BACKGROUND: The PROGINS allele of the progesterone receptor (PGR) gene has been associated with an increased risk of ovarian cancer and a decreased risk of breast cancer. We set out to refine the association between common variation at the PGR gene locus and these two diseases. METHODS: We characterized the haplotype structure of the PGR gene by genotyping 54 single-nucleotide polymorphisms (SNPs) in 349 women. We then selected a subset of 17 haplotype-tagging SNPs that captured variation across the locus and typed them in 267 ovarian cancer case patients and 397 control subjects from two case-control studies and in 1715 breast cancer case patients and 2505 control subjects from a cohort study. RESULTS: The PGR locus was characterized by four blocks of strong linkage disequilibrium. Two SNPs in block 4 were associated with an increased risk of ovarian cancer among homozygous carriers as compared with noncarriers: rs1042838 (PROGINS allele; odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.19 to 8.75, P = .022) and rs608995 (minor allele; OR = 3.10, 95% CI = 1.63 to 5.89, P<.001). The PROGINS allele was observed on a subset of chromosomes carrying the minor allele at rs608995, and its association with ovarian cancer was fully explained by its association with rs608995. In addition, rs608995 fell on two common haplotypes (4-D and 4-E), whose association with ovarian cancer was the same as that of rs608995. These same two haplotypes were associated with a non-statistically significantly reduced risk of breast cancer. CONCLUSIONS: Variation in PGR was associated with ovarian cancer risk, although the strongest result was not with the PROGINS allele. Instead, any causal allele(s) are likely in or downstream of block 4 and carried on haplotypes 4-D and 4-E. There was some evidence that the same variation was associated with a reduced risk of breast cancer, but the association was not statistically significant.
BACKGROUND: The PROGINS allele of the progesterone receptor (PGR) gene has been associated with an increased risk of ovarian cancer and a decreased risk of breast cancer. We set out to refine the association between common variation at the PGR gene locus and these two diseases. METHODS: We characterized the haplotype structure of the PGR gene by genotyping 54 single-nucleotide polymorphisms (SNPs) in 349 women. We then selected a subset of 17 haplotype-tagging SNPs that captured variation across the locus and typed them in 267 ovarian cancer case patients and 397 control subjects from two case-control studies and in 1715 breast cancer case patients and 2505 control subjects from a cohort study. RESULTS: The PGR locus was characterized by four blocks of strong linkage disequilibrium. Two SNPs in block 4 were associated with an increased risk of ovarian cancer among homozygous carriers as compared with noncarriers: rs1042838 (PROGINS allele; odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.19 to 8.75, P = .022) and rs608995 (minor allele; OR = 3.10, 95% CI = 1.63 to 5.89, P<.001). The PROGINS allele was observed on a subset of chromosomes carrying the minor allele at rs608995, and its association with ovarian cancer was fully explained by its association with rs608995. In addition, rs608995 fell on two common haplotypes (4-D and 4-E), whose association with ovarian cancer was the same as that of rs608995. These same two haplotypes were associated with a non-statistically significantly reduced risk of breast cancer. CONCLUSIONS: Variation in PGR was associated with ovarian cancer risk, although the strongest result was not with the PROGINS allele. Instead, any causal allele(s) are likely in or downstream of block 4 and carried on haplotypes 4-D and 4-E. There was some evidence that the same variation was associated with a reduced risk of breast cancer, but the association was not statistically significant.
Authors: Eunjung Lee; Sue A Ingles; David Van Den Berg; Wei Wang; Chris Lavallee; Mei-Hua Huang; Carolyn J Crandall; Frank Z Stanczyk; Gail A Greendale; Giske Ursin Journal: Menopause Date: 2012-03 Impact factor: 2.953
Authors: Jennifer Lin; Robert Y L Zee; Kuang-Yu Liu; Shumin M Zhang; I-Min Lee; JoAnn E Manson; Edward Giovannucci; Julie E Buring; Nancy R Cook Journal: Cancer Causes Control Date: 2010-02-11 Impact factor: 2.506
Authors: Catherine M Phelan; Ya-Yu Tsai; Ellen L Goode; Robert A Vierkant; Brooke L Fridley; Jonathan Beesley; Xiao Qing Chen; Penelope M Webb; Stephen Chanock; Daniel W Cramer; Kirsten Moysich; Robert P Edwards; Jenny Chang-Claude; Montserrat Garcia-Closas; Hannah Yang; Shan Wang-Gohrke; Rebecca Hein; Adele C Green; Jolanta Lissowska; Michael E Carney; Galina Lurie; Lynne R Wilkens; Roberta B Ness; Celeste Leigh Pearce; Anna H Wu; David J Van Den Berg; Daniel O Stram; Kathryn L Terry; David C Whiteman; Alice S Whittemore; Richard A DiCioccio; Valerie McGuire; Jennifer A Doherty; Mary Anne Rossing; Hoda Anton-Culver; Argyrios Ziogas; Claus Hogdall; Estrid Hogdall; Susanne Krüger Kjaer; Jan Blaakaer; Lydia Quaye; Susan J Ramus; Ian Jacobs; Honglin Song; Paul D P Pharoah; Edwin S Iversen; Jeffrey R Marks; Malcolm C Pike; Simon A Gayther; Julie M Cunningham; Marc T Goodman; Joellen M Schildkraut; Georgia Chenevix-Trench; Andrew Berchuck; Thomas A Sellers Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-02 Impact factor: 4.254
Authors: Eunjung Lee; Chris Hsu; Christopher A Haiman; Pedram Razavi; Pamela L Horn-Ross; David Van Den Berg; Leslie Bernstein; Loic Le Marchand; Brian E Henderson; V Wendy Setiawan; Giske Ursin Journal: Carcinogenesis Date: 2010-06-13 Impact factor: 4.944
Authors: L Quaye; H Song; S J Ramus; A Gentry-Maharaj; E Høgdall; R A DiCioccio; V McGuire; A H Wu; D J Van Den Berg; M C Pike; E Wozniak; J A Doherty; M A Rossing; R B Ness; K B Moysich; C Høgdall; J Blaakaer; D F Easton; B A J Ponder; I J Jacobs; U Menon; A S Whittemore; S Krüger-Kjaer; C L Pearce; P D P Pharoah; S A Gayther Journal: Br J Cancer Date: 2009-02-24 Impact factor: 7.640