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Kidney cancer (KC) is a disease with a rising worldwide incidence estimated at 400 000 new cases annually, and a worldwide mortality rate approaching 175 000 deaths per year. Current projections suggest incidence continuing to increase over the next decade, emphasizing the urgency of addressing this significant global health trend. Despite the overall increases in incidence and mortality, striking social disparities are evident. Low- and middle-income countries bear a disproportionate burden of the disease, with higher mortality rates and later-stage diagnoses, underscoring the critical role of socioeconomic factors in disease prevalence and outcomes. The major risk factors for KC, including smoking, obesity, hypertension and occupational exposure to harmful substances, must be taken into account. Importantly, these risk factors also often contribute to kidney injury, a condition that the review identifies as a significant, yet under-recognized, precursor to KC. Finally, the indispensable role of nephrologists is underscored in managing this complex disease landscape. Nephrologists are at the forefront of detecting and managing kidney injuries, and their role in mitigating the risk of KC is becoming increasingly apparent. Through this comprehensive analysis, we aim to facilitate a more nuanced understanding of KC's epidemiology and determinants providing valuable insights for researchers, clinicians and policymakers alike., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Chronic kidney disease (CKD) is highly prevalent, affecting approximately 11% of US adults. Multiple studies have evaluated a potential association between CKD and urinary tract malignancies. Summary estimates of urinary tract malignancy risk in CKD patients with and without common co-existing conditions may guide clinical practice recommendations., Methods: Four electronic databases were searched for original cohort studies evaluating the association between CKD and urinary tract cancers (kidney cancer and urothelial carcinoma) through 25 May 2023, in persons with at least moderate CKD and no dialysis or kidney transplantation. Quality assessment was performed for studies meeting inclusion criteria using the Newcastle-Ottawa Scale. Meta-analysis with a random-effects model was performed for unadjusted incidence rate ratios (IRR) as well as adjusted hazard ratios (aHR) for confounding conditions (diabetes, hypertension and/or tobacco use), shown to have association with kidney cancer and urothelial carcinoma. Sub-analysis was conducted for estimates associated with CKD stages separately., Results: Six cohort studies with 8 617 563 persons were included. Overall, the methodological quality of the studies was good. CKD was associated with both higher unadjusted incidence and adjusted hazard of kidney cancer (IRR 3.36, 95% confidence interval (CI) 2.32-4.88; aHR 2.04, 95% CI 1.77-2.36) and urothelial cancer (IRR 3.96, 95% CI 2.44-6.40; aHR 1.35, 95% CI 1.22-1.50) compared with persons without CKD. Examining incident urinary tract cancers by CKD severity, risks were elevated in stage 3 CKD (kidney aHR 1.89, 95% CI 1.56-2.30; urothelial carcinoma aHR 1.35, 95% CI 1.20-1.52) as well as in stages 4/5 CKD (kidney cancer aHR 2.30, 95% CI 2.00-2.66; urothelial carcinoma aHR 1.24, 95% CI 1.04-1.49)., Conclusions: Even moderate CKD is associated with elevated risk of kidney cancer and urothelial carcinoma. Providers should consider these elevated risks when managing individuals with CKD, particularly when considering evaluation for the presence and etiology of hematuria., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Diabetes is a risk factor for cancer in the general population. However, few data are available on the association between post-transplant diabetes mellitus (PTDM) and cancer after transplantation., Methods: We analyzed this issue in a Spanish cohort of patients without diabetes before transplantation. PTDM was diagnosed with consensus criteria at 12 months after transplantation and 12 months before the diagnosis of cancer. The association between PTDM and cancer (overall and specific types) was evaluated with regression analysis., Results: During a follow-up of 12 years (interquartile range 8-14), 85 cases of 603 developed cancer (829/100 000/year) and 164 (27%) PTDM. The most frequent cancers were renal cell cancer (RCC) n = 15, 146/cases/100 000/year), lung (n = 12, 117/cases/100 000/year), colon (n = 9, 88/cases/100 000/year) and prostate (n = 9, 88/cases/100 000/year). In logistic regression, PTDM was not associated with cancer. Eight of the 164 patients with PTDM (4.9%) vs 7 of the 439 without PTDM developed RCC (1.6%) (P = .027). In multivariate analysis, PTDM was independently associated with RCC [odds ratio (OR) 2.92, confidence interval (CI) 1.03-8.27], adjusting for smoking (OR 4.020, 95% CI 1.34-12.02) and other covariates. PTDM was not associated with other types of cancer., Conclusions: Patients with PTDM must be considered a population at risk for RCC and accordingly, the subject of active surveillance., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast (BC, 67%-78% at age 60 years), endometrial (EC, 19%-28%), and thyroid cancer (TC, 6%-38%). Current risks are likely overestimated due to ascertainment bias. We aimed to provide more accurate and personalized cancer risks., Methods: This was a European, adult PHTS cohort study with data from medical files, registries, and/or questionnaires. Cancer risks and hazard ratios were assessed with Kaplan-Meier and Cox regression analyses, and standardized incidence ratios were calculated. Bias correction consisted of excluding cancer index cases and incident case analyses., Results: A total of 455 patients were included, including 50.5% index cases, 372 with prospective follow-up (median 6 years, interquartile range = 3-10 years), and 159 of 281 females and 39 of 174 males with cancer. By age 60 years, PHTS-related cancer risk was higher in females (68.4% to 86.3%) than males (16.4% to 20.8%). Female BC risks ranged from 54.3% (95% confidence interval [CI] = 43.0% to 66.4%) to 75.8% (95% CI = 60.7% to 88.4%), with two- to threefold increased risks for PTEN truncating and approximately twofold for phosphatase domain variants. EC risks ranged from 6.4% (95% CI = 2.1% to 18.6%) to 22.1% (95% CI = 11.6% to 39.6%) and TC risks from 8.9% (95% CI = 5.1% to 15.3%) to 20.5% (95% CI = 11.3% to 35.4%). Colorectal cancer, renal cancer, and melanoma risks were each less than 10.0%., Conclusions: Females have a different BC risk depending on their PTEN germline variant. PHTS patients are predominantly at risk of BC (females), EC, and TC. This should be the main focus of surveillance. These lower, more unbiased and personalized risks provide guidance for optimized cancer risk management., (© The Author(s) 2022. Published by Oxford University Press.)

