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Grant Details

Grant Number: 3R01CA118229-03S1 Interpret this number
Primary Investigator: Shu, Xiao-Ou
Organization: Vanderbilt University
Project Title: Breast Cancer Survival: Lifestyle and Genetic Determinants
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): The population of women who survive breast cancer is rising rapidly. Despite the success of initial treatments, many patients constantly battle fears of disease recurrence and early death. However, the effect of non-clinical factors, particularly genetic factors, on breast cancer outcomes is largely unknown. The proposed study will use the existing resources of two well-established cohort studies of 3593 breast cancer patients to comprehensively evaluate the following hypotheses: 1) Breast cancer survival may be associated with genetic polymorphisms in genes encoding angiogenic factors and matrix metalloproteinases, both of which are essential for tumor growth and metastasis. 2) Infiltrating inflammatory cells, particularly tumor- associated macrophages, can produce a large variety of promalignant cytokines and growth factors. Genetic polymorphisms in inflammatory chemokine and cytokine genes may be related to breast cancer survival. 3) Transforming growth factor-B promotes the growth and progression of breast cancer, and genetic polymorphisms in TGF-R pathway genes may be related to breast cancer survival. 4) The cyclooxygenase-2 (COX2) gene is up-regulated in a large proportion of mammary tumors, and this enzyme initiates the biosynthesis of various prostaglandins with diverse, and sometimes opposing, effects on tumorigenesis. Genetic polymorphisms of prostaglandin-pathway genes may be associated with breast cancer survival. A two-phase study design will be applied. In Phase I, all functional variants plus haplotype-tagging SNPs will be genotyped among 1193 breast cancer patients who have been followed for an average of 7.1 years. All promising associations identified in Phase I will be evaluated in Phase II in an on-going cohort study of 2400 cancer patients (being followed for 5 years). The large sample size and two-phase study design will balance both Type I and Type II errors and provide credible results towards improving the understanding of associations between genetic factors and breast cancer outcomes. Identifying factors that predict risk of relapse and rates of mortality will not only affect the expanding cancer survivor population by providing evidence-based information, but will also positively influence the medical care system and economy at large by making treatment more effective and cost-efficient. The proposed study, built on successfully implemented cohort studies, will be extremely timely and cost-efficient.

