title: Progesterone receptor gene variants and risk of endometrial cancer.
abstract: Prolonged excessive estrogen exposure unopposed by progesterone is widely accepted to be a risk factor for endometrial cancer development. The physiological function of progesterone is dependent upon the presence of its receptor [progesterone receptor (PGR)] and several studies have reported single nucleotide polymorphisms (SNPs) in the PGR gene to be associated with endometrial cancer risk. We sought to confirm the associations with endometrial cancer risk previously reported for four different PGR polymorphisms. A maximum of 2888 endometrial cancer cases and 4483 female control subjects from up to three studies were genotyped for four PGR polymorphisms (rs1042838, rs10895068, rs11224561 and rs471767). Logistic regression with adjustment for age, study, ethnicity and body mass index was performed to calculate odds ratios (ORs) and associated 95% confidence intervals (CIs) and P-values. Of the four SNPs investigated, only rs11224561 in the 3' region of the PGR gene was found to be significantly associated with endometrial cancer risk. The A allele of the rs11224561 SNP was associated with increased risk of endometrial cancer (OR per allele 1.31; 95% CI 1.12-1.53, P = 0.001, adjusted for age and study), an effect of the same magnitude and direction as reported previously. We have validated the endometrial cancer risk association with a tagSNP in the 3' untranslated region of PGR previously reported in an Asian population. Replication studies will be required to refine the risk estimate and to establish if this, or a correlated SNP, is the underlying causative variant.
authors.affiliation: Genetics and Population Health Division, Queensland Institute of Medical Research, Herston, Brisbane, Queensland 4006, Australia.
authors.forename: Tracy A
authors.initials: TA
authors.lastname: O'Mara
authors.forename: Paul
authors.initials: P
authors.lastname: Fahey
authors.forename: Kaltin
authors.initials: K
authors.lastname: Ferguson
authors.forename: Louise
authors.initials: L
authors.lastname: Marquart
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Evelyn
authors.initials: E
authors.lastname: Despierre
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Shahana
authors.initials: S
authors.lastname: Ahmed
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Gregory
authors.forename: Mitul
authors.initials: M
authors.lastname: Shah
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D011980:Receptors, Progesterone