Background: The relation between blood pressure and kidney cancer risk is well established but complex and different study designs have reported discrepant findings on the relative importance of diastolic blood pressure (DBP) and systolic blood pressure (SBP). In this study, we sought to describe the temporal relation between diastolic and SBP with renal cell carcinoma (RCC) risk in detail., Methods: Our study involved two prospective cohorts: the European Prospective Investigation into Cancer and Nutrition study and UK Biobank, including >700 000 participants and 1692 incident RCC cases. Risk analyses were conducted using flexible parametric survival models for DBP and SBP both separately as well as with mutuality adjustment and then adjustment for extended risk factors. We also carried out univariable and multivariable Mendelian randomization (MR) analyses (DBP: ninstruments = 251, SBP: ninstruments = 213) to complement the analyses of measured DBP and SBP., Results: In the univariable analysis, we observed clear positive associations with RCC risk for both diastolic and SBP when measured ≥5 years before diagnosis and suggestive evidence for a stronger risk association in the year leading up to diagnosis. In mutually adjusted analysis, the long-term risk association of DBP remained, with a hazard ratio (HR) per standard deviation increment 10 years before diagnosis (HR10y) of 1.20 (95% CI: 1.10-1.30), whereas the association of SBP was attenuated (HR10y: 1.00, 95% CI: 0.91-1.10). In the complementary multivariable MR analysis, we observed an odds ratio for a 1-SD increment (ORsd) of 1.34 (95% CI: 1.08-1.67) for genetically predicted DBP and 0.70 (95% CI: 0.56-0.88) for genetically predicted SBP., Conclusion: The results of this observational and MR study are consistent with an important role of DBP in RCC aetiology. The relation between SBP and RCC risk was less clear but does not appear to be independent of DBP., (© World Health Organization, 2022. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

Background: Results of preceding studies on the relationship between blood pressure (BP) and cancers have been confounded due to individuals taking antihypertensive medications or shared risk factors. We assessed whether medication-naïve high BP is a risk factor for incident cancers., Methods: This retrospective observational study included 1,388,331 individuals without a prior history of cancer and not taking antihypertensive medications enrolled in the JMDC Claims Database between 2005 and 2018. The primary outcome was 16 cancers., Results: The median [interquartile range] age was 45 [40-52] years and 56.2% were men. Mean systolic BP (SBP) and diastolic BP (DBP) were 117.7 ± 15.8 and 72.8 ± 11.6 mm Hg. Multivariate Cox regression analysis demonstrated that SBP per 1-SD was associated with a higher incidence of thyroid (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.03-1.16), esophageal (HR: 1.15, 95% CI: 1.07-1.24), colorectal (HR: 1.04, 95% CI: 1.01-1.07), liver (HR: 1.11, 95% CI: 1.03-1.20), and kidney (HR: 1.22, 95% CI: 1.14-1.31) cancers, but with a lower incidence of stomach cancer (HR: 0.94, 95% CI: 0.91-0.98). These associations remained significant after adjustment for multiple testing. DBP was associated with higher incidences of thyroid, esophageal, colorectal, kidney, and corpus uteri cancers, but with a lower incidence of stomach cancer. The associations between SBP and incidences of thyroid, esophageal, colorectal, liver, and kidney cancers were confirmed in the Korean National Health Insurance Service database., Conclusions: Medication-naïve BP was associated with higher incidences of thyroid, esophageal, colorectal, liver, and kidney cancers. Uncovering the underlying mechanisms for our results may help identify novel therapeutic approach for hypertension and cancer., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Coffee consumption has been associated with a reduced risk of some cancers, but the evidence for renal cell carcinoma (RCC) is inconclusive. We investigated the relationship between coffee and RCC within a large cohort., Methods: Coffee intake was assessed at baseline in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Among 420 118 participants eligible for analysis, 2674 incident cases were identified. We fitted Cox-regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee consumption vs non-drinkers., Results: We observed HRs of 0.94 (95% CI 0.81, 1.09), 0.94 (0.81, 1.09), 0.80 (0.70, 0.92) and 0.77 (0.66, 0.90) for usual coffee intake of <1, 1, 2-3 and ≥4 cups/day, respectively (Ptrend = 0.00003). This relationship was observed among never-smokers (≥4 cups/day: HR 0.62, 95% CI 0.46, 0.83; Ptrend = 0.000003) but not ever-smokers (HR 0.85, 95% CI 0.70, 1.05; Ptrend = 0.35; Pinteraction = 0.0009) and remained in analyses restricted to cases diagnosed >10 years after baseline (HR 0.65, 95% CI 0.51, 0.82; Ptrend = 0.0005). Associations were similar between subgroups who drank predominately caffeinated or decaffeinated coffee (Pinteraction = 0.74)., Conclusion: In this investigation of coffee and RCC, to our knowledge the largest to date, we observed a 20% reduced risk for intake of ≥2 cups/day vs not drinking. Our findings add RCC to the growing list of cancers for which coffee consumption may be protective., (Published by Oxford University Press on behalf of the International Epidemiological Association 2021. This work is written by US Government employees and is in the public domain in the US.)

Chronic kidney disease in its later stages is associated with increased risk of kidney cancer. We investigated whether chronic kidney disease at milder stages is associated with increased kidney cancer risk, using a retrospectively selected cohort of 9,809,317 adults in the Republic of Korea who participated in a nationwide health screening (2009-2016). We examined the impact of estimated glomerular filtration rate (eGFR), dipstick proteinuria, and interactive associations between the 2 factors on the risk of incident kidney cancer. During a median follow-up period of 7.3 years, 10,634 kidney cancers were identified. After adjustment for multiple confounders, participants with a reduced eGFR had an increased risk of kidney cancer (for eGFR <30 mL/minute/1.73 m2, adjusted hazard ratio = 1.18 (95% confidence interval: 1.01, 1.39); for eGFR 30-59 mL/minute/1.73 m2, adjusted hazard ratio = 1.22 (95% confidence interval: 1.14, 1.31)) compared with those with an eGFR of 60-89 mL/minute/1.73 m2. A dose-response relationship between the severity of proteinuria and incident kidney cancer was observed. Analyses of joint effects of eGFR and dipstick proteinuria showed that with the presence of proteinuria, kidney cancer incidence was markedly increased along with decreasing eGFR. Reduced eGFR and proteinuria are significantly associated with subsequent risk of kidney cancer, possibly in a synergistic manner., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Per- and polyfluoroalkyl substances (PFAS) are highly persistent chemicals that have been detected in the serum of over 98% of the US population. Studies among highly exposed individuals suggest an association with perfluorooctanoic acid (PFOA) exposure and kidney cancer. It remains unclear whether PFOA or other PFAS are renal carcinogens or if they influence risk of renal cell carcinoma (RCC) at concentrations observed in the general population., Methods: We measured prediagnostic serum concentrations of PFOA and 7 additional PFAS in 324 RCC cases and 324 individually matched controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) relating serum PFAS concentrations and RCC risk. Individual PFAS were modeled continuously (log2-transformed) and categorically, with adjustment for kidney function and additional potential confounders. All statistical tests were 2-sided., Results: We observed a positive association with RCC risk for PFOA (doubling in serum concentration, ORcontinuous = 1.71, 95% CI = 1.23 to 2.37, P = .002) and a greater than twofold increased risk among those in the highest quartile vs the lowest (OR = 2.63, 95% CI = 1.33 to 5.20, Ptrend = .007). The association with PFOA was similar after adjustment for other PFAS (ORcontinuous = 1.68, 95% CI = 1.07 to 2.63, P = .02) and remained apparent in analyses restricted to individuals without evidence of diminished kidney function and in cases diagnosed 8 or more years after phlebotomy., Conclusions: Our findings add substantially to the weight of evidence that PFOA is a renal carcinogen and may have important public health implications for the many individuals exposed to this ubiquitous and highly persistent chemical., (Published by Oxford University Press 2020.)

