Renal tubular dysfunction and cancer mortality in the Japanese general population living in cadmium-non-contaminated areas

J Appl Toxicol. 2022 Sep;42(9):1458-1466. doi: 10.1002/jat.4304. Epub 2022 Mar 3.


The relationship between cadmium exposure, exposure-related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd-contaminated areas in Japan. The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and cancer mortality in the general population in non-contaminated areas. A 19-year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium-non-contaminated areas. Mortality risk ratios of urinary β2-microglobulin (β2MG) and N-acetyl-β-glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02-1.19, pancreas: HR, 1.10, 95%CI, 1.02-1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67-0.96) and for β2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93-1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium-non-contaminated areas in Japan.

Keywords: Fine and Gray competing risks regression model; Japanese; cancer mortality; cohort study; renal dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase
  • Cadmium / toxicity
  • Cohort Studies
  • Environmental Exposure / adverse effects
  • Environmental Exposure / analysis
  • Environmental Pollutants* / toxicity
  • Female
  • Humans
  • Japan / epidemiology
  • Kidney Diseases*
  • Male
  • Neoplasms* / chemically induced
  • Neoplasms* / epidemiology
  • beta 2-Microglobulin


  • Environmental Pollutants
  • beta 2-Microglobulin
  • Cadmium
  • Acetylglucosaminidase