Dietary Acrylamide Intake and the Risk of Lymphatic Malignancies: The Netherlands Cohort Study on Diet and Cancer

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

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

PurposeThe 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.MethodsThe prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69years. 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 20.3years of follow-up.ResultsUnexpectedly, 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.ConclusionsThis 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

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 20.3years 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

Potential role of gene-environment interactions in ion transport mechanisms in the etiology of renal cell cancer

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

Germline polymorphisms in the <i>Von Hippel-Lindau</i> and<i> Hypoxia-inducible</i> <i>factor 1-alpha</i> 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

Association between continuously modeled dietary acrylamide intake (per 10 µg/d) and the risk of follicular lymphoma and Waldenstrom macroglobulinemia and immunocytoma (WMI); the Netherlands Cohort Study on diet and cancer, 1986–2002.¹

<p>HR  =  hazard ratio; CI  =  confidence interval; py  =  person years. The number of cases and person-years are the numbers that resulted after listwise deletion of observations with missing values for the selected confounders. HRs were calculated by using Cox proportional hazards analysis.</p>1<p>Adjusted for age and sex.</p>2<p>Adjusted for age (years), sex, height (per 10 cm), education level, fiber (g/d), total fatty acids (g/d), trans unsaturated fatty acid (g/d), mono unsaturated fat (g/d), poly unsaturated fat (g/d), carbohydrates (g/d) and niacin (mg/d).</p>3<p>Insufficient number of cases for analyses with acrylamide as a continuous variable (N>20 requiered).</p

Acrylamide hazard ratios (and 95% CI) of multiple myeloma, diffuse large cell lymphoma and chronic lymphatic leukemia in <b>women</b> in strata of several covariables and <i>p</i> values for interaction: the Netherlands Cohort Study on diet and cancer, 1986–2002.

<p>Abbreviations: HR  =  hazard ratio; CI  =  confidence interval; AA/d  =  acrylamide per day, MM  =  multiple myeloma; CLL  =  chronic lymphatic leukemia; DLCL  =  diffuse large cell lymphoma.</p>1<p>Adjusted for age, sex, height (per 10 cm), education level, fiber (g/d), total fatty acids (g/d), trans unsaturated fatty acid (g/d), mono unsaturated fat (g/d), poly unsaturated fat (g/d), carbohydrates (g/d) and niacin (mg/d).</p>2<p>Insufficient number of cases.</p

Number of lymphatic malignancies in the Netherlands Cohort Study on diet and cancer (follow up: 16.3 years) according to the WHO classification.

<p>Abbreviations: ICD-O-3, International Classification of Diseases for Oncology, 3^rd edition; MALT, mucosa-associated lymphoid tissue; NOS, not otherwise specified.</p>1<p>N after exclusion of prevalent cases at baseline.</p>2<p>N cases available for analyses, after exclusion of missing and inconsistent data. Only case numbers for subtypes with sufficient number of cases are given (so subgroups do not add up to 1,233).</p