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Background Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. Methods and findings Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. Conclusions This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk., Using mendelian randomization approaches, Paul Brennan and colleagues reveal an association between 12 obesity-related factors, including insulin and the development of renal cell carcinoma., Author summary Why was this study done? Traditional observational studies wherein putative risk factors are measured directly have found several obesity-related factors associated with increased risk of renal cell carcinoma (RCC). Traditional observational studies are subject to confounding and reverse causation and have not been able to disentangle which obesity-related risk factors directly influence RCC risk. This study used an alternative methodology commonly referred to as mendelian randomization (MR). MR circumvents many of the inherent limitations of traditional observational study by use of genetic proxies of putative risk factors when evaluating their associations with disease risk, as they are not subject to reverse causation and are less likely to be confounded by other risk factors. What did the researchers do and find? First, we used large-scale genome-wide association studies (GWAS) to identify genetic variants associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose. Second, these genetic variants were used as proxies for the above-mentioned risk factors and evaluated in relation RCC risk using GWAS data from 10,000 RCC patients and 20,000 control participants. Based on these genetic data, we found that multiple measures of obesity, as well as diastolic blood pressure (DBP) and fasting insulin, are associated with RCC risk. In contrast, we found little evidence for an association with RCC risk for systolic blood pressure (SBP), circulating lipids, overall diabetes, or fasting glucose. What do these findings mean? This study provided robust and confirmatory evidence of an important role of obesity as an important risk factor of RCC. Further confirmatory evidence was found for elevated DBP as a risk factor of RCC, but it is not clear why DBP rather than SBP is important in RCC. The study, to our knowledge, provided novel evidence of an important role of circulating insulin in RCC etiology. This study provided some novel insights into the pathways involved in mediating the risk increase in RCC that is caused by obesity, most notably through insulin and DBP, but further research is needed to fully elucidate the important relationship between obesity and RCC.

Contains fulltext : 118139.pdf (Publisher’s version ) (Closed access) PURPOSE: The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. METHODS: We used data from 21 case-control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. RESULTS: Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03-1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39-2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12-1.50). For these histological types, consistent dose-response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. CONCLUSIONS: Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease.

Contains fulltext : 174140.pdf (Publisher’s version ) (Closed access) PURPOSE: Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype. METHODS: Using pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes. RESULTS: History of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01-1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88-1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87-1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35-0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03-1.40, HR = 1.28; 95% CI = 1.05-1.55, and HR = 1.63; 95% CI = 1.20-2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53-0.94. CONCLUSIONS: Histories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients. Understanding mechanisms for these observations could provide insight regarding treatment.

Background There are indications that pancreatic cancer survival may differ according to sociodemographic factors, such as residential location. This may be due to differential access to curative resection. Understanding factors associated with the decision to offer a resection might enable strategies to increase the proportion of patients undergoing potentially curative surgery. Methods Data were extracted from medical records and cancer registries for patients diagnosed with pancreatic cancer between July 2009 and June 2011, living in one of two Australian states. Among patients clinically staged with non-metastatic disease we examined factors associated with survival using Cox proportional hazards models. To investigate survival differences we examined determinants of: 1) attempted surgical resection overall; 2) whether patients with locally advanced disease were classified as having resectable disease; and 3) attempted resection among those considered resectable. Results Data were collected for 786 eligible patients. Disease was considered locally advanced for 561 (71%) patients, 510 (65%) were classified as having potentially resectable disease and 365 (72%) of these had an attempted resection. Along with age, comorbidities and tumour stage, increasing remoteness of residence was associated with poorer survival. Remoteness of residence and review by a hepatobiliary surgeon were factors influencing the decision to offer surgery. Conclusions This study indicated disparity in survival dependent on patients' residential location and access to a specialist hepatobiliary surgeon. Accurate clinical staging is a critical element in assessing surgical resectability and it is therefore crucial that all patients have access to specialised clinical services.

OBJECTIVES: To develop a composite score for the quality of care for patients with pancreatic cancer in Australia; to determine whether it was affected by patient and health service-related factors; to assess whether the score and survival were correlated. DESIGN, PARTICIPANTS AND SETTING: We reviewed medical records of patients diagnosed with pancreatic cancer during July 2009 - June 2011 and notified to the Queensland and New South Wales cancer registries. DESIGN AND MAIN OUTCOME MEASURES: Participants were allocated proportional quality of care scores based on indicators derived from a Delphi process, ranging from 0 (lowest) to 1 (highest quality care). Associations between patient and health service-related factors and the score were tested by linear regression, and associations between the score and survival with Kaplan-Meier and Cox proportional hazards methods. RESULTS: Proportional quality of care scores were assigned to 1571 patients. Scores for patients living in rural areas were significantly lower than for those in major cities (adjusted difference, 11%; 95% CI, 8-13%); they were higher for patients in the least socio-economically disadvantaged areas (v most disadvantaged areas: 8% higher; 95% CI, 6-11%), who were younger, had better Eastern Cooperative Oncology Group performance status, or who first presented to a hospital with a high pancreatic case volume. Higher scores were associated with improved survival; after adjusting for patient-related factors, each 10 percentage point increase in the score reduced the risk of dying by 6% (hazard ratio, 0.94; 95% CI, 0.91-0.97). CONCLUSION: Geographic category of residence may influence the quality of care received by patients with pancreatic cancer, and survival could be improved if they received optimal care.

Evidence suggests that breast-feeding may decrease the risk of epithelial ovarian cancer but it is not clear whether there is a relationship with duration of breast-feeding, patterns of breast-feeding, or particular histological subtypes of ovarian cancer. We sought to investigate these issues in detail.Data from participants in a population-based study of ovarian cancer in western Washington State, USA (2002-2007) who had had at least one birth (881 cases and 1,345 controls) were used to assess relations between patterns of breast-feeding and ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI).Women who ever breast-fed had a 22 % reduction in risk of ovarian cancer compared with those who never breast-fed (OR = 0.78, 95% CI 0.64-0.96) and risk reduction appeared greater with longer durations of feeding per child breast-fed (OR = 0.56, 95% CI 0.32-0.98 for 18 months average duration breast-feeding versus none). Introduction of supplementary feeds did not substantially alter these effects. The overall risk reduction appeared greatest for the endometrioid and clear cell subtypes (OR per month of average breast-feeding per child breast-fed = 0.944, 95% CI 0.903-0.987).Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype.

