Progesterone receptor (PROGINS) polymorphism and the risk of endometrial cancer development

2007 ◽  
Vol 17 (1) ◽  
pp. 229-232 ◽  
Author(s):  
M. G. Junqueira ◽  
I. D.C.G. Da Silva ◽  
N. C. Nogueira-De-Souza ◽  
C. V. Carvalho ◽  
D. B. Leite ◽  
...  

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in São Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The χ2 test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.

2010 ◽  
Vol 32 (3) ◽  
pp. 331-335 ◽  
Author(s):  
T. A. O'Mara ◽  
P. Fahey ◽  
K. Ferguson ◽  
L. Marquart ◽  
D. Lambrechts ◽  
...  

2010 ◽  
Vol 31 (8) ◽  
pp. 1392-1399 ◽  
Author(s):  
Eunjung Lee ◽  
Chris Hsu ◽  
Christopher A. Haiman ◽  
Pedram Razavi ◽  
Pamela L. Horn-Ross ◽  
...  

Cancer ◽  
2009 ◽  
Vol 115 (12) ◽  
pp. 2693-2700 ◽  
Author(s):  
Wang-Hong Xu ◽  
Ji-rong Long ◽  
Wei Zheng ◽  
Zhi-xian Ruan ◽  
Qiuyin Cai ◽  
...  

2004 ◽  
Vol 89 (12) ◽  
pp. 6340-6347 ◽  
Author(s):  
Irina U. Agoulnik ◽  
Xiao-Wen Tong ◽  
Dagmar-C. Fischer ◽  
Klaus Körner ◽  
Neely E. Atkinson ◽  
...  

Abstract Recently, we and others have detected a haplotype of the human progesterone receptor gene (PR). This haplotype consists of a 320-bp insertion in intron G together with point mutations in exons 4 and 5 and was named PROGINS. Whereas the exon 5 mutation is silent, the mutation in exon 4 results in a V660L substitution. Interestingly, this genetic polymorphism was seen to cosegregate with an increased risk of sporadic ovarian cancer in different ethnic groups. Our data provide evidence for the existence of an epidemiological link between a mutated progesterone receptor allele and ovarian cancer (odds ratio, 3.02; 95% confidence interval, 1.86–4.91). Functional characterization of the mutated receptor protein revealed a greater transcriptional activity compared with the wild-type receptor. By contrast, hormone binding and hormone dissociation rates were similar in both receptor proteins. We found that the increased transcriptional activity was due to increased stability resulting in higher expression of the mutant protein. Thus, the long-lasting hyperactivation of progesterone receptor-driven genes secondary to the increased transcriptional activity of the mutated progesterone receptor may participate in ovarian carcinogenesis. This is of special interest, because only a few genetic markers are available for the majority of women diagnosed with sporadic ovarian cancer.


2014 ◽  
Vol 291 (1) ◽  
pp. 115-122 ◽  
Author(s):  
Noel Pabalan ◽  
Maria Ruth Pineda ◽  
Hamdi Jarjanazi ◽  
Denise M. Christofolini ◽  
Caio Parente Barbosa ◽  
...  

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