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

Abstract

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

Genetic Variation in the Progesterone Receptor Gene and Ovarian Cancer Risk

“…Inconsistencies between our study results and those of previous studies concerning the PROGINS allele may be due to the differences in study design (13,14,17), restriction to BRCA1/2 carriers (18), and differences in ethnic distributions (16). Results reported by Spurdle et al (12) were not entirely inconsistent with our own.…”

“…There has been considerable interest in the relation between the progesterone receptor and ovarian cancer risk (12)(13)(14)(15)(16)(17)(18). However, the results of epidemiologic studies have been inconsistent because of differences in study design or study populations, as well as small sample sizes.…”

Genetics of endometriosis: a role for the progesterone receptor gene polymorphism PROGINS?

“…From a functional standpoint it has to be noted that this specific germline Taq I restriction fragment length polymorphism of the PR gene is thought to result in anomalous transcription of the PR gene either by recombination or by misplacement of the primary transcript (McKenna et al ., 1995). Moreover, this polymorphism has been described as being associated with an increased risk for ovarian carcinoma, albeit not consistently (McKenna et al ., 1995;Lancaster et al ., 1998;Tong et al ., 2001Tong et al ., , 2002Whittemore & McGuire, 2002). Preliminary data indicate that the PR isoform A protein associated with PROGINS has an increased stability and therefore a higher transcriptional activity that may cause an inadequate control of oestrogen receptor and PR isoform B, leading to an increased risk of tumour development ( Tong et al ., 2001).…”