Background: Cardiovascular disease death rates are higher among Australians from regional and remote areas than those from major cities.

A key assumption of indirect comparisons is similarity, which means that, in the face of differences in patient characteristics or study methods, there is no treatment-effect modification across sides of the indirect comparison. We therefore conducted a systematic review of MEDLINE and EMBASE from inception to November 2009 to summarize currently available information about how frequently, on average, treatment-effect modification occurs across trials that might be used on different sides of an indirect comparison. Although similarity is a key assumption, there is currently no published evidence specifically for indirect comparisons about how frequently treatment-effect modification occurs. Six analyses were identified that assessed treatment-effect modification across studies included in direct head-to-head meta-analyses. Such analyses are relevant to indirect comparisons because the phenomenon being investigated would occur with similar frequency. They provide important information because lack of treatment-effect modification across sides of an indirect comparison cannot be directly assessed statistically; this is in contrast to direct head-to-head meta-analyses where Cochrane's Q statistic or I2 can be used. For ratio measures such as the odds ratio and relative risk, treatment-effect modification occurred for 10-33% of meta-analyses. For the risk difference (an arithmetic measure), the range was 15-46%. It is not prudent to assume similarity in an indirect comparison, based only on the result that ratio measures such as the odds ratio are reasonably robust to treatment-effect modification. All indirect comparisons should include a thorough narrative comparison of differences in patient characteristics and study methods. This will provide end users with the best evidence with which to make an assessment of the likelihood of treatment-effect modification and the plausibility of the similarity assumption.

Several studies have found inverse associations between breastfeeding and ovarian cancer occurrence but there are inconsistencies. The relationship with breastfeeding duration is unclear, and it is uncertain whether the association varies according to histological subtype of ovarian cancer. We sought to clarify these issues. Parous women who participated in an Australia-wide population-based case–control study of epithelial ovarian cancer between 2001 and 2005 (1,092 cases and 1,288 controls) completed a reproductive/lifestyle questionnaire. Logistic regression was used to calculate odds ratios and 95% confidence intervals to investigate relations between breastfeeding and ovarian cancer. We found a strong inverse association between total duration of breastfeeding (all episodes combined) and ovarian cancer occurrence (OR = 0.986, 95% CI 0.978–0.994 per month of breastfeeding) that appeared to be independent of parity. However, individual episodes of lactation beyond 12 months conferred no appreciable additional benefit. The relation with breastfeeding appeared to vary by histological subtype such that we saw no association between duration of breastfeeding and borderline serous cancers or mucinous cancers, but inverse associations for the other subtypes, although these were not always statistically significant. A long total duration of breastfeeding appears to be associated with a substantial reduction in the overall risk of ovarian cancer, independent of the decrease in risk due to childbirth, but this may vary according to histological subtype.

Women with higher parity have a lower risk of ovarian cancer possibly because of pregnancy hormones, but the specific effect of different pregnancy hormones on ovarian cancer risk is not clear. Some clarification might be gained by considering situations where hormone levels vary between pregnancies. Study participants from an Australian population-based, case-control study of epithelial ovarian cancer (2001-2005) completed a reproductive/lifestyle questionnaire. The authors included 1,203 cases and 1,286 controls with at least 1 birth and, using multiple logistic regression, calculated odds ratios and 95% confidence intervals to investigate the effects of pregnancy-related factors on cancer risk. Women who had 1 or more preterm births had higher risks of ovarian cancer than those who had only full-term births (odds ratio (OR) = 1.48, 95% confidence interval (CI): 1.02, 2.15). The authors also found that bearing only boys was associated with a 2-fold increased risk of mucinous ovarian cancer (OR = 2.19, 95% CI: 1.15, 4.17). There was no association between multiple pregnancy and ovarian cancer (for any multiple pregnancy vs. only singleton pregnancies: OR = 1.22, 95% CI: 0.74, 2.02). The results suggest that pregnancies associated with differing hormonal milieux have different effects on ovarian cancer risk and that some of these associations may vary with histologic subtype.

Breast cancer incidence may be increasing in Thailand but very little research has assessed core breast cancer risk factors in this country. We used baseline questionnaire data from a national cohort study of Thai Open University students in an exploratory case-control study of breast cancer. The study included 43 female cases and 860 age-matched controls selected from the remaining 47,271 female cohort participants. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression. The women were predominantly premenopausal. Taller women had an increased risk of breast cancer (OR = 2.3, 95% CI 1.1–4.8, for height ≥160 cm vs ≤154 cm) as did women with non-insulin dependent diabetes mellitus (OR = 8.4, 95% CI 1.7–41). Women with older siblings had a reduced risk of breast cancer compared to those firstborn (OR = 0.3, 95% CI0.2–0.7). Although limited by small case numbers, our findings suggest substantial increases in breast cancer rates in Thailand could be expected in the future.

Endometrioid and clear cell subtypes of ovarian cancer are both known to be closely associated with endometriosis and endometrial pathology, and so have often been combined in studies of causation. We have examined these ovarian cancers separately for potentially distinct risk factors in our population-based, Australia-wide case control study of 142 women with incident invasive endometrioid, 90 with clear cell ovarian cancers and 1508 population controls. Multivariate logistic regression was used to calculated odds ratios (ORs) and 95% confidence intervals (CIs). Increasing parity, and hormonal contraceptive use for > or = 5 years, strongly decreased the risks of both subtypes. Breast feeding and tubal ligation were also inversely associated, but significantly so only for the endometrioid subtype. As expected endometriosis increased the risk of both subtypes (OR 2.2, 95% CI 1.2-3.9 for endometrioid and OR 3.0, 95% CI 1.5-5.9 for clear cell). Obesity was associated only with clear cell cancers, where we observed a two-fold increased risk (OR 2.2, 95% CI 1.2-4.1). Also a significant trend of decreasing risk with increasing intensity of smoking (p trend 0.02) and education beyond high school was associated with decreased development of clear cell cancers only. Endometrioid and clear cell ovarian cancers have some shared as well as some distinct risk factors, and therefore should be considered separately in studies of ovarian cancer.

