Ovarian cancer in Western Australia (1982–98): incidence, mortality and survival

Abstract Objectives: To investigate the trends in incidence and mortality and estimate survival for women diagnosed with ovarian cancer in Western Australia. Case selection and methods: There were 1,336 women diagnosed with ovarian cancer in 1982–98. Age‐standardised rates were calculated by the direct method. Age‐period and age‐cohort models were analysed by Poisson regression. The Kaplan‐Meier method was used to estimate survival and Cox proportional hazards regression evaluated the relative risk of dying. Results: Trends in age‐adjusted incidence and mortality rates showed little changed over the three time periods of diagnosis. A significant birth cohort effect showed a peak in the risk in the 1924 (mid‐year) cohort followed by a general decrease in both incidence and mortality risk. Survival at five years was 34% (95% CI 31.3–36.5) overall, but was only 27% (95% CI 17.4–36.7) among women with stage III and IV disease. Aboriginal women showed a risk of dying twice that of non‐Aboriginal women. Conclusions: The birth cohort analysis of ovarian cancer proved better at explaining disease trends than was time period of diagnosis. Survival continues to be poor, but Aboriginal women and those with serous and unspecified adenocarcinoma tumours fair much worse. Implications: As the leading cause of death from a gynaecological malignancy, ovarian cancer is of public health importance. Historical trends in birth rates and the use of oral contraceptives help to explain at least some of the observed birth cohort trends in this study. In the long term, an effective diagnostic technique needs to be developed or this disease will continue to be diagnosed at an advanced stage when treatment options for cure are limited

p.R270X MECP2 mutation and mortality in Rett syndrome

Among cases in the Australian Rett Syndrome Database, the nonsense mutation p.R270X is one of the most commonly occurring single pathogenic MECP2 mutations. In two recent published reports of the MECP2 mutational spectrum the p.R270X appeared to be under represented. We hypothesised that increased mortality arising from this mutation may underlie this apparent discrepancy. We investigated our hypothesis in two independent study groups from Australia and the UK with prospective data collections (total n=524). Only females with Rett syndrome and an identified MECP2 mutation were included. Significant differences in survival were detected among Rett syndrome cases grouped for the eight most frequent mutations (log-rank v2 (7)=15.71, P=0.03). Moreover, survival among cases with p.R270X, when compared with survival among cases with all the other mutations was reduced (log-rank v2 (2)=6.94, P=0.01). Our observation of a reduced survival associated with the p.R270X mutation offers an explanation for the under representation of p.R270X in older subjects with Rett syndrome