Carcinogenesis Advance Access originally published online on April 21, 2007
Carcinogenesis 2007 28(8):1680-1686; doi:10.1093/carcin/bgm097
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Genetic variation in TP53 and risk of breast cancer in a population-based case–control study
1 Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI 53726, USA
2 University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, WI 53726, USA
3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20952, USA
4 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
5 Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH 03756, USA
6 Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
7 Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA
* To whom correspondence should be addressed. Tel: +1 608 263 1946; Fax: +1 608 265 5330; Email: trentham{at}wisc.edu
Whereas germ line missense mutations in the tumor suppressor gene TP53 are associated with a marked predisposition to breast cancer, single-nucleotide polymorphisms (SNPs) may play a more modest role in breast cancer susceptibility. We examined genetic variation in TP53 in relation to breast cancer risk among women aged 20–74 years in a population-based case–control study in Wisconsin, Massachusetts and New Hampshire. Analyses were conducted separately for in situ (176 cases/581 controls) and invasive (1490 cases/1291 controls) breast cancer. Oral mucosal DNA samples were genotyped for the codon 72 polymorphism in exon 4 (rs1042522), seven intronic SNPs and three SNPs residing in the 3' untranslated region (UTR). Logistic regression was used to obtain age- and state-adjusted odds ratios for individual SNPs. Haplotypes were reconstructed using PHASE software, and the overall association with breast cancer risk was assessed using a global score test. None of the 11 individual SNPs or eight common haplotypes were significantly related to breast carcinoma in situ risk. Among all women, two linked SNPs (D' = 0.99, r2 = 0.95) on intron 7 (rs12951053, rs12947788) were associated with modest increases in invasive breast cancer risk; however, associations were only significant for heterozygous carriers. The data suggested that additional variants in the 3' UTR (rs9894946), and in two correlated SNPs (D' = 0.94, r2 = 0.81) in introns 6 (rs1625895) and 4 (rs2909430), were associated with reduced invasive breast cancer risk among women aged 50 and younger only (Pinteraction < 0.03). These results indicate that common variation in the TP53 gene could modify the risk of invasive breast cancer.
Abbreviations: 95% CI, 95% confidence interval; HWE, Hardy–Weinberg equilibrium; OR, odds ratio; SNP, single-nucleotide polymorphism; UTR, untranslated region
Received February 1, 2007; revised April 9, 2007; accepted April 11, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. E. Sehl, L. R. Langer, J. C. Papp, L. Kwan, J. L. Seldon, G. Arellano, J. Reiss, E. F. Reed, S. Dandekar, Y. Korin, et al. Associations between Single Nucleotide Polymorphisms in Double-Stranded DNA Repair Pathway Genes and Familial Breast Cancer Clin. Cancer Res., March 15, 2009; 15(6): 2192 - 2203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Ellis, D. Huo, O. Yildiz, L. J. Worrillow, M. Banerjee, M. M. Le Beau, R. A. Larson, J. M. Allan, and K. Onel MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility Blood, August 1, 2008; 112(3): 741 - 749. [Abstract] [Full Text] [PDF]
|
|