Interaction between dietary acrylamide intake and genetic variants for estrogen receptor-positive breast cancer risk.

PURPOSE: The association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+ breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+ breast cancer etiology. METHODS: The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case-cohort analysis approach. Dietary acrylamide intake of subcohort members (n = 1449) and ER+ breast cancer cases (n = 844) was assessed with a food frequency questionnaire. We genotyped single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis, based on 20.3 years of follow-up. RESULTS: Unexpectedly, there was a statistically non-significant inverse association between acrylamide and ER+ breast cancer risk among all women but with no clear dose-response relationship, and no association among never smokers. Among the results for 57 SNPs and 2 gene deletions, rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion, and rs1052133 in hOGG1 showed a statistically significant interaction with acrylamide intake for ER+ breast cancer risk. CONCLUSIONS: This study did not provide evidence for a positive association between acrylamide intake and ER+ breast cancer risk. If anything, acrylamide was associated with a decreased ER+ breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that acrylamide may influence ER+ breast cancer risk through sex hormone pathways.

Prenatal particulate air pollution exposure and cord blood homocysteine in newborns: Results from the ENVIRONAGE birth cohort.

INTRODUCTION: Particulate air pollution is probably causally related to increased risk of cardiovascular disease. Plasma homocysteine is an established cardiovascular disease risk factor. Recent studies show that exposure to particulate air pollution is associated with plasma homocysteine levels in adults but no studies on the association between prenatal air pollution and neonatal homocysteine levels exist. METHODS: In 609 newborns of the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort, we investigated the association between prenatal particulate matter exposure with a diameter ≤ 2.5 µm (PM2.5) and cord plasma homocysteine levels, and in a subset (n = 490) we studied the interaction with 11 single nucleotide polymorphism (SNPs) in oxidative stress-related genes (CAT, COMT, GSTP1, SOD2, NQO1 and HFE), through multiple linear regression. PM2.5 levels were obtained using a high resolution spatial temporal interpolation method. Homocysteine levels were measured by the homocysteine enzymatic assay on a Roche/Hitachi cobas c system. SNPs were assessed on the Biotrove OpenArray SNP genotyping platform. RESULTS: In multivariable-adjusted models, cord plasma homocysteine levels were 8.1% higher (95% CI: 1.9 to 14.3%; p = 0.01) for each 5 µg/m³ increment in average PM2.5 exposure during the entire pregnancy. With regard to pregnancy trimesters, there was only an association in the 2nd trimester: 3.6% (95% CI: 0.9% to 6.4%; p = 0.01). The positive association between PM2.5 in and homocysteine was (borderline) statistically significantly modified by genetic variants in MnSOD (p interaction = 0.02), GSTP1 (p interaction = 0.07) and the sum score of the 3 studied SNPs in the CAT gene (p interaction=0.09), suggesting oxidative stress as an underlying mechanism of action. CONCLUSIONS: Exposure to particulate air pollution in utero is associated with higher cord blood homocysteine levels, possibly through generating oxidative stress. Increased air pollution-induced homocysteine levels in early life might predispose for cardiovascular and other diseases later in life.

The Role of Genetic Variants in the Association between Dietary Acrylamide and Advanced Prostate Cancer in the Netherlands Cohort Study on Diet and Cancer.

