EPub date: 2010-08-10.
PMID: 20699374
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Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium.
Authors: Long J. , Cai Q. , Shu X.O. , Qu S. , Li C. , Zheng Y. , Gu K. , Wang W. , Xiang Y.B. , Cheng J. , et al. .
Source: PLoS genetics, 2010-06-24; 6(6), p. e1001002.
EPub date: 2010-06-24.
PMID: 20585626
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Two-stage case-control study of DNMT-1 and DNMT-3B gene variants and breast cancer risk.
Authors: Ye C. , Beeghly-Fadiel A. , Lu W. , Long J. , Shu X.O. , Gao Y.T. , Zheng W. , Cai Q. .
Source: Breast cancer research and treatment, 2010 Jun; 121(3), p. 765-9.
EPub date: 2009-10-02.
PMID: 19798569
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Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1.
Authors: Zheng W. , Long J. , Gao Y.T. , Li C. , Zheng Y. , Xiang Y.B. , Wen W. , Levy S. , Deming S.L. , Haines J.L. , et al. .
Source: Nature genetics, 2009 Mar; 41(3), p. 324-8.
EPub date: 2009-02-15.
PMID: 19219042
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