Abstract
INTRODUCTION: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common kidney diseases in childhood. Alterations in genes governing nephrogenesis may cause CAKUT, and in some cases may contribute to development of urinary tract (UT) tumors later in life. We aimed to assess the association between CAKUT and UT cancer in adulthood. METHODS: We conducted a population-based historical cohort study encompassing 1,510,042 recruits to the Israeli army between 1967 and 1997. CAKUT exposure was determined by army medical coding of CAKUT in childhood. Incidence of UT cancer (kidney, ureter, or bladder) was available through record linkage with the Israeli Cancer Registry. Recruits were followed from the prerecruitment assessment until cancer diagnosis, death, or study termination, in 2012. Cox proportional hazards models were constructed to estimate the hazard ratios (HRs) for UT cancer in participants with vs. without CAKUT. RESULTS: During a mean follow-up of 30.4 years, 2959 participants (2573 men and 386 women) developed UT cancer. Men with CAKUT exhibited an increased risk of UT cancer compared with men without CAKUT, yielding an adjusted HR of 1.98 (95% confidence interval [CI] 1.03-3.82). Among women CAKUT was associated with a HR of 5.88 (95% CI 2.19-15.76). Notably, upon stratification according to age of cancer diagnosis, the association between CAKUT and UT cancer was statistically significant only before 45 years of age in women and only after 45 years of age in men. CONCLUSION: CAKUT is associated with a significantly increased risk of UT cancer, although the incidence and absolute risk remained quite low.