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Background: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).Methods and Findings: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10-5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10-5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.Conclusions: This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer. [ABSTRACT FROM AUTHOR]

Despite overall improvements in cancer survival due to earlier diagnosis and better treatment, socio-economically disadvantaged people have lower cancer survival than more advantaged people. We aimed to examine differences in cancer survival by area-level socio-economic disadvantage in Victoria, Australia and assess whether these inequalities varied by year of diagnosis, age at diagnosis, time since diagnosis and sex. Cases diagnosed with a first primary cancer in 2001–2015 were identified using the Victorian Cancer Registry and followed to the end of 2016. Five-year net survival and the excess risk of death due to a cancer diagnosis were estimated. People living in more disadvantaged areas had lower five-year survival than residents of less disadvantaged regions for 21 of 29 cancer types: head and neck, oesophagus, stomach, colorectum, anus/anal canal, liver, gallbladder/biliary tract, pancreas, lung, melanoma, connective/soft tissue, female breast, ovary, prostate, kidney, bladder, brain and central nervous system, unknown primary, non-Hodgkin lymphoma, multiple myeloma and leukemia. The observed lower survival in more deprived regions persisted over time, except head and neck cancer, for which the gap in survival has widened. Socio-economic inequalities in survival decreased with increasing age at diagnosis for cancers of connective/soft tissue, bladder and unknown primary. For colorectal cancer, the observed survival disadvantage in lower socio-economic regions was greater for men than for women, while for brain and central nervous system tumours, it was larger for women. Cancer survival is generally lower for residents of more socio-economically disadvantaged areas. Identifying the underlying reasons for these inequalities is important and may help to identify effective interventions to increase survival for underprivileged cancer patients. [ABSTRACT FROM AUTHOR]

Objective There is evidence of a vascular contribution to the pathogenesis of osteoarthritis (OA). The aim of this study was to examine the association between popliteal artery wall thickness, which was previously shown to be associated with the risk of OA, and structural changes in the knee in an asymptomatic cohort. Methods A total of 297 adults with no significant knee pain, injury, or history of clinical knee disease were recruited. Participants underwent magnetic resonance imaging of the knee at baseline and 2 years later. Popliteal artery wall thickness, knee cartilage volume, and bone marrow lesions (BMLs) were assessed. Results Of 278 participants with valid popliteal artery wall thickness measurements, 254 (91.4%) completed the 2-year followup assessment. After adjusting for age, sex, body mass index, and tibial bone area, increased popliteal artery wall thickness was found to be associated with a reduced medial tibial cartilage volume (B = −6.7 [95% confidence interval (95% CI) −12.9, −0.6], P = 0.03) and an increased rate of medial tibial cartilage volume loss (B = 0.06 [95% CI 0.01, 0.12], P = 0.03). There was a trend toward worsening of medial tibiofemoral BMLs in relation to increased popliteal artery wall thickness (odds ratio 1.07 [95% CI 0.99, 1.15]; P = 0.07). No significant associations with the lateral tibiofemoral compartment were observed. Conclusion Increased popliteal artery wall thickness was associated with adverse changes in knee structure, as evidenced by reduced medial tibial cartilage volume, increased rate of cartilage volume loss, and a trend toward worsening of BMLs over 2 years. These findings suggest an association between vascular pathology and early structural changes in the knee, which supports the hypothesis that vascular health may play a role in the development of knee OA. [ABSTRACT FROM AUTHOR]

Objective The increased prevalence of osteoarthritis (OA) in postmenopausal women suggests that changes in either circulating sex steroid concentrations or the tissue response to sex steroids may have a role in the pathogenesis of OA. The aim of this study was to examine whether circulating sex steroid concentrations are associated with the incidence of total knee and total hip replacement for OA. Methods Study subjects (n = 2,621; all women) were recruited in 1990-1994 from the Melbourne Collaborative Cohort Study (MCCS). Circulating sex steroid concentrations were measured in blood samples obtained from the women at the time of recruitment. The incidence of total knee and total hip replacement for OA during 2001-2011 was determined by linking the MCCS records to the Australian Orthopaedic Association National Joint Replacement Registry. Results During the followup period, 115 women had undergone total knee replacement and 99 had undergone total hip replacement for OA. Greater log-transformed concentrations of estradiol were associated with a lower incidence of knee replacement (hazard ratio [HR] 0.70, 95% confidence interval [95% CI] 0.50-0.96), and greater log-transformed concentrations of androstenedione were associated with a lower incidence of hip replacement (HR 0.70, 95% CI 0.52-0.93). In contrast, greater log-transformed concentrations of sex hormone binding globulin (SHBG) were associated with a higher incidence of hip replacement (HR 1.70, 95% CI 1.05-2.77). Conclusion A lower estradiol concentration is a risk factor for knee OA, while a lower androstenedione concentration and higher SHBG concentration are risk factors for hip OA in women. These findings suggest that circulating sex steroids have a role in the pathogenesis of OA, and that modifying these steroid concentrations may provide a potential strategy for the prevention and treatment of knee and hip OA. [ABSTRACT FROM AUTHOR]

