Congenital Anomalies of the Kidney and Urinary Tract and Adulthood risk of Urinary Tract Cancer

Gil Efron ³ Ronit Calderon-Margalit ¹ Oren Pleniceanu ^2,3,4 Dorit Tzur ² Michal Stern-Zimmer ^3,5 Arnon Afek ^3,6 Tomer Erlich ^2,3,7 Estela Derazne ³ Jeremy D Kark ² Lital Keinan-Boker ^8,9 Gilad Twig ^2,3,10 Asaf Vivante ^3,5

¹Braun School of Public Health, Hadassah-Hebrew University, ישראל
²Department of Military Medicine, Hebrew University of Jerusalem, Jerusalem and the Israel Defense Forces Medical Corps, Ramat Gan, ישראל
³Sackler Faculty of Medicine, Tel Aviv University, ישראל
⁴The Nephrology Research Lab, Institute of Nephrology and Hypertension, Sheba Medical Center, ישראל
⁵Department of Pediatrics B and Pediatric Nephrology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, ישראל
⁶Central Management, Chaim Sheba Medical Center, ישראל
⁷Urology Department, Sheba Medical Center, ישראל
⁸School of Public Health, University of Haifa, ישראל
⁹Israel Center for Disease Control, Ministry of Health, ישראל
¹⁰Talpiot Medical Leadership Program, Sheba Medical Center, ישראל

Introduction Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20-30% of all anomalies identified in the neonatal period. It has been suggested that aberrant nephrogenesis might not only lead to CAKUT but also predispose to tumorigenesis.
We aimed to investigate the risk of developing urinary tract (UT) cancer (involving the kidney, ureter, or bladder) among Israeli adolescents with CAKUT.

Methods: This is a historical cohort study of Israeli adolescents that included potential army recruits aged 16-19, which were assessed by an army medical board. We linked this cohort to the Israeli National Cancer Registry. Risk of developing UT cancer in adulthood was calculated for exposure groups (with/without CAKUT).

Results: The study population included 3165 participants with CAKUT and 1,503,903 without CAKUT. During follow-up, 2959 participants developed UT cancer, of whom 2944 were without CAKUT and 15 with CAKUT. Among men, the incidence rates of UT cancer were 0.6% and 0.3% for those with and without CAKUT, respectively, yielding an unadjusted HR of 2.27 (95% CI 1.26-4.11). Controlling for BMI, origin, blood pressure and year of recruitment, yielded a HR of 1.98 (95% CI 1.03-3.82). Among women with and without CAKUT, the incidence rates of UT cancer were 0.3% and 0.1%, respectively, yielding a crude HR of 6.01 (95% CI 2.25-16.10), and an adjusted HR of 5.88 (95% CI 2.19-15.76).

Conclusion: In this population-based cohort study, CAKUT was found to be associated with a significantly increased risk of UT cancer in adulthood.