Risk Factors for Early Onset Colorectal Cancer: Further Confirmation is Needed

We read with great interest the article “Risk factors for early-onset colorectal cancer: A systematic review and meta-analysis,” by O’Sullivan et al.1O'Sullivan D.E. et al.Clin Gastroenterol Hepatol. 2022; 20: 1229-1240Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar The article included 20 studies and reported that a history of colorectal cancer in a first-degree relative, hyperlipidemia, obesity, and alcohol consumption were significant risk factors for early onset colorectal cancer (EoCRC). However, there are some aspects of research methods that need to be commented on.First, we repeated the search according to the authors’ search methods and found potentially important studies that were not included. For instance, the authors concluded that the association between smoking and EoCRC was not statistically significant. However, Glover et al2Glover M. et al.Dig Dis Sci. 2019; 64: 3602-3609Crossref PubMed Scopus (23) Google Scholar compared EoCRC with healthy individuals younger than the age of 50 in a study involving 8,873,080 individuals and found that smoking significantly increased the incidence of EoCRC (adjusted odds ratio, 2.675; P < .001). The authors also found that obesity was a significant risk factor for EoCRC. Chang et al3Chang V.C. et al.Cancer Causes Control. 2021; 32: 1063-1083Crossref PubMed Scopus (13) Google Scholar conducted a population-based case-control study. They found that body mass index in the obese range in the early 20s and 2 years before EoCRC diagnosis both showed a suggestive inverse association (both Ptrend = .06). The inclusion of these studies may have led to results opposite to those reported in the meta-analysis.Second, in the comorbidities section, the authors mentioned that obesity (pooled relative risk, 1.54; 95% confidence interval, 1.01–2.35) is significantly associated with the development of EoCRC. There was considerable heterogeneity among the study-specific estimates for obesity (I2 = 98.7%). Seven articles were included for targeting obesity as a risk factor, 5 from the United States and 2 from Israel. We believe that differences in dietary structure may exist among obese people in different regions as a confounding factor. Differences in dietary patterns remain a risk factor contributing to the development of EoCRC. According to a study, a Western diet is characterized by low fiber, high fat, and high sugar and is associated with an increased risk of EoCRC.3Chang V.C. et al.Cancer Causes Control. 2021; 32: 1063-1083Crossref PubMed Scopus (13) Google Scholar Therefore, we suggest performing further subgroup analyses according to the region to address whether obesity contributed to the development of EoCRC.Finally, in the discussion section, the authors mention that hyperlipidemia may be a stronger risk factor for colorectal cancer and future studies should examine the utility of incorporating cholesterol levels in prediction models for identifying individuals at high risk for EoCRC. For this blood lipid risk factor, triglycerides and cholesterol are not discussed separately in the 3 articles included by the author, but all articles generally study hyperlipidemia. Jung et al4Jung Y.S. et al.Gastrointest Endosc. 2015; 81: 637-645Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar reported elevated triglyceride levels as a risk factor for advanced colon neoplasia. Therefore, more studies are needed to clarify the effect of triglycerides and cholesterol, respectively, on EoCRC than just incorporating cholesterol into prediction models.We sincerely thank O’Sullivan et al1O'Sullivan D.E. et al.Clin Gastroenterol Hepatol. 2022; 20: 1229-1240Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar for providing us with an important study focusing on the risk factors for EoCRC, but believe that additional research is still needed to clarify unresolved issues. We read with great interest the article “Risk factors for early-onset colorectal cancer: A systematic review and meta-analysis,” by O’Sullivan et al.1O'Sullivan D.E. et al.Clin Gastroenterol Hepatol. 2022; 20: 1229-1240Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar The article included 20 studies and reported that a history of colorectal cancer in a first-degree relative, hyperlipidemia, obesity, and alcohol consumption were significant risk factors for early onset colorectal cancer (EoCRC). However, there are some aspects of research methods that need to be commented on. First, we repeated the search according to the authors’ search methods and found potentially important studies that were not included. For instance, the authors concluded that the association between smoking and EoCRC was not statistically significant. However, Glover et al2Glover M. et al.Dig Dis Sci. 2019; 64: 3602-3609Crossref PubMed Scopus (23) Google Scholar compared EoCRC with healthy individuals younger than the age of 50 in a study involving 8,873,080 individuals and found that smoking significantly increased the incidence of EoCRC (adjusted odds ratio, 2.675; P < .001). The authors also found that obesity was a significant risk factor for EoCRC. Chang et al3Chang V.C. et al.Cancer Causes Control. 2021; 32: 1063-1083Crossref PubMed Scopus (13) Google Scholar conducted a population-based case-control study. They found that body mass index in the obese range in the early 20s and 2 years before EoCRC diagnosis both showed a suggestive inverse association (both Ptrend = .06). The inclusion of these studies may have led to results opposite to those reported in the meta-analysis. Second, in the comorbidities section, the authors mentioned that obesity (pooled relative risk, 1.54; 95% confidence interval, 1.01–2.35) is significantly associated with the development of EoCRC. There was considerable heterogeneity among the study-specific estimates for obesity (I2 = 98.7%). Seven articles were included for targeting obesity as a risk factor, 5 from the United States and 2 from Israel. We believe that differences in dietary structure may exist among obese people in different regions as a confounding factor. Differences in dietary patterns remain a risk factor contributing to the development of EoCRC. According to a study, a Western diet is characterized by low fiber, high fat, and high sugar and is associated with an increased risk of EoCRC.3Chang V.C. et al.Cancer Causes Control. 2021; 32: 1063-1083Crossref PubMed Scopus (13) Google Scholar Therefore, we suggest performing further subgroup analyses according to the region to address whether obesity contributed to the development of EoCRC. Finally, in the discussion section, the authors mention that hyperlipidemia may be a stronger risk factor for colorectal cancer and future studies should examine the utility of incorporating cholesterol levels in prediction models for identifying individuals at high risk for EoCRC. For this blood lipid risk factor, triglycerides and cholesterol are not discussed separately in the 3 articles included by the author, but all articles generally study hyperlipidemia. Jung et al4Jung Y.S. et al.Gastrointest Endosc. 2015; 81: 637-645Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar reported elevated triglyceride levels as a risk factor for advanced colon neoplasia. Therefore, more studies are needed to clarify the effect of triglycerides and cholesterol, respectively, on EoCRC than just incorporating cholesterol into prediction models. We sincerely thank O’Sullivan et al1O'Sullivan D.E. et al.Clin Gastroenterol Hepatol. 2022; 20: 1229-1240Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar for providing us with an important study focusing on the risk factors for EoCRC, but believe that additional research is still needed to clarify unresolved issues. Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysisClinical Gastroenterology and HepatologyVol. 20Issue 6PreviewDespite the widespread increase in the incidence of early-onset colorectal cancer (EoCRC), the reasons for this increase remain unclear. The objective of this study was to determine risk factors for the development of EoCRC. Full-Text PDF ReplyClinical Gastroenterology and HepatologyPreviewWe thank Du and colleagues for their comments and the interest in our study1 because it highlights the importance of research in this area. We agree with their assessment that additional research is required to clarify unresolved issues among early onset colorectal cancers (eoCRC). Du and colleagues raised 3 points related to our study: (1) additional studies to be included, (2) the impact of the heterogeneity on the obesity evidence base, and (3) the discussion of the relative impact of hyperlipidemia. Full-Text PDF