Acrylamide intake through diet and human cancer risk.

677 Background: Acrylamide, which has been classified as a probable human carcinogen, is formed during the processing and cooking of many commonly consumed, carbohydrate-rich foods. Accumulating evidence suggests that dietary intake of acrylamide intake is not associated with the risk of most cancers in humans. A meta-analysis of five epidemiological studies, however, found a suggestion of an increased risk of kidney cancer with higher acrylamide intakes. We investigated this association in two large, prospective cohorts. Methods: Acrylamide intake was calculated from food frequency questionnaires completed every four years in the Nurses’ Health Study (NHS; 1980-2014; n = 88,770) and the Health Professionals Follow-up Study (HPFS; 1986-2014; n = 47,802). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association with renal cell carcinoma (RCC), adjusting for known and suspected risk factors. Results: We documented 569 incident cases of RCC during follow-up, 337 in women and 232 in men. There was no association between cumulative average acrylamide intake and risk of RCC risk in women (HR for top versus bottom quartile of intake: 0.85; 95% CI: 0.62-1.18; p-value for linear trend across quartiles: 0.42) or men (HR: 1.09; 95% CI: 0.77-1.55; p-trend: 0.96). Baseline acrylamide intake was also unassociated with RCC risk. Acrylamide intake was not associated with risk of fatal RCC, risk among never-smokers, or risk of clear cell RCC. Intake of foods and food groups that are the major contributors to acrylamide intake – breads, baked goods, breakfast cereal, potatoes, and coffee – were likewise not associated with risk of total or fatal RCC in women or in men. Conclusions: Dietary acrylamide was not associated with the risk of RCC in two long-term, prospective cohorts of women and men with updated measures of dietary intakes. This analysis of renal cell carcinoma adds to the body of evidence that dietary acrylamide is not an important risk factor for cancer in humans.

Until about a decade ago, acrylamide was known only as a constituent of cigarette smoke and of products such as plastics and water treatment chemicals. But in 2002 Swedish scientists were surprised to find this human neurotoxicant and probable carcinogen in many heat-processed foods, especially starchy ones such as potato chips, crackers, and french fries. A flurry of research since then has yielded general advice about reducing formation of acrylamide and other heat-generated food toxicants in home cooking and a few recommendations for healthier eating. Now, in 2010, new acrylamide studies are giving a clearer picture of the extent of exposure to the chemical in the United States. These studies also raise additional questions about whether differences in metabolism make exposure more dangerous in certain populations, including children and people who are obese.

Background: Accumulating evidence suggests that dietary acrylamide intake is not associated with the risk of most cancers in humans. However, a meta-analysis of five epidemiologic studies found a suggestion of an increased risk of kidney cancer with higher dietary acrylamide intake.Methods: We investigated this association in the prospective Health Professionals Follow-up Study (HPFS; 1986-2014) and Nurses' Health Study (NHS; 1980-2014) cohorts. Dietary acrylamide intake was calculated on the basis of 46 acrylamide-containing foods reported on food frequency questionnaires completed every 4 years. The associations with the incidence of total and fatal renal cell carcinoma (RCC; n = 292/84 HPFS, n = 337/87 NHS) during more than two decades of follow-up were assessed using Cox proportional hazards models adjusting for potential confounders.Results: There was no association between cumulative average or baseline acrylamide intake and the risk of total or fatal RCC risk in men or women. Acrylamide intake was also not associated with RCC risk among never-smokers, nor was it associated with the risk of clear cell RCC.Conclusions: Dietary acrylamide was not associated with risk of RCC in two long-term prospective cohorts with repeated measures of dietary intake.Impact: This analysis of RCC adds to the body of evidence that dietary acrylamide is not an important cancer risk factor in humans. Cancer Epidemiol Biomarkers Prev; 27(8); 979-82. ©2018 AACR.

