Linda M Liao1, Jonathan N Hofmann2, Eunyoung Cho3,4,5, Michael N Pollak6, Wong-Ho Chow7, Mark P Purdue2. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA. Linda.Liao@nih.gov. 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA. 3. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 4. Department of Dermatology, The Warren Alpert Medical School, Brown University, Providence, RI, USA. 5. Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA. 6. Oncology Department, McGill University and Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada. 7. MD Anderson Cancer Center, Houston, TX, USA.
Abstract
PURPOSE: Obesity is an established risk factor for renal cell carcinoma (RCC). It is unclear what biologic mechanisms underlie this association, although recent evidence suggests that the effects of circulating hormones such as insulin-like growth factors (IGF) and adipokines may play a role. METHODS: To address this question, we conducted a nested case-control study of RCC (252 cases, 252 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial investigating associations with pre-diagnostic serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, IGF-1, IGF-binding protein-3 (IGFBP-3), and C-peptide. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic regression. RESULTS: After adjustment for potential confounders, non-significant associations with RCC were observed for total adiponectin (OR for highest vs. lowest quartile = 0.65, 95% CI 0.37-1.14; p trend = 0.35), HMW adiponectin (0.67, 0.38-1.17; p trend = 0.36), IGF-1 (1.35, 0.77-2.39; p trend = 0.17), IGFBP-3 (1.47, 0.83-2.62; p trend = 0.53), and C-peptide (1.52, 0.86-2.70; p trend = 0.15). In a joint analysis with body mass index (BMI, kg/m2), obese individuals (BMI ≥30) with above-median levels of IGFBP-3 had a significantly higher risk versus those with BMI <25 and below-median IGFBP-3 (OR 2.42, 1.11-5.26), whereas obese individuals with low IGFBP-3 did not (1.18, 0.53-2.64) (p interaction = 0.35). CONCLUSIONS: The results of this study, while not clearly supporting associations with these obesity-related hormones, suggest that the association between obesity and RCC may be partially modified through mechanisms related to elevated IGFBP-3.
PURPOSE:Obesity is an established risk factor for renal cell carcinoma (RCC). It is unclear what biologic mechanisms underlie this association, although recent evidence suggests that the effects of circulating hormones such as insulin-like growth factors (IGF) and adipokines may play a role. METHODS: To address this question, we conducted a nested case-control study of RCC (252 cases, 252 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial investigating associations with pre-diagnostic serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, IGF-1, IGF-binding protein-3 (IGFBP-3), and C-peptide. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic regression. RESULTS: After adjustment for potential confounders, non-significant associations with RCC were observed for total adiponectin (OR for highest vs. lowest quartile = 0.65, 95% CI 0.37-1.14; p trend = 0.35), HMW adiponectin (0.67, 0.38-1.17; p trend = 0.36), IGF-1 (1.35, 0.77-2.39; p trend = 0.17), IGFBP-3 (1.47, 0.83-2.62; p trend = 0.53), and C-peptide (1.52, 0.86-2.70; p trend = 0.15). In a joint analysis with body mass index (BMI, kg/m2), obese individuals (BMI ≥30) with above-median levels of IGFBP-3 had a significantly higher risk versus those with BMI <25 and below-median IGFBP-3 (OR 2.42, 1.11-5.26), whereas obese individuals with low IGFBP-3 did not (1.18, 0.53-2.64) (p interaction = 0.35). CONCLUSIONS: The results of this study, while not clearly supporting associations with these obesity-related hormones, suggest that the association between obesity and RCC may be partially modified through mechanisms related to elevated IGFBP-3.
Authors: Y Arita; S Kihara; N Ouchi; M Takahashi; K Maeda; J Miyagawa; K Hotta; I Shimomura; T Nakamura; K Miyaoka; H Kuriyama; M Nishida; S Yamashita; K Okubo; K Matsubara; M Muraguchi; Y Ohmoto; T Funahashi; Y Matsuzawa Journal: Biochem Biophys Res Commun Date: 1999-04-02 Impact factor: 3.575
Authors: R B Hayes; D Reding; W Kopp; A F Subar; N Bhat; N Rothman; N Caporaso; R G Ziegler; C C Johnson; J L Weissfeld; R N Hoover; P Hartge; C Palace; J K Gohagan Journal: Control Clin Trials Date: 2000-12
Authors: Andrew G Renehan; Marcel Zwahlen; Christoph Minder; Sarah T O'Dwyer; Stephen M Shalet; Matthias Egger Journal: Lancet Date: 2004-04-24 Impact factor: 79.321
Authors: Shang-Tian Chuang; Kurt T Patton; Kristian T Schafernak; Veronica Papavero; Fan Lin; Robert C Baxter; Bin Tean Teh; Ximing J Yang Journal: J Urol Date: 2008-02 Impact factor: 7.450
Authors: Niki L Dimou; Nikos Papadimitriou; Daniela Mariosa; Mattias Johansson; Paul Brennan; Ulrike Peters; Stephen J Chanock; Mark Purdue; D Timothy Bishop; Manuela Gago-Dominquez; Graham G Giles; Victor Moreno; Elizabeth A Platz; Catherine M Tangen; Alicja Wolk; Wei Zheng; Xifeng Wu; Peter T Campbell; Edward Giovannucci; Yi Lin; Marc J Gunter; Neil Murphy Journal: Int J Cancer Date: 2020-10-26 Impact factor: 7.396