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Objective To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. Methods We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). Results Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99). Conclusions The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

OBJECTIVE: Smoking has been associated with a reduced risk of thyroid cancer, but whether the association varies between higher- and lower-risk cancers remains unclear. We aimed to assess the association between smoking and risk of thyroid cancer overall as well as by tumour BRAF mutational status as a marker of potentially higher-risk cancer. DESIGN AND PATIENTS: We recruited 1013 people diagnosed with thyroid cancer and 1057 population controls frequency-matched on age and sex. METHODS: Multivariable logistic regression was used to assess the association overall and in analyses stratified by tumour characteristics. We used sensitivity analysis to assess the potential for selection bias. RESULTS: We found little evidence of an association with current smoking (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.69-1.26; current vs. never smoking), but a higher number of pack-years of smoking was associated with a lower risk of thyroid cancer (OR = 0.75; 95% CI: 0.57-0.99; ≥20 pack-years vs. never). However, after correcting for potential selection bias, we observed a statistically significant inverse association between current smoking and risk of thyroid cancer (bias-corrected OR = 0.65; 95% CI: 0.51-0.83). Those with BRAF-positive cancers were less likely to be current smokers than those with BRAF-negative cancers (prevalence ratio: 0.79; 95% CI: 0.62-0.99). CONCLUSION: We found smoking was inversely related to thyroid cancer risk and, in particular, current smoking was associated with a reduced risk of potentially more aggressive BRAF-positive than the likely more indolent BRAF-negative papillary thyroid cancers.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further similar to 15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Background: Combined oral contraceptive use is associated with a decreased risk of invasive epithelial ovarian cancer (ovarian cancer). There is suggestive evidence of an inverse association between progestin-only contraceptive use and ovarian cancer risk, but previous studies have been underpowered. Methods: The current study used primary data from 7,977 women with ovarian cancer and 11,820 control women in seven case–control studies from the Ovarian Cancer Association Consortium to evaluate the association between use of depot-medroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, and ovarian cancer risk. Logistic models were fit to determine the association between ever use of DMPA and ovarian cancer risk overall and by histotype. A systematic review of the association between DMPA use and ovarian cancer risk was conducted. Results: Ever use of DMPA was associated with a 35% decreased risk of ovarian cancer overall (OR, 0.65; 95% confidence interval, 0.50–0.85). There was a statistically significant trend of decreasing risk with increasing duration of use (Ptrend < 0.001). The systematic review yielded six studies, four of which showed an inverse association and two showed increased risk. Conclusions: DMPA use appears to be associated with a decreased risk of ovarian cancer in a duration-dependent manner based on the preponderance of evidence. Further study of the mechanism through which DMPA use is associated with ovarian cancer is warranted. Impact: The results of this study are of particular interest given the rise in popularity of progestin-releasing intrauterine devices that have a substantially lower progestin dose than that in DMPA, but may have a stronger local effect.

Background: This study aimed to investigate the associations between hysterectomy for benign indications and risk of breast, colorectal, kidney, and thyroid cancer, and to explore whether these associations are modified by removal of ovaries at the time of surgery or by age at surgery. Methods: We conducted a retrospective cohort study of the female population of Western Australia (n = 839,332) linking data from electoral, hospital, births, deaths, and cancer records. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the associations between hysterectomy and diagnosis of breast, colorectal, kidney, and thyroid cancers. Results: Compared with no surgery, hysterectomy without oophorectomy (hysterectomy) and hysterectomy with bilateral salpingo-oophorectomy (hysterectomy-BSO) were associated with higher risk of kidney cancer (HR, 1.32; 95% CI, 1.11–1.56 and HR, 1.29; 95% CI, 0.96–1.73, respectively). Hysterectomy, but not hysterectomy-BSO, was related to higher risk of thyroid cancer (HR, 1.38; 95% CI, 1.19–1.60). In contrast, hysterectomy (HR, 0.94; 95% CI, 0.90–0.98) and hysterectomy-BSO (HR, 0.92; 95% CI, 0.85–1.00) were associated with lower risk of breast cancer. We found no association between hysterectomy status and colorectal cancer. Conclusions: The associations between hysterectomy and cancer varied by cancer type with increased risks for thyroid and kidney cancer, decreased risk for breast cancer, and no association for colorectal cancer. Impact: As breast, colorectal, and gynecologic cancers comprise a sizeable proportion of all cancers in women, our results suggest that hysterectomy is unlikely to increase overall cancer risk; however, further research to understand the higher risk of thyroid and kidney cancer is warranted.

Most women with ovarian cancer have a poor prognosis, but studies have reported an association between statin use and improved survival. We investigated the potential survival benefit of statins in women with ovarian cancer using data from the Ovarian cancer Prognosis and Lifestyle study, a prospective study of Australian women aged 18 to 79 years, diagnosed with ovarian cancer from 2012 to 2015 and followed for 5 to 8 years. We obtained information from patient-completed questionnaires and medical records. We defined exposure based on prediagnosis use, as most women used statins continuously (prediagnosis and postdiagnosis) and few started using statins postdiagnosis. We measured survival from date of first treatment (surgery or neoadjuvant chemotherapy) until date of death or last follow-up. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for potential confounders. To reduce bias due to confounding by indication, we also applied inverse probability of treatment weighting (IPTW). Of 955 eligible women, 21% reported statin use before diagnosis. Statin users had a slightly better survival (HR = 0.90, 95% CI = 0.70-1.15) that was driven by lipophilic statin use (HR = 0.82, 95% CI = 0.61-1.11), with no association for hydrophilic statins (HR = 1.04, 95% CI = 0.72-1.49). The IPTW model weighted to all women with ovarian cancer also suggested a possible reduction in mortality associated with lipophilic statins (HR = 0.80, 95% CI = 0.54-1.21). In analyses restricted to women with hyperlipidaemia, the HRs were further from the null. Our findings are consistent with previous evidence, suggesting that lipophilic statins might improve ovarian cancer survival. Further investigation, in larger cohorts, or preferably in a randomised trial, is required.

PURPOSE: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival. METHODS: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery. RESULTS: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend

Aims: Renal mass biopsy (RMB) is advocated to improve management of small renal masses, however there is concern about its clinical utility. This study aimed to elicit opinions about the role of RMB in small renal mass management from surgeons managing renal cell carcinomas (RCC), and examine the frequency of pre-treatment biopsy in those with RCC. Methods: All surgeons in two Australian states (Queensland: n = 59 and Victoria: n = 108) who performed nephrectomies for RCC in 2012/2013 were sent questionnaires to ascertain views about RMB. Response rates were 54% for Queensland surgeons and 38% for Victorian surgeons. We used medical records data from RCC patients to determine RMB frequency. Results: Most Queensland (81%) and Victorian (59%) surgeons indicated they rarely requested RMB; however 34% of Victorians reported often requesting RMB, compared with no Queensland surgeons. This was consistent with medical records data: 17.6% of Victorian patients with T1a tumours received RMB versus 6.7% of Queensland patients ( p Conclusions: Most surgeons report infrequent use of RMB for small renal masses, however we observed practice variation. The principal reasons for infrequent use were concerns about sampling reliability and histopathological interpretation, which may be valid in regions with less access to interventional radiologists and uropathologists. Further evidence is required to define patient groups for whom biopsy results will alter management. Level of evidence: Not applicable for this multicentre audit.

