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Acrilamida , Neoplasias de la Mama , Dieta , Exposición Dietética , Femenino , Humanos , RiesgoRESUMEN
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.
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Espectrometría de Masas en Tándem , Valina , Animales , Estudios de Cohortes , Femenino , Furanos , Hemoglobinas/metabolismo , Humanos , Recién Nacido , Ratones , EmbarazoRESUMEN
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.
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Acrilamida , Placenta , Acrilamida/toxicidad , Biomarcadores , Femenino , Sangre Fetal , Desarrollo Fetal , Hemoglobinas , Humanos , Recién Nacido , EmbarazoRESUMEN
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.
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Compuestos Epoxi/metabolismo , Sangre Fetal/química , Hemoglobinas/metabolismo , Intercambio Materno-Fetal , Propanoles/metabolismo , Valina/análogos & derivados , Adulto , Biomarcadores/sangre , Cromatografía Líquida de Alta Presión , Estudios de Cohortes , Eritrocitos/química , Femenino , Hemoglobinas/análisis , Humanos , Recién Nacido , Embarazo , Fumar/sangre , Espectrometría de Masas en Tándem , Valina/sangreRESUMEN
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.
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Carcinoma de Células Renales/genética , Epistasis Genética , Interacción Gen-Ambiente , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Renales/genética , Polimorfismo de Nucleótido Simple , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Metilación de ADN/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas/genéticaRESUMEN
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.
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Acrilamida/administración & dosificación , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/metabolismo , Dieta/métodos , Polimorfismo de Nucleótido Simple/efectos de los fármacos , Acrilamida/efectos adversos , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Variación Genética/efectos de los fármacos , Humanos , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Receptores de Estrógenos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
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⯵m (PM2.5) and cord plasma homocysteine levels, and in a subset (nâ¯=â¯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%; pâ¯=â¯0.01) for each 5⯵g/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%; pâ¯=â¯0.01). The positive association between PM2.5 in and homocysteine was (borderline) statistically significantly modified by genetic variants in MnSOD (p interactionâ¯=â¯0.02), GSTP1 (p interactionâ¯=â¯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.
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Contaminantes Atmosféricos , Contaminación del Aire/estadística & datos numéricos , Homocisteína/sangre , Exposición Materna/estadística & datos numéricos , Adulto , Femenino , Sangre Fetal , Humanos , Recién Nacido , Material Particulado , EmbarazoRESUMEN
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.
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Acrilamida/efectos adversos , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Acrilamida/farmacocinética , Anciano , Catalasa/genética , Estudios de Cohortes , Ciclooxigenasa 2/genética , Proteínas de Unión al ADN/genética , Alimentos , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , NAD(P)H Deshidrogenasa (Quinona)/genética , Países Bajos , Neoplasias de la Próstata/etiologíaRESUMEN
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.
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Acrilamida/metabolismo , Acrilamida/toxicidad , Dieta , Neoplasias Ováricas/inducido químicamente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/epidemiología , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
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.
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Acrilamida/administración & dosificación , Acrilamida/efectos adversos , Conducta Alimentaria , Melanoma/inducido químicamente , Melanoma/epidemiología , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/epidemiología , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Neoplasias Cutáneas/diagnóstico , Melanoma Cutáneo MalignoRESUMEN
We investigated the ion transport mechanism (ITM) in renal cell cancer (RCC) etiology using gene-environment interactions between candidate single nucleotide polymorphisms (SNPs) and associated environmental factors, including dietary intakes of sodium, potassium and fluid, hypertension and diuretic medication. A literature-based selection of 13 SNPs in ten ITM genes were successfully genotyped in toenail DNA of 3,048 subcohort members and 419 RCC cases from the Netherlands Cohort Study. Diet and lifestyle were measured with baseline questionnaires. Cox regression analyses were conducted for main effects and gene-environment interactions. ADD1_rs4961 was significantly associated with RCC risk, showing a Hazard Ratio (HR) of 1.24 (95% confidence intervals (CI): 1.01-1.53) for the GT + TT (versus GG) genotype. Four of 65 tested gene-environment interactions were statistically significant. Three of these interactions clustered in SLC9A3_rs4957061, including the ones with fluid and potassium intake, and diuretic medication. For fluid intake, the RCC risk was significantly lower for high versus low intake in participants with the CC genotype (HR(95% CI): 0.47(0.26-0.86)), but not for the CT + TT genotype (P-interaction = 0.002). None of the main genetic effects and gene-environment interactions remained significant after adjustment for multiple testing. Data do not support the general hypothesis that the ITM is a disease mechanism in RCC etiology.