In 1998, Risch proposed a hypothesis for the pathogenesis of ovarian cancer relating to the role of androgens in stimulating epithelial cell proliferation. Although this hypothesis has been widely discussed, direct evidence to support it is scant. To address this issue, we have conducted a detailed analysis of factors possibly associated with high circulating levels of androgens, including polycystic ovary syndrome (PCOS), hirsutism and acne (all clinically associated with hyperandrogenism) using the data collected in an Australia-wide, population-based case-control study. Cases aged 18-79 years with a new diagnosis of invasive epithelial ovarian cancer (n=1276) or borderline malignant tumour (n=315) were identified through a network of clinics and cancer registries throughout Australia. Controls (n=1508) were selected from the National Electoral Roll. Women self-reported a history of PCOS, acne, hirsutism and also use of testosterone supplements or the androgenic medication Danazol. We found no evidence that a history of PCOS, acne or hirsutism was associated with ovarian cancer overall, or with specific subtypes, with the exception of serous borderline tumours that were positively associated with a history of PCOS (OR 2.6; 95% CI 1.0-6.1). Women who had ever used testosterone supplements had an increased risk of ovarian cancer (OR 3.7; 95% CI 1.1-12.0); however, use of the androgenic medication Danazol did not increase risk (OR 1.0; 95% CI 0.4-2.9). Overall, our results do not support the hypothesis that androgen-related disorders increase the risk of ovarian cancer.

OBJECTIVE: Some molecular and histological evidence suggests that mucinous epithelial ovarian cancers develop via a sequence from benign tumor through borderline tumor to invasive cancer. Such a sequence would predict some shared risk factors between the different tumor types. To investigate this, we examined risk factors for benign, borderline and invasive mucinous ovarian tumors. METHODS: A population-based case-control study was conducted in Australia between 2002 and 2005. Women with benign (n=133), borderline (n=147) and invasive (n=43) mucinous tumors of the ovary and women from the general population (n=1487) completed comprehensive health and lifestyle questionnaires. RESULTS: Although parity was inversely related to risk of benign, borderline and invasive tumors, increasing numbers of births did not further decrease risk of any of the tumor types. Hormonal contraceptives and breast-feeding were unrelated to risk. However, 20 or more pack-years of smoking was associated with a more than twofold increase in risk of all three tumor types (OR=2.7, 95% CI 1.6-4.4 for benign tumors; OR=2.7, 95% CI 1.7-4.4 for borderline tumors; and OR=2.1, 95% CI 0.9-5.0 for invasive cancers) compared to never smoking. CONCLUSIONS: Overall, the risk factors for mucinous cancers appear to differ from other subtypes of ovarian cancer. Furthermore, patterns of risk factors across benign, borderline and invasive mucinous ovarian tumors are generally consistent with an adenoma-to-carcinoma sequence as the developmental pathway for this subtype of ovarian cancer. Our findings also suggest the potential preventability of borderline and invasive mucinous ovarian cancer by smoking cessation and by surgical excision of identifiable precursor lesions.

Overall 5-year survival for pancreatic cancer is ∼5%. Optimizing the care that pancreatic cancer patients receive may be one way of improving outcomes. The objective of this study was to establish components of care which Australian health professionals believe important to optimally manage patients with pancreatic cancer.Using a Delphi process, a multidisciplinary panel of 250 health professionals were invited to provide a list of factors they considered important for optimal care of pancreatic cancer patients. They were then asked to score and then rescore (from one [no importance/disagree] to 10 [very important/agree]) the factors. The mean and coefficient of variation scores were calculated and categorized into three levels of importance.Overall, 63 (66% of those sent the final questionnaire; 25% of those initially invited) health professionals from nine disciplines completed the final scoring of 55 statements/factors encompassing themes of presentation/staging, surgery and biliary obstruction, multidisciplinary team details and oncology. Mean scores ranged from 3.7 to 9.7 with the highest related to communication and patient assessment. There was substantial intra- and interdisciplinary variation in views about MDT membership and roles.Overall, the opinions of Australian health professionals reflect international guideline recommended care; however, they identified a number of additional factors focusing on where patients should be treated, the importance of clear communication and the need for multidisciplinary care which were not included in current clinical practice guidelines. Differences in priorities between specialty groups were also identified.

Race/ethnicity may be a newly recognized risk factor for Graves' disease.The aim of this study was to examine the prevalence of thyrotoxicosis by race/ethnicity in Americans aged 12-49 years using three National Health and Nutritional Examination Surveys (NHANES).Data were analyzed from 17,939 participants in NHANES III (1988-1994), NHANES 1999-2002, and NHANES 2007-2010 with available thyroid function test results. Thyrotoxicosis was defined as a serum thyrotropin (TSH) of ≤0.1 mIU/L or subjects taking methimazole or propylthiouracil, and overt thyrotoxicosis was defined as high serum thyroxine and a serum TSH of ≤0.1 mIU/L. Logistic regression was performed accounting for the complex sampling design of NHANES, and the results from all three NHANES surveys were combined using a random-effects model.There were 75 study participants with point prevalent thyrotoxicosis, representing a pooled prevalence of 0.4% for Americans aged 12-49 years. Prevalent thyrotoxicosis was nearly three times more likely in non-Hispanic black subjects compared with non-Hispanic whites (OR=2.9 [CI 1.5-5.7]), while there was no difference between the prevalence of thyrotoxicosis in Mexican Americans compared to non-Hispanic whites (OR=1.2 [CI 0.6-2.4]; I2 for heterogeneity=0% for both). Among 27 patients with overt thyrotoxicosis, the odds ratio was 8.7 [CI 0.7-112.6] for non-Hispanic blacks and 4.6 [CI 0.4-59.3] for Mexican Americans compared with non-Hispanic whites.The results suggest there are race/ethnicity differences in the prevalence of thyrotoxicosis. Future studies should address whether these differences are due to heritable factors, environmental exposures, or a combination of both.

