Biomarkers of Acrylamide Exposure and Risk of Endometrial and Ovarian Cancers: A Molecular Epidemiologic Study in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

  • Topic: Combination of cancers
  • Institution: IDIBELL
  • Country: Spain
  • Status: Completed

Scientific abstract

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Background:

Acrylamide (AA) is an organic chemical that has several important uses in industry including as a flocculant in water public water supplies, in paper manufacturing, textiles, and mining, as a grouting agent, as an additive in cosmetics, and in biomedical research. In 1994, AA was classified by the International Agency for Research on Cancer as ‘probably carcinogenic’ to humans. In 2002, AA was discovered in some starchy foods that are cooked at high temperature (e.g., potato crisps and chips, biscuits, breads and breakfast cereals). AA also is a common component of cigarette smoke. From 2006-2010, epidemiologic studies began to examine and report on the possible association between dietary AA intake and risk of human cancer, including endometrial cancers (EC) and epithelial ovarian cancers (EOC), some of which suggested possible associations.

Aims and objectives:

Our aims were to evaluate the association between questionnaire-based dietary AA intake and risk for EC and EOC, to measure biomarkers of AA in pre-diagnostic red blood cells and evaluate exposure determinants of biomarker levels in our population, and finally, to examine associations between pre-diagnostic AA biomarkers levels and EC and EOC risk in European women.

How the study was carried out:

We conducted a series of prospective studies of AA exposure and risk of developing EC and EOC in European women. The study population for this project was 368,010 women from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort based in 23 centers from 10 western European countries. Dietary AA intake in the full EPIC cohort was estimated using the most recent European acrylamide-content food databases, country-specific food intake questionnaires, and 24-hour dietary recalls at baseline. Full cohort analyses of EC and EOC risk included 1,382 EC and 1,191 EOC cases. Full cohort analyses of AA intake and EC or EOC risk were conducted in all women and in subgroups (by smoking status, alcohol intake, body weight, oral contraceptive use, and tumour histology) using Cox proportional hazards models. Pre-diagnostic biomarkers of AA and its epoxide metabolite, glycidamide (GA), were measured as hemoglobin adducts using HPLC-MS/MS (high performance liquid chromotography / tandem mass spectrometry) in stored red blood cells collected at baseline 5-10 years before diagnosis. Biomarkers were measured in 383 EC cases (n=171 Type-1) and 385 matched controls, and in 334 EOC cases and 417 matched controls. For the nested case-control studies, logistic regression analyses were conducted in all women and in subgroups by alcohol consumption, body weight, oral contraceptive use, and tumour histology.

Key findings and conclusions:

In general, the results of the dietary AA intake analyses showed no associations between increasing categories of AA intake and EOC and EC risk, except for a possible association between higher AA intake and Type-1 EC in women who were non-smokers and non-users of oral contraceptives (HRQ5vQ1=1.97, 95% CI=1.08-3.62). When we examined the relation between dietary and demographic factors and biomarker levels of AA and GA - results showed that the main food group determinants of AA and GA levels were biscuits, crackers and cakes (in agreement with previous studies); and that alcohol intake and body mass index were important determinants of the ratio of GA to AA – an indicator of endogenous AA metabolism. The nested case-control study of AA and GA biomarker levels and EC (383 cases, 171 Type-1) did not find any support for associations between AA or GA and EC risk (neither overall, nor Type1) or by subgroups. The nested case-control study of AA and GA biomarkers and EOC (334 cases) risk also conducted in non-smoking post-menopausal women found some weak evidence for associations between higher biomarker levels and EOC risk, but none of the associations were statistically significant, and there was no  evidence for a dose-response relation. In conclusion, our results in women from western Europe did not provide convincing support for the hypothesis that higher AA and GA exposures are associated with higher risks for endometrial and epithelial  ovarian  cancers.  Additional studies of AA biomarkers and EOC risk should be conducted to rule out any possibility of increased risk with higher AA levels.

Plain language abstract

Background:

Acrylamide (AA) is an organic chemical that has several important uses in industry including to filter public water supplies, in paper manufacturing, textiles, and mining, as a grouting agent, as an additive in cosmetics, and in biomedical research. In 1994, AA was classified by the International Agency for Research on Cancer as ‘probably carcinogenic’ to humans. In 2002, AA was discovered in some starchy foods that are cooked at high temperature (e.g., potato crisps and chips, biscuits, breads and breakfast cereals). AA also is a common component of cigarette smoke. From 2006-2010, epidemiologic studies began to examine and report on the possible association between dietary AA intake and risk of human cancer, including endometrial cancers (EC) and epithelial ovarian cancers (EOC), some of which suggested possible associations.

Aims and objectives:

Our aims were to evaluate the association between questionnaire-based dietary AA intake and risk for EC and EOC, to measure biomarkers of AA in pre-diagnostic red blood cells and evaluate exposure determinants of biomarker levels in our population, and finally, to examine associations between pre-diagnostic AA biomarkers levels and EC and EOC risk in European women

How the study was carried out:

We conducted a series of prospective studies of AA exposure and risk of developing EC and EOC in European women. The study population for this project was 368,010 women from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort based in 23 centers from 10 western European countries. Dietary AA intake in the full EPIC cohort was  estimated  using  the  most  recent  European  acrylamide-content  food databases, country-specific food intake questionnaires, and 24-hour dietary recalls at baseline. Full cohort analyses of EC and EOC risk included 1,382 EC and 1,191 EOC cases and were performed in all cohort women and in subgroups according to smoking status, alcohol intake, body weight, oral contraceptive use, and tumour histolgy. Pre-diagnostic biomarkers of AA and its epoxide metabolite, glycidamide (GA), were measured as hemoglobin adducts (using HPLC-MS) in red blood cells collected at baseline 5-10 years before diagnosis. Biomarkers were measured in 383 EC cases (n=171 Type-1) and 385 matched controls, and in 334 EOC cases and 417 matched controls.  For the nested case-control studies, logistic regression analyses were conducted in all women and in subgroups by smoking status, alcohol consumption, body weight, and tumour histology.

Key findings and conclusions:

In general, the results of the dietary AA intake analyses showed no associations with EOC and EC, except for a possible association between higher AA intake and Type-1 EC in women who were non-smokers  and  non-users  of  oral  contraceptives (HRQ5vQ1=1.97,  95%  CI=1.08-3.62). When we examined  the  relation  between  dietary  and demographic factors and biomarker levels of AA and GA - results showed that the main food group determinants of AA and GA levels were biscuits, crackers and cakes; and that alcohol intake and body mass index were important determinants of the ratio of GA to AA – an indicator of  AA metabolism. A nested case-control study of AA and GA biomarker levels and EC (383 cases, 171 Type-1) did not find any support for associations between AA or GA and EC risk (neither overall, nor Type 1). A nested case-control study of AA and GA biomarkers and EOC (334 cases) risk also conducted in non-smoking post-menopausal women found some weak evidence for associations between higher biomarker levels  and  EOC  risk,  but  none of  the associations  were  statistically  significant,  and  there  was  no  evidence  for  a  dose-response relation.  When we pooled controls from both nested studies for more statistical power, dose- response trends became statistically significant for HbGA and HbAA+HbGA and EOC risk.

In conclusion, our results in women from Western Europe did not provide convincing support for the hypothesis that higher AA and GA exposures are associated with higher risks for endometrial and epithelial ovarian cancers.  Additional studies of AA biomarkers  and  EOC  risk  should  be conducted using larger sample sizes to rule out any possibility of an association between AA exposure and EOC risk.

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