To investigate the association between dietary acrylanide and advanced prostate cancer, we examined acrylamide-gene interactions for advanced prostate cancer risk by using data from the Netherlands Cohort Study. Participants (n = 58,279 men) completed a baseline food frequency questionnaire (FFQ), from which daily acrylamide intake was calculated. At baseline, 2,411 men were randomly selected from the full cohort for case-cohort analysis. Fifty eight selected single nucleotide polymorphisms (SNPs) and two gene deletions in genes in acrylamide metabolism, DNA repair, sex steroid systems, and oxidative stress were analyzed. After 20.3 years of follow-up, 1,608 male subcohort members and 948 advanced prostate cancer cases were available for Cox analysis. Three SNPs showed a main association with advanced prostate cancer risk after multiple testing correction: catalase (CAT) rs511895, prostaglandin-endoperoxide synthase 2 (PTGS2) rs5275, and xeroderma pigmentosum group C (XPC) rs2228001. With respect to acrylamide-gene interactions, only rs1800566 in NAD(P)H quinone dehydrogenase 1 (NQO1) and rs2301241 in thioredoxin (TXN) showed a nominally statistically significant multiplicative interaction with acrylamide intake for advanced prostate cancer risk. After multiple testing corrections, none were statistically significant. In conclusion, no clear evidence was found for interaction between acrylamide intake and selected genetic variants for advanced prostate cancer risk.

Interactions between dietary acrylamide intake and genes for ovarian cancer risk.

Some epidemiological studies observed a positive association between dietary acrylamide intake and ovarian cancer risk but the causality needs to be substantiated. By analyzing gene-acrylamide interactions for ovarian cancer risk for the first time, we aimed to contribute to this. The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline in 1986, a random subcohort of 2589 women was sampled from the total cohort for a case cohort analysis approach. Dietary acrylamide intake of subcohort members and ovarian cancer cases (n = 252, based on 20.3 years of follow-up) was assessed with a food frequency questionnaire. We selected single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism and in genes involved in the possible mechanisms of acrylamide-induced carcinogenesis (effects on sex steroid systems, oxidative stress and DNA damage). Genotyping was done on DNA from toenails through Agena's MassARRAY iPLEX platform. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis. Among the results for 57 SNPs and 2 gene deletions, there were no statistically significant interactions between acrylamide and gene variants after adjustment for multiple testing. However, there were several nominally statistically significant interactions between acrylamide intake and SNPs in the HSD3B1/B2 gene cluster: (rs4659175 (p interaction = 0.04), rs10923823 (p interaction = 0.06) and its proxy rs7546652 (p interaction = 0.05), rs1047303 (p interaction = 0.005), and rs6428830 (p interaction = 0.05). Although in need of confirmation, results of this study suggest that acrylamide may cause ovarian cancer through effects on sex hormones.

Dietary acrylamide intake and the risk of colorectal cancer with specific mutations in KRAS and APC.

Acrylamide, a probable human carcinogen, is present in heat-treated carbohydrate-rich foods. Epidemiological studies have not shown a clear association between acrylamide intake and colorectal cancer (CRC) risk. This may be due to the molecular heterogeneity in colorectal tumors, which was not taken into consideration before. Since the acrylamide metabolite glycidamide induces specific DNA mutations in rodents, we investigated whether acrylamide is associated with CRC risk characterized by mutations in Kirsten-ras (KRAS) and adenomatous polyposis coli (APC); key genes in colorectal carcinogenesis. This case-cohort analysis, within the Netherlands Cohort Study on diet and cancer, was based on 7.3 years of follow-up. Acrylamide intake was assessed with a food frequency questionnaire. Mutation analysis of codons 1286-1520 in exon 15 in APC and codons 12 and 13 in exon 1 in KRAS was performed on tumor tissue of 733 cases. Hazard ratios (HR) were calculated using Cox proportional hazards analysis. Among men, acrylamide intake was statistically significantly associated with an increased risk of particularly tumors with an activating KRAS mutation {HR fourth versus first quartile: 2.12 [95% confidence interval (CI): 1.16-3.87], P trend: 0.01}. Among women, acrylamide intake was statistically significantly associated with a decreased risk of particularly tumors with a truncating APC mutation (fourth versus first quartile: 0.47 (95% CI: 0.23-0.94), P trend: 0.02), but only in the highest quartile of intake. This is the first study to show that acrylamide might be associated with CRC with specific somatic mutations, differentially in men and women. More research is needed to corroborate or refute these findings.

Gestational acrylamide exposure and biomarkers of fetal growth: Probing the mechanism underlying the association between acrylamide and reduced fetal growth.

