Increased Risk Of Kidney Cancer Research Articles

Effect of chronic viral hepatitis and metabolic factors on renal cancer risk in a large cohort in Republic of Korea

PurposeWe investigated the association between hepatic and metabolic factors and renal cancer risk. MethodsThis population-based cohort study included cancer-free individuals who underwent general health evaluation (January to December 2010) at the Korean National Health Insurance Service and followed-up through 2017. Hazard ratios (HR) and 95% confidence intervals (CI), determined by adjusted Cox regression analysis were used to investigate the effect of variables on renal cancer risk. ResultsAmong 4,518,704 subjects, 6531 patients developed renal cancer. Adjusted analyses of epidemiological factors and BMI (body mass index) (Model I) showed serum high-density lipoprotein cholesterol (HDL-C) ≥60 mg/dL (adjusted HR [aHR] 0.88, 95% CI, 0.81–0.95) reduced renal cancer risk comparing to low HDL-C, whereas hepatitis B virus (HBV) antigen (aHR 1.41, 95% CI 1.19–1.68) and chronic HBV infection (aHR 1.65, 95% CI 1.26–2.17) increased its risk. Higher BMI increased renal cancer risk in dose-dependent manner (P for trend <0.001). This association persisted after adjustment for epidemiological factors and waist circumference (Model II). Sex-specific analyses showed similar effect of HBV antigen and chronic HBV infection in both sexes. Normal (50-59 mg/dL in women) or high (≥60 mg/dL in men) HDL-C reduced renal cancer risk. Alcohol consumption increased kidney cancer risk in age ≥ 60 years, but it had no association with renal cancer in age < 60 years. ConclusionsHigh serum HDL-C levels reduced and HBV antigen and chronic HBV infection increased renal cancer risk across different adjusted analysis models. This effect of low HDL-C and chronic HBV infection persisted in sex-based subanalysis.

Association Between Glycemic Status and the Risk of Kidney Cancer in Men and Women: A Nationwide Cohort Study.

Kidney cancer predominantly affects men, suggesting a biological protection against kidney cancer in women. We investigated the dose-response association between glycemic status and kidney cancer risk in men and women. In this nationwide cohort study, 9,492,331 adults without cancer who underwent national health screening in 2009 were followed up until 31 December 2018. We estimated kidney cancer risk using multivariable Cox proportional hazard regression models after adjusting for potential confounders. During the 78.1 million person-years of follow-up, incident kidney cancer occurred in 8,834 men and 3,547 women. The male-to-female ratio of the incidence rate was 2.1:1 in never-smokers with normoglycemia (17.8 vs. 8.5/100,000 person-years). Among never-smokers, men with diabetes, but not prediabetes, had an increased risk of kidney cancer (adjusted hazard ratio [aHR] 1.25 [95% CI 1.12-1.38] and 1.06 [0.97-1.15], respectively). Among never-smokers, women with both diabetes and prediabetes had an increased risk (aHR 1.34 [95% CI 1.21-1.49] and 1.19 [1.10-1.29], respectively) (Ptrend <0.01). Among smokers, men and women with diabetes had 49% and 85% increased kidney cancer risk (aHR 1.49 [95% CI 1.37-1.61] and 1.85 [1.26-2.73], respectively). Glycemic status and kidney cancer risk exhibited a dose-response association in women. Diabetes, but not prediabetes, was associated with an increased risk in men. Although women have a lower risk of kidney cancer than men, women with even prediabetes have an increased risk. These findings should not be overlooked when monitoring for kidney complications.

Kidney Cancer Risk Associated with Historic Groundwater Trichloroethylene Contamination.

Trichloroethylene (TCE) is a well-documented kidney carcinogen based on a substantial body of evidence including mechanistic and animal studies, as well as reports from occupational settings. However, the cancer risks for those in residential exposures such as TCE contamination in groundwater are much less clear. The objective of this study was to perform a detailed spatio-temporal analysis of estimated residential TCE exposure in New Hampshire, US. We identified kidney cancer cases (n = 292) and age-, gender-matched controls (n = 448) from the Dartmouth-Hitchcock Health System and queried a commercial financial database for address histories. We used publically available data on TCE levels in groundwater measured at contaminated sites in New Hampshire and then modeled the spatial dispersion and temporal decay. We overlaid geospatial residential locations of cases and controls with yearly maps of estimated TCE levels to estimate median exposures over the 5, 10, and 15-year epochs before diagnosis. The 50th–75th percentile of estimated residential exposure over a 15-year period was associated with increased kidney cancer risk (adjusted Odds Ratio (OR) 1.78 95% CI 1.05–3.03), compared to <50th percentile. This finding supports the need for groundwater monitoring of TCE contaminated sites to identify potential public health risks.