Aim A survey of management of lung cancer diagnosed in Victoria in 2003 was commissioned by the Victorian Cooperative Oncology Group to identify gaps in the management of this disease. Results from a similar survey in 1993 were available to identify differences in the disease, management and outcomes. This paper details results of the surgically managed subset within the larger study. Methods All patients diagnosed with lung cancer in the first 6 months of 2003 were identified from the Victorian Cancer Registry. Registry research staff completed a detailed questionnaire using primary source documents from hospitals and consulting rooms. The survey data were then de-identified with respect to patient and treating clinician prior to statistical analysis by the investigators. Results From eligible cases identified, non-small cell lung cancer was confirmed in 655 cases with a minimum of 6 years of follow-up. Thoracotomy was performed in 145 cases (22%), but only 130 received the intended resection. Compared with 1993, significant differences were increased use of preoperative positron emission tomography ( PET) scanning (79% vs 0%), relatively fewer resections (20% vs 25%), lower pneumonectomy rate (14% vs 25%) and higher sub-lobar resection rate (22% vs 11%). The 30-day mortality remained below 2%. Positive resection margin (21%) and abandoned resection rates (10%) were much higher than expected. Overall 5-year survival was 42%, unchanged from 1993. Conclusion Irrespective of widespread introduction of PET scanning, thoracotomy without resection was common. While operative mortality and overall survival were well within benchmark standards, futile thoracotomy and positive resection margin rates were unacceptably high. [ABSTRACT FROM AUTHOR]

Mammographic density measurements are associated with risk of breast cancer. Few studies have investigated the concurrent associations of mammographic dense and nondense areas, body mass index (weight (kg)/height (m)2), and ages at mammogram and diagnosis with breast cancer risk. We conducted a matched, case-control study nested within the Melbourne Collaborative Cohort Study (cohort recruitment in 1990–1994 and follow-up until 2007) to estimate the associations between these factors and breast cancer risk under alternative causal models. Mammographic dense area was positively associated with risk, and the strength of this association was only slightly influenced by the choice of the causal model (relative risk per 1 standard deviation = 1.50, 95% confidence interval: 1.32, 1.70). Mammographic nondense area was inversely associated with risk under the assumption that fat in the body and fat in the breast cause breast cancer through independent mechanisms (relative risk per 1 standard deviation = 0.75, 95% confidence interval: 0.65, 0.86), whereas it was not associated with risk under the assumption that they are both proxies of adiposity. Knowledge about the biological mechanisms regulating the role played by mammographic nondense area and body fat on breast cancer risk is essential to better estimate their impacts on individual risk. [ABSTRACT FROM PUBLISHER]

Objectives. To examine the relationships between weight at early and middle adulthood and adult weight gain and the risk of total knee and hip replacement for OA.Methods. At baseline interview during 1990–94, 38 149 participants [mean age 54.9 (s.d. 8.6) years] of the Melbourne Collaborative Cohort Study were asked to recall their weight at age 18–21 years and had their middle age height and weight measured. Total knee and hip replacement for OA between 2001 and 2009 was determined by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry.Results. Greater weight and BMI at age 18–21 years and middle age, weight gain and persistent overweight during this time were associated with an increased risk of total knee and hip replacement. Middle age weight [hazard ratio (HR) per 5 kg 1.25 (95% CI 1.23, 1.27) for knee vs 1.11 (1.09, 1.14) for hip] and BMI [HR per 5 kg/m2 1.80 (1.72, 1.89) vs 1.29 (1.21, 1.37)] and adult weight gain [HR per 5 kg 1.25 (1.23, 1.28) vs 1.10 (1.07, 1.13)] were more strongly associated with the risk of total knee replacement than total hip replacement (P for heterogeneity of HRs <0.0001).Conclusion. Greater body weight and BMI at early and middle adulthood, weight gain and persistent overweight from early to middle adulthood are risk factors for knee and hip OA. Adult weight gain confers stronger risk on knee OA than hip OA. Weight control from early adulthood and avoiding weight gain are important for the prevention of OA. [ABSTRACT FROM PUBLISHER]

