Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer

被引:35
作者
Cox, DG [1 ]
Kraft, P
Hankinson, SE
Hunter, DJ
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA
[4] Harvard Univ, Sch Med, Boston, MA USA
关键词
breast cancer; BRCA1; haplotype; single nucleotide polymorphism;
D O I
10.1186/bcr973
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer. Method We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls). Results One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02-1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women. Conclusions We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear.
引用
收藏
页码:R171 / R175
页数:5
相关论文
共 12 条
[1]   Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population [J].
Dunning, AM ;
Chiano, M ;
Smith, NR ;
Dearden, J ;
Gore, M ;
Oakes, S ;
Wilson, C ;
Stratton, M ;
Peto, J ;
Easton, D ;
Clayton, D ;
Ponder, BAJ .
HUMAN MOLECULAR GENETICS, 1997, 6 (02) :285-289
[2]   Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations [J].
Durocher, F ;
ShattuckEidens, D ;
McClure, M ;
Labrie, F ;
Skolnick, MH ;
Goldgar, DE ;
Simard, J .
HUMAN MOLECULAR GENETICS, 1996, 5 (06) :835-842
[3]   The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse [J].
Hakem, R ;
delaPompa, JL ;
Sirard, C ;
Mo, R ;
Woo, M ;
Hakem, A ;
Wakeham, A ;
Potter, J ;
Reitmair, A ;
Billia, F ;
Firpo, E ;
Hui, CC ;
Roberts, J ;
Rossant, J ;
Mak, TW .
CELL, 1996, 85 (07) :1009-1023
[4]   Adaptive evolution of the tumour suppressor BRCA1 in humans and chimpanzees [J].
Huttley, GA ;
Easteal, S ;
Southey, MC ;
Tesoriero, A ;
Giles, GG ;
McCredie, MRE ;
Hopper, JL ;
Venter, DJ .
NATURE GENETICS, 2000, 25 (04) :410-413
[5]   Mobile elements: Drivers of genome evolution [J].
Kazazian, HH .
SCIENCE, 2004, 303 (5664) :1626-1632
[6]   The role of Alu repeat clusters as mediators of recurrent chromosomal aberrations in tumors [J].
Kolomietz, E ;
Meyn, MS ;
Pandita, A ;
Squire, JA .
GENES CHROMOSOMES & CANCER, 2002, 35 (02) :97-112
[7]  
*NIEHS SNPS, NIEHS ENV GEN PROJ U
[8]   Over-representation of two specific haplotypes among chromosomes harbouring BRCA1 mutations [J].
Osorio, A ;
de la Hoya, M ;
Rodríguez-López, R ;
Granizo, JJ ;
Díez, O ;
Vega, A ;
Durán, M ;
Carracedo, A ;
Baiget, M ;
Caldés, T ;
Benítez, J .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2003, 11 (06) :489-492
[9]   Minimal haplotype tagging [J].
Sebastiani, P ;
Lazarus, R ;
Weiss, ST ;
Kunkel, LM ;
Kohane, IS ;
Ramoni, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (17) :9900-9905
[10]   A comparison of Bayesian methods for haplotype reconstruction from population genotype data [J].
Stephens, M ;
Donnelly, P .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (05) :1162-1169