Progesterone receptor (PROGINS) polymorphism and the risk of ovarian cancer

Leite, Daniela; Junqueira, Michele Gilvana; Carvalho, Cristina Valletta de; Massad-Costa, A. M.; Gonçalves, Wagner José; Nicolau, Sérgio Mancini; Lopes, Luiz Anderson; Baracat, E C; Silva, Ismael D.C.G. da

doi:10.1016/j.steroids.2008.02.005

Cited by 28 publications

(16 citation statements)

References 30 publications

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“…And PR expression was associated with favorable survival [53,55]. PR polymorphisms (PROGINS) and mutations have been observed in association with increased risk of ovarian cancer [56]. In women with ovarian cancers positive for PR, progesterone mediated activation of PR may down-regulate cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and growth of ovarian surface epithelial cancer cells

Ramayya

Sheng

Moroz

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussionmentioning

confidence: 99%

Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and growth of ovarian surface epithelial cancer cells

Ramayya

Sheng

Moroz

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

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“…In vitro studies have shown that the PROGINS allele may reduce PGR transcription or signaling in several ovarian cancer cell lines (8). The PROGINS allele has been associated with increased ovarian cancer risk in a number of studies (9)(10)(11)(12)(13), although such associations have not been observed in some studies (14)(15)(16). Recently, a pooled analysis within the Ovarian Cancer Association Consortium showed that the PROGINS allele is associated with increased risk of endometrioid type ovarian cancer (17).…”

Section: Introductionmentioning

confidence: 99%

Genetic variation in the progesterone receptor gene and risk of endometrial cancer: a haplotype-based approach

et al. 2010

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Background: It is well established that estrogen increases endometrial cancer risk, whereas progesterone opposes the estrogen effects. The PROGINS allele of the progesterone receptor (PGR) gene reduces the function of PGR and has been associated with increased risk of the endometrioid type ovarian cancer. We investigated whether genetic variation in PGR is also associated with endometrial cancer risk using a haplotype-based approach. Methods: We pooled data from two endometrial cancer casecontrol studies that were nested within two prospective cohorts, the Multiethnic Cohort Study and the California Teachers Study. Seventeen haplotype-tagging single nucleotide polymorphisms (SNPs) across four linkage disequilibrium (LD) blocks spanning the PGR locus were genotyped in 583 incident cases and 1936 control women. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each haplotype were estimated using conditional logistic regression, stratified by age and ethnicity. Results: Genetic variation in LD block 3 of the PGR locus was associated with endometrial cancer risk (P global test 5 0.002), with haplotypes 3C, 3D and 3F associated with 31-34% increased risk. Among whites (383 cases/840 controls), genetic variation in all four blocks was associated with increased endometrial cancer risk (P global test 5 0.010, 0.013, 0.005 and 0.020). Haplotypes containing the PROGINS allele and several haplotypes in blocks 1, 3 and 4 were associated with 34-77% increased risk among whites. SNP analyses for whites suggested that rs608995, partially linked to the PROGINS allele (r 2 5 0.6), was associated with increased risk (OR 5 1.30, 95% CI 5 1.06-1.59). Conclusions: Our results suggest that genetic variation in the PGR region is associated with endometrial cancer risk.

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“…One of these regions contains the progesterone receptor gene (PGR). Genetic variants in the promoter and coding regions of this gene have been associated with breast, endometrial, and ovarian cancer, although there is some inconsistency among the studies [4][5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Associations of Progesterone Receptor Polymorphisms with Age at Menarche and Menstrual Cycle Length

Taylor

Small²,

Epstein³

et al. 2010

Horm Res Paediatr

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Background: Age at menarche and menstrual cycle characteristics are indicators of endocrine function and may be risk factors for diseases such as reproductive cancers. The progesterone receptor gene (PGR) has been identified as a candidate gene for age at menarche and menstrual function. Methods: Women office workers ages 19–41 self-reported age at menarche and participated in a prospective study of menstrual function and fertility. First-morning urine was used as the DNA source. 444 women were genotyped for a functional variant in PGR, rs1042838 (Val660Leu), and 264 women were also genotyped for 29 other SNPs across the extended gene region. Results: Genetic variation across PGR was associated with age at menarche using a global score statistic (p = 0.03 among non-Hispanic whites). Women carrying two copies of the Val660Leu variant experienced menarche 1 year later than women carrying one or no copies of the variant (13.6 ± 0.5 vs. 12.6 ± 0.1; p = 0.03). The Val660Leu variant was also associated with decreased odds of short menstrual cycles (17–24 days) (OR, 95% CI: 0.54 [0.36, 0.80]; p = 0.002). Conclusion: Genetic variation in PGR was associated with age at menarche and menstrual cycle length in this population. Further investigation of these associations in a replication dataset is warranted.

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Progesterone receptor (PROGINS) polymorphism and the risk of ovarian cancer

Cited by 28 publications

References 30 publications

Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and growth of ovarian surface epithelial cancer cells

Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and growth of ovarian surface epithelial cancer cells

Genetic variation in the progesterone receptor gene and risk of endometrial cancer: a haplotype-based approach

Associations of Progesterone Receptor Polymorphisms with Age at Menarche and Menstrual Cycle Length

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