Background: For adolescents and young adults (AYAs, aged 15-39 years) with cancer, metastatic disease at diagnosis is the strongest predictor of mortality, but its associations with age and sociodemographic factors are largely unexplored., Methods: Using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, we collected incident cases of poor-prognosis metastatic cancer (5-year survival < 50%) and compared the proportion, incidence, time trends, and incidence rate ratios for race and ethnicity, sex, and socioeconomic status among AYAs, middle-aged adults (aged 40-64 years) and older adults (aged 65-79 years)., Results: From 2000 to 2016, a total of 17 210 incident cases of poor-prognosis metastatic cancer were diagnosed in AYAs, 121 274 in middle-aged adults, and 364 228 in older adults. Compared with older patients, the proportion of AYAs having metastatic disease was equivalent or substantially lower in nearly every site except stomach and breast cancers, which were statistically significantly higher for AYAs compared with middle-aged and older adults (stomach: 57.3% vs 46.4% and 39.5%; breast: 6.6% vs 4.4% and 5.6%, respectively; 2-sided P  < .001 for all comparisons). Incidence rates rose significantly faster among AYAs for breast, stomach, and kidney cancers and among AYAs and middle-aged adults for colorectal cancer. Markedly higher incidence rate ratios were noted for AYA racial and ethnic minorities with breast, stomach, and especially kidney cancer, where only non-Hispanic Black AYAs were at considerably higher risk. For most sites, incidence rate ratios were higher among male patients and individuals of low socioeconomic status across age groups., Conclusions: For most cancers, AYAs are not more likely to present with metastases than middle-aged and older adults. Further investigation is warranted for the disproportionate rise in incidence of metastatic breast, stomach, and kidney cancer among AYAs and their excess burden among AYA racial and ethnic minorities. The rising incidence of colorectal cancer among AYAs and middle-aged adults remains an additional concern., (© The Author(s) 2021. Published by Oxford University Press.)

Objectives: An estimated 125 million workers are exposed to asbestos worldwide. Asbestos is classified by the International Agency for Research on Cancer as a Group 1 carcinogen. The association between occupational asbestos exposure and kidney cancer is not well established however. This study aimed to determine the mortality and incidence of kidney cancer in workers who have been exposed to asbestos. We performed a systematic review and meta-analysis to evaluate the association between occupational asbestos exposure and kidney cancer., Methods: Medline, EMBASE, and Web of Science were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for articles on occupational asbestos exposure and kidney cancer. The studies reported the standardized mortality ratio (SMR) or standardized incidence ratio (SIR) of kidney cancer in workers exposed to asbestos. SMRs or SIRs with its 95% confidence interval (CI) were pooled using a fixed-effect model., Results: Forty-nine cohort studies involving 335 492 workers were selected for analysis. These studies included 468 kidney cancer deaths and 160 incident cases. The overall pooled-SMR of kidney cancer was 0.95 (95% CI: 0.86-1.05), with no significant heterogeneity (PQ = 0.09, I2 = 24.87%). The overall pooled-SIR of kidney cancer was 0.95 (95% CI: 0.79-1.11), with no significant heterogeneity (PQ = 0.68, I2 = 0.00%). Subgroup analysis did not find any increased association with occupational asbestos exposure. There was no evidence of publication bias with Egger's test P values of 0.08 for mortality studies and 0.99 for incidence studies., Conclusions: This systematic review and meta-analysis did not show evidence of association between occupational asbestos exposure and kidney cancer mortality or incidence., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Antihypertensive drugs namely angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, beta blockers, and diuretics are among the most clearly documented regimens worldwide with an overall cardioprotective benefit. Given that malignancy is the second leading cause of mortality, numerous observational studies aimed to investigate the carcinogenic potential of these agents with conflicting results. The purpose of this review was to summarize current data in an effort to explore rare side effects and new mechanisms linking antihypertensive drugs with the risk of developing cancer., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: We previously observed a rapid increase in the incidence of renal cell carcinoma (RCC) in men and women between 1935 and 1989 in the USA, using data from the Connecticut Tumor Registry. This increase appeared to be largely explained by a positive cohort effect, but no population-based study has been conducted to comprehensively examine age-period-cohort effects by histologic types for the past decade., Methods: We calculated age-adjusted and age-specific incidence rates of the two major kidney-cancer subtypes RCC and renal urothelial carcinoma, and conducted an age-period-cohort analysis of 114 138 incident cases of kidney cancer reported between 1992 and 2014 to the Surveillance, Epidemiology, and End Results programme., Results: The age-adjusted incidence rates of RCC have been increasing consistently in the USA among both men and women (from 12.18/100 000 in 1992-1994 to 18.35/100 000 in 2010-2014 among men; from 5.77/100 000 in 1992-1994 to 8.63/100 000 in 2010-2014 among women). Incidence rates generally increased in successive birth cohorts, with a continuing increase in rates among the younger age groups (ages 0-54 years) in both men and women and among both Whites and Blacks. These observations were confirmed by age-period-cohort modelling, which suggested an increasing birth-cohort trend for RCC beginning with 1955 birth cohorts, regardless of the assumed value for the period effect for both men and women and for Whites and Blacks., Conclusions: Known risk factors for kidney cancer may not fully account for the observed increasing rates or the birth-cohort pattern for RCC, prompting the need for additional etiologic hypotheses (such as environmental exposures) to investigate these descriptive patterns., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objective: Obesity and type 2 diabetes are becoming increasingly prevalent worldwide and are both associated with the increased incidence of kidney and bladder cancers. However, previous reports have provided conflicting results. We investigated the impact of body mass index (BMI) and diabetes on the incidence of both cancers in the general population., Methods: Using nationally representative data from the Korean National Health Insurance System, 9,777,133 subjects without any malignancy who underwent health examinations in 2009 were followed to the end of 2017., Results: After a median follow-up period of 8.32 years, 12,544 incidents of kidney cancer and 15,137 incidents of bladder cancer were identified. The hazard ratio (HR) for kidney cancer was the lowest in people with a BMI <18.5 kg/m2 (HR: 0.82, 95% confidence interval (CI): 0.72-0.94) and the highest in those with a BMI ≥30 kg/m2 (HR: 1.71, 95% CI: 1.57-1.87) compared to a reference BMI group (18.5-23 kg/m2). In subjects with diabetes, obesity was associated with increased risk of kidney cancer, although the HRs were lower than observed in those without diabetes. Otherwise, there was a reduction in risk of bladder cancer with obesity in men and the HR for bladder cancer was not affected by BMI increase in women. There was a strongly positive association between diabetes and bladder cancer in the total study population., Conclusions: Obesity was a strong risk factors for kidney cancer, whereas the association between obesity and bladder cancer differed by gender. The subjects with diabetes had a higher risk for both cancers than those without diabetes.

