Intake of Red and Processed Meat, Use of Non-Steroid Anti-Inflammatory Drugs, Genetic Variants and Risk of Colorectal Cancer

A Prospective Study of the Danish "Diet, Cancer and Health" Cohort

Vibeke Andersen, Ulrich Halekoh, Anne Tjønneland, Ulla Vogel, Tine Iskov Kopp

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Abstract

Red and processed meat have been associated with increased risk of colorectal cancer (CRC), whereas long-term use of non-steroid anti-inflammatory drugs (NSAIDs) may reduce the risk. The aim was to investigate potential interactions between meat intake, NSAID use, and gene variants in fatty acid metabolism and NSAID pathways in relation to the risk of CRC. A nested case-cohort study of 1038 CRC cases and 1857 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study encompassing 57,053 persons was performed using the Cox proportional hazard model. Gene variants in SLC25A20, PRKAB1, LPCAT1, PLA2G4A, ALOX5, PTGER3, TP53, CCAT2, TCF7L2, and BCL2 were investigated. CCAT2 rs6983267 was associated with the risk of CRC per se (p < 0.01). Statistically significant interactions were found between intake of red and processed meat and CCAT2 rs6983267, TP53 rs1042522, LPCAT1 rs7737692, SLC25A20 rs7623023 (pinteraction = 0.04, 0.04, 0.02, 0.03, respectively), and the use of NSAID and alcohol intake and TP53 rs1042522 (pinteraction = 0.04, 0.04, respectively) in relation to the risk of CRC. No other consistent associations or interactions were found. This study replicated an association of CCAT2 rs6983267 with CRC and an interaction between TP53 rs1042522 and NSAID in relation to CRC. Interactions between genetic variants in fatty acid metabolism and NSAID pathways and the intake of red and processed meat were found. Our results suggest that meat intake and NSAID use affect the same carcinogenic mechanisms. All new findings should be sought replicated in independent prospective studies. Future studies on the cancer-protective effects of aspirin/NSAID should include gene and meat assessments.

Original languageEnglish
Article number1121
JournalInternational Journal of Molecular Sciences
Volume20
Issue number5
Number of pages14
ISSN1661-6596
DOIs
Publication statusPublished - 5. Mar 2019

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diets
Meats
Nutrition
health
Colorectal Neoplasms
drugs
Anti-Inflammatory Agents
cancer
Health
Prospective Studies
Diet
Pharmaceutical Preparations
Neoplasms
Genes
Meat
Fatty acids
Metabolism
genes
metabolism
fatty acids

Keywords

  • aspirin
  • candidate gene
  • colorectal cancer
  • diet
  • gene–environment interaction
  • non-steroid anti-inflammatory drugs (NSAIDs)
  • red and processed meat
  • Western-style diet

Cite this

@article{4abf163be8b04939a7401ed09552bb21,
title = "Intake of Red and Processed Meat, Use of Non-Steroid Anti-Inflammatory Drugs, Genetic Variants and Risk of Colorectal Cancer: A Prospective Study of the Danish {"}Diet, Cancer and Health{"} Cohort",
abstract = "Red and processed meat have been associated with increased risk of colorectal cancer (CRC), whereas long-term use of non-steroid anti-inflammatory drugs (NSAIDs) may reduce the risk. The aim was to investigate potential interactions between meat intake, NSAID use, and gene variants in fatty acid metabolism and NSAID pathways in relation to the risk of CRC. A nested case-cohort study of 1038 CRC cases and 1857 randomly selected participants from the Danish prospective {"}Diet, Cancer and Health{"} study encompassing 57,053 persons was performed using the Cox proportional hazard model. Gene variants in SLC25A20, PRKAB1, LPCAT1, PLA2G4A, ALOX5, PTGER3, TP53, CCAT2, TCF7L2, and BCL2 were investigated. CCAT2 rs6983267 was associated with the risk of CRC per se (p < 0.01). Statistically significant interactions were found between intake of red and processed meat and CCAT2 rs6983267, TP53 rs1042522, LPCAT1 rs7737692, SLC25A20 rs7623023 (pinteraction = 0.04, 0.04, 0.02, 0.03, respectively), and the use of NSAID and alcohol intake and TP53 rs1042522 (pinteraction = 0.04, 0.04, respectively) in relation to the risk of CRC. No other consistent associations or interactions were found. This study replicated an association of CCAT2 rs6983267 with CRC and an interaction between TP53 rs1042522 and NSAID in relation to CRC. Interactions between genetic variants in fatty acid metabolism and NSAID pathways and the intake of red and processed meat were found. Our results suggest that meat intake and NSAID use affect the same carcinogenic mechanisms. All new findings should be sought replicated in independent prospective studies. Future studies on the cancer-protective effects of aspirin/NSAID should include gene and meat assessments.",
keywords = "aspirin, candidate gene, colorectal cancer, diet, gene–environment interaction, non-steroid anti-inflammatory drugs (NSAIDs), red and processed meat, Western-style diet",
author = "Vibeke Andersen and Ulrich Halekoh and Anne Tj{\o}nneland and Ulla Vogel and Kopp, {Tine Iskov}",
year = "2019",
month = "3",
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language = "English",
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Intake of Red and Processed Meat, Use of Non-Steroid Anti-Inflammatory Drugs, Genetic Variants and Risk of Colorectal Cancer : A Prospective Study of the Danish "Diet, Cancer and Health" Cohort. / Andersen, Vibeke; Halekoh, Ulrich; Tjønneland, Anne; Vogel, Ulla; Kopp, Tine Iskov.