Association between weight cycling and risk of kidney cancer: a prospective cohort study and meta-analysis of observational studies.

Weight cycling is common in populations. However, it is unclear whether frequency and magnitude of weight cycling is associated with kidney cancer risk, independent of body mass index (BMI). A prospective cohort study followed 85,562 participants from Health Professionals Follow-up Study and Nurses' Health Study (1992-2014). At baseline, participants reported frequency and magnitude of intentional weight loss in the past 4years. Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We also conducted a meta-analysis of all available observational studies including our two cohorts. During 22years of follow-up, we identified 441 kidney cancer cases. Compared with non-weight cyclers (no attempt of intentional weight loss), severe cyclers (≥ 3 times of intentional weight loss of ≥ 4.5kg) were at increased kidney cancer risk after adjusting for BMI before weight cycling (pooled multivariable-adjusted HR, 1.78; 95% CI, 1.19, 2.66). Additional adjustment for attained BMI after weight cycling had minimal influence. There was a positive trend between weight cycling by frequency and magnitude and kidney cancer risk (P-trend = 0.01). Moreover, the observed positive association did not differ by subtypes of cyclers (e.g., adiposity status, weight-loss methods). In the meta-analysis, we found a strong positive association between weight cycling and kidney cancer risk (summary relative risk for weight cyclers vs. non-cyclers, 1.51; 95% CI, 1.16, 1.96; I2: 52.2%; 6 studies). Frequent substantial weight cycling was associated with increased risk of kidney cancer, independent of BMI. Our study suggests that weight cycling may be an important risk factor for kidney cancer.

Associations Between Kidney Function, Proteinuria, and the Risk of Kidney Cancer: A Nationwide Cohort Study Involving 10 Million Participants.

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.

Increased kidney cancer risk in diabetes mellitus patients: a population-based cohort study in Lithuania

Background Diabetes is associated with increased risk of various cancers but its association with kidney cancer is unclear. The objective of this study was to evaluate the association between T2DM with or without metformin use and the risk of kidney cancer in a population-based national cohort in Lithuania. Methods The cohort was composed of diabetic patients identified in the NHIF database during 2000–2012. Cancer cases were identified by record linkage with the national Cancer Registry. Standardized incidence ratios (SIRs) for kidney cancer as a ratio of observed number of cancer cases in diabetic patients to the expected number of cancer cases in the underlying general population were calculated. Results T2DM patients (11,592) between 2000 and 2012 were identified. Overall, 598 cases of primary kidney cancer were identified versus 393.95 expected yielding an overall SIR of 1.52 (95% CI: 1.40–1.64). Significantly higher risk was found in males and females. Significantly higher risk of kidney cancer was also found in both metformin users and never-users’ groups (SIRs 1.45, 95% CI: 1.33–1.60 and 1.78 95% CI: 1.50–2.12, respectively). Conclusions The patients with T2DM have higher risk for kidney cancer compared with the general Lithuanian population.

The association between BMI and kidney cancer risk: An updated dose-response meta-analysis in accordance with PRISMA guideline.

Obesity is considered as one of the risk factors of kidney cancer. However, the results are not consistent in reported original studies, as well as in published meta-analysis. This study aims to clarify the relationship between overweight/obesity and kidney cancer by an updated overall and dose-response meta-analysis. This meta-analysis was conducted in accordance with PRISMA guideline. Relevant studies were searched using PubMed, Embase, and Web of Science databases. The studies were limited to human cohort studies in English and Chinese language. Random-effect models and dose-response meta-analysis were used to synthesize the results. Subgroup analyses were also conducted based on the characteristics of participants. Twenty-four cohort studies with 8,953,478 participants were included in our meta-analysis. Compared to the normal weight, the pooled RRs of kidney cancer was 1.35 (1.27-1.43) in overweight and 1.76 (1.61-1.91) in obese participants. An increased kidney cancer risk of 1.06 (1.05-1.06) for each 1 kg/m increase in BMI was showed in dose-response meta-analysis. No significant heterogeneity was found across studies with I = 39.4% for overweight, and I = 43.3% for obesity. The overall and dose-response meta-analysis suggested that overweight/obesity increases the risk of kidney cancer both in men and women.

