Skip to main content
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
Back to top


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.

Back to top


Publications

Germline Variation and Breast Cancer Incidence: A Gene-Based Association Study and Whole-Genome Prediction of Early-Onset Breast Cancer.
Authors: Scannell Bryan M. , Argos M. , Andrulis I.L. , Hopper J.L. , Chang-Claude J. , Malone K.E. , John E.M. , Gammon M.D. , Daly M.B. , Terry M.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, 2018 09; 27(9), p. 1057-1064.
EPub date: 2018-06-13.
PMID: 29898891
Related Citations

Association analysis identifies 65 new breast cancer risk loci.
Authors: Michailidou K. , Lindström S. , Dennis J. , Beesley J. , Hui S. , Kar S. , Lemaçon A. , Soucy P. , Glubb D. , Rostamianfar A. , et al. .
Source: Nature, 2017-11-02; 551(7678), p. 92-94.
EPub date: 2017-10-23.
PMID: 29059683
Related Citations

Limited influence of germline genetic variation on all-cause mortality in women with early onset breast cancer: evidence from gene-based tests, single-marker regression, and whole-genome prediction.
Authors: Scannell Bryan M. , Argos M. , Andrulis I.L. , Hopper J.L. , Chang-Claude J. , Malone K. , John E.M. , Gammon M.D. , Daly M. , Terry M.B. , et al. .
Source: Breast cancer research and treatment, 2017 Aug; 164(3), p. 707-717.
EPub date: 2017-05-13.
PMID: 28503721
Related Citations

Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study.
Authors: Kibriya M.G. , Jasmine F. , Parvez F. , Argos M. , Roy S. , Paul-Brutus R. , Islam T. , Ahmed A. , Rakibuz-Zaman M. , Shinkle J. , et al. .
Source: Environmental health : a global access science source, 2017-07-18; 16(1), p. 75.
EPub date: 2017-07-18.
PMID: 28720099
Related Citations

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.
Authors: Southey M.C. , Goldgar D.E. , Winqvist R. , Pylkäs K. , Couch F. , Tischkowitz M. , Foulkes W.D. , Dennis J. , Michailidou K. , van Rensburg E.J. , et al. .
Source: Journal of medical genetics, 2016 12; 53(12), p. 800-811.
EPub date: 2016-09-05.
PMID: 27595995
Related Citations

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 M.G. , Pierce B.L. , Tong L. , Gamazon E. , McGuire V. , Felberg A. , Shi J. , Jasmine F. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014 Apr; 23(4), p. 658-69.
EPub date: 2014-02-03.
PMID: 24493630
Related Citations

Better cancer biomarker discovery through better study design.
Authors: Rundle A. , Ahsan H. , Vineis P. .
Source: European journal of clinical investigation, 2012 Dec; 42(12), p. 1350-9.
EPub date: 2012-09-23.
PMID: 22998109
Related Citations

Unidentified genetic variants influence pancreatic cancer risk: an analysis of polygenic susceptibility in the PanScan study.
Authors: Pierce B.L. , Tong L. , Kraft P. , Ahsan H. .
Source: Genetic epidemiology, 2012 Jul; 36(5), p. 517-24.
EPub date: 2012-05-29.
PMID: 22644738
Related Citations

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. , et al. .
Source: BMC research notes, 2012-02-22; 5, p. 117.
EPub date: 2012-02-22.
PMID: 22357164
Related Citations

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 M.G. .
Source: PloS one, 2012; 7(2), p. e31968.
EPub date: 2012-02-20.
PMID: 22363777
Related Citations

Optimal methods for meta-analysis of genome-wide association studies.
Authors: Zhou B. , Shi J. , Whittemore A.S. .
Source: Genetic epidemiology, 2011 Nov; 35(7), p. 581-91.
EPub date: 2011-09-15.
PMID: 21922536
Related Citations

Genome-wide "pleiotropy scan" identifies HNF1A region as a novel pancreatic cancer susceptibility locus.
Authors: Pierce B.L. , Ahsan H. .
Source: Cancer research, 2011-07-01; 71(13), p. 4352-8.
EPub date: 2011-04-15.
PMID: 21498636
Related Citations

