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Background: Kidney cancer incidence demonstrates significant geographic variation suggesting a role for environmental risk factors. This study sought to evaluate associations between groundwater exposures and kidney cancer incidence. Methods: The authors identified constituents from 18,506 public groundwater wells in all 58 California counties measured in 1996–2010, and obtained county‐level kidney cancer incidence data from the California Cancer Registry for 2003–2017. The authors developed a water‐wide association study (WWAS) platform using XWAS methodology. Three cohorts were created with 5 years of groundwater measurements and 5‐year kidney cancer incidence data. The authors fit Poisson regression models in each cohort to estimate the association between county‐level average constituent concentrations and kidney cancer, adjusting for known risk factors: sex, obesity, smoking prevalence, and socioeconomic status at the county level. Results: Thirteen groundwater constituents met stringent WWAS criteria (a false discovery rate <0.10 in the first cohort, followed by p values <.05 in subsequent cohorts) and were associated with kidney cancer incidence. The seven constituents directly related to kidney cancer incidence (and corresponding standardized incidence ratios) were chlordane (1.06; 95% confidence interval [CI], 1.02–1.10), dieldrin (1.04; 95% CI, 1.01–1.07), 1,2‐dichloropropane (1.04; 95% CI, 1.02–1.05), 2,4,5‐TP (1.03; 95% CI, 1.01–1.05), glyphosate (1.02; 95% CI, 1.01–1.04), endothall (1.02; 95% CI, 1.01–1.03), and carbaryl (1.02; 95% CI, 1.01–1.03). Among the six constituents inversely related to kidney cancer incidence, the standardized incidence ratio furthest from the null was for bromide (0.97; 95% CI, 0.94–0.99). Conclusions: This study identified several groundwater constituents associated with kidney cancer. Public health efforts to reduce the burden of kidney cancer should consider groundwater constituents as environmental exposures that may be associated with the incidence of kidney cancer. This study analyzed 180 groundwater exposures in California and used a water‐wide association study (WWAS) platform, based on XWAS methodology, to identify associations between groundwater exposures and kidney cancer incidence. Results revealed 13 groundwater constituents meeting stringent WWAS criteria, with seven directly linked to increased kidney cancer incidence, suggesting that public health efforts should consider environmental exposures that may be associated with the incidence of kidney cancer. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated that Black men may undergo definitive prostate cancer (CaP) treatment less often than men of other races, but it is unclear whether they are avoiding overtreatment of low‐risk disease or experiencing a reduction in appropriate care. The authors' aim was to assess the role of race as it relates to treatment benefit in access to CaP treatment in a single‐payer population. Methods: The authors used the Veterans Health Administration (VHA) Corporate Data Warehouse to perform a retrospective cohort study of veterans diagnosed with low‐ or intermediate‐risk CaP between 2011 and 2017. Results: The authors identified 35,427 men with incident low‐ or intermediate‐risk CaP. When they controlled for covariates, Black men had 1.05 times the odds of receiving treatment in comparison with non‐Black men (P <.001), and high‐treatment‐benefit men had 1.4 times the odds of receiving treatment in comparison with those in the low‐treatment‐benefit group (P <.001). The interaction of race and treatment benefit was significant, with Black men in the high‐treatment‐benefit category less likely to receive treatment than non‐Black men in the same treatment category (odds ratio, 0.89; P <.001). Conclusions: Although race does appear to influence the receipt of definitive treatment in the VHA, this relationship varies in the context of the patient's treatment benefit, with Black men receiving less definitive treatment in high‐benefit situations. The influence of patient race at high treatment benefit levels invites further investigation into the driving forces behind this persistent disparity in this consequential group. Race appears to influence the receipt of definitive treatment in the Veterans Health Administration, and this relationship varies in the context of the patient's treatment benefit, with Black men receiving less definitive treatment in high‐benefit situations. The influence of patient race at high treatment benefit levels invites further investigation into the driving forces behind this persistent disparity in this consequential group. [ABSTRACT FROM AUTHOR]

