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• W4210369325 abstract "See “Association of body mass index at different ages with early-onset colorectal cancer,” by Li H, Boakye D, Chen X, et al, on page 1088. See “Association of body mass index at different ages with early-onset colorectal cancer,” by Li H, Boakye D, Chen X, et al, on page 1088. The global trend in the epidemiology of colorectal cancer (CRC) appears to be changing.1Siegel R.L. Torre L.A. Soerjomataram I. et al.Global patterns and trends in colorectal cancer incidence in young adults.Gut. 2019; 68: 2179-2185Google Scholar, 2Edwards B.K. Ward E. Kohler B.A. et al.Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates.Cancer. 2010; 116: 544-573Google Scholar, 3Araghi M. Soerjomataram I. Bardot A. et al.Changes in colorectal cancer incidence in seven high-income countries: a population-based study.Lancet Gastroenterol Hepatol. 2019; 4 (Erratum in: Lancet Gastroenterol Hepatol. 2019;4:e8): 511-518Google Scholar Among 9 high-income countries (ie, Australia, Canada, Denmark, Germany, New Zealand, Slovenia, Sweden, United Kingdom, and United States), CRC among persons older than 50 years has been reported to be stable or declined by 1%–2.4% per year, whereas the incidence continues to increase by 0.8%–4% per year among those younger than 50 years for reasons that are not well understood. In the current issue of Gastroenterology, Li et al4Li H. Boakye D. Chen X. et al.Association of body mass index at different ages with early-onset colorectal cancer.Gastroenterology. 2022; 162: 1088-1097Google Scholar evaluated the association of early adulthood obesity with early-onset CRC in a large, population-based case–control study in Germany. The authors evaluated body mass index (BMI) based on self-reported height and weight during early adulthood at age 20 years, age 30 years, and at approximately 10 years before CRC diagnosis. Using multivariate logistic regression models that controlled for various standard CRC risk factors, they found significant associations between being obese (BMI >30 kg/m2) at various ages relative to participants with normal weight (BMI <25 kg/m2). The magnitude of the estimated odds ratios ranged from 1.9 to 2.6. It is well known that the susceptibility of individuals to diseases is influenced by a complex interplay of their genetic makeup and exposures in the environment. Genetic makeup is not easily mutable, but appropriate disease-specific medical interventions, including screening and lifestyle modification, may significantly reduce the risk or alter the course of the disease. However, early-onset CRC is an entity that is still being unraveled. At first glance, one would opine that genetic factors, such as familial adenomatous polyposis or Lynch syndrome, would be the underpinning etiology in early-onset CRC. After all, genetic syndromes of CRC are characterized by “early onset.” However, only approximately 20% of early-onset CRCs are attributable to hereditary causes.5Ahnen D.J. Wade S.W. Jones W.F. et al.The increasing incidence of young-onset colorectal cancer: a call to action.Mayo Clin Proc. 2014; 89: 216-224Google Scholar,6Chang D.T. Pai R.K. Rybicki L.A. et al.Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features.Mod Pathol. 2012; 25: 1128-1139Google Scholar Therefore, most early-onset CRCs are sporadic in nature. Furthermore, early-onset CRC tends to be diagnosed predominantly in the distal colon and rectum with poorly differentiated histology, in contrast to typical hereditary CRC. There has been a suggestion that widespread use of colonoscopy among young persons may be leading to over detection of CRC in the United States.7Murphy C.C. Lund J.L. Sandler R.S. Young-onset colorectal cancer: earlier diagnoses or increasing disease burden?.Gastroenterology. 2017; 152: 1809-1812.e3Google Scholar However, increasing use of colonoscopy does not adequately explain this observation. 8Lee J.K. Merchant S.A. Jensen C.D. et al.Rising early-onset colorectal cancer incidence is not an artifact of increased screening colonoscopy use in a large, diverse healthcare system.Gastroenterology. 2022; 162: 325-327Abstract Full Text Full Text PDF Scopus (3) Google Scholar Moreover, the use of colonoscopy among young persons is not common in other countries reporting similar findings. Nonetheless, some risk factors for early-onset CRC have been suggested. Interestingly, the observed risk factors for early-onset CRC are comparable with risk factors for CRC among older persons, including male sex, Black race, cigarette smoking, increased antibiotic use, changes in gut microbiome, sedentary lifestyle, high consumption of red meat and processed meat, consumption of high-fructose corn syrup, and obesity.9Kamath S.D. Torrejon N. Wei W. et al.Racial disparities negatively impact outcomes in early-onset colorectal cancer independent of socioeconomic status.Cancer Med. 2021; 10: 7542-7550Google Scholar, 10Hofseth L.J. Hebert J.R. Chanda A. et al.Early-onset colorectal cancer: initial clues and current views.Nat Rev Gastroenterol Hepatol. 2020; 17 (Erratum in: Nat Rev Gastroenterol Hepatol 2020;17:517): 352-364Google Scholar, 11Akimoto N. Ugai T. Zhong R. et al.Rising incidence of early-onset colorectal cancer - a call to action.Nat Rev Clin Oncol. 2021; 18: 230-243Google Scholar, 12Liu P.H. Wu K. Ng K. et al.Association of obesity with risk of early-onset colorectal cancer among women.JAMA Oncol. 