Introduction: Kidney cancer is the fifth most common incident cancer in Canadian men. Diesel and gasoline exhausts are common workplace exposures that have been examined as risk factors for non-lung cancer sites, including the kidney, but limitations in exposure assessment methods have contributed to inconsistent findings. The objective of this study was to assess the relationship between occupational gasoline and diesel engine exhausts and the risk of kidney cancer in men., Methods: The National Enhanced Cancer Surveillance System (NECSS) is a Canadian population-based case-control study conducted in 1994-1997. Incident kidney cancer cases were identified using provincial registries, while the control series was identified through random-digit dialing, or provincial administrative databases. Self-reported questionnaires were used to obtain information on lifetime occupational history and cancer risk factors. Two hygienists, blinded to case status, coded occupational histories for diesel and gasoline exhaust exposures using concentration, frequency, duration, and reliability. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) separately by exhaust type. The separate and combined impacts of both engine exhausts were also examined. ORs were adjusted for age, province, body mass index, occupational secondhand smoke exposure, and education., Results: Of the kidney cancer cases (n = 712), 372 (52%) had exposure to both exhausts at some point, and 984 (40%) of the controls (n = 2457) were ever exposed. Workers who had ever been exposed to engine exhausts were more likely to have kidney cancer than those who were never exposed (OR diesel = 1.23, 95% CI = 0.99-1.53; OR gasoline = 1.51, 95% CI = 1.23-1.86). Exposure to gasoline exhaust was consistently associated with kidney cancer in a dose-response manner (P value for trends in highest attained and cumulative exposure both <0.0001). Those men with high cumulative exposure to both gasoline and diesel exhaust had a 76% increased odds of kidney cancer (95% CI = 1.27-2.43)., Conclusions: This study provides evidence that occupational gasoline, and to a lesser extent, diesel exhaust exposure may increase the risk of kidney cancer.

Background: Region II in northern Chile (population 442 570) experienced a sudden major increase in arsenic water concentrations in 1958 in the main city of Antofagasta, followed by a major reduction in exposure when an arsenic removal plant was installed in 1970. It provides a unique opportunity to study latency effects of exposure to arsenic, and this is the first study with mortality data up to 40 years after exposure reduction., Methods: We previously identified high mortality rates in Region II up to the year 2000. Here we present rate ratios (RRs) for Region II compared with all the rest of Chile from 2001 to 2010, and with unexposed Region V (population 1 539 852) for all years from 1950 to 2010. All statistical tests were one-sided., Results: From 2001 to 2010, comparing Region II with the rest of Chile, lung and bladder mortality were still greatly elevated (RR = 3.38, 95% confidence interval [CI] = 3.19 to 3.58, P < .001 for lung cancer in men; RR = 2.41, 95% CI = 2.20 to 2.64, P < .001 for lung cancer in women; RR = 4.79, 95% CI = 4.20 to 5.46, P < .001 for bladder cancer in men; RR = 6.43, 95% CI = 5.49 to 7.54, P < .001 for bladder cancer in women). Kidney cancer mortality was also elevated (RR = 1.75, 95% CI = 1.49 to 2.05, P < .001 for men; RR = 2.09, 95% CI = 1.69 to 2.57, P < .001 for women). Earlier short latency acute myocardial infarction mortality increases had subsided., Conclusions: Lung, bladder, and kidney cancer mortality due to arsenic exposure have very long latencies, with increased risks manifesting 40 years after exposure reduction. Our findings suggest that arsenic in drinking water may involve one of the longest cancer latencies for a human carcinogen.

Background: The risk for colorectal cancer (CRC) and certain extracolonic cancers is thought to be increased in inflammatory bowel disease (IBD), but few recent US studies have evaluated this issue. We aimed to estimate the incidence of CRC and extracolonic cancers in IBD patients., Methods: In this case-control study, cases were all IBD patients treated in our Department of Veterans Affairs (VA) hospital who developed CRC or extracolonic cancers between 1996 and 2015. Controls were patients in the general VA population who developed these cancers during the same time. We compared cancer incidence rates (IRs) in cases and controls., Results: There was no significant difference between cases and controls in the 20-year IR for CRC (148/100 000 in IBD patients, 97/100 000 in controls; relative risk [RR], 1.53; 95% confidence interval [CI], 0.86-2.69). In contrast, IBD cases had a significantly higher 20-year IR for all extracolonic cancers than controls (2839/100 000 in IBD patients, 1960/100 000 in controls; RR, 1.45; 95% CI, 1.27-1.65). Site-specific analyses revealed that IBD patients had significantly elevated risks for nonmelanoma skin cancers (RR, 2.38; 95% CI, 1.99-2.85), melanoma skin cancers (RR, 2.85; 95% CI, 1.63-4.88), renal tumors (RR, 2.90; 95% CI, 1.46-5.84), prostate cancer (RR, 1.70; 95% CI, 1.28-2.27), and pancreatic cancer (RR, 4.23; 95% CI, 1.35-13.29)., Conclusions: The incidence of CRC was not significantly higher in our veteran patients with IBD than in control patients in the general VA population. In contrast, our IBD patients had a significantly higher risk for extracolonic cancers than controls, including cancers of the skin, kidneys, prostate, and pancreas. 10.1093/ibd/izx046&#95;video1Video 1.izx046&#95;Mosher&#95;Video5734484616001., (© 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Objective: The association between cigarette smoking and survival in patients with renal cell carcinoma is not well studied. We examined the impact of cigarette smoking on survival of patients with advanced renal cell carcinoma using the multi-institutional national database of the Japanese Urological Association., Methods: From 340 Japanese institutions, 963 patients with renal cell carcinoma of clinical Stage 3 or higher were analyzed. Univariate analysis using the Kaplan-Meier method and multivariate Cox regression models with stepwise selection was used to evaluate overall and cause-specific survival., Results: Median duration of follow-up was 842 days, and overall and cancer death occurred in 392 (40.7%) and 351 (36.4%) patients, respectively. In multivariate analysis, smoking 20 or more cigarettes daily at diagnosis was associated with poorer overall and cancer-specific survival, especially in Stage 3. According to a Cox proportional hazards model, heavy cigarette smoking at diagnosis and the variables of underweight, fever symptoms, serum lactic dehydrogenase value, serum C-reactive protein value, serum creatinine value, Eastern Cooperative Oncology Group performance status, nephrectomy and clinical stage were significant (P < 0.05) for overall and cancer-specific survival., Conclusions: We could compare the smoking status at diagnosis and the prognosis of renal cell carcinoma at national wide scale. Heavy active smoking was an independent prognostic factor for overall and cancer-specific survival in patients with advanced renal cell carcinoma, especially in Stage 3., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: The potential for an ultrasound-based screening programme for renal cell carcinoma (RCC) to improve survival through early detection has been the subject of much debate. The prevalence of ultrasound-detected asymptomatic RCC is an important first step to establishing whether a screening programme may be feasible., Methods: A systematic search of MEDLINE and Embase was performed up to March 2016 to identify studies reporting the prevalence of renal masses and RCC. Two populations of patients were chosen: asymptomatic individuals undergoing screening ultrasonography and patients undergoing ultrasonography for abdominal symptoms not related to RCC. A random-effects meta-analysis was performed. Study quality was evaluated using a validated eight-point checklist., Results: Sixteen studies (413 551 patients) were included in the final analysis. The pooled prevalence of renal mass was 0·36 (95 per cent c.i. 0·23 to 0·52) per cent and the prevalence of histologically proven RCC was 0·10 (0·06 to 0·15) per cent. The prevalence of RCC was more than double in studies from Europe and North America than in those from Asia: 0·17 (0·09 to 0·27) versus 0·06 (0·03 to 0·09) per cent respectively. Data on 205 screen-detected RCCs showed that 84·4 per cent of tumours were stage T1-T2 N0, 13·7 per cent were T3-T4 N0, and only 2·0 per cent had positive nodes or metastases at diagnosis., Conclusion: At least one RCC would be detected per 1000 individuals screened. The majority of tumours identified are early stage (T1-T2)., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Evidence on the frequency of a positive family history of colorectal cancer (CRC) among individuals aged <55 years is lacking. General practice setting might be well suited for the identification of individuals in this above-average risk group., Objective: To determine the frequency of a reported positive family history of CRC among patients aged 40 to 54 years in a general practice setting., Methods: We conducted a cross-sectional study in 21 general practices in Germany. Patients aged 40 to 54 years were identified by means of the practice software and interviewed by health care assistants using a standardized four-item questionnaire. Outcome was occurrence of a positive family history of CRC, defined as at least one first-degree relative (FDR: parents, siblings, or children) with CRC. Further measurements were FDRs with CRC / colorectal polyps (adenomas) diagnosed before the age of 50 and occurrence of three or more relatives with colorectal, stomach, cervical, ovarian, urethel or renal pelvic cancer., Results: Out of 6723 participants, 7.2% (95% confidence interval [CI] 6.6% to 7.8%) reported at least one FDR with CRC and 1.2% (95% CI 0.9% to 1.5%) reported FDRs with CRC diagnosed before the age of 50. A further 2.6% (95% CI 2.3% to 3.0%) reported colorectal polyps in FDRs diagnosed before the age of 50 and 2.1% (95% CI 1.8% to 2.5%) reported three or more relatives with entities mentioned above., Conclusion: One in 14 patients reported at least one FDR with CRC. General practice should be considered when defining requirements of risk-adapted CRC screening., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: Epidemiological evidence from relatively small cohorts suggests that obstructive sleep apnea (OSA) is associated with higher cancer incidence and mortality. Here we aimed to determine whether cancer incidence for major cancer types and risk of metastases or mortality from cancer are increased in the presence of OSA., Methods: All OSA diagnoses included in an employee-sponsored health insurance database spanning the years 2003-2012 were identified and 1:1 matched demographically based on age, gender, and state of residence, or alternatively matched by comorbidities. The incidence of 12 types of cancer was assessed. In addition, another cohort of patients with a primary diagnosis of cancer was retrieved, and the risk of metastatic disease or cancer mortality was determined as a function of the presence or absence of OSA. Multivariate Cox proportional hazards regression models were fitted to assess the independent associations between OSA and outcomes of interest., Results: Based on a cohort of ∼5.6 million individuals, the incidence of all cancer diagnoses combined was similar in OSA and retrospectively matched cases. However, the adjusted risk of pancreatic and kidney cancer and melanoma were significantly higher in patients with OSA, while the risk of colorectal, breast, and prostate cancers appeared to be lower. Among individuals with a diagnosis of cancer, the presence of OSA was not associated with an increased risk for metastasis or death., Conclusions: In a large nationally representative health insurance database, OSA appears to increase the risk for only a very selective number of cancer types, and does not appear to be associated with an increased risk of metastatic cancer or cancer-related deaths., (© 2016 Associated Professional Sleep Societies, LLC.)

