| 1. |
- Akesson, Agneta, et al.
(author)
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Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence : A population-based prospective cohort study
- 2008
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In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 68:15, s. 6435-6441
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Journal article (peer-reviewed)abstract
- Environmental pollutants mimicking the effects of estrogen are suggested to contribute to the high incidence of hormone-related cancers, but supporting data are sparse. A potent estrogen-like activity of the pollutant cadmium, mediated via the estrogen receptor-alpha, has been shown in vivo. We prospectively examined the association between cadmium exposure and incidence of postmenopausal endometrial cancer. The Swedish Mammography Cohort is a population-based prospective cohort of 30,210 postmenopausal women free of cancer diagnose at baseline (1987) and who completed a food frequency questionnaire at baseline and in 1997. We estimated the dietary cadmium intake based on the questionnaire data and the cadmium content in all foods. During 16.0 years (484,274 person-years) of follow-up between the baseline and mid-2006, we ascertained 378 incident cases of endometrioid adenocarcinoma. The average estimated dietary cadmium intake was 15 mu g/day (80% from cereals and vegetables). Cadmium intake was statistically significantly associated with increased risk of endometrial cancer in all women; the multivariate relative risk (1111) was 1.39 [95% confidence interval (CI), 1.04-1.86; P-trend = 0.019], comparing highest tertile versus lowest. Among never-smoking women with body mass index (BMI) of <27 kg/m(2), the RR was 1.86 (95% CI, 1.13-3.08; P-trend = 0.009). We observed a 2.9-fold increased risk (95% CI, 1.05-7.79) associated with long-term cadmium intake consistently above the median at both baseline 1987 and in 1997 in never-smoking women with low bioavailable estrogen (BMI of <27 kg/m(2) and nonusers of postmenopausal hormones). Our results support the hypothesis that cadmium may exert estrogenic effects and thereby increase the risk of hormone-related cancers.
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| 2. |
- Ali, Imran, et al.
(author)
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Exposure to polychlorinated biphenyls and prostate cancer : population-based prospective cohort and experimental studies
- 2016
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In: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 37:12, s. 1144-1151
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Journal article (peer-reviewed)abstract
- Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer.
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| 3. |
- Amzal, Billy, et al.
(author)
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Population Toxicokinetic Modeling of Cadmium for Health Risk Assessment
- 2009
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In: Journal of Environmental Health Perspectives. - : US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE. - 0091-6765 .- 1552-9924. ; 117:8, s. 1293-1301
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cadmium is a widespread environmental pollutant that has been shown to exert toxic effects on kidney and bones in humans after long-term exposure. Urinary cadmium concentration is considered a good biomarker of accumulated cadmium in kidney, and diet is the main source of cadmium among nonsmokers. OBJECTIVE: Modeling the link between urinary cadmium and dietary cadmium intake is a key step in the risk assessment of long-term cadmium exposure. There is, however, little knowledge on how this link may vary, especially for susceptible population strata. METHODS: We used a large population-based study (the Swedish Mammography Cohort), with repeated dietary intake data covering a period of 20 years, to compare estimated dietary cadmium intake with urinary cadmium concentrations on an individual basis. A modified version of the Nordberg-Kjellstrom model and a one-compartment model were evaluated in terms of their predictions of urinary cadmium. We integrated the models and quantified the between-person variability of cadmium half-life in the population. Finally, sensitivity analyses and Monte Carlo simulations were performed to illustrate how the latter model could serve as a robust tool supporting the risk assessment of cadmium in humans. RESULTS: The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability. We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability. CONCLUSIONS: Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.
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| 4. |
- Bergkvist, Charlotte, et al.
(author)
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Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction in men - A population-based prospective cohort study
- 2016
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In: Environment International. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0160-4120 .- 1873-6750. ; 88, s. 9-14
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Journal article (peer-reviewed)abstract
- Background: Major food contaminants such as polychlorinated biphenyls (PCBs) are proposed to play a role in the etiology of cardiovascular disease (CVD), but to date the impact of PCBs on cardiovascular health need to be explored. Methods and results: We assessed the association between validated food frequency questionnaire-based estimates of dietary PCB exposure and risk of myocardial infarction, ascertained through register-linkage, among 36,759 men from the population-based Swedish Cohort of Men, free of cardiovascular disease, diabetes and cancer at baseline (1997). Relative risks were adjusted for known cardiovascular risk factors, long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) and methyl mercury exposure. During 12 years of follow-up (433,243 person-years), we ascertained 3005 incident cases of myocardial infarction (654 fatal). Compared with the lowest quintile of dietary PCB exposure (median 113 ng/day), men in the highest quintile (median 436 ng/day) had multivariable-adjusted relative risks of 1.74 (95% confidence interval [CI], 1.30-2.33; p-trend < 0.001) for total and 1.97 (95% C11.42-2.75; p-trend < 0.001) for non-fatal myocardial infarction. In mutually adjusted models, dietary PCB exposure was associated with an increased risk of myocardial infarction, while the intake of long-chain omega-3 fish fatty acids was associated with a decreased risk. We also observed an effect modification by adiposity on the association between of dietary PCB exposure and myocardial infarction, with higher risk among lean men (p value for interaction = 0.03). Conclusions: Exposure to PCBs via diet was associated with increased risk of myocardial infarction in men. (C) 2015 Elsevier Ltd. All rights reserved.
