Factors influencing the cadmium body burden in a population study.

The cadmium body burden, as estimated from 24-h urinary cadmium (Cd-U), was determined in 1523 non-occupationally exposed subjects living in five areas of Belgium. It increased with age until 55-65 years in both sexes and thereafter decreased slightly. It was higher in smokers but was inversely associated with alcohol consumption and social class. In men only, it was also positively correlated with body mass index. After the menopause, women showed a significant increase in 24-h Cd-U independently of the other factors. In addition, the cadmium body burden was independently associated with place of residence in both sexes. Highest levels of Cd-U were found in subjects living in an area with soils heavily polluted by cadmium.     

Effects of gamma-interferon on the endocrine system: results from a phase I study

Interferon causes profound biological changes when given to patients with cancer and many of these could not be predicted from in vitro or animal model systems. We documented significant changes in hormonal levels for a group of 18 patients who were participants in a Phase I gamma-interferon trial. Adrenocorticotropic hormone, cortisol, and growth hormone were all significantly elevated 2 h after treatment with gamma-interferon, with cortisol and adrenocorticotropic hormone returning to base line by 24 h. A placebo group failed to show this change, suggesting a specific interferon effect. Possible mechanisms for these findings and implications for the use of interferons are discussed.     

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

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.     

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study

Background:

Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated.

Methods:

A population-based cohort of 41 089 Swedish men aged 45–79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases).

Results:

Mean dietary cadmium exposure was 19 μg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03–1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08–1.53) for localised, 1.05 (95% CI: 0.87–1.25) for advanced, and 1.14 (95% CI: 0.86–1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P_{heterogeneity}=0.27). For localised prostate cancer, RR was 1.55 (1.16–2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers.

Conclusion:

Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.     

Dietary supplement use among cancer survivors and the general population: a nation-wide cross-sectional study

Background

Use of dietary supplements among cancer survivors is common and controversial, but information on the amount of nutrients from supplements among cancer survivors is limited. We examined the amount of nutrients and their contribution to total nutrient intake from supplements and compared these data between cancer survivors and cancer-free individuals. We also identified factors associated with supplement use among cancer survivors.

Methods

We identified 400 cancer survivors and 10,387 cancer-free individuals, aged ≥?19 years, from the fifth Korea National Health and Nutrition Examination Survey (KNHANES) V-1, 2 (2010, 2011). We calculated the amount of nutrients consumed from foods and supplements, the percent contributions of supplement nutrients to total nutrient intakes and cancer survivors’ nutrient intakes relative to the Estimated Average Requirements (EARs) and the Tolerable Upper Intake Levels (ULs). We examined factors associated with supplement use among cancer survivors.

Results

We found that 33.3% of cancer survivors and 22.1% of cancer-free individuals reported the use of dietary supplements. Compared to cancer-free individuals, cancer survivors had higher intakes of riboflavin, folate, and iron from foods (p?<?0.05 for each), and higher intakes of calcium (p?=?0.05) and vitamin C (p?=?0.01) from foods and supplements. The similar pattern was observed for the percent contributions to total nutrient intake. Cancer survivors had higher proportion of participants below EARs than cancer-free individuals for thiamin and niacin (p?<?0.05 for each). The proportions of cancer survivors below the EARs were 61.2% for calcium, 49.1% for riboflavin, and 43.5% for folate and the proportions of cancer survivors above the ULs were 3.3% for iron, and 2.3% for vitamin A. For female cancer survivors, education above an elementary school level, moderate physical activity, low vegetable intake, and high circulating vitamin D levels were associated with supplement use. For male cancer survivors, living in an urban area, no consumption of alcohol, and lower energy intake, were associated with supplement use.

Conclusions

Korean cancer survivors have higher rate of dietary supplement use and higher contribution from supplements to total nutrient intake than cancer-free individuals. Demographic and lifestyle factors were associated with supplement use among cancer survivors.

     

Analytical quality control of cadmium and lead in blood and cadmium in urine: results of its implementation during a five-year epidemiological study.

Quality-control programmes are very important in assessing the reliability of biological analyses. Such programmes are essential if misleading results in epidemiological studies dealing with low levels of exposure to heavy metals present in the general environment (e.g., cadmium, lead) are to be avoided. Internal and external quality-control programmes for the measurement of cadmium and lead in blood and of cadmium in urine were implemented from 1985 to 1989 in support of a national epidemiological study, Cadmibel (2327 participants), conducted in Belgium to assess the effects of environmental exposure to cadmium and lead on the general population. Apart from these programmes, inter-comparisons between the two participating laboratories were carried out on 10% of the samples. The results of these quality-control programmes met external acceptability criteria, emphasizing the analytical proficiency of these measurements at the relatively low concentrations in the Cadmibel study.     