Cancer remains to be the second most common cause of death, and its incidence and mortality rates are increasing in China. According to the 2015 National Central Cancer Registry (NCCR) of China, the incidence of bladder cancer and prostate cancer ranked sixth and seventh, respectively, in male cancers. The majority of prostate cancer patients were diagnosed at an advanced stage. Early diagnosis of prostate cancer is the key to improve prostate cancer survival in China. Radical prostatectomy or radical radiotherapy is the main treatment for localized prostate cancer, and a comprehensive therapy based on androgen deprivation therapy is the treatment for advanced disease. The most common histologic types of bladder cancer in China were urothelial carcinoma, followed by adenocarcinoma and squamous carcinoma. The majority of patients were diagnosed using white-light cystoscopy with biopsy. Fluorescence and narrow-band imaging cystoscopy had additional detection rates and are becoming more popular. Following Chinese guidelines, most non-muscle invasive bladder cancer patients were treated with diagnostic transurethral resection and more than half of the muscle invasive bladder cancer patients were treated with radical cystectomy. Due to the increased detection rate of kidney tumors by ultrasound in physical examination, the number of incidentally diagnosed renal cell carcinoma has increased. Localized kidney cancers are more and more often treated by nephron-sparing surgery. Radical nephrectomy is still the main treatment option for patients with locally advanced renal cell carcinoma. Both laparoscopic and robotic-assisted laparoscopic surgeries have been used in big medical centers. Both testicular cancer and penile cancer have lower incidence levels than that in Europe. As we have an enormous population base, the absolute patient number is big. The diagnosis and treatment follows the Chinese guidelines. In China, both medical professionals and public should concern more on the early diagnosis, as there is not enough cancer prevention information available. Urologists should also take a more active role in educating the population., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In Hong Kong, urological malignancy accounted for 9.55% of all the new cases of cancer in 2012. In the male population, prostate cancer was the third most commonly diagnosed cancer, and the fifth leading cause of cancer death. Age-standardized rate of prostate cancer incidence rose from 11.5 per 100 000 men in 1992 to 28.5 per 100 000 men in 2012. On the other hand, age-standardized rate of bladder cancer incidence dropped from 6.4 per 100 000 in 2003 to 3.0 per 100 000 in 2012. The incidence of kidney cancer remained stable in recent years, with an age-standardized rate of 4.8 per 100 000 in 2012. The introduction of the robotic surgical system has made robotic-assisted laparoscopic radical prostatectomy the most common mode of surgical treatment for prostate cancer in Hong Kong. Robotic-assisted laparoscopic radical cystectomy and robotic-assisted laparoscopic partial nephrectomy have been gaining popularity in the locality. Minimal-invasive surgical techniques as well as different systemic therapies have led to revolutionary changes in the urology community in Hong Kong. The existing territory-wide surveillance of cancer incidence and mortality trends continue to provide us with clues to aetiology and the effects of improved diagnostic and treatment techniques., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Radioactive iodine (RAI) is widely used for the treatment of thyroid cancers. However, information on associations between RAI dose and second primary malignancy (SPM) is lacking., Methods: Patients without antecedent cancer age 20 years or older and newly diagnosed with thyroid cancer were recruited from the Taiwan National Health Insurance database between 1997 and 2010. Standardized incidence ratios (SIRs) for the cancers were calculated to compare the incidence of thyroid cancer with the general population. The association between RAI dosage and cancer development was estimated using time-dependent Cox regression analysis. All statistical tests were two-sided., Results: A total of 692 cases of SPM were identified among 20 235 patients with thyroid cancer. Regarding the latter, 79.7% of the patients were women, the median age was 46 years, and the follow-up period included 134 178 person-years. The SIR for any SPM was 1.41 (95% confidence interval [CI] = 1.31 to 1.52). A statistically significantly higher SIR was observed in leukemia (2.74), non-Hodgkin's lymphoma (2.38), prostate (2.30), lung and mediastinum (1.93), pancreas (1.83), kidney (1.81), breast (1.48), and colon-rectum (1.31) cancers. Cumulative RAI dose (per 30 mCi increase) conferred a strong risk for SPM (adjusted hazard ratio [aHR] = 1.01, 95% CI = 1.01 to 1.02, P < .001) and leukemia (aHR = 1.03, 95% CI = 1.02 to 1.04, P < .001) occurrences. A cumulative RAI dose greater than 150 mCi possessed a statistically significant risk for all cancer combined (aHR = 1.30) and leukemia (aHR = 6.03)., Conclusions: An increased risk of SPM was observed for thyroid cancer patients, especially with cumulative RAI doses over 150 mCi., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Cancer is a major health burden among non-communicable diseases, which has had a high impact on the healthcare system in Thailand. Based on GLOBOCAN, the prevalence of urologic cancer is increasing in Thailand. Prostate, bladder and kidney cancers are 6th, 15th and 22nd most common cancers, respectively, in both males and females. Prostate cancer is the fourth most common cancer in male. Cancer in the lower socioeconomic groups is a challenging problem due to greater exposure to the risk factors and more limited access to the healthcare service. The cancers are usually detected in advanced stages of the cancer. The most common histopathological finding of kidney cancer is a renal cell carcinoma. Transitional cell carcinoma is the most common histopathology of bladder. There is a trend of stage migration to earlier stages at first presentation, probably due to public awareness and laboratory screening. Patients with early stage are treated with minimally invasive modalities such as endoscopic, laparoscopic or robot-assisted laparoscopic surgery. Laparoscopic radical prostatectomy and robot-assisted laparoscopic radical prostatectomy is the mainstay treatment of localized prostate cancer with the better outcome and less complication. Androgen deprivation therapy is usually for elderly or unfit patients. The strategy for early detection of early cancer is the important role of Thai urologists to manage these three common urologic cancers., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The incidence and prevalence of prostate and kidney cancers have been increasing in Korea during the last decade, and a marked improvement in survival rates has been noted. With a substantial proportion of the cancers diagnosed at an earlier stage of the disease, the landscape of urologic cancer treatment in Korea has been characterized by an exponential increase in the number of patients receiving surgical treatment. Throughout the last decade, an increasing proportion of surgeries have been performed using minimally invasive methods, with a notable increase in robot-assisted surgery.The evaluation and management strategies of urologic cancer in Korea are primarily based on an existing evidence-based framework provided by international guidelines. The adoption and clinical application of novel surgical techniques and systemic agents targeted at advanced stage cancer are promptly adopted; accordingly, multidisciplinary treatment options are often available for various cancers at different stages. At the same time, treatment decisions are greatly influenced by the availability of healthcare resources, which may be limited due to the National Health Insurance reimbursement policy.A racial disparity in cancer features appears to exist for certain urologic cancers among Korean patients, and the optimal management strategy specific for the Korean population has yet to be confirmed. A national comprehensive cancer database is needed for better insight into risk factors, selection of sequential strategies, tumor biology and survival outcome of Korean urologic cancer patients., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Non-communicable diseases, including cancer, start to become more common in Indonesia. According to the government statement, incidence of malignant diseases increased annually up to 8% in the last decade and these diseases become the seventh leading cause of death in Indonesia. On the basis of the latest Globocan report on cancer incidence in Indonesia, prostate cancer ranks sixth; followed by bladder (12th) and kidney (18th). More than half of patients with kidney cancer are diagnosed in the advanced stage. Besides renal cell carcinoma, there are significant number of people affected with squamous cell and transitional cell carcinoma because of kidney stones. Radical nephrectomy or cytoreductive nephrectomy was the primary treatment, mostly done as an open procedure. Transitional cell carcinoma is the commonest histology type in bladder cancer cases followed by squamous cell carcinoma, which almost always related to bladder stones. Unfortunately, >70% of our cases were diagnosed with muscle invasive bladder cancer, and ∼60% of these patients refused further radical treatment. Incidence of prostate cancer is increasing rapidly and it becomes the third most common cancer in men. However, most of our patients are diagnosed in the advanced stage. Radical prostatectomy or external beam radiotherapy is the treatment of choice in localized disease. Nearly 40% of the elderly patients are treated with primary androgen deprivation therapy. Therefore, it requires more research by the Indonesian urologists and other healthcare providers to diagnose these cancers in earlier stage as well as community education for prevention., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: Despite increasing use of implantable cardioverter-defibrillators (ICDs) and reports linking selected bio-implants with cancer, the cancer risk associated with implanted ICDs remains unknown. The objective of our study was to examine cancer risk among ICD recipients., Methods and Results: We conducted a population-based cohort study using medical registries covering the entire Danish population. We identified all first-time ICD recipients during the period of 2000-11 and determined their subsequent cancer incidence. Standardized incidence ratios (SIRs) were computed by comparing observed cancer incidence in the ICD cohort with expected cancer incidence based on national incidence rates according to age, sex, and year of diagnosis. A total of 6723 ICD recipients were followed for up to 12 years (median 2.8 years) and contributed a total of 23 254 person-years of follow-up. Compared with the general population, ICD recipients had a slightly elevated overall risk of cancer [SIR = 1.1 (95% confidence interval (CI): 1.0-1.2)]. This was driven by the cancer risk among patients with ischaemic heart disease (IHD) [SIR = 1.1 (95% CI: 1.0-1.3)], which, as expected, was particularly elevated for tobacco-related cancers [SIR = 1.4 (95% CI: 1.2-1.6)]. Importantly, ICD recipients without IHD were not at increased cancer risk [SIR = 1.0 (95% CI: 0.8-1.3)]., Conclusion: This nationwide population-based cohort study with up to 12-year follow-up did not indicate a causal relation between ICD implantation and cancer. However, more follow-up data are needed to entirely rule out risks for individual cancer types., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival., Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided., Results: EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4(th) and 1(st) quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P trend < .001. We found similar results after adjusting for potential confounders (adjusted P trend < .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4(th) and 1(st) quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P trend < .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P trend = .02). No association was evident for the other measured biomarkers., Conclusion: Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts., (© The Author 2014. Published by Oxford University Press.)

