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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

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 SM, Gao YT, Long J, Shi J, Cai H, Li H, Chen CC, Tai ES, AGEN-T2D Consortium, Hu F, Cai Q, Zheng W, Shu XO
Source: Ann Hum Genet, 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 JY, Xiang YB, Kim MK, Iwasaki M, Long J, Ji BT, Park SK, Zheng Y, Tsugane S, Yoo KY, Wang W, Noh DY, Han W, Kim SW, Lee MH, Lee JW, Lee JY, Shen CY, Matsuo K, Ahn SH, Gao YT, Shu XO, Cai Q, Kang D, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2013 Jul;22(7), p. 1297-303.
EPub date: 2013 May 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 JY, Long J, Dennis J, Humphreys MK, Wang Q, Lu W, Gao YT, Li C, Cai H, Park SK, Yoo KY, Noh DY, Han W, Dunning AM, Benitez J, Vincent D, Bacot F, Tessier D, Kim SW, Lee MH, Lee JW, Lee JY, Xiang YB, Zheng Y, Wang W, Ji BT, Matsuo K, Ito H, Iwata H, Tanaka H, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Teo SH, Yip CH, Kang IN, Wong TY, Shen CY, Yu JC, Huang CS, Hou MF, Hartman M, Miao H, Lee SC, Putti TC, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Sangrajrang S, Shen H, Chen K, Wu PE, Ren Z, Haiman CA, Sueta A, Kim MK, Khoo US, Iwasaki M, Pharoah PD, Wen W, Hall P, Shu XO, Easton DF, Kang D
Source: Hum Mol Genet, 2013 Jun 15;22(12), p. 2539-50.
EPub date: 2013 Mar 27.
PMID: 23535825
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A common deletion in the APOBEC3 genes and breast cancer risk.
Authors: Long J, Delahanty RJ, Li G, Gao YT, Lu W, Cai Q, Xiang YB, Li C, Ji BT, Zheng Y, Ali S, Shu XO, Zheng W
Source: J Natl Cancer Inst, 2013 Apr 17;105(8), p. 573-9.
EPub date: 2013 Feb 14.
PMID: 23411593
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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 YT, Long J, Williams SM, Xiang YB, Cai H, Li HL, Hu F, Cai Q, Zheng W, Shu XO
Source: PLoS One, 2012;7(11), p. e49464.
EPub date: 2012 Nov 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 JY, Wen W, Delahanty RJ, Lu W, Gao YT, Shen H, Park SK, Chen K, Shen CY, Ren Z, Haiman CA, Matsuo K, Kim MK, Khoo US, Iwasaki M, Zheng Y, Xiang YB, Gu K, Rothman N, Wang W, Hu Z, Liu Y, Yoo KY, Noh DY, Han BG, Lee MH, Zheng H, Zhang L, Wu PE, Shieh YL, Chan SY, Wang S, Xie X, Kim SW, Henderson BE, Le Marchand L, Ito H, Kasuga Y, Ahn SH, Kang HS, Chan KY, Iwata H, Tsugane S, Li C, Shu XO, Kang DH, Zheng W
Source: PLoS Genet, 2012;8(2), p. e1002532.
EPub date: 2012 Feb 23.
PMID: 22383897
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Meta-analysis identifies common variants associated with body mass index in east Asians.
Authors: Wen W, Cho YS, Zheng W, Dorajoo R, Kato N, Qi L, Chen CH, Delahanty RJ, Okada Y, Tabara Y, Gu D, Zhu D, Haiman CA, Mo Z, Gao YT, Saw SM, Go MJ, Takeuchi F, Chang LC, Kokubo Y, Liang J, Hao M, Le Marchand L, Zhang Y, Hu Y, Wong TY, Long J, Han BG, Kubo M, Yamamoto K, Su MH, Miki T, Henderson BE, Song H, Tan A, He J, Ng DP, Cai Q, Tsunoda T, Tsai FJ, Iwai N, Chen GK, Shi J, Xu J, Sim X, Xiang YB, Maeda S, Ong RT, Li C, Nakamura Y, Aung T, Kamatani N, Liu JJ, Lu W, Yokota M, Seielstad M, Fann CS, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Wu JY, Lee JY, Hu FB, Tanaka T, Tai ES, Shu XO
Source: Nat Genet, 2012 Feb 19;44(3), p. 307-11.
EPub date: 2012 Feb 19.