Risk of Subsequent Primary Kidney Cancer After Another Malignancy: A Population-based Study.

Population-based data on the development of kidney cancer as a second malignant neoplasm following the diagnosis of other common malignancies are rare. This clinical scenario has been evaluated within the Surveillance, Epidemiology, and End Results (SEER) database. The SEER-9 database (1973-2013) was queried using the SEER*Stat program to determine the standardized incidence ratios (SIRs) of kidney cancer development following each one of 10 common invasive malignancies (colorectal, breast, prostate, lung, thyroid, corpus uteri, urinary bladder, kidney/renal pelvis, cutaneous melanoma, and non-Hodgkin lymphoma). The following data were collected for patients with a second renal cancer: age at diagnosis of the second renal cancer; gender, race, and histology of the second primary renal cancer; SEER historic stage of the second primary renal cancer; and method of diagnostic confirmation of the second primary cancer. A total of 10,145 kidney cancers were observed. Elevated SIRs for kidney cancer were noted for all 10 evaluated malignancies in the initial 12 months after diagnosis. The SIRs remained elevated 12 to 59 months after diagnosis for all cancers except breast and prostate cancers. Increased risks persisted 60 to 119 months beyond diagnosis for renal cancer (SIR, 4.13), thyroid cancer (SIR, 2.30), and non-Hodgkin lymphoma (SIR, 1.40); and 120+ months for renal cancer (SIR, 3.60), thyroid cancer (SIR, 1.90), and non-Hodgkin lymphoma (SIR, 1.27). Increased kidney cancer risk after non-Hodgkin lymphoma was not related to radiation therapy. Papillary renal cell carcinoma has the highest SIRs for subsequent kidney cancers. Many common cancers are associated with an increased risk of kidney cancer development within the first 5 years after their diagnosis. Although this can be partly interpreted by increased rates of surveillance tests, radiotherapy effects, or genetic associations for some cancers, additional research is required to explain the persistently increased risk beyond 5 years associated with some cancers.

LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk

Higher levels of LINE1 methylation in blood DNA have been associated with increased kidney cancer risk using post-diagnostically collected samples; however, this association has never been examined using pre-diagnostic samples. We examined the association between LINE1 %5mC and renal cell carcinoma (RCC) risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (215 cases/436 controls), and the Alpha-tocopherol, Beta-carotene Cancer Prevention Study (ATBC) of Finnish male smokers (191 cases/575 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, body mass index, hypertension, dietary alcohol intake, family history of cancer, and sex was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using cohort and sex-specific methylation categories. In PLCO, higher, although non-significant, RCC risk was observed for participants at or above median methylation level (M2) compared to those below the median (M1) (OR: 1.37, 95% CI: 0.96–1.95). The association was stronger in males (M2 vs. M1, OR: 1.54, 95% CI: 1.00–2.39) and statistically significant among male smokers (M2 vs. M1, OR: 2.60, 95% CI: 1.46–4.63). A significant interaction for smoking was also detected (P-interaction: 0.01). No association was found among females or female smokers. Findings for male smokers were replicated in ATBC (M2 vs. M1, OR: 1.31, 95% CI: 1.07–1.60). In a pooled analysis of PLCO and ATBC male smokers (281cases/755controls), the OR among subjects at or above median methylation level (M2) compared to those below the median (M1) was 1.89 (95% CI: 1.34–2.67, P-value: 3 x 10–4); a trend was also observed by methylation quartile (P-trend: 0.002). These findings suggest that higher LINE1 methylation levels measured prior to cancer diagnosis may be a biomarker of future RCC risk among male smokers.

Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells BothIn VitroandIn Vivo

An increased kidney cancer risk was found in hypertensive patients, who frequently exhibit hyperaldosteronism, known to contribute to kidney injury, with oxidative stress playing an important role. The capacity of kidney cells to up-regulate transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2), a key regulator of the cellular antioxidative defense, as a prevention of aldosterone-induced oxidative damage was investigated both in vitro and in vivo. Aldosterone activated Nrf2 and increased the expression of enzymes involved in glutathione (GSH) synthesis and detoxification. This activation depended on the mineralocorticoid receptor (MR) and oxidative stress. In vitro, Nrf2 activation, GSH amounts, and target gene levels decreased after 24 h, while oxidant levels remained high. Nrf2 activation could not protect cells against oxidative DNA damage, as aldosterone-induced double-strand breaks and 7,8-dihydro-8-oxo-guanine (8-oxodG) lesions steadily rose. The Nrf2 activator sulforaphane enhanced the Nrf2 response both in vitro and in vivo, thereby preventing aldosterone-induced DNA damage. In vivo, Nrf2 activation further had beneficial effects on the aldosterone-caused blood pressure increase and loss of kidney function. This is the first study showing the activation of Nrf2 by aldosterone. Moreover, the results identify sulforaphane as a substance that is capable of preventing aldosterone-induced damage both in vivo and in vitro. Aldosterone-induced Nrf2 adaptive response cannot neutralize oxidative actions of chronically increased aldosterone, which, therefore could be causally involved in the increased cancer incidence of hypertensive individuals. Enhancing the cellular antioxidative defense with sulforaphane might exhibit beneficial effects.

Blood pressure has only minor influence on aldosterone-induced oxidative stress and DNA damage in vivo

Epidemiological studies found an increased kidney cancer risk in hypertensive patients. These patients frequently present an increase in the mineralocorticoid aldosterone (Ald) due to a stimulated renin angiotensin aldosterone system (RAAS). Recently, we showed pro-oxidative and genotoxic effects of Ald in vitro. Here, we investigated the influence of blood pressure on aldosterone-induced oxidative damage. To distinguish whether effects in Sprague–Dawley rats treated with Ald were caused by Ald or by increased blood pressure, the mineralocorticoid receptor (MR) antagonist spironolactone was administered in a subtherapeutical dose, not lowering the blood pressure, and hydralazine, a RAAS-independent vasodilator, was given to normalize the pressure. With the antioxidant tempol, oxidative stress-dependent effects were demonstrated. Ald treatment caused kidney damage and oxidative and nitrative stress. Structural DNA damage and the mutagenic oxidative base modification 7,8-dihydro-8-oxoguanine were increased, as well as DNA repair activity and nuclear NF-κB translocation. Spironolactone and tempol decreased all markers significantly, whereas hydralazine had just slight effects. These data comprise the first report of essentially blood pressure-independent tissue- and DNA-damaging effects of Ald. A fully activated MR and the production of reactive oxygen and nitrogen species were crucial for these effects.

A Population-Based Nested Case-Control Study in Taiwan: Use of 5α-Reductase Inhibitors Did Not Decrease Prostate Cancer Risk in Patients with Benign Prostate Hyperplasia

5α-Reductase inhibitors (5ARIs) are commonly used to treat benign prostate hyperplasia (BPH) by blocking the conversion of testosterone into the more potent dihydrotestosterone. This study explored a possible association between the use of the 5ARIs finasteride and dutasteride and the subsequent risk of prostate cancer or other cancers. We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated. Finasteride use marginally increased the incidence of prostate and overall cancer at a level of statistical significance (prostate cancer: OR = 1.90; 95% CI: 1.00-3.59; overall cancer: OR = 1.51; 95% CI: 1.00-2.28). Dutasteride use significantly increased kidney cancer risk (OR = 9.68, 95% CI: 1.17-80.0). Dosage analysis showed that lower doses of finasteride were associated with higher overall and prostate cancer risks. The major limitation is the lack of important data in the NHIRD, such as prostate cancer histologic grades, smoking habits, alcohol consumption, body mass index, socioeconomic status, and family history of cancer. This population-based nested case-control study suggested that finasteride use may increase prostate and overall cancer risks for patients with BPH. The effects were more prominent for patients using lower doses of finasteride.