Background Hysterectomy (surgical removal of the uterus) has been consistently associated with increased thyroid cancer risk. While there may be a biologic explanation, increased ascertainment (over-diagnosis) because of greater healthcare use by women having this procedure might also contribute to the observed increased risk. We explored this association considering indications for hysterectomy, age at hysterectomy, and the potential for the association to be mediated by increased contact with health professionals or increased thyroid function testing. Methods We recruited 730 women diagnosed with thyroid cancer and 785 age-matched population controls. We estimated odds ratios (OR) using logistic regression to assess the associations and used causal mediation analysis to investigate potential mediation. Results Prior hysterectomy was associated with an increased thyroid cancer risk (OR = 1.55, 95% CI: 1.14-2.12). When stratified by indication for hysterectomy, the increased risk was apparent only among those who had undergone hysterectomy for bleeding disorders (OR = 1.79, 95% CI: 1.26-2.56). Additionally, the association varied by age at hysterectomy ( Conclusions Hysterectomy for bleeding disorders was associated with an increased risk of thyroid cancer among women and a moderate proportion of this appeared due to frequent medical contact. Key messages The way in which women use health services probably explains at least some of the association between hysterectomy and risk of thyroid cancer.

Background Despite their increased risk of developing ovarian cancer, women with an inherited BRCA1 or BRCA2 mutation have been shown to have better survival after diagnosis. Components of a healthy lifestyle, including smoking, physical activity and body mass index (BMI) have previously been associated with ovarian cancer survival; however, it is unknown whether these associations differ by BRCA mutation status. Methods We investigated this in 2 cohorts of Australian women with invasive epithelial ovarian cancer, using Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results In analyses of the combined studies (n = 1,741), the association between pre-diagnosis current smoking and poorer survival was stronger for BRCA-positive (HR 2.27; 95% CI 1.31-3.93) than BRCA-negative (HR 1.20; 95% CI 0.96-1.50) women (p-interaction 0.01). The associations between physical activity, BMI, alcohol intake and survival did not differ statistically significantly by BRCA status. A similar differential association with smoking was seen in a third independent cohort (n = 1,009) from the USA (HR 1.93 [0.78-4.82] vs. 1.02 [0.71-1.46]). Conclusions Our results suggest the association between smoking and survival may differ by BRCA status and that while smoking cessation may improve outcomes for all women diagnosed with ovarian cancer, it might provide a greater benefit among those who carry a BRCA mutation. Key messages The association between pre-diagnosis smoking and poorer survival after ovarian cancer diagnosis may be stronger for women who carry a BRCA mutation compared with those who don’t.

Background Observational studies have reported survival benefits associated with non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and non-aspirin NSAIDs (NA-NSAIDs), especially new use post-diagnosis, in women with ovarian cancer (OC). Methods Participants were women aged 18-79 diagnosed with OC in Australia, 2012-2015. Information was gathered through self-completed 3-monthly questionnaires and prescription records. Exposure was defined as any use (NA-NSAIDs/regular-dose aspirin □1/week or daily low-dose aspirin) during the year pre-diagnosis and first year post-diagnosis. We measured overall survival from start of primary treatment (surgery/neoadjuvant chemotherapy) (pre-diagnosis use) or from 12 months after the start of therapy (post-diagnosis) until the earliest of date of death/last follow-up/5 years. Cox proportional hazards regression was used to estimate survival. We also applied inverse-probability of treatment weighting (IPTW), which balances comparison groups regarding potential confounders. Results We observed improved survival associated with pre-diagnosis use of aspirin/NA-NSAIDs ≥4 days/week (frequent-users) compared to Conclusions Our findings suggest aspirin/NA-NSAID use might improve survival in women with OC. Larger cohorts or, preferably, a randomised controlled trial could clarify these findings. Key messages Use of aspirin/NA-NSAIDs may improve OC survival.

Background Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, has a five-year survival of ∼45%, and very few established modifiable risk factors. Some evidence suggests that bisphosphonates could have chemopreventive benefits, but few epidemiological studies have investigated the association between bisphosphonate use and incidence of EOC. Methods We conducted a nested case-control study using linked administrative data. We identified 9,367 women over 50 years diagnosed with EOC (cases) from 2004 to 2013, and for each case identified five controls from the Australian Medicare Enrolment database matched by age, state, area of residence, and area-level socioeconomic disadvantage. We assessed the associations between bisphosphonate use using dispensed prescription data (ever use, duration and dose) and EOC (overall, by histotype), adjusting for comorbidities and MHT use. We conducted sensitivity analyses in women with complete ascertainment of dispensing claims and for residents of one Australian state that had linked with data linked to hospital procedures, including oophorectomy. Results Our analyses show an inverse association between bisphosphonate use and risk of EOC overall (OR = 0.81, 95%CI:0.75-0.88), and for endometrioid (OR = 0.51, 95%CI:0.33-0.79) and serous (OR = 0.84, 95%CI:0.75-0.93) histotypes. There was some evidence that higher dose and duration were associated with a greater reduction in risk. Results from sensitivity analyses were not appreciably different. Conclusions Bisphosphonate use was associated with lower risk of EOC, suggesting bisphosphonates may reduce risk of ovarian cancer development. Key messages Bisphosphonates may protect against development of serous and endometrioid ovarian cancers.

Background Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4–21% in reproductive aged women. Recently, the Ovarian Cancer Association Consortium (OCAC) reported a decreased risk of invasive ovarian cancer among women with self-reported PCOS. However, given the limitations of self-reported PCOS, the validity of these observed associations remains uncertain. Therefore, we sought to use Mendelian randomization with genetic markers as a proxy for PCOS, to examine the association between PCOS and ovarian cancer. Methods Utilizing 14 single nucleotide polymorphisms (SNPs) previously associated with PCOS we assessed the association between genetically predicted PCOS and ovarian cancer risk, overall and by histotype, using summary statistics from a previously conducted genome-wide association study (GWAS) of ovarian cancer among European ancestry women within the OCAC (22 406 with invasive disease, 3103 with borderline disease and 40 941 controls). Results An inverse association was observed between genetically predicted PCOS and invasive ovarian cancer risk: odds ratio (OR)=0.92 [95% confidence interval (CI)=0.85–0.99; P = 0.03]. When results were examined by histotype, the strongest inverse association was observed between genetically predicted PCOS and endometrioid tumors (OR = 0.77; 95% CI = 0.65–0.92; P = 0.003). Adjustment for individual-level body mass index, oral contraceptive use and parity did not materially change the associations. Conclusion Our study provides evidence for a relationship between PCOS and reduced ovarian cancer risk, overall and among specific histotypes of invasive ovarian cancer. These results lend support to our previous observational study results. Future studies are needed to understand mechanisms underlying this association.

