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Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC.
Carcinogenesis 2013; 34(12):2757-66C

Abstract

Red meat intake has been linked to increased colorectal cancer (CRC) risk. Although the underlying mechanisms remain unclear, experimental studies suggest a role for dietary heme iron. Because heme iron was shown to promote specific mutations, it would be insightful to link heme iron data to CRC with mutations in key genes in an observational, population-based study. We investigated the association between dietary heme iron intake and risk of CRC with mutations in APC (adenomatous polyposis coli) and KRAS (Kirsten ras) and P53 overexpression in the Netherlands Cohort Study. After 7.3 years of follow-up, excluding the first 2.3 years due to incomplete coverage of the pathology registry and to avoid preclinical disease, adjusted hazard ratios (including adjustment for total meat) and 95% confidence intervals were calculated, using 4026 subcohort members (aged 55-69 years at baseline), 435 colon and 140 rectal cancer patients. When comparing the highest with the lowest tertile of intake, heme iron intake was associated with an increased risk of CRC harboring activating mutations in KRAS (hazard ratio = 1.71, 95% confidence interval: 1.15-2.57; P for trend = 0.03) and CRC without truncating mutations in APC (hazard ratio = 1.79, 95% confidence interval: 1.23-2.60; P for trend = 0.003). We observed a positive association between heme iron intake and the risk of CRC with activating G>A mutations in KRAS (P for trend = 0.01) and overall G>A mutations in APC (P for trend = 0.005). No associations were found with CRC harboring G>T mutations in KRAS/APC. Heme iron intake was positively associated with the risk of P53 overexpressed tumors but not with tumors without P53 overexpression (Pheterogeneity = 0.12). Heme iron intake was associated with an increased risk of colorectal tumors harboring G>A transitions in KRAS and APC and overexpression of P53. These novel findings suggest that alkylating rather than oxidative DNA-damaging mechanisms are involved in heme-induced colorectal carcinogenesis.

Pub Type(s)

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

Language

eng

PubMed ID

23983135

Citation

Gilsing, Anne M J., et al. "Dietary Heme Iron and the Risk of Colorectal Cancer With Specific Mutations in KRAS and APC." Carcinogenesis, vol. 34, no. 12, 2013, pp. 2757-66.
Gilsing AM, Fransen F, de Kok TM, et al. Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC. Carcinogenesis. 2013;34(12):2757-66.
Gilsing, A. M., Fransen, F., de Kok, T. M., Goldbohm, A. R., Schouten, L. J., de Bruïne, A. P., ... Weijenberg, M. P. (2013). Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC. Carcinogenesis, 34(12), pp. 2757-66. doi:10.1093/carcin/bgt290.
Gilsing AM, et al. Dietary Heme Iron and the Risk of Colorectal Cancer With Specific Mutations in KRAS and APC. Carcinogenesis. 2013;34(12):2757-66. PubMed PMID: 23983135.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC. AU - Gilsing,Anne M J, AU - Fransen,Fiona, AU - de Kok,Theo M, AU - Goldbohm,Alexandra R, AU - Schouten,Leo J, AU - de Bruïne,Adriaan P, AU - van Engeland,Manon, AU - van den Brandt,Piet A, AU - de Goeij,Anton F P M, AU - Weijenberg,Matty P, Y1 - 2013/08/27/ PY - 2013/8/29/entrez PY - 2013/8/29/pubmed PY - 2014/4/10/medline SP - 2757 EP - 66 JF - Carcinogenesis JO - Carcinogenesis VL - 34 IS - 12 N2 - Red meat intake has been linked to increased colorectal cancer (CRC) risk. Although the underlying mechanisms remain unclear, experimental studies suggest a role for dietary heme iron. Because heme iron was shown to promote specific mutations, it would be insightful to link heme iron data to CRC with mutations in key genes in an observational, population-based study. We investigated the association between dietary heme iron intake and risk of CRC with mutations in APC (adenomatous polyposis coli) and KRAS (Kirsten ras) and P53 overexpression in the Netherlands Cohort Study. After 7.3 years of follow-up, excluding the first 2.3 years due to incomplete coverage of the pathology registry and to avoid preclinical disease, adjusted hazard ratios (including adjustment for total meat) and 95% confidence intervals were calculated, using 4026 subcohort members (aged 55-69 years at baseline), 435 colon and 140 rectal cancer patients. When comparing the highest with the lowest tertile of intake, heme iron intake was associated with an increased risk of CRC harboring activating mutations in KRAS (hazard ratio = 1.71, 95% confidence interval: 1.15-2.57; P for trend = 0.03) and CRC without truncating mutations in APC (hazard ratio = 1.79, 95% confidence interval: 1.23-2.60; P for trend = 0.003). We observed a positive association between heme iron intake and the risk of CRC with activating G>A mutations in KRAS (P for trend = 0.01) and overall G>A mutations in APC (P for trend = 0.005). No associations were found with CRC harboring G>T mutations in KRAS/APC. Heme iron intake was positively associated with the risk of P53 overexpressed tumors but not with tumors without P53 overexpression (Pheterogeneity = 0.12). Heme iron intake was associated with an increased risk of colorectal tumors harboring G>A transitions in KRAS and APC and overexpression of P53. These novel findings suggest that alkylating rather than oxidative DNA-damaging mechanisms are involved in heme-induced colorectal carcinogenesis. SN - 1460-2180 UR - https://www.unboundmedicine.com/medline/citation/23983135/Dietary_heme_iron_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/bgt290 DB - PRIME DP - Unbound Medicine ER -