Centrosome-related genes, genetic variation, and risk of breast cancer

Janet E Olson, X. Wang, V. S. Pankratz, Z. S. Fredericksen, Celine M Vachon, R. A. Vierkant, James R Cerhan, Fergus J Couch

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Centrosome amplification has been detected in premalignant lesions and in situ tumors in the breast and in over 70% of invasive breast tumors, and has been associated with aneuploidy and tumor development. Based on these observations, the contribution of commonly inherited genetic variation in candidate genes related to centrosome structure and function to breast cancer risk was evaluated in an association study. Seven-hundred and 82 single nucleotide polymorphisms (SNPs) from 101 centrosomal genes were analyzed in 798 breast cancer cases and 843 controls from the Mayo Clinic Breast Cancer Study to assess the association between these SNPs (both individually and combined) and risk of breast cancer in this population. Eleven SNPs out of 782 from six genes displayed associations with breast cancer risk (P < 0.01). Haplotypes in five genes also displayed significant associations with risk. A two SNP combination of rs10145182 in NIN and rs2134808 in the TUBG1 locus (P-interaction = 0.00001), suggested SNPs in mediators of microtubule nucleation from the centrosome contribute to breast cancer. Evaluation of the simultaneous significance of all SNPs in the centrosome pathway suggested that the centrosome pathway is highly enriched (P = 4.76 × 10 -50) for SNPs that are associated with breast cancer risk. Collections of weakly associated genetic variants in the centrosome pathway, rather than individual highly significantly associated SNPs, may account for a putative role for the centrosome pathway in predisposition to breast cancer.

Original languageEnglish (US)
Pages (from-to)221-228
Number of pages8
JournalBreast Cancer Research and Treatment
Volume125
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Centrosome
Single Nucleotide Polymorphism
Breast Neoplasms
Genes
Aneuploidy
Microtubules
Haplotypes

Keywords

  • Breast cancer risk
  • Centrosome
  • Haplotype
  • Mitosis
  • Single nucleotide polymorphism (SNP)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Centrosome-related genes, genetic variation, and risk of breast cancer. / Olson, Janet E; Wang, X.; Pankratz, V. S.; Fredericksen, Z. S.; Vachon, Celine M; Vierkant, R. A.; Cerhan, James R; Couch, Fergus J.

In: Breast Cancer Research and Treatment, Vol. 125, No. 1, 01.2011, p. 221-228.

Research output: Contribution to journalArticle

Olson, Janet E ; Wang, X. ; Pankratz, V. S. ; Fredericksen, Z. S. ; Vachon, Celine M ; Vierkant, R. A. ; Cerhan, James R ; Couch, Fergus J. / Centrosome-related genes, genetic variation, and risk of breast cancer. In: Breast Cancer Research and Treatment. 2011 ; Vol. 125, No. 1. pp. 221-228.
@article{a288aca4594f486986e89aca6bb517fb,
title = "Centrosome-related genes, genetic variation, and risk of breast cancer",
abstract = "Centrosome amplification has been detected in premalignant lesions and in situ tumors in the breast and in over 70{\%} of invasive breast tumors, and has been associated with aneuploidy and tumor development. Based on these observations, the contribution of commonly inherited genetic variation in candidate genes related to centrosome structure and function to breast cancer risk was evaluated in an association study. Seven-hundred and 82 single nucleotide polymorphisms (SNPs) from 101 centrosomal genes were analyzed in 798 breast cancer cases and 843 controls from the Mayo Clinic Breast Cancer Study to assess the association between these SNPs (both individually and combined) and risk of breast cancer in this population. Eleven SNPs out of 782 from six genes displayed associations with breast cancer risk (P < 0.01). Haplotypes in five genes also displayed significant associations with risk. A two SNP combination of rs10145182 in NIN and rs2134808 in the TUBG1 locus (P-interaction = 0.00001), suggested SNPs in mediators of microtubule nucleation from the centrosome contribute to breast cancer. Evaluation of the simultaneous significance of all SNPs in the centrosome pathway suggested that the centrosome pathway is highly enriched (P = 4.76 × 10 -50) for SNPs that are associated with breast cancer risk. Collections of weakly associated genetic variants in the centrosome pathway, rather than individual highly significantly associated SNPs, may account for a putative role for the centrosome pathway in predisposition to breast cancer.",
keywords = "Breast cancer risk, Centrosome, Haplotype, Mitosis, Single nucleotide polymorphism (SNP)",
author = "Olson, {Janet E} and X. Wang and Pankratz, {V. S.} and Fredericksen, {Z. S.} and Vachon, {Celine M} and Vierkant, {R. A.} and Cerhan, {James R} and Couch, {Fergus J}",
year = "2011",
month = "1",
doi = "10.1007/s10549-010-0950-8",
language = "English (US)",
volume = "125",
pages = "221--228",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Centrosome-related genes, genetic variation, and risk of breast cancer