Statin use and the risk of kidney cancer: a population-based case–control study

Objective: To investigate whether the use of statins was associated with kidney cancer risk.Methods: We conducted a population-based case–control study in Taiwan. Cases consisted of all patients who were aged 50 years and older, and had a first-time diagnosis of kidney cancer for the period between 2005 and 2009. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression.Results: We examined 177 kidney cancer cases and 708 controls. The adjusted OR for any statin prescription was 1.08 (95% CI = 0.70 – 1.67). Compared with no use of statins, the adjusted ORs were 0.91 (95% CI = 0.50 – 1.63) for the group having been prescribed statins with cumulative defined daily dose (DDDs) below 105 and 1.28 (95% CI = 0.73 – 2.23) for the group with cumulative statin use of 105 DDDs or more.Conclusions: The present data do not provide evidence to support either beneficial or harmful associations between statin use and kidney cancer risk. However, there is a trend of increased kidney cancer risk with higher cumulative DDDs, and consequently that it is prudent to continue monitoring cancer incidence among long-standing statin users.

Abstract B25: Kidney cancer and female reproductive factors in two prospective cohorts

Abstract Introduction: The unexplained two-fold lower incidence of kidney cancer in women compared to men and findings from clinical and experimental studies have generated interest in the role of female reproductive factors and exogenous hormones on kidney cancer development. Endocrine system involvement in kidney cancer development is biologically plausible since sex hormone receptors have been detected in normal and malignant renal tissue, exogenous estrogens have been shown to promote and induce kidney cancer formation, and anatomic changes to the kidney during pregnancy may make nephrons more vulnerable to inflammation and oxidative stress. Findings from several epidemiologic studies suggest that parity may be associated with kidney cancer, but case numbers have generally been small. Associations with other reproductive factors have been sparse and inconsistently reported. Therefore, we conducted a pooled analysis of two large prospective studies to evaluate whether hormone-related factors are associated with risk of kidney cancer in women. Methods: We investigated the relationship between female reproductive factors and exogenous hormones and kidney cancer risk in two large prospective cohort studies: the NIH-AARP Diet and Health Study (NIH-AARP: 601 cases) and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO: 191 cases). Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression. Data from both studies were pooled and aggregate HRs were estimated. We also conducted meta-analyses of all case-control and cohort studies to summarize our new findings and previously reported associations between kidney cancer risk and select reproductive factors. Random-effects models were fit to estimate summary relative risks (RRs) and odds ratios (ORs) for cohort and case-control studies separately. Results: The analysis included 283,952 post-menopausal women, with 792 incident kidney cancer cases. Parity was not associated with risk of kidney cancer in either study (pooled HR = 1.15, 95% Cl = 0.91–1.44). Risk for kidney cancer was significantly elevated, however, in both cohorts among women who had undergone a hysterectomy (pooled HR = 1.33,95% Cl = 1.15–1.53). After allowing for a 10 year lag between study baseline and diagnosis of kidney cancer, associations remained significantly elevated (pooled HR = 1.31,95% Cl = 1.14–1.51), suggesting the elevation in association was not due to detection bias. For women with a history of endometriosis, a significant increase in risk (HR = 1.69,95% Cl = 1.09–2.62) was observed in PLCO, the only cohort that collected data on this condition. A meta-analysis of epidemiologic studies provided additional support for an association with hysterectomy (all cohort studies: summary RR = 1.29,95% Cl = 1.14–1.47; excluding NIH-AARP and PLCO Results: summary RR = 1.23,95% Cl = 0.99–1.52; case-control studies: OR = 1.39,95% Cl = 1.17–1.64). Conclusion: Our findings from two large prospective cohorts and a meta-analysis of epidemiologic studies suggests that hysterectomy is associated with increased kidney cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B25.

Insulin-like growth factors and risk of kidney cancer in men.

