Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
17592773
TITLE
Progesterone receptor polymorphisms and risk of breast cancer: results from two Australian breast cancer studies.
ABSTRACT
Association studies aimed at identifying breast cancer susceptibility variants in the progesterone receptor (PGR) gene have been previously reported in the literature with conflicting results, ranging from a protective effect conferred by the PROGINS allele in German Caucasian women, to an increased risk for the leucine variant of the Val660Leu (rs1042838) polymorphism in East Anglian cases. We report the results of genotype and haplotype analyses of five PGR polymorphisms, +44C/T (rs518162), +331G/A (rs10895068), V660L (rs1042838), H770H (rs1042839) and Q886Q (rs500760), conducted on 1,847 Australian breast cancer cases (including 276 cases from a cohort of multiple-case breast cancer families) and 833 controls. Genotype and haplotype analyses of the five polymorphisms showed no evidence of an association with breast cancer (p>0.3). We also conducted a meta-analysis of the V660 L (rs1042838) polymorphism on our and six other published studies including 10,205 cases and 11,320 controls. Compared to the VV homozygotes, VL heterozygotes and LL homozygotes were associated with a non-significant increased risk for breast cancer [Odds ratio (OR)VL, 1.06; 95% confidence intervals (95% CI), 0.97-1.15, ORLL, 1.05; 95% CI, 0.75-1.49]. Analysis of a per-leucine allele risk under a codominant model, however, suggested a significant leucine-allele dose effect, ORper-L, 1.07; 95% CI, 1.02-1.13, p=0.01. We conclude that the leucine allele of the V660L SNP may be associated with a small increase in breast cancer risk, while the other four PGR SNPs, +44C/T (rs518162), +331G/A (rs10895068), H770H (rs1042839) and Q886Q (rs500760), do not substantially increase breast cancer risk.
DATE PUBLISHED
2008 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2007/05/15
accepted 2007/05/17
aheadofprint 2007/06/26
pubmed 2007/06/27 09:00
medline 2008/11/14 09:00
entrez 2007/06/27 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Johnatty SE Johnatty Sharon E SE Cancer and Cell Biology, Queensland Institute of Medical Research, c/o Royal Brisbane Hospital Post Office, Herston, Brisbane, QLD, 4029, Australia.
Spurdle AB Spurdle Amanda B AB
Beesley J Beesley Jonathan J
Chen X Chen Xiaoqing X
Hopper JL Hopper John L JL
Duffy DL Duffy David L DL
Chenevix-Trench G Chenevix-Trench Georgia G
Kathleen Cuningham Consortium for Research in Familial Breast Cancer
INVESTIGATORS
JOURNAL
VOLUME: 109
ISSUE: 1
TITLE: Breast cancer research and treatment
ISOABBREVIATION: Breast Cancer Res. Treat.
YEAR: 2008
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0167-6806
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Breast Cancer Res Treat
COUNTRY: Netherlands
ISSNLINKING: 0167-6806
NLMUNIQUEID: 8111104
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Alleles
Australia
Breast Neoplasms genetics
Female genetics
Genotype genetics
Haplotypes genetics
Heterozygote genetics
Homozygote genetics
Humans genetics
Middle Aged genetics
Polymorphism, Genetic genetics
Polymorphism, Single Nucleotide genetics
Receptors, Progesterone genetics
Risk genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Receptors, Progesterone
OTHER ID's