OBJECTIVES: Despite pancreatic cancer being the fifth highest cause of cancer death in developed regions, there is a paucity of population-based management details for patients with pancreatic cancer. The objective of this study was to reflect on current practice and outcomes to facilitate future improvement. METHODS: A comprehensive population-based patterns-of-care study in 2 Australian states was conducted. Patients diagnosed with pancreatic adenocarcinoma between July 2009 and June 2011 were identified by cancer registries, and detailed clinical data were collected from medical records. RESULTS: Data were collected for 1863 patients, 96% of those eligible. The majority resided in major cities; their median age was 72 years, and 54% were men. Over half of the cases (58%) had metastatic disease at diagnosis. Resection was attempted for 20% of patients but only completed in 15%. The uptake of adjuvant chemotherapy (76%) and the proportion alive at 1-year (22%) were higher than reported in previous population-based reports. Of those with no complete surgical resection, 43% received palliative chemotherapy. CONCLUSIONS: This population-based overview of the management of patients with pancreatic cancer suggests that, despite evidence that the proportion surviving and the use of adjuvant chemotherapy has increased, there may still be underutilization of cancer-directed therapies.

Objectives. Although early reports suggested that smoking was not associated with ovarian cancer risk, recent studies have reported positive associations for cancers of the mucinous subtype. We sought to clarify the relationship between smoking and ovarian cancer by histological subtype. Methods. We conducted a systematic literature review and meta-analysis of studies investigating the association between smoking and risk of the different histological subtypes of epithelial ovarian cancer. Eight population-based case–control studies, one pooled analysis of case–control studies, and one cohort study met the inclusion criteria. Summary relative risks (RR), 95% confidence intervals (CI), and tests for heterogeneity were generated from random effects models. Results. Combined, these studies included a total of 910 women with mucinous and 5564 with non-mucinous ovarian cancers. There was a significant doubling of risk of mucinous ovarian cancer in current smokers compared to never smokers (summary RR 2.1, 95%CI 1.7–2.7), but no increased risk of serous (1.0, 95%CI 0.8–1.2) or endometrioid (0.8, 95%CI 0.6–1.1) cancers and a significant risk reduction for clear cell cancers (0.6, 95%CI 0.3–0.9). The risk of mucinous cancer increased with increasing amount smoked but returned to that of never smokers within 20–30 years of stopping smoking. Conclusions. Meta-analysis suggests that current smoking doubles a woman's risk of developing mucinous ovarian cancer. Stopping smoking returns the risk to normal in the long term. Smoking may thus be one of the few modifiable factors offering potential for primary prevention of mucinous ovarian cancer.

Objective: Studies evaluating the relationships between coffee, tea and caffeine and ovarian cancer risk have given inconsistent results. We have examined these associations using data from an Australian population-based case–control study. Methods: Women with epithelial ovarian cancer (EOC)(n = 696) and control women selected from the Electoral Roll (n = 786) provided comprehensive reproductive and lifestyle data and completed a food frequency questionnaire. Results: Increasing coffee consumption was associated with a decreased risk of invasive EOC (p trend = 0.009) with an odds ratio (OR) of 0.51 (95% confidence interval (CI) 0.32–0.80) for consumption of ≥4 cups of coffee per day compared to non-drinkers. The association was significant only for serous and endometrioid/clear cell histological subtypes. There was no association with borderline tumours (OR: 1.20, 95% CI: 0.58–2.47). An inverse relationship was also seen between caffeine intake and EOC but tea consumption was not related to EOC (OR: 1.10 95% CI: 0.76–1.61 for ≥4 cups/day versus none). Conclusions: As tea contributed significantly to caffeine intake in this population we conclude that the association we observed with coffee is not due to caffeine, but to other components within coffee. We suggest future studies consider the type as well as the amount of each beverage consumed.

Background: Oligomenorrhea, defined as infrequent or irregular periods has been shown to be associated with epithelial ovarian cancer risk in some but not all studies. Polycystic ovary syndrome (PCOS), which is characterized by oligomenorrhea and abnormal hormone levels including hyperandrogenism, hyperinsulinemia, and gonadotropin imbalance, has been suggested to increase ovarian cancer risk. However, these associations have been rarely examined by histologic subtype. We sought to examine these associations among 14 studies participating in the Ovarian Cancer Association Consortium. Methods: Participants included 16,594 patients with invasive (n=13,719) or borderline (n=2,875) ovarian cancers and 17,718 controls who had answered questions regarding menstrual cycle irregularity, menstrual cycle length, and/or PCOS. Study specific odds ratios (ORs; 95% confidence intervals [95% CI]), adjusted for ovarian cancer risk factors, were calculated and then combined using a random-effects meta-analysis. Pooled histologic subtype specific ORs (95% CI) were calculated using polytomous logistic regression. Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared to women reporting cycle length ≤35 days (OR=0.70; 95% CI=0.58-0.84). Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared to women with regular cycles (OR=0.83; 95% CI=0.76-0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR=0.87; 95% CI=0.65-1.15). For menstrual cycle length >35 days, decreased risk was observed for all invasive histotypes: low grade serous (OR=0.48; 95% CI=0.25-0.92), high grade serous (OR=0.62; 95% CI=0.48-0.80), mucinous (OR=0.38; 95% CI=0.19-0.76), endometrioid (OR=0.75; 95% CI=0.54-1.06), and clear cell (OR=0.70; 95% CI=0.43-1.13) but not for serous borderline tumors (OR=1.18; 95% CI=0.87-1.59) (pheterogeneity=0.006). An increased risk of serous borderline disease was observed among women reporting irregular cycles (OR=1.34; 95% CI=1.16-1.55) (pheterogeneity Conclusion: In this large consortium analysis we observed a decreased risk of most invasive epithelial ovarian cancer histotypes among women reporting longer or irregular menstrual cycles. In contrast, such cycles were associated with increased risk of the serous borderline tumors. Citation Format: Holly R. Harris, Susan Jordan, Harvey Risch, Mary Anne Rossing, Marc T. Goodman, Francesmary Modugno, Susanne Krüger Kjær, Joellen M. Schildkraut, Elisa V. Bandera, Nicolas Wentzensen, Catherine Phelan, Hoda Anton-Culver, Anna H. Wu, Kathryn L. Terry. Oligomenorrhea, polycystic ovary syndrome, and risk of ovarian cancer histotypes, evidence from the Ovarian Cancer Association Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2293. doi:10.1158/1538-7445.AM2017-2293