Background: Chronic kidney disease (CKD) following nephrectomy for kidney tumors is common, and both patient and tumor characteristics may affect postoperative kidney function. Several studies have reported that surgery for large tumors is associated with a lower likelihood of postoperative CKD, but others have reported CKD to be more common before surgery in patients with large tumors. Objective: The aim of this study was to clarify inconsistencies in the literature regarding the prognostic significance of tumor size for postoperative kidney function. Study design and setting: We analyzed data from 944 kidney cancer patients managed with radical nephrectomy between January 2012 and December 2013, and 242 living kidney donors who underwent surgery between January 2011 and December 2014 in the Australian states of Queensland and Victoria. Multivariable logistic regression was used to assess the primary outcome of CKD upstaging. Structural equation modeling was used to evaluate causal models, to delineate the influence of patient and tumor characteristics on postoperative kidney function. Results: We determined that a significant interaction between age and tumor size (P=0.03) led to the observed inverse association between large tumor size and CKD upstaging, and was accentuated by other forms of selection bias. Subgrouping patients by age and tumor size demonstrated that all patients aged ≥65 years were at increased risk of CKD upstaging, regardless of tumor size. Risk of CKD upstaging was comparable between age-matched living donors and kidney cancer patients. Conclusion: Larger tumors are unlikely to confer a protective effect with respect to postoperative kidney function. The reason for the previously reported inconsistency is likely a combination of the analytical approach and selection bias.

PURPOSE: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated. METHODS: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (N=7,022). Using age-, stage, and site-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors. RESULTS: Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR=1.37; 95% CI=1.10–1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR=1.28; 95 % CI=1.08–1.52, and HR=1.26; 95% CI=1.04–1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS. CONCLUSIONS: Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients’ survival.

The International Agency for Research on Cancer first concluded that alcohol causes cancer in humans in 1988. The World Cancer Research Fund has declared that alcohol causes cancer of the oral cavity, pharynx, larynx, oesophagus (squamous cell carcinoma), female breast, colon, rectum, stomach and liver. It recommended that alcohol be avoided altogether to prevent cancer. We aimed to quantify the impact of reducing alcohol consumption on future cancer incidence in Australia. We used PREVENT 3.01 simulation modelling software to estimate the proportion of cancers that could potentially be prevented over a 25-year period under two hypothetical intervention scenarios and two latency periods (20 and 30 years). Under a scenario where alcohol consumption abruptly ceases, we estimated up to 4% of alcohol-related cancers could be avoided over a 25-year period (~49,500 cancers, depending on assumed latency). If the maximum consumption of all Australian adults was ≤20 g/day (~two Australian standard drinks), up to 2% of alcohol-related cancers could be avoided (~29,600 cancers). The maximum proportions were higher for men (6% for no alcohol consumption; 5% for ≤20 g/day) than women (3%; 1%). The proportion avoidable was highest for oesophageal squamous cell carcinoma (17% no alcohol consumption; 9% ≤20 g/day), followed by cancers of the oral cavity (12%; 5%) and pharynx (11%; 5%). The cancer sites with the highest numbers of potentially avoidable cases were colon in men (11,500; 9,900) and breast in women (14,400; 4,100). Successful interventions to reduce alcohol intake could lead to significant reductions in cancer incidence. This article is protected by copyright. All rights reserved.

Globally, 39% of the world's adult population is overweight or obese and 23% is insufficiently active. These percentages are even larger in high-income countries with 58% overweight/obese and 33% insufficiently active. Fourteen cancer types have been declared by the World Cancer Research Fund to be causally associated with being overweight or obese: oesophageal adenocarcinoma, stomach cardia, colon, rectum, liver, gallbladder, pancreas, breast, endometrium, ovary, advanced/fatal prostate, kidney, thyroid and multiple myeloma. Colon, postmenopausal breast and endometrial cancers have also been judged causally associated with physical inactivity. We aimed to quantify the proportion of cancer cases that would be potentially avoidable in Australia if the prevalence of overweight/obesity and physical inactivity in the population could be reduced. We used the simulation modelling software PREVENT 3.01 to calculate the proportion of avoidable cancers over a 25-year period under different theoretical intervention scenarios that change the prevalence of overweight/obesity and physical inactivity in the population. Between 2013 and 2037, 10-13% of overweight/obesity-related cancers in men and 7-11% in women could be avoided if overweight and obesity were eliminated in the Australian population. If everyone in the population met the Australian physical activity guidelines for cancer prevention (i.e. engaged in at least 300 min of moderate-intensity physical activity per week), an estimated 2-3% of physical inactivity-related cancers could be prevented in men (colon cancer) and 1-2% in women (colon, breast and endometrial cancers). This would translate to the prevention of up to 190,500 overweight/obesity-related cancers and 19,200 inactivity-related cancers over 25 years.

Author(s): Lee, Alice W; Rosenzweig, Stacey; Wiensch, Ashley; Australian Ovarian Cancer Study Group; Ramus, Susan J; Menon, Usha; Gentry-Maharaj, Aleksandra; Ziogas, Argyrios; Anton-Culver, Hoda; Whittemore, Alice S; Sieh, Weiva; Rothstein, Joseph H; McGuire, Valerie; Wentzensen, Nicolas; Bandera, Elisa V; Qin, Bo; Terry, Kathryn L; Cramer, Daniel W; Titus, Linda; Schildkraut, Joellen M; Berchuck, Andrew; Goode, Ellen L; Kjaer, Susanne K; Jensen, Allan; Jordan, Susan J; Ness, Roberta B; Modugno, Francesmary; Moysich, Kirsten; Thompson, Pamela J; Goodman, Marc T; Carney, Michael E; Chang-Claude, Jenny; Rossing, Mary Anne; Harris, Holly R; Doherty, Jennifer Anne; Risch, Harvey A; Khoja, Lilah; Alimujiang, Aliya; Phung, Minh Tung; Brieger, Katharine; Mukherjee, Bhramar; Pharoah, Paul DP; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M; Pearce, Celeste Leigh | Abstract: BackgroundParity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated.MethodsA pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses.ResultsEver having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend l .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer.ConclusionsIncomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

IntroductionColorectal cancer (CRC) mortality is significantly higher in those with severe mental illness (SMI) compared with the general population, despite similar incidence rates, suggesting that barriers to optimal screening and cancer care may contribute to disparities in CRC mortality in those with SMI. This study aims to compare participation in Australia’s National Bowel Cancer Screening Programme (NBCSP) in those with SMI and those in the general population. We will also investigate treatment pathways after diagnosis to determine whether treatment variations could explain differences in CRC mortality.Methods and analysisWe will undertake a retrospective cohort study of Australians using linked administrative data to assess differences in screening and cancer care between those with and without SMI, aged 50–74 years on or after 1 January 2006. People with SMI will be defined using antipsychotic medication prescription data. The comparison group will be people enrolled in Medicare (Australia’s universal healthcare system) who have not been prescribed antipsychotic medication. Data on outcomes (NBCSP participation, follow-up colonoscopy, CRC incidence and CRC-cause and all-cause mortality) and confounders will be obtained from national-based and state-based administrative health datasets. All people in New South Wales, aged 50–74 with a new diagnosis of CRC on or after 1 January 2006, will be ascertained to examine stage at diagnosis and cancer treatment in those with and without SMI. Poisson regression will be used to calculate incidence rates and rate ratios for each outcome.Ethics and disseminationEthics approval has been obtained from the University of Queensland Human Research Ethics Committee, the Australian Institute of Health and Welfare Ethics Committee and data custodians from every Australian State/Territory. Findings will be disseminated via publications in peer-reviewed journals and presented at appropriate conferences.Trial registration numberACTRN12620000781943.

