Genes encoding hormone receptors are among candidate genes modulating the risk of ovarian cancer. We aimed to assess a frequency of PGRGC331A, FSHRAla307Thr, and FSHRSer680-Asn polymorphic variants, and the length of (CAG)n and (GGN)n repeat tracts in the androgen receptor gene (AR) with respect to ovarian cancer risk and outcome. We genotyped 215 ovarian cancer patients and 352 unaffected control subjects. Statistical analysis was performed with the logistic regression model with adjustment for age. Clinical importance of the polymorphic variants was evaluated in multivariate models on 69 patients treated with taxane-platinum chemotherapy, with respect to TP53 status. Longer AR (GGN)n and (CAG)n repeat tracts decreased the risk of ovarian cancer. For (GGN)n, each additional repeat decreased the risk by 17% (PZ0.011) or 27% (PZ0.002), while the presence of at least 23 repeats decreased the risk by 41% (PZ0.032) or 68% (PZ0.008), for the shorter or longer allele respectively. The risk of disease was also decreased by 11% with each additional (CAG)n repeat (PZ0.006 for the longer allele). FSHRAla307Ala or FSHRSer680Ser polymorphisms increased ovarian cancer risk by 1.8 times (PZ0.042). In all 69 patients, longer AR (CAG)n repeats decreased the risk of recurrence (PZ0.031). In the group with TP53 accumulation, longer AR (CAG)n repeats decreased the risk of recurrence (PZ0.003) and death (PZ0.03), while the FSHRSer680Ser polymorphism increased the risk of recurrence (PZ0.037). Progesterone receptor polymorphisms analyzed did not show any associations. Our results support both the androgen and gonadotropin hypotheses of ovarian cancer development.

SummaryThe TP53 gene mutational spectrum in human tumours shows variations related to tissue of origin, carcinogen exposure or molecular background. We have compared TP53 mutations in ovarian carcinomas from different geographical regions; this study was based on data extracted and verified from the IARC database (R10, 2005), and on our results from 127 carcinomas. In total 873 mutations were evaluated. Tumours from Japan and Korea had a higher frequency of exon 7 mutations (38% vs 25%, p = 0.011) and lower frequency of exon 8 mutations (11% vs 29%, p = 0.0003) than those from Western countries; they were particularly different from Norwegian tumours which showed the lowest proportion of exon 7 (19%, p = 0.001) and highest proportion of exon 8 (37%, p < 0.0001) mutations. There were also differences in the profile of TP53 hotspots. The third hotspot in tumours from Poland was amino acid (AA) 176 (8.2% of substitutions vs 1.7% in other countries, p < 0.001), while in tumours from the UK it was AA 220 (8.9% vs 2.3%, p < 0.001). Codon 273 was the only apparent hotspot in the Norwegian tumours, while it was rarely mutated in Polish and Asian tumours. In contrast to other data tumours from Norway presented with 273 HIS codon (82% of mutations at AA 273, p = 0.002), while tumours from the UK shared the 273 CYS codon (80%, p < 0.001). Further analysis of TP53 gene mutations in ovarian cancer by geography could provide greater insights.

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