Hormone replacement therapy and risk of epithelial ovarian cancer

It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case–control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32–4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% Cl 1.54–5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours. © 1999 Cancer Research Campaig

Estimating the referral rate for cancer genetic assessment from a systematic review of the evidence

To estimate the optimal proportion of new patients diagnosed with cancer who require assessment and evaluation for familial cancer genetic risk, based on the best evidence available. We identified evidence of the patients who require assessment for familial genetic risk when diagnosed with cancer through extensive literature reviews and searches of guidelines. Epidemiological data on the distribution of cancer type, presence of a family history, age and other factors that influence referral for genetic assessment were identified. Decision trees were constructed to merge the evidence-based recommendations with the epidemiological data to calculate the optimal proportion of patients who should be referred. We identified ‘high probability' and ‘moderate probability' groups for having a genetic susceptibility. The proportion of patients diagnosed with cancer in Australia who have a high probability of having a genetic predisposition and who should be referred for genetic assessment is 1%. If the moderate probability group is also assessed this proportion increases to 6%. This model has identified the proportion of new patients diagnosed with cancer who should be referred for genetic assessment. This data is the first step in determining the resources required for provision of an adequate cancer genetic service

Socio-demographic and clinical characteristics of re-presentation to an Australian inner-city emergency department: implications for service delivery

BACKGROUND: People who have complex health care needs frequently access emergency departments for treatment of acute illness and injury. In particular, evidence suggests that those who are homeless, or suffer mental illness, or have a history of substance misuse, are often repeat users of emergency departments. The aim of this study was to describe the socio-demographic and clinical characteristics of emergency department re-presentations. Re-presentation was defined as a return visit to the same emergency department within 28 days of discharge from hospital. METHODS: A retrospective cohort study was conducted of emergency department presentations occurring over a 24-month period to an Australian inner-city hospital. Characteristics were examined for their influence on the binary outcome of re-presentation within 28 days of discharge using logistic regression with the variable patient fitted as a random effect. RESULTS: From 64,147 presentations to the emergency department the re-presentation rate was 18.0% (n = 11,559) of visits and 14.4% (5,894/40,942) of all patients. Median time to re-presentation was 6 days, with more than half occurring within one week of discharge (60.8%; n = 6,873), and more than three-quarters within two weeks (80.9%; n = 9,151). The odds of re-presentation increased three-fold for people who were homeless compared to those living in stable accommodation (adjusted OR 3.09; 95% CI, 2.83 to 3.36). Similarly, the odds of re-presentation were significantly higher for patients receiving a government pension compared to those who did not (adjusted OR 1.73; 95% CI, 1.63 to 1.84), patients who left part-way through treatment compared to those who completed treatment and were discharged home (adjusted OR 1.64; 95% CI, 1.36 to 1.99), and those discharged to a residential-care facility compared to those who were discharged home (adjusted OR 1.46: 95% CI, 1.03 to 2.06). CONCLUSION: Emergency department re-presentation rates cluster around one week after discharge and rapidly decrease thereafter. Housing status and being a recipient of a government pension are the most significant risk factors. Early identification and appropriate referrals for those patients who are at risk of emergency department re-presentation will assist in the development of targeted strategies to improve health service delivery to this vulnerable group

A prognostic index for operable, node-negative breast cancer

Clinical data and samples from patients diagnosed, more than 10 years previously, with operable node-negative breast cancer (participants in the Scottish Adjuvant Tamoxifen trial), were revisited, Cases with two distinct categories of outcome were selected; more than 10 years disease-free survival ('good outcome') or distant relapse within 6 years of diagnosis ('poor outcome'). An initial set of cases was analysed for a range of putative prognostic markers and a prognostic index, distinguishing the two outcome categories, was calculated. This index was then validated by testing its predictive power on a second, independent set of cases. A combination of histological grade plus immunochemical staining for BCL-2, p27 and Cyclin D 1, generated a useful prognostic index for tamoxifen-treated patients but not for those treated by surgery alone, The value of the index was confirmed in a second set of tamoxifen-treated, early stage breast cancers. Over-all, it correctly predicted good and poor outcome in 79 and 74% of cases, respectively (odds ratio 11.0). Other markers assessed added little to prediction of outcome. In the case of molecular assays, sensitivity and reliability were compromised by the age of the tissue specimens and the variability of fixation protocols. In selecting patients for adjuvant systemic chemotherapy, the proposed index improves considerably on current international guidelines and matches the performance reported for 'gene-expression signature' analysis. (C) 2004 Cancer Research UK.</p

Postmenopausal hormones and sleep quality in the elderly: a population based study