INTRODUCTION: Four epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth. METHODS: In newborns of the ENVIRONAGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes. RESULTS: We observed lower cord plasma TSH (-10.2% [95% CI: -15.0, -4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of -2.9% (95% CI: -5.7, -0.1) and -3.9% (95% CI: -6.2, -1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (-11.2% [95% CI: -19.5, -0.1]). Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight. CONCLUSIONS: A decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study.

Detection of a Hemoglobin Adduct of the Food Contaminant Furfuryl Alcohol in Humans: Levels of N-((Furan-2-yl)methyl)-valine in Two Epidemiological Studies.

SCOPE: Furfuryl alcohol is a heat-induced food contaminant, classified as possibly carcinogenic to humans. The proximal carcinogen 2-sulfoxymethylfuran leads to adduct formation in DNA and proteins (e.g., N-((furan-2-yl)methyl)-Val (FFA-Val) in hemoglobin). METHODS AND RESULTS: This study analyzed human erythrocyte samples from two studies for the presence of FFA-Val: the Risks and Benefits of a Vegan Diet study (RBVD; 72 adults) and the ENVIRonmental influence ON early AGEing birth cohort study (ENVIRONAGE; 100 mother-newborn pairs). In the RBVD study, FFA-Val levels are lower in vegans compared to omnivores (median 13.0 vs 15.8 pmol g-1 hemoglobin, p = 0.008), and lower in non-smokers compared to smokers (median 14.1 vs 17.0 pmol g-1 hemoglobin, p = 0.003). In the birth cohort, FFA-Val levels are distinctly higher in maternal compared to newborn samples (median 15.2 vs 2.2 pmol g-1 hemoglobin, p < 0.001). CONCLUSIONS: FFA-Val, hitherto detected only in blood samples of mice, is quantifiable in all human samples, indicating a general exposure to furfuryl alcohol. The low adduct levels in blood samples from newborn children suggested that the placenta is a barrier to furfuryl alcohol. Dietary habits and tobacco smoking are two main influencing factors on the formation of FFA-Val, which may be of use as a biomarker of exposure to furfuryl alcohol.

Dietary acrylamide intake and estrogen and progesterone receptor-defined postmenopausal breast cancer risk.

Acrylamide, a potential human carcinogen, has been discovered in a variety of heat-treated carbohydrate-rich food products. Previously, dietary acrylamide intake was shown to be associated with endocrine-related cancers in humans. We assessed the association between dietary acrylamide intake and risk of postmenopausal breast cancer stratified by estrogen and progesterone receptor status. This study was embedded within the Netherlands Cohort Study on diet and cancer, which was initiated in 1986 enrolling 62,573 women aged 55-69 years at baseline. After 13.3 years of follow-up, 2225 incident breast cancer cases were ascertained, with hormone receptor status information for 43%. Cox proportional hazards analysis was applied to determine hazard ratios in quintiles of dietary acrylamide intake stratifying on estrogen receptor (ER) and progesterone receptor (PR) and smoking status. No association was observed for overall breast cancer or receptor-negative breast cancer risk, irrespective of smoking status. A statistically non-significantly increased risk of ER positive, PR positive and joint receptor-positive breast cancer was found in never-smoking women. The multivariable-adjusted hazard ratios were 1.31 (95% CI: 0.87-1.97, P (trend) = 0.26) for ER+, 1.47 (0.86-2.51, P (trend) = 0.14) for PR+, and 1.43 (0.83-2.46, P (trend) = 0.16) for ER+PR+, when comparing women in the highest quintile of acrylamide intake (median 36.8 microg/day) to women in the lowest (median 9.5 microg/day). This study showed some indications of a positive association between dietary acrylamide intake and receptor-positive breast cancer risk in postmenopausal never-smoking women. Further studies are needed to confirm or refute our observations.

The carcinogenicity of dietary acrylamide intake: a comparative discussion of epidemiological and experimental animal research.