Background: Estimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory‐wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer. Methods: The authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false‐discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts. Results: A total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate‐specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06‐1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20‐1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76‐0.80]; and creatinine: HR, 1.05 [95% CI, 1.03‐1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98‐1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09‐1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort. Conclusions: The authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making. Lay Summary: This article examined routine laboratory tests associated with survival among veterans with prostate cancer.Using laboratory‐wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making. The current study identifies common clinical laboratory tests that are associated with mortality in patients with prostate cancer. These tests may aid in the challenging task of estimating life expectancy among men with prostate cancer, among whom overdiagnosis is common and in whom competing risks of mortality dominate prostate cancer–specific mortality risk. [ABSTRACT FROM AUTHOR]

Background: The mammalian target of rapamycin (mTOR) pathway is up-regulated in many human cancers, and agents targeting the mTOR pathway are in various stages of clinical development. The goal of the study was to evaluate the potential and limitations of targeting the mTOR pathway in renal cell carcinoma (RCC).Methods: Immunohistochemical analysis using antibodies against pAkt, PTEN, p27, and pS6 was performed on a tissue microarray constructed from paraffin-embedded specimens from 375 patients treated by nephrectomy for RCC. The expression was associated with pathological parameters and survival.Results: The mTOR pathway was more significantly altered in clear-cell RCC, high-grade tumors, and tumors with poor prognostic features. PS6 and PTEN showed the strongest associations with pathological parameters. Survival tree analysis regarding expression of cytoplasmic pAkt, nuclear pAkt, PTEN, cytoplasmic p27, and pS6 identified staining percentages of 40%, 10%, 75%, 7%, and 70%, respectively, as ideal cutoff values for stratification, with corresponding P-values of .03, .001, .02, .005, and <.0001, respectively. Interestingly, high nuclear pAkt expression was associated with a favorable prognosis, whereas high cytoplasmic pAkt expression was associated with a poor prognosis. In multivariate Cox regression analysis, ECOG PS, T classification, N classification, M classification, cytoplasmic Akt, nuclear pAkt, PTEN, and pS6 were independent prognostic factors of DSS.Conclusions: Components of the mTOR pathway are significantly associated with pathological features and survival. Not all RCC tumor types seem to be equally amenable to mTOR targeted therapy. PTEN, pAkt, p27, and pS6 may serve as surrogate parameters for patient selection and predicting prognosis. Patients with a highly activated mTOR pathway should benefit most from this therapy. External validation of our results is recommended. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The Oncotype DX Genomic Prostate Score (ODX‐GPS) is a gene expression assay that predicts disease aggressiveness. The objective of this study was to identify sociodemographic and regional factors associated with ODX‐GPS uptake.Data from Surveillance Epidemiology and End Results registries on men with localized prostate cancer with a Gleason score of 3 + 3 or 3 + 4, PSA ≤20 ng/mL, and stage T1c to T2c disease from 2013 through 2017 were linked with ODX‐GPS data. Census‐tract level neighborhood socioeconomic status (nSES) quintiles were constructed using a composite socioeconomic score. Multivariable logistic regression was used to estimate the associations of ODX‐GPS uptake with age at diagnosis, race and ethnicity, nSES, geographic region, insurance type, and marital status, accounting for National Comprehensive Cancer Network risk group, year of diagnosis, and clustering by census tract.Among 111,434 eligible men, 5.5% had ODX‐GPS test uptake. Of these, 78.3% were non‐Hispanic White, 9.6% were Black, 6.7% were Hispanic, and 3.6% were Asian American. Black men had the lowest odds of ODX‐GPS uptake (odds ratio, 0.70; 95% confidence interval [CI], 0.63–0.76). Those in the highest versus lowest quintile of nSES were 1.64 times more likely (95% CI, 1.38–2.94) to have ODX‐GPS uptake. The odds of ODX‐GPS uptake were statistically significantly higher among men residing in the Northeast, West, and Midwest compared to the South.Disparities in ODX‐GPS uptake by race, ethnicity, nSES, and geographical region were identified. Concerted efforts should be made to ensure that this clinical test is equitably available. [ABSTRACT FROM AUTHOR]