There has been considerable discourse about whether exposure to acrylamide in foods could increase the risk of human cancer. Acrylamide is classified as a probable human carcinogen, and animal studies have demonstrated an increased incidence of tumors in rats exposed to very high levels. Still, epidemiologic data of the effect of dietary acrylamide remain scant. We have undertaken the first prospective study of acrylamide in food and risk of colon and rectal cancers using prospective data from the Swedish Mammography Cohort. The cohort comprised 61,467 women at baseline between 1987 and 1990. Through 2003, the cohort contributed 823,072 person-years, and 504 cases of colon and 237 of rectal cancer occurred. Mean intake of acrylamide through diet was 24.6 mug/day (Q25-70 = 18.7-29.9). Coffee (44%), fried potato products (16%), crisp bread (15%) and other breads (12%) were the greatest contributors. After adjusting for potential confounders, there was no association between estimated acrylamide intake and colorectal cancer. Comparing extreme quintiles, the adjusted relative risks (95% CI; p for trend) were for colorectal cancer 0.9 (0.7-1.3; p = 0.80), colon cancer 0.9 (0.6-1.4; p = 0.83) and rectal cancer 1.0 (0.6-1.8; p = 0.77). Furthermore, intake of specific food items with elevated acrylamide (e.g., coffee, crisp bread and fried potato products) was not associated with cancer risk. In this large prospective study, we found no evidence that dietary intake of acrylamide is associated with cancers of the colon or rectum. Epidemiologic studies play an important role in assessing the possible health effects of acrylamide intake through food.

Acrylamide, a probable human carcinogen, can be formed in carbohydrate-rich foods cooked at high temperatures. Whether dietary acrylamide intake is associated with the risk of cancer in humans is uncertain. We aimed to assess the relation between dietary acrylamide intake and the incidence of epithelial ovarian cancer. The Swedish Mammography Cohort is a population-based prospective study of 61,057 Swedish women. Diet was assessed with a food-frequency questionnaire at baseline in 1987-1990 and again in 1997. During a mean follow-up of 17.5 years, we ascertained 368 incident cases of ovarian cancer. We observed no association between acrylamide intake and the risk of ovarian cancer. Compared with the lowest quartile of acrylamide intake (mean intake, 16.9 microg/day), the multivariable rate ratios for the highest quartile (mean intake, 32.5 microg/day) were 0.86 (95% confidence interval, 0.63-1.16) for total ovarian cancer and 1.05 (95% confidence interval, 0.68-1.63) for serous ovarian cancer (n=182 cases). The results from this prospective study provide no evidence that dietary acrylamide in amounts typically consumed by Swedish women is associated with the risk of ovarian cancer.

Acrylamide, a probable human carcinogen, is formed during high-temperature cooking of many commonly consumed foods. It is widespread; approximately 30% of calories consumed in the United States are from foods containing acrylamide. In animal studies, acrylamide causes mammary tumors, but it is unknown whether the level of acrylamide in foods affects human breast cancer risk. The authors studied the association between acrylamide intake and breast cancer risk among 90,628 premenopausal women in the Nurses' Health Study II. They calculated acrylamide intake from food frequency questionnaires in 1991, 1995, 1999, and 2003. From 1991 through 2005, they documented 1,179 cases of invasive breast cancer. They used Cox proportional hazards models to assess the association between acrylamide and breast cancer risk. The multivariable-adjusted relative risk of premenopausal breast cancer was 0.92 (95% confidence interval: 0.76, 1.11) for the highest versus the lowest quintile of acrylamide intake (P(trend) = 0.61). Results were similar regardless of smoking status or estrogen and progesterone receptor status of the tumors. The authors found no associations between intakes of foods high in acrylamide, including French fries, coffee, cereal, potato chips, potatoes, and baked goods, and breast cancer risk. They found no evidence that acrylamide intake, within the range of US diets, is associated with increased risk of premenopausal breast cancer.

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. 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. 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. In this prospective cohort study, acrylamide intake was not associated with brain cancer risk.

Dietary acrylamide intake and risk of colorectal cancer in a prospective cohort of men

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 55–69 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.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.

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. 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. 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). 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.

Dietary Acrylamide Intake Is Not Associated with Gastrointestinal Cancer Risk

To assess the association between dietary acrylamide intake and the risk of cancer among male smokers. The study consisted of 27,111 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry. During an average 10.2 year follow-up, 1,703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest versus the lowest quintile in the multivariable-adjusted model was 1.18 ((95% confidence interval (CI) 1.01-1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake. High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers.