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| 5. |
- Engstrom, Annette, et al.
(author)
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Associations between dietary cadmium exposure and bone mineral density and risk of osteoporosis and fractures among women
- 2012
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In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 50:6, s. 1372-1378
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Journal article (peer-reviewed)abstract
- Osteoporosis and its main health outcome, fragility fractures, are large and escalating public health problems. Cadmium, a widespread food contaminant, is a proposed risk factor; still the association between estimated dietary cadmium exposure and bone mineral density (BMD) has never been assessed. Within a sub-cohort of the Swedish Mammography Cohort, we assessed dietary cadmium exposure based on a food frequency questionnaire (1997) and urinary cadmium (2004-2008) in relation to total-body BMD and risk of osteoporosis and fractures (1997-2009) among 2676 women (aged 56-69 years). In multivariable-adjusted linear regression, dietary cadmium was inversely associated with BMD at the total body and lumbar spine. After further adjustment for dietary factors important for bone health and cadmium bioavailability-calcium, magnesium, iron and fiber, the associations became more pronounced. A 32% increased risk of osteoporosis (95% Cl: 2-71%) and 31% increased risk for any first incident fracture (95% Cl; 2-69%) were observed comparing high dietary cadmium exposure (>= 13 mu g/day, median) with lower exposures (<13 mu g/day). By combining high dietary with high urinary cadmium (>= 0.50 mu g/g creatinine), odds ratios among never-smokers were 2.65 (95% Cl: 1.43-4.91) for osteoporosis and 3.05 (95% Cl; 1.66-5.59) for fractures. In conclusion, even low-level cadmium exposure from food is associated with low BMD and an increased risk of osteoporosis and fractures. The partial masking of the associations by essential nutrients indicates important interplay between dietary factors and contaminants present in food. In separate analyses, dietary and urinary cadmium underestimated the association with bone effects.
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| 6. |
- Julin, Bettina, et al.
(author)
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Association between sociodemographic determinants and health outcomes in individuals with type 2 diabetes in Sweden
- 2018
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In: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 34:4, s. -9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Concurrent multifactorial treatment is needed to reduce consequent risks of diabetes, yet most studies investigating the relationship between sociodemographic factors and health outcomes have focused on only one risk factor at a time. Swedish health care is mainly tax-funded, thus providing an environment that should facilitate equal health outcomes in patients, independent of background, socioeconomic status or health profile. This study aimed at investigating the association between several sociodemographic factors and diabetes-related health outcomes represented by HbA1c , systolic blood pressure, LDL cholesterol, predicted 5-year risk of cardiovascular disease as well as statin use.METHODS: This large retrospective registry-study was based on patient-level data from individuals diagnosed with type 2 diabetes mellitus during 2010-2011 (n = 416,228) in any of seven Swedish regions (~65% of the Swedish population). Health equity in diabetes care was analyzed through multivariate regression analyses on intermediary outcomes (HbA1c , systolic blood pressure, LDL), predicted 5-year risk of cardiovascular disease and process (i.e. statin use) after one-year follow-up, adjusting for several sociodemographic factors.RESULTS: We observed differences in intermediary risk measures, predicted 5-year risk of cardiovascular disease as well as process dependent on place of birth, sex, age, education and social setting, despite Sweden's articulated vision of equal health care.CONCLUSIONS: Diabetes patients' health was associated with sociodemographic prerequisites. In addition to demographics (age, sex) and disease history; educational level, marital status and region of birth are important factors to consider when benchmarking health outcomes, e.g. average HbA1c level, between organizational units or between different administrative regions.
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| 7. |
- Julin, Bettina, et al.
