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Grant Details

Grant Number: 5U01CA122171-05 Interpret this number
Primary Investigator: Ahsan, Habibul
Organization: University Of Chicago
Project Title: Genomewide Association in Early-Onset Breast Cancer
Fiscal Year: 2010
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Abstract

DESCRIPTION (provided by applicant): We plan to conduct a genome-wide association study of young (<50 years) invasive female breast cancer to identify new genes responsible for young cases who are negative for BRCA1 and BRCA2 gene mutations. This collaborative study will exploit the availability of biological samples and epidemiological data from 2,330 population-based, individually matched case-control pairs ascertained by large breast cancer study resources in Australia, Canada, the US and Germany. We will focus on early-onset BRCA1- and BRCA2-negative invasive cases because this group has high public health importance and high likelihood of harboring unidentified breast cancer genes. To enhance cost-efficiency and validity, the study will proceed in two phases. Phase I will genotype and analyze population-based samples of 1,500 non-Hispanic Caucasian matched case-control pairs. We will perform Phase I in two stages. In Stage 1, we will genotype and analyze 1,000 case-control pairs, using the Affymetrix 500k SNP array augmented by the ParAllele non-synonymous 20k cSNP panel. In Stage 2, we will genotype the remaining 500 case-control pairs only for the SNPs identified as promising in Stage 1. We will then analyze these SNPs using all 1,500 case-control pairs, adjusting for established breast cancer risk factors. Phase II will genotype and analyze an independent set of 830 population-based sister case-control pairs for all promising SNPs from Phase I and also the surrounding haplotype-tagging and functional SNPs in the haplotypes containing these SNPs. Phase II provides robustness against false positives due either to confounding by population structure or to multiple comparisons in Phase I analyses. This genome-wide association study offers several strengths, including the availability of large numbers of population-based, well-matched young cases and controls, the ability to control confounding by population structure using a robust sister-pair design, and the extended genomic coverage provided by the combined Affymetrix and ParAllele high-density SNP panels. In conclusion, this research aims to identify new genes for early-onset breast cancer, which is a major source of morbidity, mortality and loss of life expectancy throughout the world.