Tremor severity and age: a cross-sectional, population-based study of 2,524 young and midlife normal adults.
Authors: Louis E.D. , Hafeman D. , Parvez F. , Liu X. , Alcalay R.N. , Islam T. , Ahmed A. , Siddique A.B. , Patwary T.I. , Melkonian S. , et al. .
Source: Movement disorders : official journal of the Movement Disorder Society, 2011 Jul; 26(8), p. 1515-20.
EPub date: 2011-03-25.
PMID: 21442657
Related Citations

A genome-wide DNA methylation study in colorectal carcinoma.
Authors: Kibriya M.G. , Raza M. , Jasmine F. , Roy S. , Paul-Brutus R. , Rahaman R. , Dodsworth C. , Rakibuz-Zaman M. , Kamal M. , Ahsan H. .
Source: BMC medical genomics, 2011-06-23; 4, p. 50.
EPub date: 2011-06-23.
PMID: 21699707
Related Citations

Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data.
Authors: Pierce B.L. , Austin M.A. , Ahsan H. .
Source: Cancer causes & control : CCC, 2011 Jun; 22(6), p. 877-83.
EPub date: 2011-03-29.
PMID: 21445555
Related Citations

Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants.
Authors: Pierce B.L. , Ahsan H. , Vanderweele T.J. .
Source: International journal of epidemiology, 2011 Jun; 40(3), p. 740-52.
EPub date: 2010-09-02.
PMID: 20813862
Related Citations

Analyses and interpretation of whole-genome gene expression from formalin-fixed paraffin-embedded tissue: an illustration with breast cancer tissues.
Authors: Kibriya M.G. , Jasmine F. , Roy S. , Paul-Brutus R.M. , Argos M. , Ahsan H. .
Source: BMC genomics, 2010-11-08; 11, p. 622.
EPub date: 2010-11-08.
PMID: 21059268
Related Citations

Genetic susceptibility to type 2 diabetes is associated with reduced prostate cancer risk.
Authors: Pierce B.L. , Ahsan H. .
Source: Human heredity, 2010; 69(3), p. 193-201.
EPub date: 2010-03-05.
PMID: 20203524
Related Citations

Case-only genome-wide interaction study of disease risk, prognosis and treatment.
Authors: Pierce B.L. , Ahsan H. .
Source: Genetic epidemiology, 2010 Jan; 34(1), p. 7-15.
PMID: 19434715
Related Citations

A pilot genome-wide association study of early-onset breast cancer.
Authors: Kibriya M.G. , Jasmine F. , Argos M. , Andrulis I.L. , John E.M. , Chang-Claude J. , Ahsan H. .
Source: Breast cancer research and treatment, 2009 Apr; 114(3), p. 463-77.
EPub date: 2008-05-08.
PMID: 18463975
Related Citations

Whole-genome amplification enables accurate genotyping for microarray-based high-density single nucleotide polymorphism array.
Authors: Jasmine F. , Ahsan H. , Andrulis I.L. , John E.M. , Chang-Claude J. , Kibriya M.G. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Dec; 17(12), p. 3499-508.
PMID: 19064567
Related Citations

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 M.G. , Jasmine F. , Santella R.M. , Senie R.T. , Ahsan H. .
Source: Cancer research, 2008-12-01; 68(23), p. 9729-34.
PMID: 19047151
Related Citations

Genomewide scan for loss of heterozygosity and chromosomal amplification in breast carcinoma using single-nucleotide polymorphism arrays.
Authors: Argos M. , Kibriya M.G. , Jasmine F. , Olopade O.I. , Su T. , Hibshoosh H. , Ahsan H. .
Source: Cancer genetics and cytogenetics, 2008-04-15; 182(2), p. 69-74.
PMID: 18406867
Related Citations

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 M.D. , Teitelbaum S.L. , Britton J.A. , Terry M.B. , Shantakumar S. , Eng S.M. , Wang Q. , Gurvich I. , Neugut A.I. , et al. .
Source: Carcinogenesis, 2008 Apr; 29(4), p. 766-71.
EPub date: 2008-02-14.
PMID: 18281250
Related Citations




Back to Top