2019; 5: 37-44Google Scholar, 13Low E.E. Demb J. Liu L. et al.Risk factors for early-onset colorectal cancer.Gastroenterology. 2020; 159: 492-501Google Scholar A truly global phenomenon that may mirror the global increase in the incidence of early-onset CRC is obesity. This important study by Li et al,4Li H. Boakye D. Chen X. et al.Association of body mass index at different ages with early-onset colorectal cancer.Gastroenterology. 2022; 162: 1088-1097Google Scholar which evaluated early adulthood obesity, certainly sheds more light on risk factors for early-onset CRC by demonstrating that earlier exposure to CRC risk factors may play a significant role in this disease. Similar to this current report, Liu et al12Liu P.H. Wu K. Ng K. et al.Association of obesity with risk of early-onset colorectal cancer among women.JAMA Oncol. 2019; 5: 37-44Google Scholar analyzed data from the Nurses’ Health Study II in the United States on the association of obesity with early-onset CRC. In that prospective cohort involving 114 cases of early-onset CRC, the authors reported that obesity in general, increasing BMI at age 18 years, and weight gain of 40 kg or more since age 18 years were associated with an increased risk of early-onset CRC. However, the Nurses’ Health Study II cohort was restricted to women. The current report by Li et al4Li H. Boakye D. Chen X. et al.Association of body mass index at different ages with early-onset colorectal cancer.Gastroenterology. 2022; 162: 1088-1097Google Scholar was conducted among men and women and involved an analysis of a larger number of people diagnosed with early-onset CRC (n = 621). Future studies would be more informative to evaluate this relationship with childhood obesity. The result of this study by Li et al4Li H. Boakye D. Chen X. et al.Association of body mass index at different ages with early-onset colorectal cancer.Gastroenterology. 2022; 162: 1088-1097Google Scholar and the extant literature suggest that the global increase of obesity may be contributing to increasing rates of early-onset CRC. Obesity as a noncommunicable pandemic deserves more attention by all and sundry, including patients, the average population at large, health care personnel, governments, and policy makers, in order to achieve meaningful control. At this point in time, it is unclear how we should intervene. It is noteworthy that approximately one-third of children and adolescents in the United States are overweight or obese. The subsequent morbidity associated with obesity prompted the US Preventive Services Task Force in 2017 to recommend that clinicians should screen for obesity among children and adolescents from 6 years of age and offer or refer them to comprehensive, intensive behavioral interventions to promote improvements in weight status.14Grossman D.C. Bibbins-Domingo K. et al.US Preventive Services Task ForceScreening for obesity in children and adolescents: US Preventive Services Task Force Recommendation Statement.JAMA. 2017; 317: 2417-2426Google Scholar Furthermore, in response to the rising incidence of early-onset CRC, there has been a major shift in CRC screening recommendations by reducing the age of initiation of CRC screening for average risk persons from 50 years to 45 years.15Wolf A.M.D. Fontham E.T.H. Church T.R. et al.Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.CA Cancer J Clin. 2018; 68: 250-281Google Scholar, 16Patel S.G. May F.P. Anderson J.C. et al.Updates on age to start and stop colorectal cancer screening: recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2022; 162: 285-299Abstract Full Text Full Text PDF Scopus (36) Google Scholar, 17Davidson K.W. Barry M.J. Mangione C.M. et al.US Preventive Services Task ForceScreening for colorectal cancer: US Preventive Services Task Force Recommendation Statement.JAMA. 2021; 325: 1965-1977Google Scholar An additional strategy to combat the increasing early-onset CRC is to adequately evaluate young people who present with alarm symptoms, such as hematochezia, unexplained weight loss, and iron deficiency anemia. As the understanding of early-onset CRC improves, it is important to encourage a healthful lifestyle and promote healthy weight among patients. It remains unclear whether obesity can have a meaningful role in refining current recommendations for screening as part of a risk-based strategy. However, modeling studies incorporating putative risk factors for CRC, such as obesity, into evaluations of early-onset CRC will be informative. In conclusion, known modifiable risk factors for CRC in the older population need to be modified among young persons as well. It is well understood that CRC is a disease with relatively long latency from when the inciting exposure occurs, when subsequent molecular changes take place, when colorectal neoplasia develops, and when CRC manifests. Therefore, the earlier we intervene based on what we currently know, the better the chances of CRC control. After all, as the saying goes, “a stitch in time, saves nine.” Associations of Body Mass Index at Different Ages With Early-Onset Colorectal CancerGastroenterologyVol. 162Issue 4PreviewEvidence from a large population-based case–control study in Germany shows that obesity at early adulthood is strongly associated with increased risk of early-onset colorectal cancer. Full-Text PDF Open Access" @default.
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• W4210369325 title "Understanding Early-Onset Colorectal Cancer: The Role of Obesity" @default.
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