Ovarian cancer is the most fatal gynecologic malignancy, causing more than 140000 deaths each year worldwide (1). Although early stage ovarian cancer can be successfully treated, the disease is commonly detected at advanced stages with extensive local and systemic spread and poor survival. Early detection strategies have not been shown to reduce mortality (2,3), and biomarker candidates have had insufficient performance to improve early detection efforts thus far (4,5). Primary prevention strategies have not been widely studied but may present alternatives to reduce ovarian cancer burden. Multiple lines of evidence suggest that ovarian cancer may be related to chronic inflammation (6). In addition to inflammatory factors associated with ovarian epithelial disruption through ovulation (7–9), inflammation-related exposures such as endometriosis (10–12) and exposure to talc or genital powder and asbestos (13) have been associated with increased ovarian cancer risk. Recently, intervention trials have shown that regular aspirin use is associated with reduced risk of several malignancies (14). However, these trials were not powered for rare cancer endpoints, and none of the clinical trials to date have evaluated ovarian cancer separately. Recent meta-analyses of aspirin use have reached various conclusions that range from no effect (15) to a weak risk reduction among regular users of aspirin (16–18). For nonsteroidal anti-inflammatory drug (NSAID) use, a recent summary suggested a greater risk reduction among cohort studies than among case–control studies (15), whereas, the results from individual epidemiologic studies have been largely inconclusive (13,19–33), possibly because of limited sample size and limited data on dose, duration, and frequency of use across the studies. We conducted an analysis of pooled individual-level data of NSAID use and ovarian cancer risk in the Ovarian Cancer Association Consortium (OCAC), including more than 7500 ovarian cancer cases from 12 population-based case–control studies.

Objective: To describe survival patterns in a nationally complete cohort of Australian women with epithelial ovarian cancer, by sociodemographic and clinical factors. Design, setting and participants: All 1192 women diagnosed with invasive epithelial ovarian cancer in 2005 were identified through state-based cancer registries. We obtained detailed information from their medical records in 2009 and updated survival data in 2012. Main outcome measures: Crude 3-year, 5-year and 7-year survival rates; 3-year and 5-year conditional survival; and hazard ratios (HRs) for the association of participant and cancer characteristics with survival, from multivariable Cox proportional hazards models. Results: Overall crude 5-year survival was 35% (95% CI, 33%-38%). Conditional survival increased moderately for women who lived beyond a year from diagnosis, although for women alive 2 years after diagnosis, the probability of surviving a further 5 years was still only 53% (95% CI, 49%-57%). Increasing age and disease stage were most strongly associated with poor survival. After adjusting for these, survival was significantly worse for women with carcinosarcomas (HR, 2.1 [95% CI, 1.3-3.2]), clear cell (HR, 1.7 [95% CI, 1.2-2.3]) and mucinous (HR, 2.6 [95% CI, 1.6-4.0]) cancers than for women with serous cancers. Presence of ascites at diagnosis (HR, 1.5 [95% CI, 1.3-1.8]), Charlson comorbidity score ≥ 3 (HR, 1.5 [95% CI, 1.1-2.1]), relative socioeconomic disadvantage (HR, 1.2 [95% CI, 1.1-1.4]) and regional-remote residence (HR, 1.2 [95% CI, 1.0-1.4]) were also associated with poorer survival. Conclusions: Along with expected adverse effects of age and stage, we found survival differences by histological subtype, presence of ascites and comorbidities. Whether geographic and socioeconomic differences relate to treatment access or other factors warrants further investigation. Conditional survival estimates confirm the ongoing poor long-term prognosis for women with ovarian cancer, reinforcing the need for prevention and better treatments.

BACKGROUND: Much of South East Asia is experiencing an epidemiological transition. In Thailand, chronic disease has emerged and the prevalence of diabetes has tripled. As part of a large cohort study of the Thai transition to chronic disease, we gathered data on self-reported diabetes. Epidemiological studies commonly ascertain such data by self-report but the validity of this method has not been assessed in Thailand. Therefore, we aimed to investigate the validity of self-reported type 2 diabetes (T2DM) in Thai adults participating in the Thai Cohort Study (TCS). METHODS: Data were collected by mailed questionnaire from adults involved in the TCS, a nationwide community-based longitudinal health study of distance learning adult students enrolled at Sukhothai Thammathirat Open University. Participants were surveyed in 2005, 2009 and 2013. We sampled all participants with self-reported T2DM status (878 cases) for telephone interview with our study physician along with a random selection of 650 participants who self-reported not having diabetes in all three TCS surveys. These physician telephone interviews allowed us to validate self-reported questionnaire responses. RESULTS: Questionnaire self-report of diabetes slightly over-estimated the incidence of T2DM in this cohort; the overall proportion of confirmed T2DM cases was 78%. Participants with a consistent pattern of diabetes reporting at the 2009 and 2013 questionnaire follow-ups had the highest validity of self-reported responses (96%; 95%CI 92.9-99.1).The lowest proportion of confirmed T2DM cases was recorded among participants who reported diabetes in 2009 and not in 2013 (32%)(95%CI 22.6-41.4), mostly young women with transient (gestational) diabetes. CONCLUSIONS: Our results, derived mainly from young, educated Thai adults nationwide, show that self-reported doctor diagnosed T2DM is a feasible and acceptable method for assessing diabetes in epidemiological studies.

In a recent issue of the Journal, Rossing et al. presented sensitivities, specificities, and positive predictive values that were associated with consensus criteria for diagnosis of ovarian cancer and with the Goff symptom index. It is important to validate predictive models in different settings, and so we repeated the analyses with data from patients with invasive epithelial ovarian cancer (n = 1215) and population-based control subjects (n = 1456) who were aged 20–79 years and who participated in an Australian study between 2002 and 2005. Whether earlier diagnosis can alter outcomes for women with ovarian cancer is uncertain, but rapid diagnosis in symptomatic women may have benefits beyond enhanced survival. © The Author 2010. Published by Oxford University Press. All rights reserved.