The World Health Organization study on health effects of exposure to cadmium: morbidity studies.

Studies according to the protocol of the WHO Regional Office for Europe were performed in Germany, the Netherlands and Belgium. Pilot studies were performed in Czechoslovakia, Hungary and Poland. The results of the Belgian study are described elsewhere; some striking results of the other studies are reported here. The highest levels of cadmium in blood (Cd-B) were reported in a cadmium-polluted area in Hungary, the lowest in a non-polluted urban area. In Poland, levels were enhanced in polluted and non-polluted areas. The highest levels of cadmium in urine (Cd-U) were found in Hungary, the lowest in the Netherlands. In nearly all the studies significant increases in both Cd-B and Cd-U were found in cadmium-polluted areas. The picture is less clear with regard to the biological effect parameters. The renal parameters were sometimes significantly enhanced for the polluted areas, but sometimes the opposite was reported. Because of the many confounding variables, stratification at least by smoking behaviour, sex and age is necessary if firm conclusions are to be reached. A better approach, however, is to use multivariate regression analysis. This technique allowed the calculation of the relation between Cd-U and age in the German and Dutch studies, and between Cd-U and age in the German and Dutch studies, and between Cd-U and NAG, AAP, Alb-U and Creat-S levels.     

Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study

The ubiquitous food contaminant cadmium has features of an estrogen mimetic that may promote the development of estrogen-dependent malignancies, such as breast cancer. However, no prospective studies of cadmium exposure and breast cancer risk have been reported. We examined the association between dietary cadmium exposure (at baseline, 1987) and the risk of overall and estrogen receptor (ER)-defined (ER(+) or ER(-)) breast cancer within a population-based prospective cohort of 55,987 postmenopausal women. During an average of 12.2 years of follow-up, 2,112 incident cases of invasive breast cancer were ascertained (1,626 ER(+) and 290 ER(-)). After adjusting for confounders, including consumption of whole grains and vegetables (which account for 40% of the dietary exposure, but also contain putative anticarcinogenic phytochemicals), dietary cadmium intake was positively associated with overall breast cancer tumors, comparing the highest tertile with the lowest [rate ratio (RR), 1.21; 95% confidence interval (CI), 1.07-1.36; P(trend) = 0.02]. Among lean and normal weight women, statistically significant associations were observed for all tumors (RR, 1.27; 95% CI, 1.07-1.50) and for ER(+) tumors (RR, 1.25; 95% CI, 1.03-1.52) and similar, but not statistically significant associations were found for ER(-) tumors (RR, 1.22; 95% CI, 0.76-1.93). The risk of breast cancer increased with increasing cadmium exposure similarly within each tertile of whole grain/vegetable consumption and decreased with increasing consumption of whole grain/vegetables within each tertile of cadmium exposure (P(interaction) = 0.73). Overall, these results suggest a role for dietary cadmium in postmenopausal breast cancer development.     

Different measures of smoking exposure and mammographic density in postmenopausal Norwegian women: a cross-sectional study

Background  

Recent cohort studies have suggested an increased risk of breast cancer with long duration of smoking, and with smoking initiation before first birth. Cigarette smoking may have both carcinogenic effects and antiestrogenic effects on the breast tissue. We decided to examine the relationship between different measures of smoking exposure and mammographic density.     

Alcohol exposure and breast cancer: results of the women's contraceptive and reproductive experiences study.

OBJECTIVES: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship.METHODS: In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately.RESULTS: Recent consumption (at reference age minus two) of >/=7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor-positive/progesterone receptor-negative tumors (OR 1.6; 95% CI, 1.2-2.3).CONCLUSIONS: The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact.     

Effects of calcium and magnesium acetates on the carcinogenicity of cadmium chloride in Wistar rats