RESUMEN
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.
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Acrilamida/toxicidad , Dieta/efectos adversos , Neoplasias Endometriales/etiología , Neoplasias Endometriales/genética , Polimorfismo de Nucleótido Simple , Acrilamida/administración & dosificación , Acrilamida/metabolismo , Anciano , Carcinógenos/administración & dosificación , Carcinógenos/metabolismo , Carcinógenos/toxicidad , Estudios de Cohortes , Citocromo P-450 CYP2E1/genética , Neoplasias Endometriales/enzimología , Femenino , Eliminación de Gen , Estudios de Asociación Genética , Glutatión Transferasa/genética , Humanos , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Nails contain genomic DNA that can be used for genetic analyses, which is attractive for large epidemiologic studies that have collected or are planning to collect nail clippings. Study participants will more readily participate in a study when asked to provide nail samples than when asked to provide a blood sample. In addition, nails are easy and cheap to obtain and store compared with other tissues. METHODS: We describe our findings on toenail DNA in terms of yield, quality, genotyping a limited set of SNPs with the Sequenom MassARRAY iPLEX platform and high-density genotyping with the Illumina HumanCytoSNP_FFPE-12 DNA array (>262,000 markers). We discuss our findings together with other studies on nail DNA and we compare nails and other frequently used tissue samples as DNA sources. RESULTS: Although nail DNA is considerably degraded, genotyping a limited set of SNPs with the Sequenom MassARRAY iPLEX platform (average sample call rate, 97.1%) and high-density genotyping with the Illumina HumanCytoSNP_FFPE chip (average sample call rate, 93.8%) were successful. CONCLUSIONS: Nails are a suitable source of DNA for genotyping in large-scale epidemiologic studies, provided that methods are used that are suitable or optimized for degraded DNA. For genotyping through (next generation) sequencing where DNA degradation is less of an issue, nails may be an even more attractive DNA source, because it surpasses other sources in terms of ease and costs of obtaining and storing the samples. IMPACT: It is worthwhile to consider nails as a source of DNA for genotyping in large-scale epidemiologic studies. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology." Cancer Epidemiol Biomarkers Prev; 23(12); 2703-12. ©2014 AACR.
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ADN/genética , Estudios Epidemiológicos , Uñas/metabolismo , Anciano , Estudios de Cohortes , Femenino , Pruebas Genéticas , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Uñas/citología , Estudios ProspectivosRESUMEN
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.
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Acrilamida/efectos adversos , Neoplasias Colorrectales/etiología , Dieta , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Anciano , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas p21(ras) , Riesgo , Factores SexualesRESUMEN
BACKGROUND: Acrylamide, a probable human carcinogen, is present in many everyday foods. Since the finding of its presence in foods in 2002, epidemiological studies have found some suggestive associations between dietary acrylamide exposure and the risk of various cancers. The aim of this prospective study is to investigate for the first time the association between dietary acrylamide intake and the risk of several histological subtypes of lymphatic malignancies. METHODS: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women followed-up since September 1986. The number of person years at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n =5,000). Acrylamide intake was estimated from a food frequency questionnaire combined with acrylamide data for Dutch foods. Hazard ratios (HRs) were calculated for acrylamide intake as a continuous variable as well as in categories (quintiles and tertiles), for men and women separately and for never-smokers, using multivariable-adjusted Cox proportional hazards models. RESULTS: After 16.3 years of follow-up, 1,233 microscopically confirmed cases of lymphatic malignancies were available for multivariable-adjusted analysis. For multiple myeloma and follicular lymphoma, HRs for men were 1.14 (95% CI: 1.01, 1.27) and 1.28 (95% CI: 1.03, 1.61) per 10 µg acrylamide/day increment, respectively. For never-smoking men, the HR for multiple myeloma was 1.98 (95% CI: 1.38, 2.85). No associations were observed for women. CONCLUSION: We found indications that acrylamide may increase the risk of multiple myeloma and follicular lymphoma in men. This is the first epidemiological study to investigate the association between dietary acrylamide intake and the risk of lymphatic malignancies, and more research into these observed associations is warranted.
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Acrilamida/efectos adversos , Dieta , Trastornos Linfoproliferativos/epidemiología , Anciano , Estudios de Cohortes , Femenino , Humanos , Trastornos Linfoproliferativos/etiología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiologíaRESUMEN
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.
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Acrilamida/toxicidad , Carcinógenos/toxicidad , Neoplasias/etiología , Acrilamida/farmacocinética , Administración Oral , Animales , Animales de Laboratorio , Pruebas de Carcinogenicidad , Carcinógenos/farmacocinética , Dieta , Encuestas sobre Dietas , Modelos Animales de Enfermedad , Conducta Alimentaria , Femenino , Humanos , Masculino , Neoplasias/epidemiología , Sistema de Registros , Medición de Riesgo , Factores de RiesgoRESUMEN
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.
