Study
PLCO
(Learn more about this study)
Project ID
2012-0016
Initial CDAS Request Approval
Mar 7, 2012
Title
Circulating levels of obesity-related markers and risk of renal cell carcinoma
Summary
Obesity is an established risk factor for renal cell carcinoma (RCC). It is unclear what biologic mechanisms underlie this association, though it may be partly mediated through the effects of circulating hormones such as insulin-like growth factors (IGF) and adipokines. Recent investigations in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study suggest that pre-diagnostic circulating levels of IGF-1 and adiponectin are associated with subsequent RCC risk in this population of male smokers. Confirmation of these findings in larger prospective studies that include women and non-smokers is needed. We propose to conduct a nested case-control study of RCC in relation to circulating levels of IGF-1, IGF binding protein-3 (IGFBP-3), C-peptide, high-molecular-weight (HMW) adiponectin, and total adiponectin using pre-diagnostic serum samples collected from 375 cases and 375 matched controls in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Cases and controls will be matched on age, sex, race, date of phlebotomy, time of day of phlebotomy, number of freeze-thaw cycles, and study year of serum specimen collection. Assays will be performed in the laboratory of Dr. Michael Pollak (Jewish General Hospital, Montreal, Canada); Dr. Pollak's laboratory has a long track record of measuring these analytes with excellent reproducibility. Conditional logistic regression models will be used to estimate odds ratios and 95% confidence intervals for RCC risk in relation to quartiles of each analyte (based on the distribution among controls) as well as the ratios of IGF-1 to IGFBP-3 and HMW adiponectin to total adiponectin. With 375 cases and 375 controls, this study will be well powered to detect associations of comparable magnitude to those reported in the ATBC study.
Aims
To better understand the underlying biologic mechanisms through which obesity is associated with an increased risk of renal cell carcinoma (RCC), we propose to conduct a nested case-control study of RCC risk in relation to obesity-related markers in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. This study will be, to our knowledge, the largest prospective investigation of obesity-related markers and RCC, and the first to assess risk among women and non-smokers. The specific aims of this study are: 1) to measure circulating levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), C-peptide, high-molecular-weight (HMW) adiponectin, and total adiponectin in pre-diagnostic serum samples from RCC cases and matched controls in the PLCO cohort; and 2) to evaluate RCC risk in relation to the serum concentration of each marker and the ratios of IGF-1 to IGFBP-3 and HMW adiponectin to total adiponectin.
Collaborators
Wong-Ho Chow (DCEG)
Eunyoung Cho (Brigham and Women's Hospital)
Linda Liao (DCEG)
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