AU - Olson, Janet E

AU - Wang, X.

AU - Pankratz, V. S.

AU - Fredericksen, Z. S.

AU - Vachon, Celine M

AU - Vierkant, R. A.

AU - Cerhan, James R

AU - Couch, Fergus J

PY - 2011/1

Y1 - 2011/1

N2 - Centrosome amplification has been detected in premalignant lesions and in situ tumors in the breast and in over 70% of invasive breast tumors, and has been associated with aneuploidy and tumor development. Based on these observations, the contribution of commonly inherited genetic variation in candidate genes related to centrosome structure and function to breast cancer risk was evaluated in an association study. Seven-hundred and 82 single nucleotide polymorphisms (SNPs) from 101 centrosomal genes were analyzed in 798 breast cancer cases and 843 controls from the Mayo Clinic Breast Cancer Study to assess the association between these SNPs (both individually and combined) and risk of breast cancer in this population. Eleven SNPs out of 782 from six genes displayed associations with breast cancer risk (P < 0.01). Haplotypes in five genes also displayed significant associations with risk. A two SNP combination of rs10145182 in NIN and rs2134808 in the TUBG1 locus (P-interaction = 0.00001), suggested SNPs in mediators of microtubule nucleation from the centrosome contribute to breast cancer. Evaluation of the simultaneous significance of all SNPs in the centrosome pathway suggested that the centrosome pathway is highly enriched (P = 4.76 × 10 -50) for SNPs that are associated with breast cancer risk. Collections of weakly associated genetic variants in the centrosome pathway, rather than individual highly significantly associated SNPs, may account for a putative role for the centrosome pathway in predisposition to breast cancer.

AB - Centrosome amplification has been detected in premalignant lesions and in situ tumors in the breast and in over 70% of invasive breast tumors, and has been associated with aneuploidy and tumor development. Based on these observations, the contribution of commonly inherited genetic variation in candidate genes related to centrosome structure and function to breast cancer risk was evaluated in an association study. Seven-hundred and 82 single nucleotide polymorphisms (SNPs) from 101 centrosomal genes were analyzed in 798 breast cancer cases and 843 controls from the Mayo Clinic Breast Cancer Study to assess the association between these SNPs (both individually and combined) and risk of breast cancer in this population. Eleven SNPs out of 782 from six genes displayed associations with breast cancer risk (P < 0.01). Haplotypes in five genes also displayed significant associations with risk. A two SNP combination of rs10145182 in NIN and rs2134808 in the TUBG1 locus (P-interaction = 0.00001), suggested SNPs in mediators of microtubule nucleation from the centrosome contribute to breast cancer. Evaluation of the simultaneous significance of all SNPs in the centrosome pathway suggested that the centrosome pathway is highly enriched (P = 4.76 × 10 -50) for SNPs that are associated with breast cancer risk. Collections of weakly associated genetic variants in the centrosome pathway, rather than individual highly significantly associated SNPs, may account for a putative role for the centrosome pathway in predisposition to breast cancer.

KW - Breast cancer risk

KW - Centrosome

KW - Haplotype

KW - Mitosis

KW - Single nucleotide polymorphism (SNP)

UR - http://www.scopus.com/inward/record.url?scp=78651107342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651107342&partnerID=8YFLogxK

U2 - 10.1007/s10549-010-0950-8

DO - 10.1007/s10549-010-0950-8

M3 - Article

C2 - 20508983

AN - SCOPUS:78651107342

VL - 125

SP - 221

EP - 228

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 1

ER -