Background: Obesity increases risk for clear-cell renal cell carcinoma (ccRCC), yet obese patients appear to experience longer survival than nonobese patients. We examined body mass index (BMI) in relation to stage, grade, and cancer-specific mortality (CSM) while considering detection bias, nutritional status, and molecular tumor features., Methods: Data were available from 2119 ccRCC patients who underwent renal mass surgery at Memorial Sloan-Kettering Cancer Center between 1995 and 2012. Logistic regression models produced associations between BMI and advanced disease. Multivariable competing risks regression models estimated associations between BMI and CSM. Somatic mutation, copy number, methylation, and expression data were examined by BMI among a subset of 126 patients who participated in the Cancer Genome Atlas Project for ccRCC using the Kruskal-Wallis or Fisher exact tests. All statistical tests were two-sided., Results: Obese and overweight patients were less likely to present with advanced-stage disease compared with normal-weight patients (odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.48 to 0.79 vs OR = 0.65, 95% CI = 0.51 to 0.83, respectively). Higher BMI was associated with reduced CSM in univariable analyses (P < .005). It remained statistically significant after adjustment for comorbidities and albumin level, but it became non-statistically significant after adjusting for stage and grade (P > .10). Genome-wide interrogation by BMI suggested differences in gene expression of metabolic and fatty acid genes, including fatty acid synthase (FASN), consistent with the obesity paradox., Conclusions: Our findings suggest that although BMI is not an independent prognostic factor for CSM after controlling for stage and grade, tumors developing in an obesogenic environment may be more indolent.