Since 2002, it is known that the probable human carcinogen acrylamide is present in commonly consumed carbohydrate-rich foods, such as French fries and potato chips. In this review, the authors discuss the body of evidence on acrylamide carcinogenicity from both epidemiological and rodent studies, including variability, strengths and weaknesses, how both types of evidence relate, and possible reasons for discrepancies. In both rats and humans, increased incidences of various cancer types were observed. In rats, increased incidences of mammary gland, thyroid tumors and scrotal mesothelioma were observed in both studies that were performed. In humans, increased risks of ovarian and endometrial cancers, renal cell cancer, estrogen (and progesterone) receptor-positive breast cancer, and oral cavity cancer (the latter in non-smoking women) were observed. Some cancer types were found in both rats and humans, e.g., endometrial cancer (observed in one of the two rat studies), but there are also some inconsistencies. Interestingly, in humans, some indications for inverse associations were observed for lung and bladder cancers in women, and prostate and oro- and hypopharynx cancers in men. These latter observations indicate that genotoxicity may not be the only mechanism by which acrylamide causes cancer. The estimated risks based on the epidemiological studies for the sites for which a positive association was observed were considerably higher than those based on extrapolations from the rat studies. The observed pattern of increased risks in the rat and epidemiological studies and the decreased risks in the epidemiological studies suggests that acrylamide might influence hormonal systems, for which rodents may not be good models.

Levels of the hemoglobin adduct N-(2,3-Dihydroxypropyl)-valine in cord and maternal blood: Prenatal transfer of glycidol in the ENVIRONAGE birth cohort.

BACKGROUND: Glycidol, a probable human carcinogen, is a reactive chemical released in the gastrointestinal tract from glycidyl fatty acid esters, which are heat-induced dietary contaminants. OBJECTIVES: To investigate the prenatal transfer of glycidol, a specific hemoglobin adduct was measured as a biomarker for internal glycidol exposure in paired cord and maternal blood samples. METHODS: In 100 mother-newborn pairs from the Belgian ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort, we studied the correlation between levels of the glycidol-derived hemoglobin adduct N-(2,3-dihydroxypropyl)-valine (2,3-diHOPr-Val) in paired cord and maternal blood samples. The adduct levels were determined after cleavage with a modified Edman degradation by using ultra-high performance liquid chromatography-tandem mass spectrometry and an isotope-labeled reference standard. RESULTS: 2,3-DiHOPr-Val was detectable in all 100 maternal blood samples and in 96 cord blood samples (LOD =0.5 pmol 2,3-diHOPr-Val/g hemoglobin), with medians of 5.4 (range: 2.3-29.2) and 1.6 (range: LOD - 8.9) pmol/g hemoglobin), respectively. In blood samples of mothers who smoked during pregnancy and in the cord blood samples of their newborns (n = 6), the median 2,3-diHOPr-Val levels were 16.7 (range: 6.4-29.2) and 6.2 (range: LOD - 8.6) pmol/g hemoglobin, respectively. The median ratio of 2,3-diHOPr-Val levels of cord to maternal blood was 0.35 (range: 0.19-1.14) (n = 49). The Spearman correlation coefficient between 2,3-diHOPr-Val levels in cord and maternal blood samples was 0.63 (p < 0.001) among all mother-newborn pairs and 0.59 (p < 0.001) among mother-newborn pairs of non-smoking mothers. DISCUSSION: Maternal data confirm widespread exposure to glycidol, also in non-smokers. Neonatal levels indicate prenatal exposure to glycidol, due to an obviously relatively unhindered passive transfer through the placental barrier. Possible health effects of fetal (and postnatal) glycidol exposure in children may be addressed in epidemiological studies.

Germline polymorphisms in the Von Hippel-Lindau and Hypoxia-inducible factor 1-alpha genes, gene-environment and gene-gene interactions and renal cell cancer.

