Rising cancer incidence in younger adults: is obesity to blame?
Authors: Catherine R Marinac, Brenda M Birmann
Journal: The Lancet Public Health (2019)

Although cancer has historically been considered a disease of aging, a reported sharp rise in colorectal cancer incidence among adults aged 54 years and younger beginning in the mid-1980s for the colon and mid-1970s for the rectum1Siegel RL Fedewa SA Anderson WF et al.Colorectal cancer incidence patterns in the United States, 1974–2013.J Natl Cancer Inst. 2017; 109Crossref Scopus (280) Google Scholar has motivated researchers to examine risk factors for early onset disease.2Liu PH Wu K Ng K et al.Association of obesity with risk of early-onset colorectal cancer among women.JAMA Oncol. 2018; (published online Oct 11.)DOI:10.1001/jamaoncol.2018.4280Google Scholar In The Lancet Public Health, Hyuna Sung and colleagues3Sung H Siegel RL Rosenberg PS Jemal A Emerging cancer trends among young adults in the USA: analysis of population-based cancer registry.Lancet Public Health. 2019; (published online Feb 4.)http://dx.doi.org/10.1016/S2468-2667(18)30267-6Summary Full Text Full Text PDF PubMed Scopus (244) Google Scholar report a rigorous and extensive analysis of data from 25 state cancer registries, in which they examined contemporary incidence trends for 30 cancers in the USA. This analysis, which included 14 672 409 incident cancers ascertained from registries covering 67% of the US population between Jan 1, 1995, and Dec 31, 2014, extends their previous work on colorectal cancer incidence.1Siegel RL Fedewa SA Anderson WF et al.Colorectal cancer incidence patterns in the United States, 1974–2013.J Natl Cancer Inst. 2017; 109Crossref Scopus (280) Google Scholar The new study included 12 cancers considered to be related to obesity according to a 2016 report from a working group convened by the International Agency for Research on Cancer,4Lauby-Secretan B Scoccianti C Loomis D Grosse Y Bianchini F Straif K Body fatness and cancer—viewpoint of the IARC working group.N Engl J Med. 2016; 375: 794-798Crossref PubMed Scopus (1614) Google Scholar and 18 additional common cancers not designated as obesity-related in the same report. The investigators examined trends in incidence, based on annual percentage changes and incidence rate ratios, for each of the 30 cancer types by age and birth cohort. The most striking finding was that cancer incidence appears to be rising disproportionately in younger adults (aged 25–49 years), and in consecutively younger birth cohorts for half of the cancers classified as obesity-related. These cancers include colorectal, corpus uteri, gallbladder, kidney, pancreatic, and multiple myeloma. Thyroid cancer, also considered to be obesity-related, showed markedly rising incidence in both younger and older adults. By contrast, only two of the other 18 cancers had similar trends of increasing incidence in younger adults. The investigators speculate that these findings are driven in part by the obesity epidemic, a hypothesis that is both provocative and plausible. As the investigators state, the prevalence of obesity in the USA more than doubled between 1980 and 2014,5Centers for Disease Control and PreventionPrevalence of overweight, obesity, and extreme obesity among adults aged 20 and over: United States, 1960–1962 Through 2013–2014.https://www.cdc.gov/nchs/data/hestat/obesity_adult_13_14/obesity_adult_13_14.pdfDate: 2016Date accessed: January 5, 2019Google Scholar providing compelling evidence that obesity could be a causal factor. However, despite the plausibility, the investigators' hypothesis and report have constraints that are important to consider. First, the hypothesis assumes that cancer risk factors have a similar influence on cancer development across the lifespan. However, some early onset cancers can have a distinct cause from their later onset forms, as has been hypothesised for Hodgkin lymphoma6Hjalgrim H Engels EA Infectious aetiology of Hodgkin and non-Hodgkin lymphomas: a review of the epidemiological evidence.J Intern Med. 2008; 264: 537-548Crossref PubMed Scopus (104) Google Scholar and well documented for breast cancer in women.7Huang Z Hankinson SE Colditz GA et al.Dual effects of weight and weight gain on breast cancer risk.JAMA. 1997; 278: 1407-1411Crossref PubMed Scopus (698) Google Scholar In general, most studies have investigated associations of obesity measured in adulthood with overall cancer risk, rather than associations of obesity in earlier life with early onset cancer risk. This method probably reflects that few studies have large enough populations for robust analyses of risk factors for early onset cancer—especially for the less common cancers highlighted in Sung and colleagues' report,3Sung H Siegel RL Rosenberg PS Jemal A Emerging cancer trends among young adults in the USA: analysis of population-based cancer registry.Lancet Public Health. 