PMID: 22344219
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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 JY, Chen K, Shen H, Shen CY, Sung H, Matsuo K, Haiman CA, Khoo US, Ren Z, Iwasaki M, Gu K, Xiang YB, Choi JY, Park SK, Zhang L, Hu Z, Wu PE, Noh DY, Tajima K, Henderson BE, Chan KY, Su F, Kasuga Y, Wang W, Cheng JR, Yoo KY, Lee JY, Zheng H, Liu Y, Shieh YL, Kim SW, Lee JW, Iwata H, Le Marchand L, Chan SY, Xie X, Tsugane S, Lee MH, Wang S, Li G, Levy S, Huang B, Shi J, Delahanty R, Zheng Y, Li C, Gao YT, Shu XO, Zheng W
Source: Hum Mol Genet, 2011 Dec 15;20(24), p. 4991-9.
EPub date: 2011 Sep 9.
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 YB, Zheng W, Long J, Ou Shu X
Source: Ann Hum Genet, 2011 Sep;75(5), p. 621-9.
PMID: 21834910
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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 WH, Shu XO, Long J, Lu W, Cai Q, Zheng Y, Xiang YB, Dai Q, Zhao GM, Gu K, Bao PP, Gao YT, Zheng W
Source: Am J Epidemiol, 2011 Apr 15;173(8), p. 923-31.
EPub date: 2011 Mar 7.
PMID: 21382839
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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 XO, Lu W, Long J, Cai Q, Xiang YB, Zheng Y, Zhao Z, Gu K, Gao YT, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2011 Jan;20(1), p. 33-41.
EPub date: 2010 Nov 30.
PMID: 21119072
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Identification of new genetic risk variants for type 2 diabetes.
Authors: Shu XO, Long J, Cai Q, Qi L, Xiang YB, Cho YS, Tai ES, Li X, Lin X, Chow WH, Go MJ, Seielstad M, Bao W, Li H, Cornelis MC, Yu K, Wen W, Shi J, Han BG, Sim XL, Liu L, Qi Q, Kim HL, Ng DP, Lee JY, Kim YJ, Li C, Gao YT, Zheng W, Hu FB
Source: PLoS Genet, 2010 Sep 16;6(9), p. e1001127.
EPub date: 2010 Sep 16.
PMID: 20862305
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Evaluation of breast cancer susceptibility loci in Chinese women.
Authors: Long J, Shu XO, Cai Q, Gao YT, Zheng Y, Li G, Li C, Gu K, Wen W, Xiang YB, Lu W, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2010 Sep;19(9), p. 2357-65.
EPub date: 2010 Aug 10.
PMID: 20699374
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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 JJ, Hwang M, Lopater Z, Chen H, Ray GL, Perez C, Cai Q, Wills ML, Lu B
Source: Int J Radiat Oncol Biol Phys, 2011 Apr 1;79(5), p. 1330-5.
EPub date: 2010 Jun 3.
PMID: 20605361
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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 XO, Qu S, Li C, Zheng Y, Gu K, Wang W, Xiang YB, Cheng J, Chen K, Zhang L, Zheng H, Shen CY, Huang CS, Hou MF, Shen H, Hu Z, Wang F, Deming SL, Kelley MC, Shrubsole MJ, Khoo US, Chan KY, Chan SY, Haiman CA, Henderson BE, Le Marchand L, Iwasaki M, Kasuga Y, Tsugane S, Matsuo K, Tajima K, Iwata H, Huang B, Shi J, Li G, Wen W, Gao YT, Lu W, Zheng W
Source: PLoS Genet, 2010 Jun 24;6(6), p. e1001002.
EPub date: 2010 Jun 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 XO, Gao YT, Zheng W, Cai Q
Source: Breast Cancer Res Treat, 2010 Jun;121(3), p. 765-9.
EPub date: 2009 Oct 2.
PMID: 19798569
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No evidence for association of the MDM2-309 T/G promoter polymorphism with prostate cancer outcomes.
Authors: Jaboin JJ, Hwang M, Perez CA, Cooper C, Chen H, Ye C, Cai Q, Wills ML, Lu B
Source: Urol Oncol, 2011 May-Jun;29(3), p. 319-23.
EPub date: 2009 Jun 12.
PMID: 19523862
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Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1.
Authors: Zheng W, Long J, Gao YT, Li C, Zheng Y, Xiang YB, Wen W, Levy S, Deming SL, Haines JL, Gu K, Fair AM, Cai Q, Lu W, Shu XO
Source: Nat Genet, 2009 Mar;41(3), p. 324-8.
EPub date: 2009 Feb 15.
PMID: 19219042
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