The effects of calcium and magnesium acetates on the formation of injection site and testicular tumors in male Wistar rats over 2 years following s.c. injections of cadmium chloride (CdCl2) were determined. The rats (25/group) received a single s.c. dose of CdCl2 (0.02 or 0.04 mmol/kg; 0.9% NaCl solutions). Calcium and magnesium acetates were administered as 3% dietary supplements for 2 weeks prior to and 2 weeks after the CdCl2 injection, or as three daily s.c. injections (0.16 mmol calcium acetate per kg, 4 mmol magnesium acetate per kg; 0.9% NaCl solutions) at the same site as CdCl2 on the day before, the day of, and the day after CdCl2 dosing. Control groups were given 0.9% NaCl solution instead of CdCl2 plus s.c. or dietary calcium and magnesium acetates. In rats given injections of CdCl2 alone, the final tumor yields were 33 and 34% of rats at risk at the injection site (mostly fibrosarcomas) and 86 and 85% of rats at risk in the testes (mostly interstitial cell tumors), respectively, for the low- and high-CdCl2 doses. In control rats, the corresponding tumor yields were 0% at the site of 0.9% NaCl solution injection and 30% in the testes. Dietary calcium and magnesium acetates or s.c. calcium acetate did not affect significantly the tumor yields and latent periods. Simultaneous injections of magnesium acetate at the same site completely prevented the development of injection site tumors for both CdCl2 doses but had no effect on the final yields of testicular tumors. CdCl2 injection also caused significant elevation of incidence of the pancreatic islet cell tumors (8.5 versus 2.2%) regardless of any other experimental treatment. These results provide further evidence that the divalent carcinogenic metals may exert their activity through an antagonism with the physiologically essential divalent metals.     

The use of denial in an ethnically diverse British cancer population: a cross-sectional study

A total of 82 Asian and 117 randomly selected white Caucasian patients at the Leicestershire Cancer Centre were assessed using measures of coping and adaption to cancer. On the Mental Adjustment to Cancer (MAC) scale, Asian patients were more fatalistic (P < 0.0001) and had more significant hopeless/helpless scores (P = 0.007). The two ethnic groups answered the three questions thought to assess denial differently. Caucasians were more likely not to dwell on their illness (73 vs 55.5%, P < 0.0001) and agree with the statement 'I have difficulty believing this is happening to me' (73 vs 60.5%, P < 0.0001). However, Asian patients were more likely to agree with the statement 'I don't really believe I have cancer' (48.2 vs 31.3%, P = 0.019). Within both groups there was an association with denial and anxious preoccupation (P < 0.001). On the Hospital Anxiety and Depression (HAD) scale, there was no difference in anxiety scores between either sexes or between the Asian and Caucasian groups. However, Asian patients were more depressed (P = 0.001). Although denial was significantly related to the presence of both depression (P < 0.0001) and anxiety (P = 0.001) in the entire patient population, there were different predictors of denial in each subgroup. On multiple regression analysis depression was linked with denial in Caucasians, whereas Fighting Spirit (minus helplessness/hopelessness) was linked with denial in Asian patients. There are definite differences in coping styles in British cancer patients according to ethnicity. While significant numbers in both groups employ denial in some form, Caucasian patients appear to adapt to the psychological pressures of cancer more successfully than Asian patients at a particular point in time. Further work is required to elucidate longitudinal relationships between denial and adaption to cancer.     

Prognosis of screen-detected breast cancers: results of a population based study

Background  

The reduced mortality rate from breast carcinoma among women offered screening mammography is demonstrated after 15–20 years of follow-up. However, the assessment of 5-year overall and event-free survival could represent an earlier measure of the efficacy of mammography screening program (MSP).     

Low bone mineral density linked to colorectal adenomas: a cross-sectional study of a racially diverse population

Background

Epidemiologic studies suggest that lower bone mineral density (BMD) is associated with an increased risk for colorectal adenoma/cancer, especially in postmenopausal women. The aim of this study is to investigate the association between osteopenia and/or osteoporosis and colorectal adenomas in patients from a New York community hospital.

Methods

We performed a cross-sectional observational study on 200 patients who underwent screening colonoscopies and bone density scan (dual-energy X-ray absorptiometry) at Nassau University Medical Center from November 2009 to March 2011. Among these, 83 patients were identified as osteoporosis (T score of −2.5 or below) and 67 were osteopenia (T score between −1.0 and −2.5). Logistic regression model was performed to assess the association between osteopenia and/or osteoporosis and colorectal adenomas.

Results

Among the patients with osteopenia and osteoporosis, the mean ages were 59.1 years [standard deviation (SD) =8.9] and 61.5 (SD =8.9), respectively. There were 94.0%, 85.1% and 74.7% women, respectively, in normal BMD, osteopenia and osteoporosis groups. The prevalence of colorectal adenomas was 17.9% and 25.3% in the osteopenia and osteoporosis groups, respectively, and 18.0% in the normal BMD group. After adjustment for potential confounders including age, sex, race, body mass index (BMI), tobacco use, alcohol use, history of diabetes, hypertension, or dyslipidemia, osteoporosis was found to be associated with presence of colorectal adenomas more than 2, compared to the normal BMD group. No significant associations were found for the prevalence, size, and location of adenomas.

