A germline TaqI restriction fragment length polymorphism in the progesterone receptor gene in ovarian carcinoma

McKenna, Neil J.; Kieback, D. G.; Carney, Desmond N.; Fanning, M. D.; McLinden, James H.; Headon, Denis R.

doi:10.1038/bjc.1995.92

Cited by 73 publications

(48 citation statements)

References 17 publications

(12 reference statements)

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“…The PROGINS polymorphism consists of a 306 bp Alu insertion in the G intron of the PGR gene, which always occurs with the L allele of the V660L polymorphism. The insert-carrying allele exhibits higher mRNA stability and is transcribed to a more stable and transcriptionally active protein (24). The PROGINS insertion allele has been reported as inversely correlated with risk of breast cancer (25,26), ovarian cancer (27), and endometriosis (28) in some populations, whereas in other studies, no association has been reported (29)(30)(31).…”

Section: Introductionmentioning

confidence: 71%

Association of theProgesterone ReceptorGene with Breast Cancer Risk: A Single-Nucleotide Polymorphism Tagging Approach

Pooley¹,

Healey²,

Smith

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Association studies on susceptibility to breast cancer using single nucleotide polymorphisms (SNP) in the progesterone receptor (PGR) gene have been previously published, but the results have been inconclusive. We used a comprehensive SNP-tagging approach to search for low-penetrance susceptibility alleles in a study of up to 4,647 cases and 4,564 controls, in a two-stage study design. We identified seven tagging SNPs using genotype data from the National Institute of Environmental Health Sciences (NIEHS) Environmental Genome Project and typed these, and an additional three SNPs, in 2,345 breast cancer cases and 2,284 controls (set 1). Three SNPs showed no evidence for association and were not studied further, whereas seven SNPs (rs11571171, rs7116336, rs660149, rs10895068, rs500760, rs566351, and rs1042838) exhibited significant associations at P < 0.1 using either a heterogeneity or trend test and progressed to be genotyped in set 2. After both stages, only one SNP was significantly associated with an increased risk of breast cancer -the PGR-12 (rs1042638) V660L valine to leucine polymorphism [VL heterozygotes (odds ratio, 1.13; 95% confidence interval, 1.03-1.24) and the LL homozygotes (odds ratio, 1.30; 95% confidence interval, 0.98-1.73), P het = 0.008, P trend = 0.002]. Similar estimates were obtained in a combined analysis of our data with those from three other published studies. We conclude that the 660L allele may be associated with a moderately increased risk of breast cancer, but that other common SNPs in the PGR gene are unlikely to be associated with a substantial risk of breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(4):675 -82)

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Section: Introductionmentioning

confidence: 71%

Association of theProgesterone ReceptorGene with Breast Cancer Risk: A Single-Nucleotide Polymorphism Tagging Approach

Pooley¹,

Healey²,

Smith

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Alelos mutantes desse gene foram descritos recentemente, destacandose o polimorfismo PROGINS, que consiste em uma inserção da família Alu de 306 pares de base (pb) no íntron G, entre os éxons 7 e 8 -região codificante do domínio de ligação hormonal. Essa inserção levaria à transcrição anômala do gene, codificando uma forma variante do éxon 8 10,11 . A codificação de um éxon alternativo, por sua vez, resultaria em perda da capacidade de ligação do hormônio ao receptor e da sua subseqüente ativação, com queda da atividade final mediada pela progesterona 12 .…”

Section: Métodosunclassified

Relação entre polimorfismo do gene do receptor de progesterona, raça, paridade e ocorrência de leiomioma uterino

Gomes¹,

Castro²,

Villanova³

et al. 2006

Rev. Bras. Ginecol. Obstet.