Objective A recent paper suggested all women with endometrial cancer should take statins but it is unclear whether there is sufficient evidence to justify this recommendation. Methods We identified all women diagnosed with uterine cancer in Australia between July 2003 and December 2013 (2012 in New South Wales) through the Australian Cancer Database (N = 16,501) and linked these to the national prescription database and National Death Index to identify statin use and survival outcomes to December 2015. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between statin use and survival. Results Among the 15,703 women with endometrial cancer, pre-diagnosis statin use was not associated with survival. Endometrial cancer-specific mortality was lower among women who used statins after diagnosis (time-varying models: HR = 0.92; 95%CI 0.82–1.03) but the association was only seen among women with type 1 cancers (0.87; 0.76–1.00), for hydrophilic statins (0.84; 0.68–1.03) and for new use of statins after diagnosis (0.75; 0.59–0.95). There was a weak dose-response with increasing number of statin prescriptions. Sensitivity analyses using inverse probability of treatment weights were similar. Conclusion Women with endometrial cancer who take statins after diagnosis may have better survival than those who do not use statins. However, it is impossible to completely rule out bias, particularly reverse causation where disease status may affect statin use. We believe it is too early to recommend all women with endometrial cancer take statins, but there is sufficient evidence to justify a randomized trial.

BACKGROUND: While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. METHODS: We performed a pooled analysis among parous participants from 12 case-controls studies comprising 6,872 EOC patients and 9,101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case-control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders. RESULTS: In general, no associations were found between offspring sex and EOC risk. However, compared to bearing only female offspring, bearing one or more male offspring was associated with increased risk of mucinous EOC (OR=1.45; 95%CI=1.01–2.07), which appeared to be limited to women reporting menarche before age 13 compared to later menarche (OR=1.71 vs 0.99; P-interaction=0.02). Bearing increasing numbers of male offspring was associated with greater risks of mucinous tumors (OR=1.31, 1.84, 2.31, for 1, 2 and 3 or more male offspring, respectively; trend-p = 0.005). Stratifying by hormonally-associated conditions suggested that compared to bearing all female offspring, bearing a male offspring was associated with lower risk of endometrioid cancer among women with a history of adult acne, hirsutism, or polycystic ovary syndrome (OR=0.49, 95%CI=0.28–0.83) but with higher risk among women without any of those conditions (OR=1.64 95%CI=1.14–2.34; P-interaction=0.003). CONCLUSION: Offspring sex influences the childbearing-EOC risk relationship for specific histotypes and conditions. These findings support the differing etiologic origins of EOC histotypes and highlight the importance of EOC histotype-specific epidemiologic studies. These findings also suggest the need to better understand how pregnancy affects EOC risk

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed.METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR RESULTS: Absolute risks of stage 3b or higher CKD were CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

Background - Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. Patients and methods - We pooled individual-level data from seven cohort and five case–control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. Results - At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76–0.98] and 0.86 [95% CI 0.76–0.97], respectively, for aspirin; 0.87 [95% CI 0.76–1.00] and 0.84 [0.74–0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index 2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2–6 times/week (OR = 0.81, 95% CI 0.68–0.96) than for daily use (0.91, 0.80–1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. Conclusion - Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.

To describe the use of partial nephrectomy (PN) for patients with stage T1a renal cell carcinoma (RCC) by age group (65 and ≥65 years) in two Australian states.All adults diagnosed with RCC in 2012 and 2013 were identified through population-based cancer registries in the Australian states of Queensland and Victoria. For each patient, research assistants extracted patient, tumour and treatment data from medical records. Percentages of patients treated by PN were determined for the two age groups. Multivariable logistic regression analyses examined factors associated with PN. Clinicians treating RCC were sent surveys to assess attitudes towards PN.Data were collected on 956 patients (Victoria: n = 548; Queensland: n = 404) with stage T1a RCC. Of those undergoing surgery (n = 865), PN was more common for those aged65 years (61%) than for those aged ≥65 years (44%), with this difference significant after adjusting for patient, tumour (odds ratio 0.50, 95% confidence interval 0.36-0.70). There were significant interactions between age and treatment centre volume (P0.05) and residential state (P0.05). PN was less likely for younger patients treated at lower-volume hospitals (24 patients a year) but hospital volume was not associated with PN for older patients. PN was less likely for older patients in Queensland than Victoria. In multivariable analyses, age was not related to laparoscopic surgery. Queensland clinicians were less likely than those from Victoria to agree that PN was the treatment of choice for most T1aN0M0 tumours (P0.001).In Australia, patients aged65 years with small renal cancers were less likely to be treated by PN than younger patients. The variation in the surgical procedure used to treat older T1a RCC patients by state and hospital volume indicates that better evidence is needed to direct practice in this area.

Background and objectives We investigated the incidence of ESKD after surgical management of kidney cancer in the Australian state of Queensland, and described patterns in the initiation of kidney replacement therapy resulting from kidney cancer across Australia. Design, setting, participants, & measurements All newly diagnosed cases of kidney cancer in the Australian state of Queensland between January of 2009 and December of 2014 were ascertained through the Queensland Cancer Registry. There were 2739 patients included in our analysis. Patients who developed ESKD were identified using international classification of disease–10–coded hospital administrative data. Incidence rate and 3-year cumulative incidence were calculated, and multivariable Cox proportional hazards models were used to identify factors associated with ESKD. Additional descriptive analysis was undertaken of Australian population data. Results The incidence rate of ESKD in all patients was 4.9 (95% confidence interval [95% CI], 3.9 to 6.2) per 1000 patient-years. The 3-year cumulative incidence was 1.7%, 1.9%, and 1.0% for all patients, and patients managed with radical or partial nephrectomy, respectively. Apart from preoperative kidney disease, exposures associated with increased ESKD risk were age≥65 years (adjusted hazard ratio [aHR], 2.0; 95% CI, 1.2 to 3.2), male sex (aHR, 2.3; 95% CI, 1.3 to 4.3), preoperative diabetes (aHR, 1.8; 95% CI, 1.0 to 3.3), American Society of Anesthesiologists classification ≥3 (aHR, 4.0; 95% CI, 2.2 to 7.4), socioeconomic disadvantage (aHR, 1.6; 95% CI, 0.9 to 2.7), and postoperative length of hospitalization ≥6 days (aHR, 2.1; 95% CI, 1.4 to 3.0). Australia-wide trends indicate that the rate of kidney replacement therapy after oncologic nephrectomy doubled between 1995 and 2015, from 0.3 to 0.6 per 100,000 per year. Conclusions In Queensland between 2009 and 2014, one in 53 patients managed with radical nephrectomy and one in 100 patients managed with partial nephrectomy developed ESKD within 3 years of surgery. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_28_CJASNPodcast_18_1_.mp3

