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

247/300)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 models. Gene variants in SLC25A20, PRKAB1, LPCAT1, PLA2G4A, ALOX5, PTGER3, TP53, CCAT2, TCF7L2, BCL2 were investigated. CCAT2 rs6983267 was associated with 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 (p interaction =0.04, 0.04, 0.02, 0.03, respectively), and use of NSAID and alcohol intake and TP53 rs1042522 (p interaction =0.04, 0.04, respectively) in relation to 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 pathway and 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. Author Summary (150-200)Intake of red and processed meat has been associated with risk of cancer and in particular colorectal cancer. However, the underlying biological mechanisms are only incompletely understood. Geneenvironment interaction analysis may be used for identifying underlying mechanisms for e.g. meat carcinogenesis. In this work, we have analyzed the interaction between the intake of red and processed meat, use of non-steroid anti-inflammatory drugs (including the anti-carcinogenic drug aspirin) and

Long non-coding RNA colon cancer-associated transcript 2: role and function in human cancers

“…In the same year, Shah et al [8] showed that the cancer-related rs6983267 SNP and its corresponding CCAT2 promoted myeloid cancers through certain SNP-specific RNA gene mutations. In 2019, Andersen et al [84] highlighted that the CCAT2 rs6983267 GG genotype was correlated with an elevated CRC risk, which was in agreement with the results of previous studies. In 2021, Yu et al [85] found that the rs6983267 G allele is related to a greater risk of lung cancer than the T allele.…”

Intake of dietary fibre, red and processed meat and risk of late-onset Chronic Inflammatory Diseases: A prospective Danish study on the “diet, cancer and health” cohort

“…Thirdly, the prospective study design with the collection of dietary and lifestyle factors before diagnosis eliminates the risk of recall bias. A fourth advantage is diverse and high intake of meat and fibre in the cohort enabled investigations of the effects of diet and therefore the prospective “Diet, Cancer and Health” cohort has been proven suitable to detect effects of meat and fibre intake 61 - 64 . A fifth strength of this study is the consideration that individuals diagnosed with CID within 0.5, 1, and 5 years after filling out the questionnaire may have biased the results if they had systematically different exposure levels than the other late-onset CID cases.…”

Preventive potential and mechanism of dietary polyphenols on the formation of heterocyclic aromatic amines

“…Interestingly, several large-scale cohort studies that showed association between the intakes of HAAs (e.g., PhIP and MeIQx) and higher cancer risk revealed that red meat consumption largely contributed to the above positive associations (Gibis, 2016). Athough the causality between meat consumption and cancer risk is difficult to clarify, dietary intake information obtained from questionnaires and epidemiological investigations links high dietary red meat and processed meat consumption with a higher risk of human cancers, including breast cancer (Farvid et al, 2018), colorectal cancer (Wang et al, 2015), and gastric cancer (Andersen, Halekoh, Tjønneland, Vogel, & Kopp, 2019). Other studies highlighted that consumption of processed meat (50 g/day) increased the probability of some cancers, such as prostate by 4%, 18% for colonic, 9% for breast, and 19% for pancreatic (Wolk, 2017).…”