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Publications

A Genome-wide Association Study of Early-Onset Breast Cancer Identifies PFKM as a Novel Breast Cancer Gene and Supports a Common Genetic Spectrum for Breast Cancer at Any Age.
Authors: Ahsan H, Halpern J, Kibriya MG, Pierce BL, Tong L, Gamazon E, McGuire V, Felberg A, Shi J, Jasmine F, Roy S, Brutus R, Argos M, Melkonian S, Chang-Claude J, Andrulis I, Hopper JL, John EM, Malone K, Ursin G, Gammon MD, Thomas DC, Seminara D, Casey G, Knight JA, Southey MC, Giles GG, Santella RM, Lee E, Conti D, Duggan D, Gallinger S, Haile R, Jenkins M, Lindor NM, Newcomb P, Michailidou K, Apicella C, Park DJ, Peto J, Fletcher O, Dos Santos Silva I, Lathrop M, Hunter DJ, Chanock SJ, Meindl A, Schmutzler RK, Müller-Myhsok B, Lochmann M, Beckmann L, Hein R, Makalic E, Schmidt DF, Bui QM, Stone J, Flesch-Janys D, Dahmen N, Nevanlinna H, Aittomäki K, Blomqvist C, Hall P, Czene K, Irwanto A, Liu J, Rahman N, Turnbull C, Familial Breast Cancer Study, Dunning AM, Pharoah P, Waisfisz Q, Meijers-Heijboer H, Uitterlinden AG, Rivadeneira F, Nicolae D, Easton DF, Cox NJ, Whittemore AS
Source: Cancer Epidemiol Biomarkers Prev, 2014 Apr;23(4), p. 658-69.
EPub date: 2014 Feb 3.
PMID: 24493630
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Better cancer biomarker discovery through better study design.
Authors: Rundle A, Ahsan H, Vineis P
Source: Eur J Clin Invest, 2012 Dec;42(12), p. 1350-9.
EPub date: 2012 Sep 23.
PMID: 22998109
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Unidentified genetic variants influence pancreatic cancer risk: an analysis of polygenic susceptibility in the PanScan study.
Authors: Pierce BL, Tong L, Kraft P, Ahsan H
Source: Genet Epidemiol, 2012 Jul;36(5), p. 517-24.
EPub date: 2012 May 29.
PMID: 22644738
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A genome-wide study of cytogenetic changes in colorectal cancer using SNP microarrays: opportunities for future personalized treatment.
Authors: Jasmine F, Rahaman R, Dodsworth C, Roy S, Paul R, Raza M, Paul-Brutus R, Kamal M, Ahsan H, Kibriya MG
Source: PLoS One, 2012;7(2), p. e31968.
EPub date: 2012 Feb 20.
PMID: 22363777
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Interpretation of genome-wide infinium methylation data from ligated DNA in formalin-fixed, paraffin-embedded paired tumor and normal tissue.
Authors: Jasmine F, Rahaman R, Roy S, Raza M, Paul R, Rakibuz-Zaman M, Paul-Brutus R, Dodsworth C, Kamal M, Ahsan H, Kibriya MG
Source: BMC Res Notes, 2012 Feb 22;5, p. 117.
EPub date: 2012 Feb 22.
PMID: 22357164
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Optimal methods for meta-analysis of genome-wide association studies.
Authors: Zhou B, Shi J, Whittemore AS
Source: Genet Epidemiol, 2011 Nov;35(7), p. 581-91.
EPub date: 2011 Sep 15.
PMID: 21922536
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A genome-wide DNA methylation study in colorectal carcinoma.
Authors: Kibriya MG, Raza M, Jasmine F, Roy S, Paul-Brutus R, Rahaman R, Dodsworth C, Rakibuz-Zaman M, Kamal M, Ahsan H
Source: BMC Med Genomics, 2011 Jun 23;4, p. 50.
EPub date: 2011 Jun 23.
PMID: 21699707
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Genome-wide "pleiotropy scan" identifies HNF1A region as a novel pancreatic cancer susceptibility locus.
Authors: Pierce BL, Ahsan H
Source: Cancer Res, 2011 Jul 1;71(13), p. 4352-8.
EPub date: 2011 Apr 15.
PMID: 21498636
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Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data.
Authors: Pierce BL, Austin MA, Ahsan H
Source: Cancer Causes Control, 2011 Jun;22(6), p. 877-83.
EPub date: 2011 Mar 29.
PMID: 21445555
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Analyses and interpretation of whole-genome gene expression from formalin-fixed paraffin-embedded tissue: an illustration with breast cancer tissues.
Authors: Kibriya MG, Jasmine F, Roy S, Paul-Brutus RM, Argos M, Ahsan H
Source: BMC Genomics, 2010 Nov 8;11, p. 622.
EPub date: 2010 Nov 8.
PMID: 21059268
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Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants.
Authors: Pierce BL, Ahsan H, Vanderweele TJ
Source: Int J Epidemiol, 2011 Jun;40(3), p. 740-52.
EPub date: 2010 Sep 2.
PMID: 20813862
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Genetic susceptibility to type 2 diabetes is associated with reduced prostate cancer risk.
Authors: Pierce BL, Ahsan H
Source: Hum Hered, 2010;69(3), p. 193-201.
EPub date: 2010 Mar 5.
PMID: 20203524
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Case-only genome-wide interaction study of disease risk, prognosis and treatment.
Authors: Pierce BL, Ahsan H
Source: Genet Epidemiol, 2010 Jan;34(1), p. 7-15.
PMID: 19434715
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Whole-genome amplification enables accurate genotyping for microarray-based high-density single nucleotide polymorphism array.
Authors: Jasmine F, Ahsan H, Andrulis IL, John EM, Chang-Claude J, Kibriya MG
Source: Cancer Epidemiol Biomarkers Prev, 2008 Dec;17(12), p. 3499-508.
PMID: 19064567
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Do placental genes affect maternal breast cancer? Association between offspring's CGB5 and CSH1 gene variants and maternal breast cancer risk.
Authors: Chen Y, Kibriya MG, Jasmine F, Santella RM, Senie RT, Ahsan H
Source: Cancer Res, 2008 Dec 1;68(23), p. 9729-34.
PMID: 19047151
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A pilot genome-wide association study of early-onset breast cancer.
Authors: Kibriya MG, Jasmine F, Argos M, Andrulis IL, John EM, Chang-Claude J, Ahsan H
Source: Breast Cancer Res Treat, 2009 Apr;114(3), p. 463-77.
EPub date: 2008 May 8.
PMID: 18463975
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Genomewide scan for loss of heterozygosity and chromosomal amplification in breast carcinoma using single-nucleotide polymorphism arrays.
Authors: Argos M, Kibriya MG, Jasmine F, Olopade OI, Su T, Hibshoosh H, Ahsan H
Source: Cancer Genet Cytogenet, 2008 Apr 15;182(2), p. 69-74.
PMID: 18406867
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Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project.
Authors: Chen Y, Gammon MD, Teitelbaum SL, Britton JA, Terry MB, Shantakumar S, Eng SM, Wang Q, Gurvich I, Neugut AI, Santella RM, Ahsan H
Source: Carcinogenesis, 2008 Apr;29(4), p. 766-71.
EPub date: 2008 Feb 14.
PMID: 18281250
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