Until recently most studies suggested that hysterectomy with ovarian conservation was associated with a decreased risk of ovarian cancer. However, several recent studies have reported modestly increased risks of ovarian cancer following hysterectomy. Given that as many as 35% of women will have a hysterectomy, the nature of the association requires clarification. We conducted a systematic review and meta-analysis of the published literature on the relationship between hysterectomy and ovarian cancer to investigate whether there has been a temporal change in the association. Twenty observational studies that have reported a quantitative assessment of the association between hysterectomy and risk of histologically-confirmed ovarian cancer were included in the meta-analysis. The overall relative risk (RR) estimate was 0.81 (95% confidence interval (CI) 0.72–0.92) suggesting hysterectomy decreases the risk of ovarian cancer. However, there was significant heterogeneity in the results (I2 = 74%). Our exploration of sources of heterogeneity and metaregression showed that median year of cancer diagnosis of included cases explained most of the heterogeneity relative risk (RR = 0.70 (95% CI 0.65–0.76) for median year diagnosis pre 2000; RR = 1.18 (95% CI 1.06–1.31) for post 2000). This study shows that there has been a temporal shift in the association between hysterectomy and risk of ovarian cancer. One explanation may be the trend away from hysterectomy in younger women. Other speculative possibilities include the decline in oophorectomy rates and the use of oestrogen-only hormone replacement therapy in hysterectomised women. Until further evidence becomes available, clinicians should not advise women that a hysterectomy without salpingo-oophorectomy will favourably influence their future risk of ovarian cancer.

Objective: To measure progress, over the past decade, in reducing the disadvantage in cancer death rates among people living in regional and remote areas of Australia.Design: Analysis of routinely collected death certificate and corresponding population data from the Australian Bureau of Statistics.Setting: Population-based, Australia-wide comparison of mortality rates in regional and remote areas compared with metropolitan areas from 1 January 2001 to 31 December 2010.Main outcome measures: Absolute and relative excess of cancer deaths in regional and remote areas.Results: The number of excess cancer deaths in regional and remote areas from 2001 to 2010 was 8878 (95% Cl, 8187-9572). For men, the age-standardised mortality ratios (comparing regional and remote areas with metropolitan areas) showed no evidence of improvement, from 1.08 in 1997-2000 to 1.11 in 2006-2010. For women, they increased from 1.01 in 1997-2000 to 1.07 in 2006-2010. The age-standardised cancer death rate in regional and remote areas (annual percentage change [APC], - 0.6%; 95% Cl, - 0.8% to - 0.4%) is decreasing more slowly than in metropolitan areas (APC, - 1.1%; 95% CI, -1.3% to -1.0%).Conclusions: The regional and remote disadvantage for cancer deaths has been recognised as a problem for more than two decades, yet we have made little progress. This is not surprising - we have not invested in research into solutions. The benefits of laboratory and clinical research to identify innovative cancer treatments will not be fully realised across the entire Australian population unless we also invest in health systems and policy research.

Ovarian cancer is the most lethal gynecological cancer and currently disease prevention offers the best opportunity for reducing fatalities. The wealth of laboratory data indicating both pro- and anti-carcinogenic activity for components of tea and coffee has generated great interest in the effects of their consumption on the occurrence of ovarian cancer. Additionally, comparison of their effects in populations might help us to understand carcinogenic mechanisms. A systematic review of the epidemiological literature has been undertaken to assess these relationships. Overall, 17 studies of tea and ovarian cancer and 29 of coffee were found. The data suggest that moderate tea consumption may be associated with a decreased risk of ovarian cancer. Moderate coffee consumption has no effect on risk but heavy coffee consumption may be associated with a slightly increased risk. Whether these relations are modified by factors such as tea/coffee type or individual genotype remain unresolved but are worthy of further investigation. Overall, women who consume moderate amounts of tea or coffee should not be discouraged from this habit in order to alter their risk of developing ovarian cancer.

Contains fulltext : 117896.pdf (Publisher’s version ) (Closed access) BACKGROUND: Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes. METHODS: We pooled primary data from 13 population-based case-control studies, including 10 157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13 904 control women. Invasive cases were analysed by histological type, grade and stage, and borderline cases were analysed by histological type. Pooled odds ratios were estimated using conditional logistic regression to match on site, race/ethnicity and age categories, and to adjust for age, oral contraceptive use duration and number of full-term births. RESULTS: Tubal ligation was associated with significantly reduced risks of invasive serous (OR, 0.81; 95% CI, 0.74-0.89; P < 0.001), endometrioid (OR, 0.48; 95% CI, 0.40-0.59; P < 0.001), clear cell (OR, 0.52; 95% CI, 0.40-0.67; P < 0.001) and mucinous (OR, 0.68; 95% CI, 0.52-0.89; P = 0.005) cancers. The magnitude of risk reduction was significantly greater for invasive endometrioid (P < 0.0001) and clear cell (P = 0.0018) than for serous cancer. No significant associations were found with borderline serous or mucinous tumours. CONCLUSIONS: We found that the protective effects of tubal ligation on ovarian cancer risk were subtype-specific. These findings provide insights into distinct aetiologies of ovarian cancer subtypes and mechanisms underlying the protective effects of tubal ligation.

Background: There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied. Methods: Data from 14 ovarian cancer case–control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes. A genetic “risk score” was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk. Results: Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared with women in the lowest [95% confidence interval (CI), 1.48–1.84]. Analyses by histologic subtype yielded risk differences across subtype for endometriosis (Phet < 0.001), parity (Phet < 0.01), and tubal ligation (Phet = 0.041). Conclusions: The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of the effect of each risk factor that sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histologic subtype is warranted. Cancer Epidemiol Biomarkers Prev; 22(5); 880–90. ©2013 AACR.

Evidence is accumulating to suggest that higher exposure to solar ultraviolet radiation (UVR) is associated with decreased risk of internal cancers, but data for ovarian cancer are unclear. We aimed to examine the association between lifetime ambient UVR and ovarian cancer in a population-based-case–control study. The study included women aged 18 to 79 years with a new diagnosis of invasive (n = 1,215) or borderline (n = 285) epithelial ovarian cancer identified through a network of clinics and state cancer registries throughout Australia. Controls (n = 1,459), frequency matched to cases by age (5-year groups) and state of residence, were randomly selected from the National Electoral Roll. We asked participants to report where they had lived at different periods of their life and assigned an estimate of UVR using data from NASA's Total Ozone Mapping Spectrometer database (1997–2003). We estimated the association between ambient UVR and risk of ovarian cancer using conditional logistic regression adjusted for potential confounders. Women in the highest third of average daily ambient UVR over their lifetime were at significantly lower risk of all epithelial ovarian cancers than those in the lowest third [OR, 0.70; 95% confidence interval (CI), 0.56–0.88]. The inverse association was stronger for borderline tumors (0.47, 0.31–0.71) than invasive tumors (0.78, 0.61–1.00). The effect sizes for overall and borderline tumors were unchanged after adjusting for confounders, whereas the inverse association for invasive tumors was attenuated. These data suggest that exposure to ambient UVR may reduce the risk of ovarian cancer. Cancer Prev Res; 5(11); 1330–6. ©2012 AACR.