Millions of people worldwide are exposed to arsenic in drinking water. The International Agency for Research on Cancer has concluded that ingested arsenic causes lung, bladder, and skin cancer. However, a similar conclusion was not made for kidney cancer because of a lack of research with individual data on exposure and dose-response. With its unusual geology, high exposures, and good information on past arsenic water concentrations, northern Chile is one of the best places in the world to investigate the carcinogenicity of arsenic. We performed a case-control study in 2007-2010 of 122 kidney cancer cases and 640 population-based controls with individual data on exposure and potential confounders. Cases included 76 renal cell, 24 transitional cell renal pelvis and ureter, and 22 other kidney cancers. For renal pelvis and ureter cancers, the adjusted odds ratios by average arsenic intakes of <400, 400-1,000, and >1,000 µg/day (median water concentrations of 60, 300, and 860 µg/L) were 1.00, 5.71 (95% confidence interval: 1.65, 19.82), and 11.09 (95% confidence interval: 3.60, 34.16) (Ptrend < 0.001), respectively. Odds ratios were not elevated for renal cell cancer. With these new findings, including evidence of dose-response, we believe there is now sufficient evidence in humans that drinking-water arsenic causes renal pelvis and ureter cancer.

Objective: To investigate the associations of diabetes mellitus with recurrence and prognosis after surgery for non-metastatic renal cell carcinoma and the effect modification of obesity on the above relationships., Methods: We retrospectively evaluated 543 patients with non-metastatic renal cell carcinoma (pT1-4N0M0) who underwent radical or partial nephrectomy. The association of diabetes mellitus with recurrence was analyzed using the Kaplan-Meier method and the Cox regression model. We also examined whether the above relationships were modified by obesity using subgroup analysis and tests of interaction. For subgroup analysis, the body mass index was categorized as non-obese (<25 kg/m(2)) and obese (≥25 kg/m(2))., Results: Eighty-two patients (15.1%) had a history of diabetes mellitus. During the mean follow-up of 66.7 months, 68 patients (12.5%) developed recurrence. Although the body mass index was not associated with recurrence, diabetes mellitus was an independent predictor of recurrence in multivariate analysis (hazard ratio 2.43, P = 0.003), along with tumor diameter, grade and pathological T stage. In further subgroup analysis, the same relationship between diabetes mellitus and recurrence was clearly shown in the obese group (hazard ratio 4.07, P = 0.010), but not in the non-obese group (hazard ratio 1.95, P = 0.125). At the same time, obesity modified the effect of diabetes mellitus on recurrence with a trend (P-interaction = 0.086). In the obese group, 5-year recurrence-free survival rates were 75.3 and 91.9% for diabetes mellitus and non-diabetes mellitus patients, respectively (P < 0.001). Restricting analyses to patients with clear cell type histology did not materially change these results., Conclusions: Diabetes mellitus is a predictor of recurrence following surgery for non-metastatic renal cell carcinoma, especially in obese patients.

Background: Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma., Methods: We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided., Results: Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkin's lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased., Conclusions: Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.

Clinical and experimental findings suggest that female hormonal and reproductive factors could influence kidney cancer development. To evaluate this association, we conducted analyses in 2 large prospective cohorts (the National Institutes of Health-AARP Diet and Health Study (NIH-AARP), 1995-2006, and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), 1993-2010). Cohort-specific and aggregated hazard ratios and 95% confidence intervals relating reproductive factors and kidney cancer risk were computed by Cox regression. The analysis included 792 incident kidney cancer cases among 283,952 postmenopausal women. Women who had undergone a hysterectomy were at a significantly elevated kidney cancer risk in both NIH-AARP (hazard ratio = 1.28, 95% confidence interval: 1.09, 1.50) and PLCO (hazard ratio = 1.41, 95% confidence interval: 1.06, 1.88). Similar results were observed for both cohorts after analyses were restricted to women who had undergone a hysterectomy with or without an oophorectomy. For the NIH-AARP cohort, an inverse association was observed with increasing age at menarche (P for trend = 0.02) and increasing years of oral contraceptive use (P for trend = 0.02). No clear evidence of an association with parity or other reproductive factors was found. Our results suggest that hysterectomy is associated with increased risk of kidney cancer. The observed associations with age at menarche and oral contraceptive use warrant further investigation.

Background: Although the kidney is a primary organ for vitamin D metabolism, the association between vitamin D and renal cell cancer (RCC) remains unclear., Methods: We prospectively evaluated the association between predicted plasma 25-hydroxyvitamin D [25(OH)D] and RCC risk among 72,051 women and 46,380 men in the period from 1986 to 2008. Predicted plasma 25(OH)D scores were computed using validated regression models that included major determinants of vitamin D status (race, ultraviolet B flux, physical activity, body mass index, estimated vitamin D intake, alcohol consumption, and postmenopausal hormone use in women). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. All statistical tests were two-sided., Results: During 22 years of follow-up, we documented 201 cases of incident RCC in women and 207 cases in men. The multivariable hazard ratios between extreme quintiles of predicted 25(OH)D score were 0.50 (95% CI = 0.32 to 0.80) in women, 0.59 (95% CI = 0.37 to 0.94) in men, and 0.54 (95% CI = 0.39 to 0.75; P trend < .001) in the pooled cohorts. An increment of 10 ng/mL in predicted 25(OH)D score was associated with a 44% lower incidence of RCC (pooled HR = 0.56, 95% CI = 0.42 to 0.74). We found no statistically significant association between vitamin D intake estimated from food-frequency questionnaires and RCC incidence., Conclusion: Higher predicted plasma 25(OH)D levels were associated with a statistically significantly lower risk of RCC in men and women. Our findings need to be confirmed by other prospective studies using valid markers of long-term vitamin D status.

Adult survivors of childhood cancer are known to be at increased risk of subsequent malignancy, but only limited data exist describing the incidence and risk factors for secondary renal carcinoma. Among 14 358 5-year survivors diagnosed between 1970 and 1986, we estimated standardized incidence ratios (SIRs) for subsequent renal carcinoma and identified associations with primary cancer therapy using Poisson regression. Twenty-six survivors were diagnosed with renal carcinoma (median = 22.6 years from diagnosis; range = 6.3-35.7 years), reflecting a statistically significant excess (SIR = 8.0, 95% confidence interval [CI] = 5.2 to 11.7) compared with the general population. Highest risk was observed among neuroblastoma survivors (SIR = 85.8, 95% CI = 38.4 to 175.2) and, in multivariable analyses, with renal-directed radiotherapy of 5 Gy or greater (relative risk [RR] = 3.8, 95% CI = 1.6 to 9.3) and platinum-based chemotherapy (RR = 3.5, 95% CI = 1.0 to 11.2). To our knowledge, this is the first report of an association between cisplatin and subsequent renal carcinoma among survivors of childhood cancer.