Little evidence exists regarding associations between age-related macular degeneration (AMD) and moderate alcohol consumption, patterns of consumption, or different types of alcoholic beverage. The authors examined associations between AMD prevalence and alcohol intake using 20,963 participants from the Melbourne Collaborative Cohort Study aged 40–69 years at baseline (1990–1994). Participants' alcohol consumption was determined from a structured interview at baseline. At follow-up from 2003 to 2007, digital macula photographs of both eyes were taken and evaluated for early and late AMD signs. Drinking more than 20 g of alcohol per day was associated with an approximate 20% increase in the odds of early AMD (odds ratio = 1.21, 95% confidence interval: 1.06, 1.38; P = 0.004) when compared with those who reported no alcohol intake at baseline, having adjusted for sex, age, smoking, country of birth, education, physical activity, and energy from food. This positive association was apparent for wine, beer, and spirits. The estimates were similar for both sexes. The odds ratio for those drinking more than 20 g of alcohol per day for late AMD was 1.44 (95% confidence interval: 0.85, 2.45; P = 0.17). These results show a modest association between alcohol consumption and increased AMD risk. [ABSTRACT FROM PUBLISHER]

The apolipoprotein E gene (APOE) has been found to be associated with age-related macular degeneration (AMD). Reported associations have been questioned, as they are opposite those for Alzheimer’s disease and cardiovascular disease. The authors examined associations between APOE genotype and AMD using a case-control study (2,287 cases and 2,287 controls individually matched on age, sex, and country of origin) nested within Melbourne Collaborative Cohort Study participants aged 48–86 years at AMD detection. The odds ratio for early AMD among participants with ε2-containing genotypes (ε2ε2/ε2ε3/ε2ε4) was 1.32 (95% confidence interval (CI): 1.11, 1.58; P = 0.002) versus persons with genotype ε3ε3. Associations with early AMD varied by smoking status; ε2-containing genotypes were positively associated with early AMD for never and previous smokers (never smokers: odds ratio (OR) = 1.40, 95% CI: 1.12, 1.76 (P = 0.003); previous smokers: OR = 1.39, 95% CI: 1.00, 1.93 (P = 0.05)) but not for current smokers (OR = 0.66, 95% CI: 0.34, 1.30 (P = 0.2; interaction P = 0.05). The ε4-containing genotype group (ε3ε4/ε4ε4) had an inverse association with early AMD among current smokers only (OR = 0.41, 95% CI: 0.22, 0.77 (P = 0.005)). These results highlight the importance of stratifying by smoking status in elderly populations. Smokers who survive to old age may be more likely to possess unknown genotypes which modify exposure-disease associations. [ABSTRACT FROM PUBLISHER]

The article discusses research which was conducted to determine whether the angle of the trochlear groove is associated with the rate of loss of patella cartilage volume and whether this association is influenced by particular modifiable and nonmodifiable factors. Researchers evaluated 297 people with no history of knee pathologic disease. They found that a more flattened proximal trochlear groove is associated with increased patella cartilage volume loss, particularly for physically active men, and that that lifestyle factors, such as physical activity, may modify the association between joint incongruity and cartilage loss and can be further affected by subjects' characteristics such as gender.

Evidence for an association between age-related macular degeneration (AMD) and obesity is inconsistent. The authors examined associations between adiposity and AMD prevalence using 21,287 participants from the Melbourne Collaborative Cohort Study aged 40–69 years at baseline (1990–1994). For men, each increase of 0.1 in waist/hip ratio (∼1 standard deviation) was associated with a 13% increase in the odds of early AMD (odds ratio = 1.13, 95% confidence interval: 1.01, 1.26; P = 0.03) and a 75% increase in the odds of late AMD (odds ratio = 1.75, 95% confidence interval: 1.11, 2.76; P = 0.02). No other adiposity measure was associated with early AMD for men. Smoking status modified the relation between waist/hip ratio and early AMD (P = 0.05), with no association for former smokers. For women, there were inverse associations with early AMD for all adiposity measures (odds ratios = 0.89–0.93; P = 0.002–0.02), but no associations were observed for late AMD. This study confirms abdominal obesity as an AMD risk factor for men despite a survivorship effect from competing risks in morbidity and mortality. The inverse associations for women may reflect weaker true positive associations with AMD that are insufficient to overcome the survivorship effect. New data are provided on complex interactions between environmental exposures and AMD risk. [ABSTRACT FROM PUBLISHER]