The levonorgestrel intrauterine system (LNG-IUS) provides effective contraception and treatment for menorrhagia and is used to prevent endometrial hyperplasia (EH) in women taking unopposed oestrogens.The aim of this study was to assess whether the LNG-IUS was also a safe and effective treatment for EH and to conduct a systematic review of the literature.A retrospective record review was undertaken in a private gynaecology practice in Brisbane, Australia, and included all women with EH treated with hysterectomy, oral progestins or LNG-IUS between January 2004 and April 2007. Histopathological findings from hysterectomy specimens or endometrial biopsies were used to calculate rates of regression of the EH.Twenty-one women elected to have a hysterectomy and seven of those (33%) had no persisting hyperplasia at surgery. Twenty-six women had a LNG-IUS inserted at initial hysteroscopy dilatation and curettage or shortly afterwards; seven of those elected to proceed to hysterectomy when their diagnosis was known. Among ten women who used oral progestin treatment, 90% showed initial regression; two with recurrent EH were subsequently treated successfully with LNG-IUS. All 21 women (100%), including one with atypia, treated with LNG-IUS for more than seven weeks had normal endometrial histology on subsequent assessment. No women developed endometrial cancer. Pooled analysis of the published literature gave a 96% regression rate for non-atypical EH treated with LNG-IUS.These data contribute further evidence that LNG-IUS is a safe and effective method for treating non-atypical EH. Whether LNG-IUS could provide a safe and cost-effective alternative to hysterectomy for atypical EH warrants further examination.

Invasive serous cancers are diagnosed in the ovary, fallopian tube and peritoneum. It is widely believed that these are variants of the same malignancy but little is known about fallopian tube and primary peritoneal cancers. A comparison of risk factors for these tumor types may shed light on common or distinct aetiological pathways involved in these types of cancer. We investigated risk factors for the three cancers using data from a large Australian population-based case-control study. We included women with incident invasive serous ovarian (n = 627), primary peritoneal (n = 129) and fallopian tube (n = 45) cancer and 1,508 control women. Participants completed a comprehensive reproductive and lifestyle questionnaire. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Hormonal contraceptive use was inversely related to risk of all three cancers. Parity and breast-feeding were also inversely related to risk of serous ovarian and fallopian tube cancer. In contrast, parous women had an increased risk of peritoneal cancer (OR = 1.8, 95%CI 0.8-3.9), and increasing parity did not lower risk. There was also no association between breast-feeding and peritoneal cancer. However, obesity was associated with a doubling of risk for peritoneal cancer alone (OR = 2.1, 95%CI = 1.3-3.4). The strikingly similar patterns of risk for serous ovarian and fallopian tube cancers and the somewhat different results for primary peritoneal cancer suggest that peritoneal cancers may develop along a different pathway. These results also call into question the role of the physical effects of ovulation in the development of serous ovarian cancer.

OBJECTIVE: To investigate the risk factors for benign serous and mucinous epithelial ovarian tumors. METHODS: Cases were women newly diagnosed with benign serous ovarian tumors (n=230) or benign mucinous tumors (n=133) between 2002 and 2005. Control women were selected at random from the general population (n=752). All participants completed a comprehensive reproductive and lifestyle questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and to simultaneously adjust for potential confounding factors. RESULTS: Current smoking was associated with a three-fold increase in risk of benign mucinous tumors (OR 3.25, 95% CI 1.97-5.34), and there was a trend of increasing risk with increasing amount smoked (P

Introduction: In 2008 The International Agency for Research on Cancer concluded that combined oral contraceptives (OCs) are a cause of cancer of the breast and cervix but decrease the risk of ovarian and endometrial cancer. They also concluded that estrogen-only hormone replacement therapy (HRT) increases the risk of both endometrial and ovarian cancer, while use of estrogen plus progestogen (combined) HRT increases the risks of breast cancer. The level of risk associated with each cancer type varies by duration and recency of use of hormones. Our aim was to calculate the proportion of breast and gynecological cancers arising in Australian women (population attributable fractions - PAF) that could be attributed to these commonly used hormonal medications. Methods: We calculated PAFs using the standard formula, which requires an estimate of the relative risk for each exposure-cancer association and the prevalence of the causal factor in the population. Relative risks were obtained from published pooled or meta-analyses of the associations and prevalence estimates were derived from Australian National Health Survey estimates or other large national studies. For factors inversely associated with cancer we calculated the “prevented fraction” and estimated the number of cancers that were prevented due to exposure to the factor. Results: The estimated PAFs suggested that fewer than 5% of breast and gynecological cancers in Australia in 2010 could be attributed to oral contraceptive use and estimates were similar for HRT use. However, the calculated preventive fractions for oral contraceptives suggested that the numbers of endometrial and ovarian cancers may have been 46% and 24% higher respectively if no Australian women had used OCs. Given combined HRT increases breast cancer risk and breast cancer is much more common than endometrial or ovarian cancer we also assessed the likely effect if all women taking combined HRT instead took estrogen-only HRT. Under this scenario, we estimate the absolute numbers of ovarian and endometrial cancers would increase slightly but the number of breast cancers attributable to HRT use would decrease substantially. Conclusions: Our analyses suggest that the use of combined OCs confers more benefit than harm with respect to cancer incidence, with a small increase in breast/cervical cancer diagnoses weighed against a much larger decrease in numbers of endometrial and ovarian cancers. In contrast, our results indicate that there would be fewer cancers overall if women did not use HRT. When HRT is required, most guidelines recommend that women with a uterus take combined HRT to prevent endometrial cancer. However, our findings suggest that, in terms of total cancer burden, it might be safer for women to avoid progestogens and use estrogen-only HRT for symptom relief. Future studies should examine this possibility. Citation Format: Susan J. Jordan, Louise Wilson, David Whiteman, Penelope Webb, PAF Project Group. The proportion of breast and gynecological cancers in Australian women that can be attributed to the use of oral contraceptives and hormone replacement therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 866. doi:10.1158/1538-7445.AM2015-866