Objective Risk factors for ovarian borderline tumors and low-grade serous carcinoma (LGSC) are poorly understood. The aim of this study was to examine the association between infertility, pelvic inflammatory disease (PID), endometriosis, ectopic pregnancy, hysterectomy, tubal ligation and parity and the risk of serous borderline tumor (SBT), mucinous borderline tumor (MBT) and LGSC. Methods This was a population-based cohort study using linked administrative and hospital data. Participants were 441,382 women born between 1945 and 1975 who had been admitted to hospital in Western Australia between 1 January 1980 and 30 June 2014. We used Cox regression to estimate hazard ratios (HRs). Results We observed an increased rate of SBT associated with infertility, PID and ectopic pregnancy (HRs and 95% CIs were, respectively, 1.98 (1.20–3.26); 1.95 (1.22–3.10) and 2.44 (1.20–4.96)). We did not detect an association between any of the factors under study and the rate of MBT. A diagnosis of PID was associated with an increased rate of LGSC (HR 2.90, 95% CI 1.21–6.94). Conclusions The association with PID supports the hypothesis that inflammatory processes within the upper gynaecological tract and/or peritoneum may predispose to the development of SBT and LGSC.

Background Ovarian carcinoma is not a single disease, but rather a collection of subtypes with differing molecular properties and risk profiles. The most common of these, and the subject of this work, is high-grade serous ovarian carcinoma (HGSC). Methods In this population-based study we identified a cohort of 441,382 women resident in Western Australia who had ever been admitted to hospital in the State. Of these, 454 were diagnosed with HGSC. We used Cox regression to derive hazard ratios (HRs) comparing the risk of disease in women who had each of a range of medical diagnoses and surgical procedures with women who did not. Results We found an increased risk of HGSC associated with a diagnosis of pelvic inflammatory disease (PID) (HR 1.47, 95% CI 1.04–2.07) but not with a diagnosis of infertility or endometriosis with HRs of 1.12 (95% CI 0.73–1.71) and 0.82 (95% CI 0.55–1.22) respectively. A personal history of breast cancer was associated with a three-fold increase in the rate of HGSC. Increased parity was associated with a reduced risk of HGSC in women without a personal history of breast cancer (HR 0.57; 95% CI 0.44-0.73), but not in women with a personal history of breast cancer (HR 1.48; 95% CI 0.74–2.95). Conclusions Our finding of an increased risk of HGSC associated with PID lends support to the hypothesis that inflammatory processes may be involved in the etiology of HGSC.

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies. Methods: We analyzed data from 14 case–control studies including 16,594 women with invasive ovarian cancer (n = 13,719) or borderline ovarian disease (n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression. Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58–0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with 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). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors (Pheterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors (Pheterogeneity < 0.0001). Conclusions: Our results suggest that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype. Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174–82. ©2017 AACR.

We aimed to describe management of biliary obstruction (BO) in the context of pancreatic cancer within a population-based cohort.We examined management of BO in 1863 patients diagnosed as having pancreatic cancer in 2010/2011. We used descriptive statistics and logistic regression to describe patterns of biliary stent usage, complications and duration of patency, associations between preoperative stenting and surgical outcomes, and between patient factors and management of jaundice.Almost half of the people in the cohort (n = 909) were jaundiced within 12 months of diagnosis. Two-thirds of these had at least 1 stent inserted. Preoperative stenting, mostly with plastic stents, occurred for 72% of patients who experienced jaundice prior to an attempted resection but was not associated with surgical outcomes. Seventy percent of the jaundiced patients who did not have an attempted resection were stented. Metal stents were less frequently replaced within 30 days than plastic (9% vs 42%). Living in a rural area was associated with reduced likelihood of having jaundice managed.Plastic stents were still used frequently, despite guidelines recommending metal in most contexts. Patients living in rural areas were less likely to have BO managed. This work highlights the need to monitor current practice.

Purpose The incidence of renal cell carcinoma (RCC) is rising. Use of analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol may affect renal function. The aim of this study was to assess associations between analgesic use and risk of RCC. Methods A population-based case-control family design was used. Cases were recruited via two Australian state cancer registries. Controls were siblings or partners of cases. Analgesic use was captured by self-completed questionnaire. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for RCC risk associated with regular analgesic use (at least 5 times per month for 6 months or more) and duration and frequency of use. Results The analysis included 1064 cases and 724 controls. Regular use of paracetamol was associated with an increased risk of RCC (OR 1.41, 95%CI 1.13–1.77). Regular use of NSAIDs was associated with increased risk of RCC for women (OR 1.71, 95% CI 1.23–2.39) but not men (OR 0.83, 95% CI 0.58–1.18; p-interaction=0.003). There was no evidence of a dose-response for duration of use of paracetamol (linear trend p = 0.77) and weak evidence for non- aspirin NSAID use by women (linear trend p = 0.054). Conclusion This study found that regular use of paracetamol was associated with increased risk of RCC. NSAID use was associated with increased risk only for women.

Hysterectomy remains a common procedure worldwide, hence better understanding of the long-term health consequences, including for cancer risk, is imperative to enable effective counselling about the risks and benefits of the surgery. At present, the association between hysterectomy and ovarian cancer is unclear. Most earlier studies reported a protective effect, while studies including women diagnosed more recently have not reported a reduction in risk (Jordan SJ et al. Eur J Cancer. 2013 Nov;49(17):3638-47).

Background Hysterectomy has been associated with increased thyroid cancer risk but whether this reflects a biological link or increased diagnosis of indolent cancers due to greater medical contact remains unclear. Methods We recruited 730 women diagnosed with thyroid cancer and 785 age-matched population controls. Multivariable logistic regression was used to assess the association overall, and by tumour BRAF mutational status as a marker of potentially higher-risk cancers. We used causal mediation analysis to investigate potential mediation of the association by healthcare service use. Results Having had a hysterectomy was associated with an increased risk of thyroid cancer (odds ratio [OR] = 1.45, 95 % confidence interval [CI] 1.07–1.96). When stratified by indication for hysterectomy, the risk appeared stronger for those who had a hysterectomy for menstrual disorders (OR = 1.67, 95 % CI 1.17–2.37) but did not differ by tumour BRAF status. Approximately 20 % of the association between hysterectomy and thyroid cancer may be mediated by more frequent use of healthcare services. Conclusions The observed increased risk of thyroid cancer among those with hysterectomy may be driven, at least partly, by an altered sex steroid hormone milieu. More frequent healthcare service use by women with hysterectomy accounts for only a small proportion of the association.