2019; (published online Feb 4.)http://dx.doi.org/10.1016/S2468-2667(18)30267-6Summary Full Text Full Text PDF PubMed Scopus (244) Google Scholar such as multiple myeloma and gallbladder cancer. Pooled analyses of multiple prospective studies will be required to characterise associations of risk factors with the early onset of most cancers, and to estimate latency for early life exposures. These considerations do not diminish the plausibility of the hypotheses discussed by Sung and colleagues; however, they do underscore the speculative nature of the investigators' interpretation and highlight the need for additional experimental and population-based studies that test the hypothesis more directly. We find several additional aspects of the work by Sung and colleagues important to consider alongside the investigators' generally thoughtful discussion of their data. The first corresponds to inherent limitations of the International Agency for Research on Cancer working group report on which they based their approach. In particular, the report4Lauby-Secretan B Scoccianti C Loomis D Grosse Y Bianchini F Straif K Body fatness and cancer—viewpoint of the IARC working group.N Engl J Med. 2016; 375: 794-798Crossref PubMed Scopus (1614) Google Scholar acknowledged insufficient evidence regarding the association of obesity with some cancers grouped with the 18 additional cancers investigated by Sung and colleagues, including several for which emerging data strongly suggest a link (such as bladder cancer and diffuse large B-cell lymphoma).8Sun JW Zhao LG Yang Y Ma X Wang YY Xiang YB Obesity and risk of bladder cancer: a dose-response meta-analysis of 15 cohort studies.PLoS One. 2015; 10: e0119313Crossref PubMed Scopus (75) Google Scholar, 9Castillo JJ Ingham RR Reagan JL Furman M Dalia S Mitri J Obesity is associated with increased relative risk of diffuse large B-cell lymphoma: a meta-analysis of observational studies.Clin Lymphoma Myeloma Leuk. 2014; 14: 122-130Summary Full Text Full Text PDF PubMed Scopus (27) Google Scholar Such cancers did not show temporal trends of increasing incidence in younger adults in Sung and colleagues' study. Additionally, although the investigators diligently separated gastric cardia and non-cardia cancers for analysis, as well as HPV-related and HPV–unrelated oral and pharyngeal cancers, they chose to aggregate subtypes for other cancer types. These aggregated groups included non-Hodgkin lymphomas, comprising numerous aetiologically heterogeneous tumours,10Morton LM Slager SL Cerhan JR et al.Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.J Natl Cancer Inst Monogr. 2014; 2014: 130-144Crossref PubMed Scopus (224) Google Scholar and all lung cancers, all Hodgkin lymphomas, and all leukaemias except chronic lymphocytic leukaemia (which was appropriately grouped with the non-Hodgkin lymphomas). The interpretation of the data for the aggregated groups is challenging; notably, the small number of subtype-specific findings presented in the appendix suggest moderate differences in age-specific and birth cohort-specific incidence across distinct subtypes of leukaemia and non-Hodgkin lymphoma. Lastly, Sung and colleagues did not comment on why only some obesity-related cancers, and not all 12, showed temporal trends of markedly rising younger adult incidence, or why some obesity-related cancers appeared to have declining rather than increasing incidence in the older age groups. Such observations could reflect varying influences of other risk factors across such cancer types and age groups, and warrant further investigation. Despite these considerations and modest constraints, the report from Sung and colleagues yields timely insights. Importantly, the findings suggest the need for further close epidemiological monitoring of cancer incidence trends in younger adults and highlight the need for rigorous aetiological studies of exposures that could be responsible for the trends. We declare no competing interests. Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registryThe risk of developing an obesity-related cancer seems to be increasing in a stepwise manner in successively younger birth cohorts in the USA. Further studies are needed to elucidate exposures responsible for these emerging trends, including excess bodyweight and other risk factors. Full-Text PDF Open Access