s / Pancreatology 15 (2015) S1eS141 S85 Patients & methods: Data were collected manually from patient records in two states of Australia for all patients diagnosed with pancreatic cancer between July 2009 and June 2011. Determinants of attempted resectionwere estimated using multivariable logistic regression analyses. Results: Of the cohort 740 patients had stage I-III disease. Of these 38 (5%) declined surgery and 320 (43%) had an attempted resection. Patient factors associated with likelihood of surgery were being male (adjusted odds ratio (AOR) 1.48; 95% confidence interval (CI) 1.00 e 2.18), decreasing performance status (AOR 0.38, 95% CI 0.29 to 0.50), age (AOR 0.93, 95% CI 0.91 to 0.95 per year of age) and increasing Charlson co-morbidity index (AOR 0.79, 95% CI 0.64 to 0.97). Patients seen initially in the private system were more likely to undergo surgery (AOR 1.48, 95% CI 1.00 to 2.19). Being first seen in a facility that admittedmore pancreatic cancer cases increased the likelihood of receiving an attempted resection (AOR 1.47, 95% CI 1.08 to 2.01). Conclusion: Health service and patient factors are determinants of attempted resection for patients with non-metastatic pancreatic cancer.

Objective: We hypothesized that the hormonal changes of adolescence influence ovarian cancer risk particularly in younger women. We investigated this possibility by examining the relationship between ovarian cancer and adult height and age at menarche as both factors reflect pubertal hormonal levels. Methods: Participants were a population-based sample of women with incident ovarian cancer (n = 794) and control women randomly selected from the Australian Electoral Roll (n = 855). The women provided comprehensive reproductive and lifestyle data during a standard interview. Results: Although neither height nor age at menarche was significantly related to the risk of ovarian cancer overall, increasing height was associated with increasing risk of the subgroup of mucinous borderline ovarian cancer (odds ratio, 5.3; 95% confidence interval, 1.5-19.1 for women ≥175 cm compared with women Conclusions: Development of mucinous borderline ovarian cancers, predominantly diagnosed in women ages under 50 years, seems to be associated with age at menarche and attained adult height. These results are consistent with our original hypothesis that pubertal levels of reproductive hormones and insulin-like growth factor-I influence ovarian cancer risk in younger women.

The natural history of the development of epithelial ovarian cancer remains obscure and no effective screening test exists. In several human malignancies progression from benign to invasive tumour occurs, but this sequence has not been established for epithelial ovarian cancer. We have reviewed epidemiological, histopathological and molecular studies of benign epithelial ovarian tumours to assess the evidence for and against such a progression in ovarian cancer. These data suggest that a diagnosis of a benign ovarian cyst or tumour is associated with an increased risk of ovarian cancer later in life. Current evidence also suggests that benign serous tumours can progress to low-grade serous cancer and that benign mucinous tumours can progress to mucinous cancer. The more common high-grade serous ovarian cancers are likely to arise de novo.

Objective. To document symptoms associated with borderline, early and advanced ovarian cancer and identify personal characteristics associated with early versus late diagnosis. Methods. Information concerning symptoms and diagnosis history was available from 811 women with ovarian cancer who took part in an Australian case–control study in the early 1990s. Women were classified into three groups for comparison based on their diagnosis: borderline, early (stage I–II) and advanced (stage III–IV) invasive cancer. Results. Sixteen percent of women with borderline tumors, 7% with early cancer and 4% with advanced cancer experienced no symptoms before diagnosis (P < 0.0001). Among women with symptoms, abdominal pain (44%) or swelling (39%) were most frequently reported; an abdominal mass (12%) and gynecological symptoms (12%) were less common. Compared to advanced stage cancer, women with early stage cancer were more likely to report an abdominal mass or urinary symptoms but less likely to report gastrointestinal problems or general malaise. General malaise and ‘other’ symptoms were least common in borderline disease. Older women, and those with higher parity or a family history of breast or ovarian cancer, were more likely to be diagnosed at an advanced stage of disease. Conclusions. Women who experience persistent or recurrent abdominal symptoms, particularly swelling and/or pain should be encouraged to seek medical attention and physicians should be alert to the possibility of ovarian cancer even in the absence of an abdominal mass. Further information about the prevalence of these symptoms in the general population is essential to assist physicians in patient management.

Objective: To describe the diagnostic pathways experienced by a large, representative group of Australian women with ovarian cancer, and to document the time between first presentation to a medical professional and clinical diagnosis. Design, setting and participants: 1463 women with epithelial ovarian cancer from an Australia-wide population-based study (2002-2005) completed a telephone interview in which they described the events that led to the diagnosis of their cancer. Main outcome measures: Number and type of doctors consulted, investigations performed, referral patterns and the time from first presentation to diagnosis. Results: Of the 1463 women, 145 had their cancer diagnosed incidentally and were excluded from analysis. Most of the remaining 1318 women (1222, 93%) presented first to their general practitioner. As a result of their first medical consultation, 75 women (6%) were given a diagnosis, and 484 (37%) were referred to a gynaecologist, gynaecological oncologist or oncologist for further assessment. Overall, 85% of women visited three or fewer doctors before their cancer was diagnosed; 66% of cancers were diagnosed within 1 month of the initial presentation, and 80% were diagnosed within 3 months. For 12% of women, the diagnostic process took longer than 6 months; this was more likely for women residing in remote Australia, those with lower incomes, and those presenting with abdominal pain or bowel symptoms, or with more than one symptom. Conclusions: Despite anecdotal suggestions to the contrary, most women with ovarian cancer in Australia are investigated and diagnosed promptly. The diagnostic process is more protracted for a minority of women, and the factors we found to be associated with diagnostic delay warrant further investigation.

BACKGROUND: Patient and health system determinants of outcomes following pancreatic cancer resection, particularly the relative importance of hospital and surgeon volume, are unclear. Our objective was to identify patient, tumour and health service factors related to mortality and survival amongst a cohort of patients who underwent completed resection for pancreatic cancer. METHODS: Eligible patients were diagnosed with pancreatic adenocarcinoma between July 2009 and June 2011 and had a completed resection performed in Queensland or New South Wales, Australia, with either tumour-free (R0) or microscopically involved margins (R1) (n = 270). Associations were examined using logistic regression (for binary outcomes) and Cox proportional hazards or stratified Cox models (for time-to-event outcomes). RESULTS: Patients treated by surgeons who performed