We investigated the relationship between germline single nucleotide polymorphisms (SNPs) in Von Hippel-Lindau (VHL) and Hypoxia-inducible factor 1-alpha (HIF1A), and their gene-environment and gene-gene interactions, and clear-cell RCC (ccRCC) risk. Furthermore, we assessed the relationship between VHL SNPs and VHL promoter methylation. Three VHL polymorphisms and one HIF1A polymorphism were genotyped in the Netherlands Cohort Study. In 1986, 120,852 participants aged 55-69 completed a self-administered questionnaire on diet and lifestyle and toenail clippings were collected. Toenail DNA was genotyped using the Sequenom MassARRAY platform. After 20.3 years, 3004 subcohort members and 406 RCC cases, of which 263 ccRCC cases, were eligible for multivariate case-cohort analyses. VHL_rs779805 was associated with RCC (Hazard Ratio (HR) 1.53; 95% Confidence Interval (CI) 1.07-2.17) and ccRCC risk (HR 1.88; 95% CI 1.25-2.81). No associations were found for other SNPs. Potential gene-environment interactions were found between alcohol consumption and selected SNPs. However, none remained statistically significant after multiple comparison correction. No gene-gene interactions were observed between VHL and HIF1A. VHL promoter methylation was not associated with VHL SNPs. VHL SNPs may increase (cc)RCC susceptibility. No associations were found between gene-environment and gene-gene interactions and (cc)RCC risk and between VHL promoter methylation and VHL SNPs.

Dietary acrylamide intake and the risk of head-neck and thyroid cancers: results from the Netherlands Cohort Study.

Acrylamide exposure has been related to an increased incidence of oral and thyroid tumors in animal studies. In 1986, 120,852 persons (aged 55-69 years) were included in the Netherlands Cohort Study. Dietary acrylamide intake was assessed with a food frequency questionnaire and was based on chemical analysis of all relevant Dutch foods. Hazard ratios were adjusted for smoking and other confounders. After 16.3 years of follow-up, there were 101, 83, 180, and 66 cases of oral cavity, oro-hypopharynx, larynx, and thyroid cancer, respectively. Average daily dietary acrylamide intake was 21.8 microg (standard deviation, 12.1). Dietary acrylamide intake was not associated with increased risk of oral cavity (hazard ratio (HR) per 10-microg intake/day = 0.90, 95% confidence interval (CI): 0.73, 1.10), oro-hypopharynx (HR = 0.74, 95% CI: 0.53, 1.03), larynx (HR = 1.05, 95% CI: 0.91, 1.21), or thyroid (HR = 1.03, 95% CI: 0.82, 1.27) cancer. For nonsmokers, hazard ratios were not increased either. Dietary acrylamide was statistically significantly associated with increased risk of oral cavity cancer in female nonsmokers, but case numbers were small. Dietary acrylamide intake was not positively associated with risk of head-neck and thyroid cancer, except with oral cavity cancer risk for female nonsmokers. A negative association for males was indicated.

Dietary acrylamide intake and brain cancer risk.

BACKGROUND: Acrylamide is a probable human carcinogen, which is present in several heat-treated foods. In epidemiologic studies, positive associations with endometrial, ovarian, and renal cell cancer risk have been observed. The incidence of central nervous system tumors was increased upon acrylamide administration in drinking water to rats. In the current study, the association between dietary acrylamide intake and human brain cancer risk was investigated for the first time. METHODS: In 1986, 120,852 persons (ages 55-69 years) were included in the Netherlands Cohort Study on diet and cancer. At baseline, a random subcohort of 5,000 participants was randomly selected from the total cohort for a case-cohort approach. Acrylamide intake was assessed with a food frequency questionnaire at baseline and based on acrylamide analyses in relevant Dutch foods. Hazard ratios (HR) were calculated using Cox proportional hazards analysis. Subgroup analyses were done for microscopically verified brain cancer, astrocytic gliomas, high-grade astrocytic gliomas, and never-smokers. The acrylamide risk estimates were adjusted for possible brain cancer risk factors. RESULTS: After 16.3 years of follow-up, 216 brain cancer cases were available for analysis. The multivariable-adjusted HR per 10 microg/d increment of acrylamide intake was 1.02 (95% confidence interval, 0.89-1.16). HRs were not significantly increased either when dietary acrylamide intake was analyzed as a categorical variable. Also, there was no association in the subgroups based on histology and smoking. CONCLUSION: In this prospective cohort study, acrylamide intake was not associated with brain cancer risk.