Conclusions

Our study suggests that osteoporosis is significantly associated with the presence of multiple colorectal adenomas. Prospective studies with a larger sample size are warranted in the future.     

Prevalence of breast cancer in thyroid diseases: results of a cross-sectional study of 3,921 patients

Results from national cancer registries reveal an association of thyroid cancers with extra-thyroidal malignancies. In this study, we evaluated the prevalence of breast cancer (BC) in women affected by both benign and malignant thyroid diseases (TD) in comparison to the general population. To this end, 3,921 female patients from central and southern regions of Italy were evaluated. Age-matched analysis of the prevalence of BC was carried out after dividing the patients into three diagnostic categories: (1) 1,149 patients with non-nodular TD; (2) 2350 patients with nodular TD; (3) 422 patients affected by differentiated thyroid cancers. Furthermore, the patients were grouped according to the absence (2,344 patients) or presence (1,453 patients) of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) or anti-TSH receptor auto-antibodies (124 patients). BC prevalence in TD patients as a whole was significantly higher compared to the general population, with an odds ratio (OR) of 3.33. Age-matched analysis showed that the risk of a BC in TD patients was higher in younger patients (age 0–44 years), with an OR of 15.24, which decreased with increasing age. Patients without thyroid auto-antibodies showed a higher OR for BC (p = 0.0005) than TD patients with TgAb and/or TPOAb. The results demonstrate that women affected by either benign or malignant thyroid disease have a significantly greater risk of BC, which is higher at a younger age. Furthermore, thyroid auto-antibodies appear to be protective against BC. These findings may contribute to the identification of common genetic and environmental factors underlying this disease association.     

Biological monitoring of the general population for cadmium.

Over 2000 blood samples and about 1000 24-h total food duplicates were collected in 49 non-polluted regions in Japan, and analysed for cadmium (Cd-B and Cd-F). Cd-B increased with age to reach a plateau at 40-59 years, where the geometric mean (GM) Cd-B was 3.2 ng/ml in men and 3.7 ng/ml in women. Smoking also increased Cd-B. The GMs of Cd-F were 43.9 and 37.0 micrograms/day for men and women, respectively, with boiled rice as a major source of cadmium (> 40%). Cd-B correlated significantly with Cd-F when compared on a regional mean basis. Similar Cd-B analyses among non-smoking women showed that Cd-B was lower in Korea (ca. 1.6 ng/ml) and in China (1.3 ng/ml) than in Japan. This observation is in accordance with the fact that rice in Korea (16.1 ng/g dry weight) and China (7.6 ng/g) contained less cadmium than that in Japan (52.5 ng/g). A preliminary follow-up in 1989 suggests a decrease in Cd-B (by ca. 30%) among the Japanese population, probably due to a reduction in cadmium in rice (ca. 14%) and a decreased rice intake.     

Prevalence of type-specific human papillomavirus and pap results in Chinese women: a multi-center, population-based cross-sectional study

Purpose

To estimate the burden of human papillomavirus (HPV) infection among sexually active women in China.

Methods

We conducted a multi-center, population-based study between May 2006 and April 2007. A total of 4,215 women aged 17–54 years were surveyed from five geographical sites: Beijing, Shanghai, Shanxi, Henan, and Xinjiang. Direct endocervical exfoliated cells were collected from consenting participants for Sure Path liquid-based cytology (BD) and HPV testing. HPV testing was performed with Hybrid Capture II (Qiagen) with high-risk and low-risk probes, and Linear Array (Roche) was utilized for HPV genotyping.

Results

Approximately 11 % of the study population had a cytological abnormality (ASCUS or worse). HPV prevalence in the entire study population was 14.3 % (age-standardized to the world standard female population 14.5 %). The most prevalent types found were HPV16 (2.9 %), HPV52 (1.7 %), HPV58 (1.5 %), HPV33 (1 %), and HPV18 (0.8 %). Patterns of HPV prevalence differed by age, geographic region, and cytology findings. However, HPV16 was predominant among all grades of cytological abnormalities for all areas.

Conclusions

Although HPV18 appeared to be less frequent among population-based samples of China, given the high prevalence of HPV 16 and 18 in high-grade squamous intraepithelial lesion (HSIL) or worse pap abnormalities, prophylactic HPV16/18 vaccines should substantially reduce the burden of cervical cancer in China.     

Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study.