Background: Cohort studies can provide valuable evidence of cause and effect relationships but are subject to loss of participants over time, limiting the validity of findings. Computerised record linkage offers a passive and ongoing method of obtaining health outcomes from existing routinely collected data sources. However, the quality of record linkage is reliant upon the availability and accuracy of common identifying variables. We sought to develop and validate a method for linking a cohort study to a state-wide hospital admissions dataset with limited availability of unique identifying variables. Methods: A sample of 2000 participants from a cohort study (n = 41 514) was linked to a state-wide hospitalisations dataset in Victoria, Australia using the national health insurance (Medicare) number and demographic data as identifying variables. Availability of the health insurance number was limited in both datasets; therefore linkage was undertaken both with and without use of this number and agreement tested between both algorithms. Sensitivity was calculated for a sub-sample of 101 participants with a hospital admission confirmed by medical record review. Results: Of the 2000 study participants, 85% were found to have a record in the hospitalisations dataset when the national health insurance number and sex were used as linkage variables and 92% when demographic details only were used. When agreement between the two methods was tested the disagreement fraction was 9%, mainly due to "false positive" links when demographic details only were used. A final algorithm that used multiple combinations of identifying variables resulted in a match proportion of 87%. Sensitivity of this final linkage was 95%. Conclusions: High quality record linkage of cohort data with a hospitalisations dataset that has limited identifiers can be achieved using combinations of a national health insurance number and demographic data as identifying variables. [ABSTRACT FROM AUTHOR]

Objective: To evaluate FFQ estimates of dietary intake of individual antioxidants, fruit and vegetables in comparison to plasma concentrations of each antioxidant, and to determine which individual foods are associated with plasma antioxidant concentrations. Design: Dietary (α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, retinol, and vitamin E) intakes over 12 months were estimated from a 121-item FFQ. Correlation coefficients, corrected for within-person variability in diet and plasma antioxidants, were used to examine associations between antioxidant concentrations in diet and plasma. Setting: Melbourne Collaborative Cohort Study (MCCS). Subjects: Men and women (n 3110) who were randomly selected from the MCCS. Participants were aged 36-72 years and were born in Australia, Greece, Italy or the UK. Results: Correlation coefficients for the carotenoids ranged from 0·28 for lycopene to 0·46 for b-cryptoxanthin. There was no association between dietary and plasma retinol or dietary vitamin E with plasma α- and γ-tocopherol. Individual plasma carotenoid concentrations were associated with intakes of fruit and vegetables. Conclusions: Our data suggest that the FFQ provides useful information on intakes of each of the carotenoids: α-carotene, β-carotene, β-cryptoxanthin, lycopene and lutein/zeaxanthin. There was no association between diet and plasma markers of retinol or vitamin E; this may reflect the importance of factors other than intake in modifying circulating levels of these nutrients. [ABSTRACT FROM AUTHOR]

Aim: This study describes the management of and outcomes for adult patients with newly diagnosed intramedullary spinal cord tumors during 1998–2000 in Victoria. Methods: The adult patients were identified in a retrospective cohort study conducted by surveying doctors involved in managing incident glioma cases identified from the population-based Victorian Cancer Registry. Results: Sixteen patients were considered eligible for this review. Of these 15 (94%) had a histological diagnosis: an ependymoma was diagnosed in 13 patients (81%). A complete macroscopic resection was achieved in eight patients (50%). A variety of tumor types and grades were observed with surgery and radiotherapy the mainstays of therapy. One patient received chemotherapy (7%). One patient died from disease within six months of diagnosis. Of the remaining 15 patients, all were alive at 5 years and 10 (63%) remain disease free. Conclusion: This review documents characteristics of a rare condition and suggests that, overall, prognosis is excellent. [ABSTRACT FROM AUTHOR]

Introduction: Diffuse large B cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma for which a cure is usually the therapeutic goal of optimal treatment. Using a large population-based cohort we sought to examine the factors associated with optimal DLBCL treatment and survival. Methods: DLBCL cases were identified through the population-based Victorian Cancer Registry, capturing new diagnoses for two time periods: 2008–2009 and 2012–2013. Treatment was pre-emptively classified as 'optimal' or 'suboptimal', according to compliance with current treatment guidelines. Univariable and multivariable logistic regression models were fitted to determine factors associated with treatment and survival. Results: Altogether, 1442 DLBCL cases were included. Based on multivariable analysis, delivery of optimal treatment was less likely for those aged ≥80 years (p < 0.001), women (p = 0.012), those with medical comorbidity (p < 0.001), those treated in a non-metropolitan hospital (p = 0.02) and those who were ex-smokers (p = 0.02). Delivery of optimal treatment increased between 2008–2009 and the 2012–2013 (from 60% to 79%, p < 0.001). Delivery of optimal treatment was independently associated with a lower risk of death (hazard ratio (HR) = 0.60 (95% confidence interval (CI) 0.45–0.81), p = 0.001). Conclusion: Delivery of optimal treatment for DLBCL is associated with hospital location and category, highlighting possible demographic variation in treatment patterns. Together with an increase in the proportion of patients receiving optimal treatment in the more recent time period, this suggests that treatment decisions in DLBCL may be subject to non-clinical influences, which may have implications when evaluating equity of treatment access. The positive association with survival emphasizes the importance of delivering optimal treatment in DLBCL. [ABSTRACT FROM AUTHOR]