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Acrilamidas/efectos adversos , Neoplasias de la Mama/epidemiología , Carcinógenos Ambientales/efectos adversos , Dieta , Estrógenos , Neoplasias Hormono-Dependientes/epidemiología , Posmenopausia , Progesterona , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Acrilamidas/análisis , Anciano , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/química , Carcinógenos Ambientales/análisis , Estudios de Cohortes , Conducta Alimentaria , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/inducido químicamente , Neoplasias Hormono-Dependientes/química , Países Bajos/epidemiología , Modelos de Riesgos Proporcionales , Riesgo , Fumar/epidemiologíaRESUMEN
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.
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Acrilamidas/efectos adversos , Aditivos Alimentarios/efectos adversos , Neoplasias de Cabeza y Cuello/etiología , Neoplasias de la Tiroides/etiología , Acrilamidas/análisis , Anciano , Estudios de Casos y Controles , Femenino , Aditivos Alimentarios/análisis , Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos/epidemiología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Distribución por Sexo , Fumar/epidemiología , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/prevención & controlRESUMEN
BACKGROUND: Acrylamide is a probable human carcinogen that is present in several heat-treated foods. In epidemiological studies, positive associations between dietary acrylamide intake and the risks of endometrial, ovarian, estrogen receptor-positive breast, and renal cell cancers have been observed. The association between dietary acrylamide intake and lung cancer risk is not known. METHODS: We conducted a case-cohort study among 58 279 men and 62 573 women (aged 55-69 years) in the Netherlands Cohort Study on Diet and Cancer. Intakes of acrylamide-containing foods and risk factors for cancer were assessed with a self-administered questionnaire at baseline in 1986 and combined with acrylamide levels in relevant Dutch foods to assess total dietary acrylamide intake. The number of person-years at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n = 5000). Incident lung cancer cases in the total cohort were detected by computerized record linkages to the Netherlands Cancer Registry and the Netherlands Pathology Registry. Hazard ratios and 95% confidence intervals (CIs) for the risk of lung cancer associated with acrylamide intakes were estimated using Cox proportional hazards models that controlled for smoking (status, quantity, and duration) and other lung cancer risk factors. All statistical tests were two-sided. RESULTS: After 13.3 years of follow-up (September 17, 1986 up to January 1, 2000) there were 2649 cases of primary, histologically verified lung cancer (International Classification of Diseases for Oncology-3 code: C34) when cases with prevalent cancer at baseline (other than skin cancer) were excluded. The multivariable-adjusted hazard ratio of lung cancer for a 10-microg/d increment of acrylamide intake was 1.03 (95% CI = 0.96 to 1.11) for men and 0.82 (95% CI = 0.69 to 0.96) for women. The hazard ratio of lung cancer for the highest (median intake [microg/d]: men = 37.6 and women = 36.8) vs the lowest (median intake [microg/d]: men = 10.8 and women = 9.5) quintile of acrylamide intake was 1.03 (95% CI = 0.77 to 1.39, P(trend) = .85) for men and 0.45 (95% CI = 0.27 to 0.76, P(trend) = .01) for women. The inverse association in women was strongest for adenocarcinoma (hazard ratio for highest vs lowest tertile of intake = 0.40, 95% CI = 0.21 to 0.78; P(trend) = .01). CONCLUSIONS: Acrylamide intake was not associated with lung cancer risk in men but was inversely associated in women, most strongly for adenocarcinoma. This finding suggests that acrylamide is involved in human carcinogenesis through pathways other than genotoxicity.
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Acrilamida/administración & dosificación , Acrilamida/efectos adversos , Carcinógenos/administración & dosificación , Conducta Alimentaria , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiología , Adenocarcinoma/inducido químicamente , Adenocarcinoma/epidemiología , Anciano , Estudios de Casos y Controles , Encuestas sobre Dietas , Neoplasias Endometriales/inducido químicamente , Neoplasias Endometriales/epidemiología , Femenino , Estudios de Seguimiento , Hormonas Esteroides Gonadales/sangre , Humanos , Neoplasias Pulmonares/sangre , Masculino , Registro Médico Coordinado , Persona de Mediana Edad , Análisis Multivariante , Países Bajos/epidemiología , Oportunidad Relativa , Neoplasias Ováricas/inducido químicamente , Neoplasias Ováricas/epidemiología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Fumar/efectos adversosRESUMEN
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.