Context: Epidemiological studies have observed associations between diabetes and a number of different cancers. Yet the association with cancer overall and the interrelationship of diabetes and obesity with cancer have been unclear. OBJECTIVE, DESIGN, SETTING, AND PARTICIPANTS: We evaluated the association between self-reported diabetes and cancer incidence in the NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health Study, a prospective cohort in which 295,276 men and 199,591 women completed a questionnaire in 1995-1996 and were followed up for cancer through 2006., Main Outcome Measures: Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer incidence, overall and by type, were estimated from multivariate Cox proportional hazards models., Results: Diabetes was positively associated with total incident cancer in women (1.07, 95% CI 1.02-1.12) but inversely in men (0.96, 95% CI 0.93-0.98). However, diabetes was inversely associated with prostate cancer (HR 0.74, 95% CI 0.70-0.78), which constituted 42% of cancers in men. After excluding prostate cancer, diabetes was also positively associated with cancer in men (HR 1.09, 95% CI 1.04-1.14). By site, diabetes was positively associated with anal, bladder, colon, kidney, liver, pancreatic, rectal, and stomach cancers and in women with endometrial cancer. We also evaluated the joint effect of obesity and diabetes and observed that diabetes conferred additional risk, beyond that of overweight or obesity, for cancer overall, excluding prostate, and for certain sites including the bladder, colon, endometrium, kidney, liver, pancreas, rectum, and stomach., Conclusion: Our results suggest an etiological role for diabetes in a number of cancers, independent of obesity, and that preventing diabetes may contribute to reduced cancer risk.

Objective: Patients with end-stage renal disease are suggestive to have a higher risk for the development of some kinds of cancer. The aim of this study is to evaluate the possible association between malignancy and end-stage renal disease in Taiwan., Methods: We used the data of the National Health Insurance system of Taiwan to assess this issue. The end-stage renal disease cohort contained 21 817 patients, and each patient was randomly frequency-matched with two people from the general population without end-stage renal disease based on their age and sex. The Cox proportional hazard regression analysis was conducted to estimate the effects of end-stage renal disease on the cancer risk., Results: In patients with end-stage renal disease, the risk of developing overall cancer was significantly higher than the normal healthy subjects (adjusted hazard ratio = 1.64, 95% confidence interval = 1.54-1.74). This was also true when we analyzed males and females separately. For individual cancer, the risks for developing urinary tract cancers, liver cancer and breast cancer among patients with end-stage renal disease were significantly higher. On the contrary, lung, prostate and esophageal cancer risks were significantly lower when compared with the normal healthy subjects., Conclusions: Our study found Taiwanese patients with end-stage renal disease to have a higher risk to develop urinary tract, liver and breast cancer. We unexpectedly discovered these patients to have a lower risk to get lung, prostate and esophageal cancer.

Unlabelled: Kidney cancer accounts for approximately 2% of all cancers worldwide, with renal cell carcinoma being the most common form and this report is focused on renal cell carcinoma. Globally, the incidence and mortality rates are increasing by 2-3% per decade. Kidney cancer is less common in Asia compared with the West. Cigarette smoking, obesity, acquired cystic kidney disease and inherited susceptibility are known risk factors for kidney cancer. The National Comprehensive Cancer Network Guidelines recommend surgical excision as first line of treatment for Stage I, II or III kidney cancer patients and Stage IV patients with resectable tumours. Immunotherapy has a 20-year history in treatment of metastatic kidney cancer. High-dose interleukin-2 (IL-2) is administered in some countries, whereas low-dose IL-2 and interferon-alpha (IFN-α) are popular in Japan. Molecular-targeted drugs, including sunitinib, bevacizumab and sorafenib, are being used for previously untreated and refractory patients. Asian and non-Asian populations have shown large differences in the incidences of adverse events with sorafenib and sunitinib., Consensus Statement: Kidney cancer is relatively uncommon in Asia compared with the West, but its incidence is increasing in more developed Asian nations. Guidelines from the National Comprehensive Cancer Network , etc., for treating metastatic renal cell carcinoma are based on Phase III clinical trials conducted primarily in Western patients. Targeted therapies are now becoming primary recommendations, but efficacy/toxicity data from Asian patients are lacking. Some drugs cause adverse effects in Asians because their recommended dosages are optimal for Caucasians but may be too high for Asians. Further research is necessary to develop optimal treatment strategies for Asians.

Background: The occurrence of subsequent neoplasms has direct impact on the quantity and quality of life in cancer survivors. We have expanded our analysis of these events in the Childhood Cancer Survivor Study (CCSS) to better understand the occurrence of these events as the survivor population ages., Methods: The incidence of and risk for subsequent neoplasms occurring 5 years or more after the childhood cancer diagnosis were determined among 14,359 5-year survivors in the CCSS who were treated from 1970 through 1986 and who were at a median age of 30 years (range = 5-56 years) for this analysis. At 30 years after childhood cancer diagnosis, we calculated cumulative incidence at 30 years of subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess absolute risks (EARs) for invasive second malignant neoplasms, and relative risks for subsequent neoplasms by use of multivariable Poisson regression., Results: Among 14,359 5-year survivors, 1402 subsequently developed 2703 neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma, and treatment with radiation therapy were associated with increased risk of subsequent neoplasm., Conclusions: As childhood cancer survivors progress through adulthood, risk of subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at greatest risk. There is no evidence of risk reduction with increasing duration of follow-up.

The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974-2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50-<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations.

The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) brought together 10 cohorts to conduct a prospective study of the association between vitamin D status, measured as serum concentrations of 25-hydroxyvitamin D (25(OH)D), and the development of 7 rarer cancer sites: endometrial, esophageal, gastric, kidney, non-Hodgkin lymphoma, ovarian, and pancreatic cancers. The cohorts come from 3 continents, with participants from a wide range of latitude who are racially diverse. Across each cancer site, there was no evidence of a protective association between higher concentrations of 25-hydroxyvitamin D (>75 nmol/L) and cancer outcome. An increased risk at very high levels (> or =100 nmol/L) was noted for pancreatic cancer, confirming previous reports. The articles included in this issue detail the overall design and governance of the project, correlates of vitamin D status, and results from the cancer site-specific investigations. The Vitamin D Pooling Project realizes a major goal of consortium efforts, namely, to rigorously test hypotheses for rarer cancer outcomes that may not be adequately addressed in any one prospective cohort study. The results of this study have application for the planning and conduct of intervention trials, especially in determining potential risks.

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.

Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of > or =75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically.

Context: Von Hippel-Lindau (VHL) disease, caused by germline mutations in the VHL gene, is a hereditary tumor syndrome manifested by hemangioblastomas, clear cell renal cell carcinomas, and pheochromocytomas. In addition, a multitude of other rare tumors, including parasympathetic paragangliomas, can occur and even be the sole manifestation of VHL disease. The VHL gene is a bona fide tumor suppressor gene with biallelic inactivation contributing to tumor formation. However, in parasympathetic paragangliomas occurring in VHL disease, biallelic inactivation of the VHL gene has not been demonstrated to date., Design: The head and neck paragangliomas of two VHL patients were analyzed for mutations by direct sequencing of the VHL gene. In addition loss of heterozygosity analysis was performed for three microsatellite loci near the VHL gene. To rule out other underlying genetic causes of the parasympathetic paragangliomas, mutation analysis of the SDHB, SDHC, and SDHD genes was also performed., Results: Apart from germline VHL mutations, no additional mutations were found in the paraganglioma-related tumor suppressor genes SDHB, SDHC, and SDHD. Analysis of paraganglioma tissue revealed loss of the VHL wild-type allele in both tumors, indicating that in these tumors biallelic VHL gene inactivation occurred., Conclusions: These findings indicate that parasympathetic paragangliomas in VHL disease, although rare, are part of the syndrome and related to VHL gene inactivation. Clinicians should be aware of the potential occurrence of parasympathetic paragangliomas in VHL disease.