Cancer is a leading cause of disease burden in Australia, particularly fatal burden, accounting for an estimated thirty percent of deaths. Many cancers develop because of exposure to lifestyle and environmental factors that are potentially modifiable. We aimed to quantify the proportions and numbers of cancer deaths and cases in Australia in 2013 attributable to 20 modifiable factors in eight broad groupings that are established causes of cancer, namely: tobacco smoke (smoking and second-hand), dietary factors (low intake of fruit, non-starchy vegetables and dietary fibre; and high intake of red and processed meat), overweight/obesity, alcohol, physical inactivity, solar ultraviolet radiation, infections (seven agents), and reproductive factors (lack of breastfeeding, menopausal hormone therapy use, combined oral contraceptive use). We estimated population attributable fractions (PAF) using standard formulae incorporating exposure prevalence and relative risk data. Of all cancer deaths in Australia in 2013, approximately 38% overall (males 41%, females 34%) could be attributed to the factors assessed; the corresponding PAF for cancer cases was 33% (males 34%, females 32%). Tobacco smoke was the leading cause of cancer deaths and cases, with PAFs of 23 and 13%, respectively, followed by dietary factors (5% deaths/5% cases), overweight/obesity (5%/4%) and infections (5%/3%). Cancer sites with the highest numbers of potentially preventable deaths/cases were lung (n = 6,776/9,272), colorectum (n = 1,974/7,380) and cutaneous melanoma (n = 1,390/7,918). We estimate that about 16,700 cancer deaths and 41,200 cancer cases could be prevented in Australia each year if people's exposures to 20 causal factors were aligned with levels recommended to minimise cancer risk.

Menstrual pain, a common gynecological condition, has been associated with increased risk of ovarian cancer in some, but not all studies. Furthermore, potential variations in the association between menstrual pain and ovarian cancer by histologic subtype have not been adequately evaluated due to lack of power. We assessed menstrual pain using either direct questions about having experienced menstrual pain, or indirect questions about menstrual pain as indication for use of hormones or medications. We used multivariate logistic regression to calculate the odds ratio (OR) for the association between severe menstrual pain and ovarian cancer, adjusting for potential confounders, and multinomial logistic regression to calculate odds ratios for specific histologic subtypes. We observed no association between ovarian cancer and menstrual pain assessed by indirect questions. Among studies using direct question, severe pain was associated with a small but significant increase in overall risk of ovarian cancer (OR=1.07, 95% CI: 1.01-1.13), after adjusting for endometriosis and other potential confounders. The association appeared to be more relevant for clear cell (OR=1.48, 95% CI: 1.10-1.99) and serous borderline (OR=1.31, 95% CI: 1.05-1.63) subtypes. In this large international pooled analysis of case-control studies, we observed a small increase in risk of ovarian cancer for women reporting severe menstrual pain. While we observed an increased ovarian cancer risk with severe menstrual pain, the possibility of recall bias and undiagnosed endometriosis cannot be excluded. Future validation in prospective studies with detailed information on endometriosis is needed. This article is protected by copyright. All rights reserved.

Ovarian neoplasia comprises a heterogenous group of tumors with distinct clinicopathologic and molecular features and therefore assessment of potential risk factors should be tumor subtype specific. As part of ongoing epidemiological investigations of ovarian neoplasia in Western Australia, we performed an initial review of original pathology reports followed, in selected cases, by reassessment of histology material to optimize accurate diagnosis. Additional immunohistochemistry, often using antibodies unavailable at the time of initial assessment, was also performed as required. From an initial cohort of 1660 cases identified through the Western Australia Cancer Registry, benign, nonepithelial, nonovarian, miscellaneous, and indeterminate cases were excluded. Also excluded were 33 cases that were reclassified as ovarian metastases rather than primary ovarian tumors. Following exclusions there remained 1321 borderline and malignant epithelial neoplasms. The diagnosis was considered accurate in 1186 cases (89.8%) based upon information in the initial pathology reports and clinical follow-up data but uncertain in 135 cases (10.2%). Histologic review was possible in 92 of the latter tumors leading to an amended diagnosis in 63 cases (68.5%). The most common types of diagnostic amendment were the reclassification of high-grade carcinomas of undifferentiated, endometrioid, or transitional appearance as high-grade serous carcinoma, and the reclassification of most carcinomas of mixed epithelial type as "pure'' carcinomas. This review illustrated specific pitfalls in the diagnosis of ovarian epithelial neoplasia and helped to maintain the accuracy of the Western Australia Cancer Registry. Accurate diagnosis will optimize further epidemiological studies assessing risk factors in specific subtypes of ovarian neoplasia.

Globally, ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death, with five-year survival rates below 45%. Although age-standardised rates are stable or falling in most high-income countries, they are rising in many low and middle income countries. Furthermore, with increasing life-expectancy, the number of cases diagnosed each year is increasing. To control ovarian cancer we need to understand the causes. This will allow better prediction of those at greatest risk for whom screening might be appropriate, while identification of potentially modifable causes provides an opportunity for intervention to reduce rates. In this paper we will summarise the current state of knowledge regarding the known and possible causes of epithelial ovarian cancer and discuss some of the main theories of ovarian carcinogenesis. We will also briefly review the relationship between lifestyle and survival after a diagnosis of ovarian cancer.

To compare trends in ovarian cancer incidence in the USA and Australia in relation to changes in oral contraceptive pill (OCP) and menopausal hormone therapy (MHT) use. US cancer incidence data (1973–2013) were accessed via SEER*Stat; Australian data (1982–2012) were accessed from the Australian Institute of Health and Welfare Cancer Incidence and Mortality books. Age-period-cohort models were constructed to assess trends in ovarian cancer incidence by birth cohort and year of diagnosis. Ovarian cancer rates were increasing until the cohorts born around 1918 in the USA and 1923 in Australia who were the first to use the OCP. They then declined dramatically across subsequent cohorts such that rates for the 1968 cohort were about half those of women born 45 years earlier; however, there are early suggestions that this decline may not continue in more recent cohorts. In contrast, despite the large reduction in MHT use, there was no convincing evidence that ovarian cancer incidence rates in either country were lower after 2002 than would have been expected based on the declining trend from 1985. The major driver of ovarian cancer incidence rates appears to be the OCP. This means that when those women born since the late 1960s (who have used the OCP at high rates from an early age) reach their 60s and 70s, incidence rates are likely to stop falling and may even increase with changes in the prevalence of other factors such as tubal ligation and obesity. Forward predictions based on past trends may thus underestimate future rates and numbers of women likely to be affected.

Contains fulltext : 169777.pdf (Publisher’s version ) (Closed access) Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation.