In: International Journal of Molecular Sciences , Vol. 20, No. 5, 1121, 05.03.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Intake of Red and Processed Meat, Use of Non-Steroid Anti-Inflammatory Drugs, Genetic Variants and Risk of Colorectal Cancer

T2 - A Prospective Study of the Danish "Diet, Cancer and Health" Cohort

AU - Andersen, Vibeke

AU - Halekoh, Ulrich

AU - Tjønneland, Anne

AU - Vogel, Ulla

AU - Kopp, Tine Iskov

PY - 2019/3/5

Y1 - 2019/3/5

N2 - Red and processed meat have been associated with increased risk of colorectal cancer (CRC), whereas long-term use of non-steroid anti-inflammatory drugs (NSAIDs) may reduce the risk. The aim was to investigate potential interactions between meat intake, NSAID use, and gene variants in fatty acid metabolism and NSAID pathways in relation to the risk of CRC. A nested case-cohort study of 1038 CRC cases and 1857 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study encompassing 57,053 persons was performed using the Cox proportional hazard model. Gene variants in SLC25A20, PRKAB1, LPCAT1, PLA2G4A, ALOX5, PTGER3, TP53, CCAT2, TCF7L2, and BCL2 were investigated. CCAT2 rs6983267 was associated with the risk of CRC per se (p < 0.01). Statistically significant interactions were found between intake of red and processed meat and CCAT2 rs6983267, TP53 rs1042522, LPCAT1 rs7737692, SLC25A20 rs7623023 (pinteraction = 0.04, 0.04, 0.02, 0.03, respectively), and the use of NSAID and alcohol intake and TP53 rs1042522 (pinteraction = 0.04, 0.04, respectively) in relation to the risk of CRC. No other consistent associations or interactions were found. This study replicated an association of CCAT2 rs6983267 with CRC and an interaction between TP53 rs1042522 and NSAID in relation to CRC. Interactions between genetic variants in fatty acid metabolism and NSAID pathways and the intake of red and processed meat were found. Our results suggest that meat intake and NSAID use affect the same carcinogenic mechanisms. All new findings should be sought replicated in independent prospective studies. Future studies on the cancer-protective effects of aspirin/NSAID should include gene and meat assessments.

AB - Red and processed meat have been associated with increased risk of colorectal cancer (CRC), whereas long-term use of non-steroid anti-inflammatory drugs (NSAIDs) may reduce the risk. The aim was to investigate potential interactions between meat intake, NSAID use, and gene variants in fatty acid metabolism and NSAID pathways in relation to the risk of CRC. A nested case-cohort study of 1038 CRC cases and 1857 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study encompassing 57,053 persons was performed using the Cox proportional hazard model. Gene variants in SLC25A20, PRKAB1, LPCAT1, PLA2G4A, ALOX5, PTGER3, TP53, CCAT2, TCF7L2, and BCL2 were investigated. CCAT2 rs6983267 was associated with the risk of CRC per se (p < 0.01). Statistically significant interactions were found between intake of red and processed meat and CCAT2 rs6983267, TP53 rs1042522, LPCAT1 rs7737692, SLC25A20 rs7623023 (pinteraction = 0.04, 0.04, 0.02, 0.03, respectively), and the use of NSAID and alcohol intake and TP53 rs1042522 (pinteraction = 0.04, 0.04, respectively) in relation to the risk of CRC. No other consistent associations or interactions were found. This study replicated an association of CCAT2 rs6983267 with CRC and an interaction between TP53 rs1042522 and NSAID in relation to CRC. Interactions between genetic variants in fatty acid metabolism and NSAID pathways and the intake of red and processed meat were found. Our results suggest that meat intake and NSAID use affect the same carcinogenic mechanisms. All new findings should be sought replicated in independent prospective studies. Future studies on the cancer-protective effects of aspirin/NSAID should include gene and meat assessments.

KW - aspirin

KW - candidate gene

KW - colorectal cancer

KW - diet

KW - gene–environment interaction

KW - non-steroid anti-inflammatory drugs (NSAIDs)

KW - red and processed meat

KW - Western-style diet

U2 - 10.3390/ijms20051121

DO - 10.3390/ijms20051121

M3 - Journal article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 5

M1 - 1121

ER -