Elsevier

The Lancet Oncology

Volume 7, Issue 2, February 2006, Pages 119-126
The Lancet Oncology

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Environmental exposure to cadmium and risk of cancer: a prospective population-based study

https://doi.org/10.1016/S1470-2045(06)70545-9Get rights and content

Summary

Background

Cadmium is a ubiquitous environmental pollutant, which accumulates in the human body such that 24-h urinary excretion is a biomarker of lifetime exposure. We aimed to assess the association between environmental exposure to cadmium and cancer.

Methods

We recruited a random population sample (n=994) from an area close to three zinc smelters and a reference population from an area with low exposure to cadmium. At baseline (1985–89), we measured cadmium in urine samples obtained over 24 h and in the soil of participants' gardens, and followed the incidence of cancer until June 30, 2004. We used Cox regression to calculate hazard ratios for cancer in relation to internal (ie, urinary) and external (ie, soil) exposure to cadmium, while adjusting for covariables.

Findings

Cadmium concentration in soil ranged from 0·8 mg/kg to 17·0 mg/kg. At baseline, geometric mean urinary cadmium excretion was 12·3 nmol/day for people in the high-exposure area, compared with 7·7 nmol/day for those in the reference (ie, low-exposure) area (p<0·0001). During follow-up (median 17·2 years [range 0·6–18·8]), 50 fatal cancers and 20 non-fatal cancers occurred, of which 18 and one, respectively, were lung cancers. Overall cancer risk was significantly associated with a doubling of 24-h cadmium excretion (hazard ratio 1·31 [95% CI 1·03–1·65], p=0·026. Population-attributable risk of lung cancer was 67% (95% CI 33–101) in the high-exposure area, compared with that of 73% (38–108) for smoking. For lung cancer, adjusted hazard ratio was 1·70 (1·13–2·57, p=0·011) for a doubling of 24-h urinary cadmium excretion, 4·17 (1·21–14·4, p=0·024) for residence in the high-exposure area versus the low-exposure area, and 1·57 (1·11–2·24, p=0·012) for a doubling of cadmium concentration in soil.

Interpretation

Historical pollution from non-ferrous smelters continues to present a serious health hazard, necessitating targeted preventive measures.

Introduction

Cadmium is a metal with high toxic effects, has an elimination half-life of 10–30 years, and accumulates in the human body, particularly the kidney. Urinary excretion of cadmium over 24 h is a biomarker of lifetime exposure.1, 2 Exposure to cadmium occurs through intake of contaminated food or water, or by inhalation of tobacco smoke or polluted air.1, 2 We have shown that environmental exposure to cadmium in north-east Belgium in the neighbourhood of zinc smelters was associated with about 30% increased urinary cadmium excretion,3 renal dysfunction,4, 5 increased calciuria,6 osteoporosis,7 and a 35% population-attributable risk of fractures.7

In 1993, the International Agency for Research on Cancer (IARC) classified cadmium as a human carcinogen.8 As reviewed by Verougstraete and colleagues,9 longitudinal studies have shown consistently that workers exposed to cadmium or cadmium compounds are at increased risk of lung cancer. In five large cohorts of industrial workers,10, 11, 12, 13, 14 standardised mortality ratios ranged from 101 to 176 (median 120).9 However, in a study15 of 926 men who manufactured nickel-cadmium batteries in the UK followed up from 1947 to 2000, the ratio was non-significantly increased to 111. Few population-based studies, mostly Japanese,16, 17, 18 have addressed the association between cancer and environmental exposure to cadmium, and have reported inconsistent results. We started recruitment of Flemish participants of the Cadmium in Belgium Study (CadmiBel)19 on Sept 1, 1985.3, 4, 5, 6, 7 We aimed to assess prospectively the incidence of fatal cancer and non-fatal cancer until June 30, 2004, to investigate whether environmental exposure to cadmium is associated with increased risk of cancer, particularly that of the lung.

Section snippets

Study population

The Flemish CadmiBel participants were recruited from Sept 1, 1985, to Dec 17, 1989,19 and were from north-east Belgium (Noorderkempen); this region has an area contaminated with cadmium and a reference area with low exposure to cadmium. We selected ten districts where we expected mean concentration of cadmium in soil to be more than 3 mg/kg or less than 1 mg/kg on the basis of a preliminary screen done 1983–84 by the Research Institute for Ecology and Forestry, Genk, Belgium. The

Results

At baseline, the characteristics of the 521 residents of the districts near the smelters (ie, in high-exposure areas) did not differ from those living in the low-exposure area with the exception of internal and external exposure to cadmium, internal exposure to arsenic and socioeconomic status (table 1). The median number of follow-up visits for ascertainment of non-fatal health outcomes was three (range 2–4). The proportion of smokers in districts with low exposure and high exposure were much

Discussion

We have shown an association between risk of cancer and cadmium exposure as shown by 24-h urinary excretion—a finding that remained consistent after: adjustment for sex, age, and smoking; exclusion of 42 cadmium-exposed workers; and accounting for exposure to inorganic arsenic.

Cadmium is a ubiquitous environmental pollutant in industrialised countries. Residence in the area with high environmental exposure to cadmium was associated with a hazard ratio for lung cancer of 3·58. Our current

Glossary

Aqua regia
A highly corrosive liquid used to dissolve metals, formed by a fresh mixture of concentrated nitric acid and concentrated hydrochloric acid, usually in a ratio of one to three.

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