Prenatal arachidonic acid exposure and selected immune-related variables in childhood.

Arachidonic acid (AA) is considered essential in fetal development and some of its metabolites are thought to be important mediators of the immune responses. Therefore, we studied whether prenatal exposure to AA is associated with some immune-related clinical conditions and plasma markers in childhood. In 280 children aged 7 years, atopy, lung function and plasma inflammation markers were measured and their relationships with early AA exposure were studied by linear and logistic regression analyses. AA exposure was deduced from AA concentrations in plasma phospholipids of the mothers collected at several time points during pregnancy and at delivery, and in umbilical cord plasma and arterial and venous wall phospholipids. In unadjusted regression analyses, significant positive associations were observed between maternal AA concentrations at 16 and 32 weeks of pregnancy (proxies for fetal AA exposure) and peak expiratory flow decline after maximal physical exercise and plasma fibrinogen concentrations of their children, respectively. However, after correction for relevant covariables, only trends remained. A significant negative relationship was observed between AA concentrations in cord plasma (reflecting prenatal AA exposure) and the average daily amplitude of peak expiratory flow at rest, which lost significance after appropriate adjustment. Because of these few, weak and inconsistent relationships, a major impact of early-life exposure to AA on atopy, lung function and selected plasma inflammation markers of children at 7 years of age seems unlikely.

Dietary acrylamide intake is not associated with gastrointestinal cancer risk.

Acrylamide is a probable human carcinogen that was detected in several heat-treated foods, such as French fries and crisps, in 2002. Prospective studies are needed on acrylamide and human cancer risk. We prospectively investigated the association between acrylamide and gastrointestinal cancer risk. In 1986, 120,852 men and women (aged 55-69 y) were included in the Netherlands Cohort Study on diet and cancer. At baseline, a random subcohort of 5000 participants was selected for a case-cohort approach. Acrylamide intake was assessed with a FFQ at baseline and was based on acrylamide analyses in relevant Dutch foods. After 13.3 y of follow-up, 2190, 563, 349, and 216 cases of colorectal, gastric, pancreatic, and esophageal cancer, respectively, were available for analysis. The daily acrylamide intake of the subcohort was (mean +/- SD) 21.7 +/- 12.1 microg. A 10-microg/d increment of acrylamide intake was associated with multivariable-adjusted Cox proportional hazard rate ratios (HR) (95% CI) of 1.00 (0.96-1.06), 1.02 (0.94-1.10), 1.06 (0.96-1.17), and 0.96 (0.85-1.09) for colorectal, gastric, pancreatic, and esophageal cancer, respectively. For former or never-smokers, the corresponding HR were: 1.03 (0.94-1.12), 1.09 (0.98-1.22), 1.07 (0.93-1.24), and 0.92 (0.76-1.11). There were some significantly increased risks within subgroups stratified by obesity, nonoccupational physical activity, and age, factors that were a priori selected based on their capacity to modify cytochrome P4502E1 activity. Overall, acrylamide intake was not associated with colorectal, gastric, pancreatic, and esophageal cancer risk, but some subgroups deserve further attention.

A prospective cohort study on dietary acrylamide intake and the risk for cutaneous malignant melanoma.