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Publications

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 SK, Kweon SS, Lu W, Shi J, Long J, Wen W, Choi JY, Noh DY, Shen CY, Matsuo K, Teo SH, Kim MK, Khoo US, Iwasaki M, Hartman M, Takahashi A, Ashikawa K, Matsuda K, Shin MH, Park MH, Zheng Y, Xiang YB, Ji BT, Park SK, Wu PE, Hsiung CN, Ito H, Kasuga Y, Kang P, Mariapun S, Ahn SH, Kang HS, Chan KY, Man EP, Iwata H, Tsugane S, Miao H, Liao J, Nakamura Y, Kubo M, DRIVE GAME-ON Consortium, Delahanty RJ, Zhang Y, Li B, Li C, Gao YT, Shu XO, Kang D, Zheng W
Source: Nat Genet, 2014 Aug;46(8), p. 886-90.
EPub date: 2014 Jul 20.
PMID: 25038754
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Urinary biomarkers of oxidative stress and breast cancer survival.
Authors: Nechuta S, Cai Q, Zheng Y, Milne GL, Cai H, Dai Q, Yang G, Zheng W, Lu W, Shu XO
Source: Cancer Causes Control, 2014 Jun;25(6), p. 701-7.
EPub date: 2014 Mar 29.
PMID: 24820618
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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 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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Lifetime cigarette smoking and breast cancer prognosis in the After Breast Cancer Pooling Project.
Authors: Pierce JP, Patterson RE, Senger CM, Flatt SW, Caan BJ, Natarajan L, Nechuta SJ, Poole EM, Shu XO, Chen WY
Source: J Natl Cancer Inst, 2014 Jan;106(1), p. djt359.
EPub date: 2013 Dec 7.
PMID: 24317179
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Menopausal symptoms among breast cancer patients: a potential indicator of favorable prognosis.
Authors: Chen Y, Dorjgochoo T, Bao PP, Zheng Y, Cai H, Lu W, Shu XO
Source: PLoS One, 2013;8(9), p. e75926.
EPub date: 2013 Sep 30.
PMID: 24098745
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Exercise after diagnosis and metabolic syndrome among breast cancer survivors: a report from the Shanghai Breast Cancer Survival Study.
Authors: Bao PP, Zheng Y, Nechuta S, Gu K, Cai H, Peng P, Shu XO, Lu W
Source: Cancer Causes Control, 2013 Sep;24(9), p. 1747-56.
EPub date: 2013 Jul 17.
PMID: 23860950
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No association between genetic variants in angiogenesis and inflammation pathway genes and breast cancer survival among Chinese women.
Authors: Dorjgochoo T, Zheng Y, Gao YT, Ma X, Long J, Bao P, Zhang B, Wen W, Lu W, Zheng W, Shu XO, Beeghly-Fadiel A
Source: Cancer Epidemiol, 2013 Oct;37(5), p. 619-24.
EPub date: 2013 Jul 11.
PMID: 23850146
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Postdiagnosis cruciferous vegetable consumption and breast cancer outcomes: a report from the After Breast Cancer Pooling Project.
Authors: Nechuta S, Caan BJ, Chen WY, Kwan ML, Lu W, Cai H, Poole EM, Flatt SW, Zheng W, Pierce JP, Shu XO
Source: Cancer Epidemiol Biomarkers Prev, 2013 Aug;22(8), p. 1451-6.
EPub date: 2013 Jun 13.
PMID: 23765086
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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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Postdiagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project.
Authors: Poole EM, Shu X, Caan BJ, Flatt SW, Holmes MD, Lu W, Kwan ML, Nechuta SJ, Pierce JP, Chen WY
Source: Breast Cancer Res Treat, 2013 Jun;139(2), p. 529-37.
EPub date: 2013 May 10.
PMID: 23660948
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Comorbidities and breast cancer survival: a report from the Shanghai Breast Cancer Survival Study.
Authors: Nechuta S, Lu W, Zheng Y, Cai H, Bao PP, Gu K, Zheng W, Shu XO
Source: Breast Cancer Res Treat, 2013 May;139(1), p. 227-35.
EPub date: 2013 Apr 19.
PMID: 23605082
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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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Gene-environment interactions for breast cancer risk among Chinese women: a report from the Shanghai Breast Cancer Genetics Study.
Authors: Li H, Beeghly-Fadiel A, Wen W, Lu W, Gao YT, Xiang YB, Cai Q, Long J, Shi J, Chen K, Zheng Y, Shu XO, Zheng W
Source: Am J Epidemiol, 2013 Jan 15;177(2), p. 161-70.
EPub date: 2012 Dec 6.
PMID: 23221726
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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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Postdiagnosis alcohol consumption and breast cancer prognosis in the after breast cancer pooling project.
Authors: Kwan ML, Chen WY, Flatt SW, Weltzien EK, Nechuta SJ, Poole EM, Holmes MD, Patterson RE, Shu XO, Pierce JP, Caan BJ
Source: Cancer Epidemiol Biomarkers Prev, 2013 Jan;22(1), p. 32-41.
EPub date: 2012 Nov 13.
PMID: 23150063
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Ginseng and Ganoderma lucidum use after breast cancer diagnosis and quality of life: a report from the Shanghai Breast Cancer Survival Study.
Authors: Bao PP, Lu W, Cui Y, Zheng Y, Gu K, Chen Z, Zheng W, Shu XO
Source: PLoS One, 2012;7(6), p. e39343.
EPub date: 2012 Jun 20.
PMID: 22745737
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Weight change and survival after breast cancer in the after breast cancer pooling project.
Authors: Caan BJ, Kwan ML, Shu XO, Pierce JP, Patterson RE, Nechuta SJ, Poole EM, Kroenke CH, Weltzien EK, Flatt SW, Quesenberry CP Jr, Holmes MD, Chen WY
Source: Cancer Epidemiol Biomarkers Prev, 2012 Aug;21(8), p. 1260-71.
EPub date: 2012 Jun 13.
PMID: 22695738
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Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women.
Authors: Nechuta SJ, Caan BJ, Chen WY, Lu W, Chen Z, Kwan ML, Flatt SW, Zheng Y, Zheng W, Pierce JP, Shu XO
Source: Am J Clin Nutr, 2012 Jul;96(1), p. 123-32.
EPub date: 2012 May 30.
PMID: 22648714
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Exome sequencing generates high quality data in non-target regions.
Authors: Guo Y, Long J, He J, Li CI, Cai Q, Shu XO, Zheng W, Li C
Source: BMC Genomics, 2012 May 20;13, p. 194.
EPub date: 2012 May 20.
PMID: 22607156
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Pathway analyses identify TGFBR2 as potential breast cancer susceptibility gene: results from a consortium study among Asians.
Authors: Ma X, Beeghly-Fadiel A, Lu W, Shi J, Xiang YB, Cai Q, Shen H, Shen CY, Ren Z, Matsuo K, Khoo US, Iwasaki M, Long J, Zhang B, Ji BT, Zheng Y, Wang W, Hu Z, Liu Y, Wu PE, Shieh YL, Wang S, Xie X, Ito H, Kasuga Y, Chan KY, Iwata H, Tsugane S, Gao YT, Shu XO, Moses HL, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2012 Jul;21(7), p. 1176-84.
EPub date: 2012 Apr 26.
PMID: 22539603
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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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Replication study for reported SNP associations with breast cancer survival.
Authors: Beeghly-Fadiel A, Zheng W, Lu W, Long J, Zheng Y, Cai H, Gu K, Chen Z, Cai Q, Gao YT, Shu XO
Source: J Cancer Res Clin Oncol, 2012 Jun;138(6), p. 1019-26.
EPub date: 2012 Feb 25.
PMID: 22367361
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