Background:Insulin-like growth factor-I (IGF-I) has been shown to increase kidney growth, glomerular filtration rate, and renal function.Methods:In the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study of 29 133 Finnish male smokers aged 50–69 years, serum concentrations of IGF were measured in samples collected in 1985–1988. A total of 100 men with kidney cancer diagnosed ⩾5 years after blood collection through 1997 were compared with a subcohort of 400 men; logistic regression models were used to estimate the risk of developing kidney cancer.Results:Men with IGF-I levels >113 ng ml−1 were 59% less likely to develop kidney cancer than men with levels ⩽113 ng ml−1 (odds ratio=0.41; 95% confidence interval=0.23–0.75). The IGF binding protein-3 (IGFBP-3) levels did not alter the association. No association was observed between IGFBP-3, or molar ratio of IGF-I/IGFBP-3, and kidney cancer.Conclusions:Low serum IGF-I levels in this cohort of older middle-aged male smokers are associated with increased kidney cancer risk, independent of IGFBP-3.

Abstract 4830: Insulin-like growth factors and kidney cancer risk in men

Abstract Context: Causes of kidney cancer are not fully understood. Incidence is highest in those ages 50 to 70, and almost twice as high in men as in women. Smokers are twice as likely as non-smokers to develop renal cell carcinoma and about four times as likely to develop cancer of the renal pelvis. Insulin-like growth factor-I (IGF-I) has been shown to increase kidney microvascular growth and glomerular filtration rate, and its administration increases renal function in animal models of chronic renal failure, and has been proposed as a possible therapeutic agent (Hirschberg et al, 1998). However, the possible roles of IGF in the development of kidney cancer have not been well-studied. Objective: To examine the relation of serum levels of IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) to kidney cancer risk. Methods: We conducted a case-cohort study nested within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of 29,133 Finnish male smokers who were 50-69 years of age and not diagnosed with cancer at study entry. Serum concentrations of IGF-I, IGFBP-3 were measured in blood samples collected in 1985 to 1988. One hundred men were identified who had a diagnosis of kidney cancer &amp;gt;5 years after blood collection through the end of 1997. Self-reported information on lifestyle and medical history was collected and weight and height were measured at baseline. Multivariable logistic regression models were used to estimate the relative risk of kidney cancer associated with IGF levels. Results: A history of hypertension (known to be increased in those who are older, overweight, or heavier smokers) was more common among cases than among noncases. Men with IGF-I levels &amp;gt;108 ng/mL were 63% less likely to develop kidney cancer than men with IGF-I levels ≤108 ng/mL (OR=0.37; 95% CI=0.20-0.69). IGFBP-3 levels did not alter the association between IGF-I and kidney cancer risk. Further, no association was observed between IGFBP-3 levels and the development of kidney cancer. Conclusions: Low serum IGF-I levels in this cohort of older middle-aged male smokers are associated with increased kidney cancer risk, independent of IGFBP-3, age, anthropometry, lifestyle and medical history. Further research is needed to confirm the findings and examine the association in women and non-smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4830.

Kidney cancer and hydrocarbon exposures among petroleum refinery workers.

To evaluate the hypothesis of increased kidney cancer risk after exposure to hydrocarbons, especially those present in gasoline, we conducted a case-control study in a cohort of approximately 100,000 male refinery workers from five petroleum companies. A review of 18,323 death certificates identified 102 kidney cancer cases, to each of whom four controls were matched by refinery location and decade of birth. Work histories, containing an average of 15.7 job assignments per subject, were found for 98% of the cases and 94% of the controls. To each job, industrial hygienists assigned semiquantitative ratings for the intensity and frequency of exposures to three hydrocarbon categories: nonaromatic liquid gasoline distillates, aromatic hydrocarbons, and the more volatile hydrocarbons. Ratings of "present" or "absent" were assigned for seven additional exposures: higher boiling hydrocarbons, polynuclear aromatic hydrocarbons, asbestos, chlorinated solvents, ionizing radiation, and lead. Each exposure had either no association or a weak association with kidney cancer. For the hydrocarbon category of principal a priori interest, the nonaromatic liquid gasoline distillates, the estimated relative risk (RR) for any exposure above refinery background was 1.0 (95% confidence interval [CI] 0.5-1.9). Analyses of cumulative exposures and of exposures in varying time periods before kidney cancer occurrence also produced null or near-null results. In an analysis of the longest job held by each subject (average duration 9.2 years or 40% of the refinery work history), three groups appeared to be at increased risk: laborers (RR = 1.9, 95% CI 1.0-3.9); workers in receipt, storage, and movements (RR = 2.5, 95% CI 0.9-6.6); and unit cleaners (RR = 2.3, 95% CI 0.5-9.9).