Hong Xu1,2, Kunihiro Matsushita3, Guobin Su4,5, Marco Trevisan6, Johan Ärnlöv7,8, Peter Barany9, Bengt Lindholm9, Carl-Gustaf Elinder9, Mats Lambe6, Juan-Jesus Carrero6. 1. Departments of Medical Epidemiology and Biostatistics and hong.xu.2@ki.se. 2. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, and. 3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 4. Public Health Sciences. 5. Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou City, China. 6. Departments of Medical Epidemiology and Biostatistics and. 7. School of Health and Social Studies, Dalarna University, Falun, Sweden; and. 8. Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden. 9. Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Abstract
BACKGROUND AND OBJECTIVES: Community-based reports regarding eGFR and the risk of cancer are conflicting. We here explore plausible links between kidney function and cancer incidence in a large Scandinavian population-based cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the Stockholm Creatinine Measurements project, we quantified the associations of baseline eGFR with the incidence of cancer among 719,033 Swedes ages ≥40 years old with no prior history of cancer. Study outcomes were any type and site-specific cancer incidence rates on the basis of International Classification of Diseases-10 codes over a median follow-up of 5 years. To explore the possibility of detection bias and reverse causation, we divided the follow-up time into different time periods (≤12 and >12 months) and estimated risks for each of these intervals. RESULTS: In total, 64,319 cases of cancer (affecting 9% of participants) were detected throughout 3,338,226 person-years. The relationship between eGFR and cancer incidence was U shaped. Compared with eGFR of 90-104 ml/min, lower eGFR strata associated with higher cancer risk (adjusted hazard ratio, 1.08; 95% confidence interval, 1.05 to 1.11 for eGFR=30-59 ml/min and adjusted hazard ratio, 1.24; 95% confidence interval, 1.15 to 1.35 for eGFR<30 ml/min). Lower eGFR strata were significantly associated with higher risk of skin, urogenital, prostate, and hematologic cancers. Any cancer risk as well as skin (nonmelanoma) and urogenital cancer risks were significantly elevated throughout follow-up time, but they were higher in the first 12 months postregistration. Associations with hematologic and prostate cancers abrogated after the first 12 months of observation, suggesting the presence of detection bias and/or reverse causation. CONCLUSIONS: There is a modestly higher cancer risk in individuals with mild to severe CKD driven primarily by skin and urogenital cancers, and this is only partially explained by bias.
BACKGROUND AND OBJECTIVES: Community-based reports regarding eGFR and the risk of cancer are conflicting. We here explore plausible links between kidney function and cancer incidence in a large Scandinavian population-based cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the Stockholm Creatinine Measurements project, we quantified the associations of baseline eGFR with the incidence of cancer among 719,033 Swedes ages ≥40 years old with no prior history of cancer. Study outcomes were any type and site-specific cancer incidence rates on the basis of International Classification of Diseases-10 codes over a median follow-up of 5 years. To explore the possibility of detection bias and reverse causation, we divided the follow-up time into different time periods (≤12 and >12 months) and estimated risks for each of these intervals. RESULTS: In total, 64,319 cases of cancer (affecting 9% of participants) were detected throughout 3,338,226 person-years. The relationship between eGFR and cancer incidence was U shaped. Compared with eGFR of 90-104 ml/min, lower eGFR strata associated with higher cancer risk (adjusted hazard ratio, 1.08; 95% confidence interval, 1.05 to 1.11 for eGFR=30-59 ml/min and adjusted hazard ratio, 1.24; 95% confidence interval, 1.15 to 1.35 for eGFR<30 ml/min). Lower eGFR strata were significantly associated with higher risk of skin, urogenital, prostate, and hematologic cancers. Any cancer risk as well as skin (nonmelanoma) and urogenital cancer risks were significantly elevated throughout follow-up time, but they were higher in the first 12 months postregistration. Associations with hematologic and prostate cancers abrogated after the first 12 months of observation, suggesting the presence of detection bias and/or reverse causation. CONCLUSIONS: There is a modestly higher cancer risk in individuals with mild to severe CKD driven primarily by skin and urogenital cancers, and this is only partially explained by bias.
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