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The Kidney Cancer Prevention Research Program in the Department of Epidemiology and Biostatistics is dedicated to impactful research that is translatable to the primary and secondary prevention of cancer. Our current research focuses on the identification of new environmental risk factors and gene-environment interactions.
Since the initiation of the National Cancer Institute’s (NCI) Surveillance, Epidemiology and End Results (SEER) Program in the 1970s, the annual age-adjusted incidence of kidney cancer in the United States has increased more than twofold. Worldwide, increasing incidence (~2 to 8% annually) of kidney cancer has been most rapid among women, young adults and minority groups. Over the past decade, renal cell cancer (RCC) incidence rates have continued to increase despite substantial improvements in controlled hypertension and roughly constant rates of obesity and smoking. Risk factors for nearly half of the roughly 65,000 U.S. cases of kidney cancer diagnosed each year remain unexplained. RCCs comprise over 90% of cancers of the kidney, with approximately half of all RCC cases attributed to hypertension, obesity and tobacco smoking. Despite gains in overall survival, median survival among late stage RCC patients is 10 months. Taken together, these trends underscore the need for identification of new risk factors and improved prevention.
Per- and polyfluorinated substances (PFAS) are compounds used in a wide variety of consumer products as well as fire-fighting foams that have impacted drinking water sources. Mean blood concentrations of some PFAS compounds in the general U.S. population are currently at or above concentrations of circulating hormones involved in gene regulation including calcitriol, estrogen and testosterone. Hypothesized carcinogenic mechanisms of PFAS include altered expression of nuclear hormone receptors and oxidative stress-mediated DNA damage via suppression of oxidative stress signaling.
In the general population, cancers of the kidney and thyroid are among a few cancer sites with a greater proportion of within-family and within-individual recurrence risk. The Enhanced Family Cancer Surveillance for Cancers of the Kidney and Thyroid Project is a family-based case-control study designed to investigate whether four PFAS compounds (PFHxS, PFOA, PFOS, and PFNA) may play a role in the development of these two cancers.
This project is funded in part by the Investigator-Initiated research portion of the Centers for Disease Control and Prevention (CDC) Agency for Toxic Substances and Disease Registry (ATSDR). Collaborating institutions include Brown University, Case Comprehensive Cancer Center, National Institutes of Health, Pennsylvania Department of Health, Pennsylvania State University, RTI International and the University of Sydney. (Researcher: Robin Taylor Wilson)
Nearly all sporadic (non-familial) renal cell cancer (RCC) tumors arise from the proximal convoluted tubule (PCT) epithelium of the kidney. The PCT is the body’s major production site of the active form of vitamin D, as well as a key site of calcium retention, via its reabsorption of calcium (~70%) into blood circulation. Several divalent heavy metals (e.g., Cd, Pb and Hg) are renal toxicants, mechanistically shown to hijack renal calcium transport mechanisms and bioaccumulate in the kidney.
The purpose of this research is to identify environmental and gene-environmental risk factors associated with RCC risk. To date, we have identified higher whole blood lead (Pb) concentrations and a prevalent calbindin D28k gene variant (minor allele frequency = 0.29) associated with new RCC development. Among cases alone, we report that lower serum concentrations of vitamin D (25-hydroxyvitamin D) and calcium are independent predictors of more rapid RCC development (i.e., 5 to 9 years v. 15 to 21 years). We also report continuing heavy metal exposures to children through a major dietary staple in a mining-impacted region of Bolivia. Our research identifying genetic differences in circulating concentrations of vitamin D metabolites (25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3) may also shed new light on differential renal metals uptake.
This research has been funded by the American Institute for Cancer Research and the National Cancer Institute. Collaborating institutions include Baylor University, Case Comprehensive Cancer Center, El Centro de Investigación en Ciencias y Recursos GeoAgroAmbientales (Corhuila University, Neiva, Colombia), Engineers in Action (Bolivia), Ipsen Bioscience, National Institutes of Health, Pennsylvania State University and University of Iowa. (Researcher: Robin Taylor Wilson)