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Objetivos: analisamos raça, paridade e presença do polimorfismo do gene do receptor de progesterona, denominado PROGINS, como fatores relacionados à ocorrência de leiomioma uterino em mulheres brasileiras. Métodos: realizamos estudo caso-controle, no qual foram incluídas 122 pacientes com diagnóstico de leiomioma e 125 mulheres sem a doença. Após registro dos dados clínicos, coletamos material biológico para extração de DNA, reação em cadeia da polimerase e eletroforese em gel de agarose, a fim de identificar a presença do polimorfismo PROGINS. A análise estatística foi feita pelo teste não paramétrico de Mann-Whitney ou pelo teste do χ 2 , a depender da variável estudada. O risco para ocorrência da doença foi calculado pelo modelo de regressão logística, com obtenção da odds ratio (OR) (razão de chances). O nível de significância adotado foi de 5% (p<0,05) e o intervalo de confiança foi de 95% (IC 95%). Resultados: observamos maior prevalência de "não-brancas" -pardas e negras -(50 vs 22,4%) e de nulíparas (23,8 vs 11,2%) nos casos, ao passo que o genótipo do receptor de progesterona foi mais freqüentemente PROGINS positivo -heterozigoto ou homozigoto mutante -entre os controles (21,6 vs 10,7%). A razão de chances indicou elevação do risco para leiomioma relacionada à raça "não branca" (OR=3,46; IC 95%: 2,0-6,0) e à nuliparidade (OR=3,30; IC 95%: 1,9-5,6), com redução na presença de genótipos PROGINS positivo (OR=0,43; IC 95%: 0,2-0,9). Conclusões: a raça "não branca" e a nuliparidade foram consideradas fatores de risco para a ocorrência de leiomioma uterino em mulheres da população estudada, ao passo que o polimorfismo PROGINS demonstrou ser fator protetor. PALAVRAS-CHAVE: ABSTRACTPurpose: to analyze race, parity and presence of the progesterone receptor polymorphism, named PROGINS, as factors related to uterine leiomyoma occurrence in Brazilian women. Methods: we carried out a case-control study, composed of 122 patients with the diagnosis of uterine fibroid and 125 women without the disease. After recording the clinical data, we collected biological material for DNA extraction, polymerase chain reaction and agarose gel electrophoresis in order to identify the presence of PROGINS polymorphism. Statistical analysis was performed using the non-parametric MannWhitney test or the χ 2 test, depending on the studied variable. The risk for the occurrence of the disease was calculated byRelação entre polimorfismo do gene do receptor de progesterona, raça, paridade e ocorrência de leiomioma uterinoRelation between progesterone receptor gene polymorphism, race, parity, and uterine leiomyoma occurrence

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“…It also varied from 1.8% to 5% in healthy women. [2][3][4][5][6][7] These differences might be partly due to small sample sizes. Thus, based on these data one should be very careful in drawing any conclusion about the functional role of the PROGINS variant for ovarian cancer.…”

Section: Dear Sirmentioning

confidence: 99%

No association between the human progesterone receptor gene polymorphism PROGINS and risk for ovarian carcinoma in Austrian women

Tong

Fabjani

Heinze

et al. 2002

Intl Journal of Cancer

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Dear Sir,It is correct that the data presented in our report 1 on the impact of the progesterone receptor gene variant PROGINS indicate a statistically significant higher likelihood to carry 2 copies of the PROGINS allele for patients with ovarian carcinoma than for healthy women. However, we did not stress this because of the very few PROGINS homozygous individuals among the cancer patients (9/226) and the control group (1/ 194).In the meantime, we collected and analyzed 46 more DNA samples from ovarian carcinoma patients and from 226 healthy controls. The summarized results (Table I) from the new data and the original data demonstrate that there is no statistically significant difference in the distribution of the genotypes between the ovarian carcinoma patients (patients with borderline tumors excluded) and healthy volunteers. In particular, the frequency of the PROGINS allele A2 was 0.15 in both groups. Analysis of the PROGINS allele as a potential risk factor showed that there is no increased risk of ovarian cancer for either PROGINS allele carriers in general (heterozygotes ϩ homozygotes) or PROGINS homozygotes compared to non-PROGINS carriers [odds ratio (OR) ϭ 0.92, 95% confidence interval (CI) 0.65-1.30, p ϭ 0.64; OR ϭ 2.05, 95% CI 0.80 -5.44, p ϭ 0.14, respectively].The frequency of the A2/A2 genotype in patients with ovarian carcinoma was reported contradictory for various populations (0 -5%). It also varied from 1.8% to 5% in healthy women. 2-7 These differences might be partly due to small sample sizes. Thus, based on these data one should be very careful in drawing any conclusion about the functional role of the PROGINS variant for ovarian cancer. Further studies with larger numbers of samples are needed.Yours

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A germline TaqI restriction fragment length polymorphism in the progesterone receptor gene in ovarian carcinoma

Cited by 73 publications

References 17 publications

Association of theProgesterone ReceptorGene with Breast Cancer Risk: A Single-Nucleotide Polymorphism Tagging Approach

Association of theProgesterone ReceptorGene with Breast Cancer Risk: A Single-Nucleotide Polymorphism Tagging Approach

Relação entre polimorfismo do gene do receptor de progesterona, raça, paridade e ocorrência de leiomioma uterino

No association between the human progesterone receptor gene polymorphism PROGINS and risk for ovarian carcinoma in Austrian women

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