Pelucchi et al.1 reported in a study including approximately 9,000 cancer cases and 20,000 controls no correlation between fried/baked potato intake and human cancer. Patients and controls were asked for the weekly frequency of consumption of fried/baked potatoes in a food frequency questionnaire. For statistical analysis, successive levels of consumption frequency of 0, 1 and > 1 portion/week were chosen, representing approximate tertiles among controls. None of the computed odds ratios for the highest tertile of intake was significantly different from the null value. This finding is not surprising since there is no evident reason why the consumption of fried potatoes as part of a balanced diet should increase cancer risk. However, we assume that the study of Pelucchi et al.1 was conducted to investigate if the consumption of foods rich in acrylamide may be important in relation to human cancer. Fried/baked potatoes are an important source of acrylamide,2 a substance formed during food processing and preparation of food3, 4 and probably carcinogenic to humans.5 It is therefore of major importance to undertake additional research to understand any potential relation of acrylamide intake via foods and cancer risk. Unfortunately, the study of Pelucchi et al.1 was not designed to answer this important question. In their analysis, the authors did not include some very important variables: intake of other foods important in regard to total daily acrylamide intake, e.g., coffee, biscuits and bread, and browning degree of the potato products. In a recent study (Swiss Federal Office of Public Health assessment of acrylamide intake by duplicate diet study; www.bag.admin.ch), we were able to show that coffee intake may be responsible for up to 36% of the daily acrylamide intake. Therefore, a heavy coffee drinker but restrictive on fried potatoes may have a significantly higher acrylamide intake than a person drinking no coffee but consuming 2 portions of French fries per week. As shown by Noti et al.,2 another important factor not included in the analysis is the degree of browning of the consumed potato products. French fries may have acrylamide concentrations of 20–1,000 μg/kg, depending on starting material (variety and storage) and method of preparation. The concentration of acrylamide strongly correlates with the color of the French fries: the darker the product, the higher its acrylamide content. In regard to daily acrylamide intake and cancer risk, 1 serving of very dark French fries may therefore be much more important than 5 servings of very light French fries. A few months ago, Mucci et al.6 were the first to report an absence of an association of acrylamide intake and cancer. However, the authors put their results into perspective by discussing possible limitations. Mucci et al.6 detected the same possible weaknesses that we criticize in the study by Pelucchi et al.1: lack of inclusion of other foods important in regard to total daily acrylamide intake, and large variation of the acrylamide content of included foods making intake calculations difficult. Both factors may lead to an incorrect estimation of acrylamide intake leading to an underestimation of a true association with cancer risk.6 The formation of acrylamide in foods is a complex issue with many important parameters. Therefore, epidemiologic studies have to be specifically designed taking this complexity into account. Mucci et al.6 proposed validation studies of acrylamide dose using existing food questionnaires leading to more reliable data of actual acrylamide intake. The conclusion of Pelucchi et al.1 that there is no association between an increased consumption of fried/baked potato products and cancer risk may therefore be very misleading—it all depends on the way of preparation of the potato products, on the intake of other foods rich in acrylamide and on the intake of foods carrying protective factors (e.g., vegetables and fruits). Reanalysis of already-assessed data is very tempting but in the case of acrylamide it may not lead to important answers. Acrylamide is a potential carcinogenic agent and it is important that industry, scientists and food authorities undertake joint efforts to reduce its concentration in our diet. However, we are in agreement with the authors that a moderate consumption of fried/baked potatoes may not be the most important risk to human health caused by food intake. Even more so if this moderate intake is on the background of a diet rich in vegetables and fruits. Yours sincerely, Michael U. Beer, Josef Schlatter, Vincent Dudler, Otmar Zoller

Background:Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk.Methods:Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method.Results:No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08–3.62; likelihood ratio test (LRT) P-value: 0.01, n=203).Conclusions:Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.

BackgroundAcrylamide, 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.MethodsThe 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.ResultsAfter 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.ConclusionWe 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.