Progesterone receptor polymorphisms and risk of breast cancer: results from two Australian breast cancer studies.
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.
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
Amanda B
AB
Beesley
Jonathan
J
Chen
Xiaoqing
X
Hopper
John L
JL
Duffy
David L
DL
Chenevix-Trench
Georgia
G
D000328:Adult; D000483:Alleles; D001315:Australia; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011980:Receptors, Progesterone / Q000235:genetics*; D012306:Risk
D011980:Receptors, Progesterone