Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta‐analysis of prospective studies (cohort, nested case‐control or case‐cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta‐analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork.

Estimates of absolute risk of colorectal cancer (CRC) are needed to facilitate communication and better inform the public about the potentials and limits of cancer prevention. Using data from a large population-based case-control study in Germany (Darmkrebs: Chancen der Verhütung durch Screening [DACHS] study, which began in 2003) and population registry data, we calculated 30-year absolute risk estimates for development of CRC based on a healthy lifestyle score (derived from 5 modifiable lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body fatness), a polygenic risk score (based on 90 single-nucleotide polymorphisms), and colonoscopy history. We analyzed data from 4220 patients with CRC and 3338 individuals without CRC. Adherence to a healthy lifestyle and colonoscopy in the preceding 10 years were associated with a reduced relative risk of CRC in men and women. We observed a higher CRC risk in participants with high or intermediate genetic risk scores. For 50-year-old men and women without a colonoscopy, the absolute risk of CRC varied according to the polygenic risk score and the healthy lifestyle score (men, 3.5%-13.4%; women, 2.5%-10.6%). For 50-year-old men and women with a colonoscopy, the absolute risk of developing CRC was much lower but still varied according to the polygenic risk score and the healthy lifestyle score (men, 1.2%-4.8%; women, 0.9%-4.2%). Among all risk factor profiles, the 30-year absolute risk estimates consistently decreased with adherence to a healthy lifestyle. In a population-based study, we found that a colonoscopy can drastically reduce the absolute risk of CRC and that the genetically predetermined risk of CRC can be further reduced by adherence to a healthy lifestyle. Our results show the magnitude of CRC prevention possible through colonoscopy and lifestyle at a predefined genetic risk. This observational study has been registered in the German Clinical Trials Register (DRKS00011793), which is a primary registry in the World Health Organization Registry Network.

Background: Smoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear. Methods: This population-based case–control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways. Results: Current smoking showed higher ORs for MSI-high (OR = 2.79, 95% CI: 1.86–4.18) compared to MSS (OR = 1.41, 1.14–1.75, p-heterogeneity (p-het) = 0.001), BRAF-mutated (mut) (OR = 2.40, 1.41–4.07) compared to BRAF-wild type (wt) (OR = 1.52, 1.24–1.88, p-het = 0.074), KRAS-wt (OR = 1.70, 1.36–2.13) compared to KRAS-mut (OR = 1.26, 0.95–1.68, p-het = 0.039) and CIMP-high (OR = 2.01, 1.40–2.88) compared to CIMP-low/negative CRC (OR = 1.50, 1.22–1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high + BRAF-mut; OR = 2.39, 1.27–4.52) than with traditional pathway CRC (MSS + CIMP-low/negative + BRAF-wt; OR = 1.50, 1.16–1.94) and no association was observed with alternate pathway CRC (MSS + CIMP-low/negative + KRAS-wt; OR = 1.08, 0.77–1.43). No heterogeneity was observed in alcohol consumption association by molecular subtypes. Conclusions: In this large case–control study, smoking was more strongly associated with MSI-high and KRAS-wt CRC and with cases showing features of the sessile serrated pathway. Association patterns were less clear for alcohol consumption.

The association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status. PubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC. Meta-analyses were carried out to calculate summary relative risks (sRR). Overall, 31 studies reporting on the association between lifestyle factors and CRC according to MSI status were included in this review. Ever smoking was associated with MSI-H (sRR = 1.62; 95% CI: 1.40–1.88) and MSS/MSI-low CRC (sRR = 1.10; 95% CI: 1.01–1.20), but the association was significantly stronger for MSI-H CRC. The use of HRT was associated with a 20% decrease (sRR = 0.80; 95% CI: 0.73–0.89) in the risk of MSS CRC, but was not associated with MSI-H CRC. An increase in body mass index per 5 kg/m² was equally associated with MSS and MSI-H CRC (sRR = 1.22, in both cases), but was statistically significant for MSS CRC only (95% CI: 1.11–1.34 and 0.94–1.58, respectively). Limited evidence for associations between other lifestyle factors and CRC by MSI status exists. Lifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC. Further research on associations of lifestyle factors and CRC subtypes is necessary to provide a better understanding of the CRC disease pathway.