Epidemiological studies have shown inconsistent associations between dietary acrylamide exposure and the risk for various malignancies. This is the first epidemiological study on the association between acrylamide intake and the risk for cutaneous malignant melanoma (CMM). A case-cohort analysis was carried out within the prospective Netherlands Cohort Study on diet and cancer. Acrylamide intake was estimated from a food frequency questionnaire combined with acrylamide data for Dutch foods. After 17.3 years of follow-up, 501 microscopically confirmed cases of CMM were identified. There was an increased risk for CMM when dietary acrylamide was modeled as a continuous variable [hazard ratio: 1.13 (95% confidence interval: 1.01-1.26)] per 10 µg increment among men but there was no clear linear trend over the quintiles (Ptrend=0.12). No associations were observed for women. Our study provides some indications that dietary acrylamide may increase the risk for CMM in men.

Toxicological assessment of ambient and traffic-related particulate matter: a review of recent studies.

Particulate air pollution (PM) is an important environmental health risk factor for many different diseases. This is indicated by numerous epidemiological studies on associations between PM exposure and occurrence of acute respiratory infections, lung cancer and chronic respiratory and cardiovascular diseases. The biological mechanisms behind these associations are not fully understood, but the results of in vitro toxicological research have shown that PM induces several types of adverse cellular effects, including cytotoxicity, mutagenicity, DNA damage and stimulation of proinflammatory cytokine production. Because traffic is an important source of PM emission, it seems obvious that traffic intensity has an important impact on both quantitative and qualitative aspects of ambient PM, including its chemical, physical and toxicological characteristics. In this review, the results are summarized of the most recent studies investigating physical and chemical characteristics of ambient and traffic-related PM in relation to its toxicological activity. This evaluation shows that, in general, the smaller PM size fractions (

Relationship between radical generation by urban ambient particulate matter and pulmonary function of school children.

The mechanisms by which particulate matter (PM) produces adverse effects on the respiratory system, such as pulmonary dysfunction in children, are largely unknown. However, oxidative stress is thought to play an important role. Various chemical compounds in ambient particulate matter, including transition metals and aromatic organic compounds, may contribute to adverse effects through intrinsic generation of reactive oxygen species (ROS). It was hypothesized that ROS generation by PM, as determined through electron spin resonance (ESR) spectroscopy, may be negatively associated with pulmonary function in school children. PM(2.5), PM(10), and total suspended particulates (TSP) were sampled at the playgrounds of six elementary schools in the city of Maastricht, the Netherlands. All children (8-13 yr) from the six schools were asked to undergo spirometry. Multivariate linear regression models were constructed to evaluate associations between oxygen radical formation by PM and lung function. The radical-generating capacity per microgram PM correlated negatively to forced expiratory volume in 1 s (FEV(1)) and forced expiratory flow at 50% (FEF(50%)) of forced vital capacity (FVC). The data indicate that chemical features that contribute to intrinsic generation of ROS may be relevant for PM risk assessment.

The influence of single nucleotide polymorphisms on the association between dietary acrylamide intake and endometrial cancer risk.

It is unclear whether the association between dietary acrylamide intake and endometrial cancer risk as observed in some epidemiological studies reflects a causal relationship. We aimed at clarifying the causality by analyzing acrylamide-gene interactions for endometrial cancer risk. The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline, a random subcohort of 2589 women was selected for a case cohort analysis approach. Acrylamide intake of subcohort members and endometrial cancer cases (n = 315) was assessed with a food frequency questionnaire. Single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair were assessed through a MassARRAY iPLEX Platform. Interaction between acrylamide and SNPs was assessed with Cox proportional hazards analysis, based on 11.3 years of follow-up. Among the results for 57 SNPs and 2 gene deletions, there were no statistically significant interactions after adjustment for multiple testing. However, there were nominally statistically significant interactions for SNPs in acrylamide-metabolizing enzymes: CYP2E1 (rs915906 and rs2480258) and the deletions of GSTM1 and GSTT1. Although in need of confirmation, the interactions between acrylamide intake and CYP2E1 SNPs contribute to the evidence for a causal relationship between acrylamide and endometrial cancer risk.