Background: Type 2 diabetes mellitus (T2DM) is increasingly prevalent in countries undergoing rapid development, including Thailand. We assessed T2DM incidence over an 8-year period in a nationwide cohort of Thai adults.Methods: Thai Cohort Study participants were surveyed in 2005, 2009 and 2013. The analysed cohort members were aged (15–88), did not have diabetes in 2005 and were followed up by questionnaire in 2013 (n=39 507). T2DM was ascertained using self-report, which has been validated using physician interviews. We calculated the 8-year cumulative incidence of T2DM. Multivariable logistic regression assessed associations between potential risk factors and T2DM incidence.Results: 8-year cumulative incidence of T2DM (2005 to 2013) was 177 per 10 000 (95% CI 164 to 190). Crude and age-standardised cumulative incidences of T2DM by sex were 249 per 10 000 (95% CI 226 to 272) and 222 per 10 000 (95% CI 219 to 225) for men; and 119 per 10 000 (95% CI 105 to 133) and 96 per 10 000 (95% CI 94 to 98) for women, respectively. T2DM increased significantly for both sexes with increasing age and body mass index (BMI) (p trend Conclusions: This study found that the sociodemographic and lifestyle changes that have accompanied Thailand's economic development are associated with T2DM risk in a large cohort of Thai adults. Our findings highlight the need to address these transitions to prevent a further increase in the national incidence of T2DM, particularly among Thai men.

Background Recent studies have called into question the long-held belief that hysterectomy without oophorectomy protects against ovarian cancer. This population-based longitudinal record-linkage study aimed to explore this relationship, overall and by age at hysterectomy, time period, surgery type, and indication for hysterectomy. Methods We followed the female adult Western Australian population (837 942 women) across a 27-year period using linked electoral, hospital, births, deaths, and cancer records. Surgery dates were determined from hospital records, and ovarian cancer diagnoses (n = 1640) were ascertained from cancer registry records. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer incidence. Results Hysterectomy without oophorectomy (n = 78 594) was not associated with risk of invasive ovarian cancer overall (HR = 0.98, 95% CI = 0.85 to 1.11) or with the most common serous subtype (HR = 1.05, 95% CI = 0.89 to 1.23). Estimates did not vary statistically significantly by age at procedure, time period, or surgical approach. However, among women with endometriosis (5.8%) or with fibroids (5.7%), hysterectomy was associated with substantially decreased ovarian cancer risk overall (HR = 0.17, 95% CI = 0.12 to 0.24, and HR = 0.27, 95% CI = 0.20 to 0.36, respectively) and across all subtypes. Conclusions Our results suggest that for most women, having a hysterectomy with ovarian conservation is not likely to substantially alter their risk of developing ovarian cancer. However, our results, if confirmed, suggest that ovarian cancer risk reduction could be considered as a possible benefit of hysterectomy when making decisions about surgical management of endometriosis or fibroids.

The incidence of thyroid cancer has rapidly increased, and ecological evidence suggests this is due in some part to over-diagnosis. Understanding pathways to diagnosis could help determine whether unnecessary diagnosis can be avoided.A population-based sample (n = 1007) of thyroid cancer patients diagnosed between July 2013 and August 2016 was recruited from Queensland, Australia (response rate 67%). Information from structured telephone interviews was used to describe diagnostic pathways for thyroid cancer, to investigate factors associated with diagnostic pathways, and to assess the most prevalent modes of diagnoses by which the lowest-risk, potentially over-diagnosed thyroid cancers (intrathyroidal microcarcinomas) are detected.Only 38% of participants presented with symptoms potentially related to thyroid cancer. Older age at diagnosis was associated with a lower prevalence of symptomatic diagnosis (prevalence ratio [PR] = 0.46 [confidence interval (CI) 0.31-0.68] for 70-79 vs.30 years), as was frequent medical contact, while living in rural/regional areas was associated with a higher prevalence of symptomatic diagnosis (PR = 1.17 [CI 1.00-1.37] for rural/regional areas vs. major cities). Symptomatic diagnosis also occurred more for those whose tumors had adverse histopathological features (larger size, lymph node involvement, lymphovascular invasion). The likelihood of diagnosis of intrathyroidal microcarcinomas was greatest for those having surgical resection or monitoring for benign thyroid disease (PR = 3.87 [CI 2.81-5.32] and PR = 2.21 [CI 1.53-3.18], respectively).A minority of newly detected thyroid cancer cases were diagnosed because of symptoms. Access to medical care and factors related to cancer aggressiveness were associated with how diagnoses occurred. The likelihood of diagnosing the lowest-risk thyroid cancers was higher in situations related to management of other thyroid conditions. Adherence to thyroid management guidelines could reduce some thyroid cancer over-diagnosis, but ultimately better diagnostic tools are needed to differentiate between indolent cancers and those of clinical significance.

Background Chronic kidney disease (CKD) after surgery for kidney cancer is common, and is associated with increased morbidity and mortality. This study aimed to identify factors associated with incident CKD in patients managed with radical nephrectomy. Patients and Methods All patients diagnosed with renal cell carcinoma between January 2012 and December 2013 were ascertained from state-based cancer registries in Queensland and Victoria. Information on patient, tumor, and health service characteristics was obtained via chart review. Multivariable logistic regression was used to evaluate exposures associated with incident CKD (estimated glomerular filtration rate [eGFR] Results Older age (adjusted odds ratio [aOR] per 5-year increase, 1.5; 95% confidence interval [CI], 1.4-1.6), male sex (aOR, 1.4; 95% CI, 1.0-2.0), obese compared with not obese (aOR, 1.8; 95% CI, 1.2-2.7), rural compared with urban place of residence (aOR, 1.8; 95% CI, 1.1-3.0) were associated with a higher risk of incident CKD. Lower preoperative eGFR was also associated with a higher risk of incident CKD. Management in private compared with public hospitals was also associated with a higher risk of CKD (aOR, 1.6; 95% CI, 1.2-2.2). Factors related to tumor size and cancer severity were also associated with worse postoperative kidney function, although it is likely this was a consequence of selection bias. Conclusion Patient characteristics have the strongest associations with incident CKD after radical nephrectomy. Potential risk factors were reasonably similar to recognized CKD risk factors for the general population. Patients who undergo nephrectomy who have CKD risk factors might benefit from ongoing postoperative screening for deterioration of kidney function.

Objective: People with severe mental illness have similar cancer incidence, but higher mortality than the general population. Participation in cancer screening may be a contributing factor but existing studies are conflicting. The aim of this study was to investigate the frequency of colorectal, prostate and cervical cancer screening among people with and without severe mental illness in Australia, who have access to universal health care. Methods: We followed three cohorts using de-identified data from a random 10% sample of people registered for Australia’s universal health care system: those aged 50–69 years ( n = 760,058) for colorectal cancer screening; women aged 18–69 years ( n = 918,140) for cervical cancer screening and men aged 50–69 years ( n = 380,238) for prostate cancer screening. We used Poisson regression to estimate incidence rate ratios and 95% confidence intervals for the association between severe mental illness and rates of faecal occult blood testing, pap smears and prostate-specific antigen testing. Results: Having severe mental illness was associated with a 17% reduction in rates of pap smear (incidence rate ratio = 0.83, 95% confidence interval: 0.82–0.84) and prostate-specific antigen testing (incidence rate ratio = 0.83, 95% confidence interval: 0.81–0.85), compared to the general population. By contrast, incidence rates of faecal occult blood testing were only lower in people with severe mental illness among the participants who visited their general practitioner less than an average of five times per year (incidence rate ratio = 0.83, 95% confidence interval = [0.73, 0.94]). Conclusion: Our results suggest that differences in screening frequency may explain some of the mismatch between cancer incidence and mortality in people with severe mental illness and indicate that action is required to improve preventive screening in this very disadvantaged group.

Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk. Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index. Results: The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14–1.57), and similar associations were observed for each histotype. Conclusions: In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes. Impact: These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114–24. ©2016 AACR.

Background Hysterectomy is one of the most commonly performed gynecological surgeries, with an estimated 30% of women in Australia undergoing the procedure by age 70. In the USA, about 45% of women have a hysterectomy in their lifetime. Some studies have suggested this procedure increases the risk of premature mortality. With many women making the decision to have a hysterectomy for a benign indication each year, additional research is needed to clarify whether there are long-term health consequences of hysterectomy. Objective Our aim was to examine the association between hysterectomy for benign indications, with or without removal of the ovaries, and cause-specific and all-cause mortality. Study Design Our cohort of 666,588 women comprised the female population of Western Australia with linked hospital and health records from 1970 to 2015. We used Cox regression models to assess the association between hysterectomy and all-cause, cardiovascular disease, cancer and other mortality by oophorectomy type (categorized as none, unilateral and bilateral), with no hysterectomy or oophorectomy as the reference group. We repeated these analyses using hysterectomy without oophorectomy as the reference group. We also investigated whether associations varied by age at the time of surgery, although small sample size precluded this analysis in women who had a hysterectomy with unilateral salpingo-oophorectomy. In our main analysis, women who had hysterectomy and/or oophorectomy undertaken as part of treatment for cancer were retained in the analysis and considered unexposed to that surgery. As a sensitivity analysis, we censored procedures undertaken for cancer. Results Compared to no surgery, having a hysterectomy without oophorectomy before age 35 was associated with an increase in all-cause mortality (HR=1.29, 95% CI:1.19-1.40); for surgery after age 35, there was an inverse association (35-44 years: HR=0.93, 95%CI:0.89,0.97). Similarly, hysterectomy with bilateral salpingo-oophorectomy was associated with increased all-cause mortality when undertaken before age 45 (35-44 years: HR=1.15, 95%CI:1.04-1.27), but decreased mortality rates when surgery was undertaken after age 45. In our sensitivity analysis, censoring gynecological surgeries for cancer resulted in many cancer-related deaths being excluded for women who did not have surgery for benign indications, and thus increased the hazard ratios for the associations between both hysterectomy without oophorectomy and hysterectomy with bilateral salpingo-oophorectomy and risk of all-cause and cancer-specific mortality. The sensitivity analysis therefore potentially biased the results in favor of no surgery. Conclusion Among women having surgery for benign indications, hysterectomy without oophorectomy performed prior to 35 years and hysterectomy with bilateral salpingo-oophorectomy performed prior to 45 years were associated with an increase in all-cause mortality. These procedures are not associated with poorer long-term survival when performed at older ages.

IMPORTANCE: Breastfeeding has been associated with a reduced risk of epithelial ovarian cancer in multiple studies, but others showed no association. Whether risk reduction extends beyond that provided by pregnancy alone or differs by histotype is unclear. Furthermore, the observed associations between duration and timing of breastfeeding with ovarian cancer risk have been inconsistent. OBJECTIVE: To determine the association between breastfeeding (ie, ever/never, duration, timing) and ovarian cancer risk overall and by histotype. DESIGN, SETTING, AND PARTICIPANTS: A pooled analysis of parous women with ovarian cancer and controls from 13 case-control studies participating in the Ovarian Cancer Association Consortium was performed. Odds ratios (ORs) and 95% CIs of the overall association were calculated using multivariable logistic regression and polytomous logistic regression for histotype-specific associations. All data were collected from individual sites from November 1989 to December 2009, and analysis took place from September 2017 to July 2019. EXPOSURES: Data on breastfeeding history, including duration per child breastfed, age at first and last breastfeeding, and years since last breastfeeding were collected by questionnaire or interview and was harmonized across studies. MAIN OUTCOMES AND MEASURES: Diagnosis of epithelial ovarian cancer. RESULTS: A total of 9973 women with ovarian cancer (mean [SD] age, 57.4 [11.1] years) and 13 843 controls (mean [SD] age, 56.4 [11.7] years) were included. Breastfeeding was associated with a 24% lower risk of invasive ovarian cancer (odds ratio [OR], 0.76; 95% CI, 0.71-0.80). Independent of parity, ever having breastfed was associated with reduction in risk of all invasive ovarian cancers, particularly high-grade serous and endometrioid cancers. For a single breastfeeding episode, mean breastfeeding duration of 1 to 3 months was associated with 18% lower risk (OR, 0.82; 95% CI, 0.76-0.88), and breastfeeding for 12 or more months was associated with a 34% lower risk (OR, 0.66; 95% CI, 0.58-0.75). More recent breastfeeding was associated with a reduction in risk (OR, 0.56; 95% CI, 0.47-0.66 for

It has come to our attention that authors Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, and Cezary Cybulski were not assigned to the correct affiliations. Their correct affiliations are as in the list above. Conflicts of interest: The authors have nothing to disclose.

1 Aim Palliative chemotherapy improves symptom control and prolongs survival in patients with unresectable pancreatic cancer, but there is a paucity of data describing its use and effectiveness in everyday practice. We explored patterns of chemotherapy use in patients with unresected pancreatic cancer in Australia and the impact of use on survival. 2 Methods We reviewed the medical records of residents of New South Wales or Queensland, Australia, diagnosed with unresectable pancreatic adenocarcinoma between July 2009 and June 2011. Associations between receipt of chemotherapy and sociodemographic, clinical and health service factors were evaluated using logistic regression. We used Cox proportional hazards models to analyze associations between chemotherapy use and survival. 3 Results Data were collected for 1173 eligible patients. Chemotherapy was received by 44% (n = 184/414) of patients with localized pancreatic cancer and 53% (n = 406/759) of patients with metastases. Chemotherapy receipt depended on clinical factors, such as performance status and comorbidity burden, and nonclinical factors, such as age, place of residence, multidisciplinary team review and the type of specialist first encountered. Consultation with an oncologist mitigated most of the sociodemographic and service‐related disparities in chemotherapy use. The receipt of chemotherapy was associated with prolonged survival in patients with inoperable pancreatic cancer, including after adjusting for common prognostic factors. 4 Conclusions These findings highlight the need to establish referral pathways to ensure that all patients have the opportunity to discuss treatment options with a medical oncologist. This is particularly relevant for health care systems covering areas with a geographically dispersed population.