BACKGROUND: Few epidemiologic studies have examined the association between fertility drugs and breast cancer risk, and results have been contradicting. Using data from the largest cohort of infertile women to date, the aim of this study was to examine the effects of fertility drugs on breast cancer risk overall and according to histologic subtypes. METHOD: A cohort of 54,362 women with infertility problems referred to all Danish fertility clinics between 1963 and 1998 was established. A detailed data collection, including information of type and amount of treatment, was conducted. We used case-cohort techniques to calculate rate ratios (RR) of breast cancer associated with use of five groups of fertility drugs, after adjustment for parity status. RESULTS: Three hundred thirty-one invasive breast cancers were identified in the cohort during follow-up through 1998. Analyses within cohort showed no overall increased breast cancer risk after use of gonadotrophins, clomiphene, human chorionic gonadotrophin, or gonadotrophin-releasing hormone, whereas use of progesterone increased breast cancer risk (RR, 3.36; 95% confidence interval, 1.3-8.6). For all groups of fertility drugs, no relationships with number of cycles of use or years since first use of fertility drug were found. However, gonadotrophins may have a stronger effect on breast cancer risk among nulliparous women (RR, 1.69; 95% confidence interval, 1.03-2.77). Similar risk patterns were present for ductal, lobular, and tumors of other histologies, indicating identical etiologies. CONCLUSION: The results showed no strong association between breast cancer risk and use of fertility drugs. Follow-up is, however, needed to assess long-term breast cancer risk after use of progesterone and among nulliparous women exposed to gonadotrophins.     

Serum calcium and breast cancer risk: results from a prospective cohort study of 7,847 women

Experimental and epidemiological studies suggest that calcium-regulating hormones--parathyroid hormone (PTH) and vitamin D--may be associated with breast cancer risk. No prospective cohort study has investigated the association between pre-diagnostic calcium levels and subsequent risk of breast cancer. We have examined this in a cohort of 7,847 women where serum calcium levels and established risk factors for breast cancer had been assessed at baseline. During a mean follow-up of 17.8 years, 437 incident breast cancer cases were diagnosed. Incidence of breast cancer was calculated in different quartiles of serum calcium levels and a Cox's proportional hazards analysis was used to obtain corresponding relative risks (RR), with a 95% confidence interval (CI), adjusted for potential confounders. In premenopausal women, serum calcium levels were inversely associated with breast cancer risk in a dose-response manner. The adjusted RR (95% CI) of breast cancer was in the 2nd calcium quartile 0.91 (0.65-1.30), in the 3rd quartile 0.89 (0.60-1.31), and in the 4th quartile 0.56 (0.32-0.98), as compared to the 1st calcium quartile. In postmenopausal overweight women (BMI > 25), breast cancer risk was higher in calcium quartiles 2-4 as compared to the 1st quartile. Our findings may have implications for primary prevention of breast cancer and for the management of asymptomatic primary hyperparathyroidism.     

Biomonitoring on carcinogenic metals and oxidative DNA damage in a cross-sectional study.

Oxidative DNA damage is mediated by reactive oxygen species and is supposed to play an important role in various diseases including cancer. The endogenous amount of reactive oxygen species may be enhanced by the exposure to genotoxic metals. A cross-sectional study was conducted from 1993 to 1994 in an urban population in Germany to investigate the association between metal exposure and oxidative DNA damage. The cross-sectional sample of 824 participants was recruited from the registry of residents in Bremen, comprising about two-third males and one-third females with an average age of 61.1 years. A standardized questionnaire was used to obtain the occupational and smoking history. The incorporated dose of exposure to metals was assessed by biological monitoring. Chromium, cadmium, and nickel were measured in 593 urine samples. Lead was determined in blood samples of 227 participants. As a biomarker for oxidative DNA damage, 7,8-dihydro-8-oxoguanine has been analyzed in lymphocytes of 201 participants. Oxidative lesions were identified by single strand breaks induced by the bacterial formamidopyrimidine-DNA glycosylase (Fpg) in combination with the alkaline unwinding approach. The concentrations of metals indicate a low body load (median values: 1.0 microg nickel/l urine, 0.4 microg cadmium/l urine, and 46 microg lead/l blood; 83% of chromium measures were below the technical detection limit of 0.3 microg/l). The median level of Fpg-sensitive DNA lesions was 0.23 lesions/10(6) bp. A positive association between nickel and the rate of oxidative DNA lesions (Fpg-sensitive sites) was observed (odds ratio, 2.15; tertiles 1 versus 3, P < 0.05), which provides further evidence for the genotoxic effect of nickel in the general population.