<p>Abstract</p> <p>Background</p> <p>Sleep disturbance and insomnia are commonly reported by postmenopausal women. However, the relationship between hormone therapy (HT) and sleep disturbances in postmenopausal community-dwelling adults is understudied. Using data from the multicenter Study of Osteoporotic Fractures (SOF), we tested the relationship between HT and sleep-wake estimated from actigraphy.</p> <p>Methods</p> <p>Sleep-wake was ascertained by wrist actigraphy in 3,123 women aged 84 ± 4 years (range 77-99) from the Study of Osteoporotic Fractures (SOF). This sample represents 30% of the original SOF study and 64% of participants seen at this visit. Data were collected for a mean of 4 consecutive 24-hour periods. Sleep parameters measured objectively included total sleep time, sleep efficiency (SE), sleep latency, wake after sleep onset (WASO), and nap time. All analyses were adjusted for potential confounders (age, clinic site, race, BMI, cognitive function, physical activity, depression, anxiety, education, marital status, age at menopause, alcohol use, prior hysterectomy, and medical conditions).</p> <p>Results</p> <p>Actigraphy measurements were available for 424 current, 1,289 past, and 1,410 never users of HT. Women currently using HT had a shorter WASO time (76 vs. 82 minutes, P = 0.03) and fewer long-wake (≥ 5 minutes) episodes (6.5 vs. 7.1, P = 0.004) than never users. Past HT users had longer total sleep time than never users (413 vs. 403 minutes, P = 0.002). Women who never used HT had elevated odds of SE <70% (OR,1.37;95%CI,0.98-1.92) and significantly higher odds of WASO ≥ 90 minutes (OR,1.37;95%CI,1.02-1.83) and ≥ 8 long-wake episodes (OR,1.58;95%CI,1.18-2.12) when compared to current HT users.</p> <p>Conclusions</p> <p>Postmenopausal women currently using HT had improved sleep quality for two out of five objective measures: shorter WASO and fewer long-wake episodes. The mechanism behind these associations is not clear. For postmenopausal women, starting HT use should be considered carefully in balance with other risks since the vascular side-effects of hormone replacement may exceed its beneficial effects on sleep.</p

Wine and other alcohol consumption and risk of ovarian cancer in the California Teachers Study cohort

OBJECTIVE: Whether alcohol consumption influences ovarian cancer risk is unclear. Therefore, we investigated the association between alcohol intake at various ages and risk of ovarian cancer. METHODS: Among 90,371 eligible members of the California Teachers Study cohort who completed a baseline alcohol assessment in 1995–1996, 253 women were diagnosed with epithelial ovarian cancer by the end of 2003. Multivariate Cox proportional hazards regression analysis was performed to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Consumption of total alcohol, beer, or liquor in the year prior to baseline, at ages 30–35 years, or at ages 18–22 years was not associated with risk of ovarian cancer. Consumption of at least one glass per day of wine, compared to no wine, in the year before baseline was associated with increased risk of developing ovarian cancer: RR = 1.57 (95% CI 1.11–2.22), P(trend) = 0.01. The association with wine intake at baseline was particularly strong among peri-/post-menopausal women who used estrogen-only hormone therapy and women of high socioeconomic status. CONCLUSIONS: Alcohol intake does not appear to affect ovarian cancer risk. Constituents of wine other than alcohol or, more likely, unmeasured determinants of wine drinking were associated with increased risk of ovarian cancer

Role of biological markers in the clinical outcome of colon cancer

We investigated a number of biological markers, evaluated under strict intralaboratory quality control conditions, in terms of their role in predicting clinical outcome of patients with colon cancer treated with 5-FU-containing regimens. Colon cancer tissue from 263 patients enrolled onto two randomised clinical trials were studied for their cytofluorimetrically determined DNA content and their immunohistochemically evaluated microvessel density, vascular endothelial growth factor expression, thymidylate synthase expression and tumour lymphocyte infiltration. Disease-free survival and overall survival of patients were analysed as a function of the different variables. At a median follow up of 57 months, age, gender and Dukes' stage showed an impact on disease-free survival, whereas no biological marker emerged as an indicator of better or worse disease-free survival. Only histological grade and Dukes' stage were found to influence overall survival. The different biological variables, studied with particular attention for determination reliability, proved to have no impact on the clinical outcome of patients with colon cancer. Therefore, other markers must be identified to complement clinico-pathological variables in the management of this disease

Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer

A survey to assist in targeting the adults who undertake risky behaviours, know their health behaviours are not optimal and who acknowledge being worried about their health

Background: Research indicates that those who are worried about their health are more likely to change their in-appropriate behavioural-related risk factors. A national survey was undertaken to determine adults who correctly perceive and actually undertake in-appropriate behavioural-related risk factors (smoking, physical activity, alcohol intake, fruit and vegetable consumption, weight and psychological distress) and are worried about their health. Methods: Australian 2010 CATI survey of 3003 randomly selected adults. Perception and self-reported levels of each risk factor, and whether they worried that the level was affecting their health were assessed using univariate and multivariate analyses. Results: The comparisons between perception of healthy behaviour and actual behaviour varied for each risk factor with 44.1% of people in the un-healthy weight range and 72.9% of those eating less than sufficient fruit and vegetables having the perception that their behaviour was healthy. The demographic and other related variables in the multivariate analyse for each risk factor varied considerably. For example the variables in the final multivariate model for smokers who were worried about their risk factor were markedly different to the other risk factor models and 45 to 54 year olds were more likely to be included in the final models for nearly all of the risk factor analyses. Conclusion: By limiting this analyses to those who are acknowledging (correctly or otherwise) that their perception of behaviour is making their health worse, this study has shown that the profile for each risk factor varies considerably. As such, evidence suggests specific targeted programs are required rather than a broad brush approach.Anne W Taylor, Kay Price and Simon Fullerto

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe