Diabetes and adiposity: a heavy load for cancer
Authors: Yikyung Park, Graham A Colditz
Journal: The Lancet Diabetes & Endocrinology (2017)

Cancer is the second leading cause of death from non-communicable diseases in the world.1GBD 2016 Causes of Death CollaboratorsGlobal, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet. 2017; 390: 1151-1210Summary Full Text Full Text PDF PubMed Scopus (2927) Google Scholar In 2015, there were 17·5 million new cases of cancer and 8·7 million cancer-related deaths, with 208·3 million disability-adjusted life-years.2Fitzmaurice C Allen C Barber RM et al.Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease Study.JAMA Oncol. 2017; 3: 524-548Crossref PubMed Scopus (2728) Google Scholar Cancer incidence is expected to continue to increase, partly due to changes in the prevalence of risk factors such as obesity, diabetes, and other lifestyle factors. Obesity, defined as body-mass index (BMI) of 30 kg/m2 or more, has become increasingly common in all age groups and every country over the past few decades, irrespective of the country's sociodemographic status or region.3NCD Risk Factor Collaboration (NCD-RisC)Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults.Lancet. 2017; (published online Oct 10.)https://doi.org/10.1016/S0140-6736(17)32129-3Google Scholar Many countries have experienced a rapid change in their populations' BMIs from underweight to overweight and obesity, which has coincided with an increase in the prevalence of diabetes.4NCD Risk Factor Collaboration (NCD-RisC)Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants.Lancet. 2016; 387: 1513-1530Summary Full Text Full Text PDF PubMed Scopus (2300) Google Scholar In 2016, 125 million children and adolescents aged 5–19 years were obese and an additional 213 million were overweight worldwide, while among adults, 671 million were obese and 1·3 billion were overweight.3NCD Risk Factor Collaboration (NCD-RisC)Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults.Lancet. 2017; (published online Oct 10.)https://doi.org/10.1016/S0140-6736(17)32129-3Google Scholar A sizeable body of evidence supports causal links between obesity and diabetes and many types of cancer, suggesting that many cancer cases might be due to obesity and diabetes. On this basis, Jonathan Pearson-Stuttard and colleagues assessed the impact of the prevalence of high BMI—overweight and obese defined as a BMI greater than or equal to 25 kg/m2—and diabetes on the number of new cancer cases 2012, assuming a 10-year lag for cancer development.5Pearson-Stuttard J Zhou B Kontis V Bentham J Gunter MJ Ezzati M Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment.Lancet Diabetes Endocrinol. 2018; 6: e6-e15Summary Full Text Full Text PDF PubMed Scopus (178) Google Scholar Overall, 5·7% of all cancer in 2012 was attributable to high BMI and diabetes in 2002. When the estimation was restricted to 12 obesity-related cancers and six diabetes-related cancers, 15·3% of cancer cases in men and 13·5% of cases in women were due to the combined effect of high BMI and diabetes. However, there was substantial variation in a proportion of cancer due to high BMI and diabetes by cancer sites—for example, 23·3% of liver cancer, 18·0% of pancreatic cancer, and 9·5% of colorectal cancer cases in men were attributable to the combined effect of high BMI and diabetes. Pearson-Stuttard and colleagues suggest that 25·8% of diabetes-related cancers and 31·9% of cancers related to high BMI in 2012 were due to increases in the prevalence of these risk factors from 1980 to 2002. The burden of cancer due to diabetes and high BMI is projected to continue to increase in the future: in 2035, more than a third of liver cancer cases in men and half of endometrial cancer cases in women will be attributable to a combination of diabetes and high BMI. Pearson-Stuttard and colleagues' data highlight the substantial burden of cancer due to diabetes and high BMI at global, regional, and national levels. However, the study might have underestimated the burden of cancer because the time lag between exposure and cancer was limited to 10 years. Although the 10 year lag takes into account the process of carcinogenesis and cumulative exposure over time, it understates the importance of early life exposure, especially from high BMI, on cancer. Emerging evidence suggests that high BMI in late adolescence and young adulthood is directly related to risk of cancer in old age.6Genkinger JM Kitahara CM Bernstein L et al.Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies.Ann Oncol. 2015; 26: 2257-2266Crossref PubMed Scopus (102) Google Scholar, 7Kitahara CM McCullough ML Franceschi S et al.Anthropometric factors and thyroid cancer risk by histological subtype: pooled analysis of 22 prospective studies.Thyroid. 2016; 26: 306-318Crossref PubMed Scopus (115) Google Scholar, 8Teras LR Kitahara CM Birmann BM et al.Body size and multiple myeloma mortality: a pooled analysis of 20 prospective studies.Br J Haematol. 2014; 166: 667-676Crossref PubMed Scopus (73) Google Scholar, 9Hidayat K Yang CM Shi BM Body fatness at an early age and risk of colorectal cancer.Int J Cancer. 2017; (published online Oct 12.)DOI:10.1002/ijc.31100PubMed Google Scholar, 10Levi Z Kark JD Twig G et al.Body mass index at adolescence and risk of noncardia gastric cancer in a cohort of 1.79 million men and women.Cancer. 2017; (published online Oct 20.)DOI:10.1002/cncr.31049Crossref PubMed Scopus (38) Google Scholar Results from a pooled analyses of individual participant data from prospective cohort studies showed that each five unit increase in BMI in young adulthood was associated with an increased risk of pancreatic cancer (relative risk [RR] 1·18, 95% CI 1·11–1·25),6Genkinger JM Kitahara CM Bernstein L et al.Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies.Ann Oncol. 2015; 26: 2257-2266Crossref PubMed Scopus (102) Google Scholar thyroid cancer (RR 1·13, 1·02–1·25),7Kitahara CM McCullough ML Franceschi S et al.Anthropometric factors and thyroid cancer risk by histological subtype: pooled analysis of 22 prospective studies.Thyroid. 2016; 26: 306-318Crossref PubMed Scopus (115) Google Scholar and myeloma (RR 1·22, 1·09–1·35).8Teras LR Kitahara CM Birmann BM et al.Body size and multiple myeloma mortality: a pooled analysis of 20 prospective studies.Br J Haematol. 2014; 166: 667-676Crossref PubMed Scopus (73) Google Scholar A meta-analysis of studies in colorectal cancer noted an RR of 1·13 (1·08–1·19) for the risk of colorectal cancer per five unit increase in BMI during young adulthood.9Hidayat K Yang CM Shi BM Body fatness at an early age and risk of colorectal cancer.Int J Cancer. 2017; (published online Oct 12.)DOI:10.1002/ijc.31100PubMed Google Scholar Adolescent obesity was also associated with an increased risk of non-cardia gastric cancer in mid-life (median age 47 years; RR 1·78, 1·12–2·83) compared with normal weight.10Levi Z Kark JD Twig G et al.Body mass index at adolescence and risk of noncardia gastric cancer in a cohort of 1.79 million men and women.Cancer. 2017; (published online Oct 20.)DOI:10.1002/cncr.31049Crossref PubMed Scopus (38) Google Scholar The lag between high BMI in adolescence and young adulthood and development of cancer far exceeds the 10 years used in this study and is consistent with the longer carcinogenesis process reported in cancer development models.11Yachida S Jones S Bozic I et al.Distant metastasis occurs late during the genetic evolution of pancreatic cancer.Nature. 2010; 467: 1114-1117Crossref PubMed Scopus (1906) Google Scholar A focus on adiposity in midlife or later and insufficient consideration of lifetime adiposity could lead to substantial underestimation of the contribution of high BMI to the global burden of cancers, especially given the rapidly increasing prevalence of childhood and adolescent adiposity. Future projections that include the changing global patterns of obesity in childhood and adult populations might better account for the impact of lifetime adiposity. For their assessment of diabetes-related cancers, Pearson-Stuttard and colleagues selected colorectal, gallbladder, pancreatic, liver, breast, and endometrial cancer, on the basis of the results of an umbrella review of meta-analyses of diabetes and cancer studies.12Tsilidis KK Kasimis JC Lopez DS Ntzani EE Ioannidis JP Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies.BMJ. 2015; 350: g7607Crossref PubMed Scopus (481) Google Scholar Although the review comprehensively summarised the associations between diabetes and cancer, the use of stringent statistical criteria excluded several cancer types and sites—including bladder, kidney, and oesophageal cancer and myeloma—that might also be associated with diabetes.12Tsilidis KK Kasimis JC Lopez DS Ntzani EE Ioannidis JP Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies.BMJ. 2015; 350: g7607Crossref PubMed Scopus (481) Google Scholar Given the methodological limitations of the umbrella review and accumulating evidence of the role of diabetes13Satija A Spiegelman D Giovannucci E Hu FB Type 2 diabetes and risk of cancer.BMJ. 2015; 350: g7707Crossref PubMed Scopus (26) Google Scholar, 14Garcia-Jimenez C Gutierrez-Salmeron M et al.From obesity to diabetes and cancer: epidemiological links and role of therapies.Br J Cancer. 2016; 114: 716-722Crossref PubMed Scopus (100) Google Scholar in these cancers, it is likely that Pearson-Stuttard and colleagues' study underestimated the burden of cancer due to diabetes. As predicted in this study, the global burden of cancer due to high BMI and diabetes will continue to increase unless the prevalences of these conditions fall. Both obesity and diabetes are preventable causes of cancer for which intervention is possible at multiple levels—in individuals, communities, health-care systems, and policy. More prompt actions are needed to help people maintain a healthy bodyweight throughout the life course, starting at an early age. This online publication has been corrected. The corrected version first appeared at thelancet.com/diabetes-endocrinology on May 23, 2018 This online publication has been corrected. The corrected version first appeared at thelancet.com/diabetes-endocrinology on May 23, 2018 We declare no competing interests. Retracted: Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessmentA substantial number of cancer cases are attributable to diabetes and high BMI. As the prevalence of these cancer risk factors increases, clinical and public health efforts should focus on identifying optimal preventive and screening measures for whole populations and individual patients. Full-Text PDF Open AccessCorrection to Lancet Diabetes Endocrinol 2018; 6: 82–83Park Y, Colditz GA. Diabetes and adiposity: a heavy load for cancer. Lancet Diabetes Endocrinol 2018; 6: 82–83—In this Comment, the third, fourth, fifth, and sixth sentences of the second paragraph should read "5·7% of all cancer in 2012 was attributable to high BMI and diabetes in 2002. When the estimation was restricted to 12 obesity-related cancers and six diabetes-related cancers, 15·3% of cancer cases in men and 13·5% of cases in women were due to the combined effect of high BMI and diabetes. Full-Text PDF Open Access