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Dietary acrylamide intake and the risk of colorectal cancer with specific mutations in KRAS and APC.
Carcinogenesis 2014; 35(5):1032-8C

Abstract

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.

Authors+Show Affiliations

Department of Epidemiology.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24398672

Citation

Hogervorst, Janneke G F., et al. "Dietary Acrylamide Intake and the Risk of Colorectal Cancer With Specific Mutations in KRAS and APC." Carcinogenesis, vol. 35, no. 5, 2014, pp. 1032-8.
Hogervorst JG, de Bruijn-Geraets D, Schouten LJ, et al. Dietary acrylamide intake and the risk of colorectal cancer with specific mutations in KRAS and APC. Carcinogenesis. 2014;35(5):1032-8.
Hogervorst, J. G., de Bruijn-Geraets, D., Schouten, L. J., van Engeland, M., de Kok, T. M., Goldbohm, R. A., ... Weijenberg, M. P. (2014). Dietary acrylamide intake and the risk of colorectal cancer with specific mutations in KRAS and APC. Carcinogenesis, 35(5), pp. 1032-8. doi:10.1093/carcin/bgu002.
Hogervorst JG, et al. Dietary Acrylamide Intake and the Risk of Colorectal Cancer With Specific Mutations in KRAS and APC. Carcinogenesis. 2014;35(5):1032-8. PubMed PMID: 24398672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary acrylamide intake and the risk of colorectal cancer with specific mutations in KRAS and APC. AU - Hogervorst,Janneke G F, AU - de Bruijn-Geraets,Daisy, AU - Schouten,Leo J, AU - van Engeland,Manon, AU - de Kok,Theo M C M, AU - Goldbohm,R Alexandra, AU - van den Brandt,Piet A, AU - Weijenberg,Matty P, Y1 - 2014/01/07/ PY - 2014/1/9/entrez PY - 2014/1/9/pubmed PY - 2014/6/25/medline SP - 1032 EP - 8 JF - Carcinogenesis JO - Carcinogenesis VL - 35 IS - 5 N2 - 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. SN - 1460-2180 UR - https://www.unboundmedicine.com/medline/citation/24398672/Dietary_acrylamide_intake_and_the_risk_of_colorectal_cancer_with_specific_mutations_in_KRAS_and_APC_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgu002 DB - PRIME DP - Unbound Medicine ER -