(author)
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Cadmium in Diet and Risk of Cardiovascular Disease in Women
- 2013
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In: Epidemiology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1044-3983 .- 1531-5487. ; 24:6, s. 880-885
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Journal article (peer-reviewed)abstract
- Background: The toxic metal cadmium is suggested to increase the risk of cardiovascular disease, but only one incidence study has explored this association. We evaluated the association between quartiles of food frequency questionnaire-based estimates of cadmium exposure from food (the predominant source of exposure to the metal) and incident cardiovascular disease and its subtypes. Methods: From the population-based Swedish Mammography cohort, 33,333 women were followed prospectively from baseline (1997) through 2010. We estimated relative risks (RRs) with 95% confidence intervals (CIs) using Cox proportional hazard models. Results: During 12 years of follow-up, we identified 3155 incident cases of total cardiovascular disease (1322 cases of myocardial infarction and 1833 cases of total stroke [1485 ischemic and 208 hemorrhagic stroke]). Dietary cadmium exposure was not associated with risk of total cardiovascular disease, myocardial infarction, or total stroke or its subtypes. For total cardiovascular disease, the multivariable-adjusted RR comparing the highest quartile of cadmium exposure with the lowest was 0.96 (95% CI = 0.85-1.09). The corresponding RRs were 1.07 (0.88-1.29) for myocardial infarction, 0.90 (0.76-1.05) for total stroke, 0.89 (0.74-1.06) for ischemic stroke, and 1.11 (0.68-1.80) for hemorrhagic stroke. Conclusions: Our study lends no support to an overall association between low-level exposure to cadmium via food and incident cardiovascular disease.
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| 8. |
- Julin, Bettina, et al.
(author)
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Dietary Cadmium Exposure and Risk of Postmenopausal Breast Cancer : A Population-Based Prospective Cohort Study
- 2012
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 72:6, s. 1459-1466
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Journal article (peer-reviewed)abstract
- 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, 125; 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 textile 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.
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| 9. |
- Julin, Bettina
(author)
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Dietary cadmium exposure and the risk of hormone-related cancers
- 2012
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Doctoral thesis (other academic/artistic)abstract
- The toxic metal cadmium has been widely dispersed into the environment mainly through anthropogenic activities. Even in industrially non-polluted areas, farmland and consequently foods are, to a varying degree, contaminated. Food is the main source of exposure besides tobacco smoking. Cadmium accumulates in the body, particularly in the kidney where it may cause renal tubular damage. Recently, cadmium was discovered to possess endocrine disrupting properties, mainly mimicking the in vivo- effects of estrogen. The metal is classified as a human carcinogen by the International Agency for Research on Cancer based on lung cancer studies of occupational inhalation. It is, however, not clear whether cadmium exposure via the diet may cause cancer. Possible health consequences related to estrogenic effects such as increased risk of hormone-related cancers are virtually unexplored. The aims of this thesis were to: 1) estimate the dietary exposure to cadmium, 2) estimate cadmium’s toxicokinetic variability using a population model and to establish the link between urinary cadmium concentrations (a biomarker of accumulated kidney cadmium) and the corresponding long-term dietary exposure to cadmium in the population, 3) evaluate the comparability between food frequency questionnaire (FFQ)-based estimates of dietary cadmium exposure and urinary cadmium concentrations and 4) prospectively assess the association between dietary cadmium exposure and incidence of hormone-related cancers (endometrial, breast, ovarian and prostate cancers) in two population-based cohorts consisting of around 60 000 Swedish women and 40 000 men. The main sources of dietary cadmium exposure (~80%) in both women and men were bread and other cereals, potatoes, root vegetables, and other vegetables. A one- compartment toxicokinetic model provided similar predictions of individual urinary cadmium concentrations as a more complex toxicokinetic model. We estimated the cadmium half-life to be about 11.6 years with 25% between-person variability in the population. The Pearson correlation between FFQ-based estimates of dietary cadmium exposure and urinary cadmium concentration was 0.2 and the observed sensitivity and specificity was 58% and 51%, respectively. Estimated dietary cadmium exposure was associated with a statistically significant increased risk of cancer of the endometrium, breast, and prostate (39%, 21% and 13% respectively) – but not with ovarian cancer – comparing the highest tertile of cadmium with the lowest. The risk estimates were higher in lean and normal weight women and men: we observed statistically significant increased risks of 52%, 27% and 49% for endometrial cancer, overall breast cancer and localized prostate cancer, respectively. Never-smoking women with lower endogenous (normal body mass index) and exogenous estrogens (no postmenopausal hormone use) and with a consistently high dietary exposure to cadmium assessed twice, 10 years apart, had a 2.9-fold increased risk of endometrial cancer, which may indicate an estrogenic effect. The highest risk of breast cancer (60% increase) was observed for diets high in cadmium and low in whole grain and vegetables, as compared to diets low in cadmium and high in whole grain and vegetables. Taken together these results indicate that dietary cadmium exposure may play a role in the development of hormone-related cancers.
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| 10. |
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