Article | Published:

Epidemiology

Midlife weight gain is a risk factor for obesity-related cancer

British Journal of Cancervolume 118pages16651671 (2018) | Download Citation

Abstract

Background

Overweight and diabetes are known cancer risk factors. This study examines independent and combined effects of weight gain and metabolic dysfunction during middle-adult years on obesity-related cancer risk.

Methods

Subjects (n = 3850) aged 45–69 years at exams 3–5 in the Framingham Offspring Study were classified according to current and prior (~14 years earlier) weight status, interim weight change and prevalent metabolic dysfunction. Cancer risk among subjects who were overweight at baseline and remained overweight, as well as those who became overweight during follow-up, was compared with risk among normal-weight individuals.

Results

Gaining ≥0.45 kg (≥1.0 pound)/year (vs. maintaining stable weight) over ~14 years increased cancer risk by 38% (95% confidence interval (CI), 1.09, 1.76); combined with metabolic dysfunction, weight gain increased cancer risk by 77% (95% CI, 1.21, 2.59). Compared with non-overweight adults, men and women who became overweight during midlife had 2.18-fold and 1.60-fold increased cancer risks; those who were overweight from baseline had non-statistically significant 28 and 33% increased cancer risks, respectively, despite having a midlife body mass index that was 3.4 kg/m2 higher than those who gained weight later.

Conclusion

Midlife weight gain was a strong cancer risk factor. This excess risk was somewhat stronger among those with concurrent metabolic dysfunction.

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References

  1. 1.

    Renehan, A. G., Tyson, M., Egger, M., Heller, R. F. & Zwahlen, M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371, 569–578 (2008).

  2. 2.

    Ahn, J. et al. Adiposity, adult weight change, and postmenopausal breast cancer risk. Arch. Intern Med. 167, 2091–2102 (2007).

  3. 3.

    Eliassen, A. H., Colditz, G. A., Rosner, B., Willett, W. C. & Hankinson, S. E. Adult weight change and risk of postmenopausal breast cancer. JAMA 296, 193–201 (2006).

  4. 4.

    Morimoto, L. M. et al. Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative. Cancer Causes Control 13, 741–751 (2002).

  5. 5.

    De Mutsert, R., Sun, Q., Willett, W. C., Hu, F. B. & Van Dam, R. M. Overweight in early adulthood, adult weight change, and risk of type 2 diabetes, cardiovascular diseases, and certain cancers in men: a cohort study. Am. J. Epidemiol. 179, 1353–1365 (2014).

  6. 6.

    Schlesinger, S. et al. Body weight gain and risk of colorectal cancer: a systematic review and meta-analysis of observational studies. Obes. Rev. 16, 607–619 (2015).

  7. 7.

    Arnold, M. et al. Duration of adulthood overweight, obesity, and cancer risk in the Women’s Health Initiative: a longitudinal study from the United States. PLoS Med. 13, 1–16 (2016).

  8. 8.

    Han, X. et al. Body mass index at early adulthood, subsequent weight change and cancer incidence and mortality. Int. J. Cancer 135, 2900–2909 (2014).

  9. 9.

    Zheng, Y. et al. Associations of weight gain from early to middle adulthood with major health outcomes later in life. JAMA 318, 255–269 (2017).

  10. 10.

    Cowey, S. & Hardy, R. W. The metabolic syndrome: a high-risk state for cancer? Am. J. Pathol. 169, 1505–1522 (2006).

  11. 11.

    Berger, S. M. et al. Associations between metabolic disorders and risk of cancer in Danish men and women--a nationwide cohort study. BMC Cancer 16, 133 (2016).

  12. 12.

    Kannel, W. B., Feinleib, M., McNamara, P., Garrison, R. & Castelli, W. An investigation of coronary heart disease in families. The Framingham Offspring Study. Am. J. Epidemiol. 110, 281–290 (1979).

  13. 13.

    Garrison, R. J., Kannel, W. B., Stokes, J. & Castelli, W. P. Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev. Med. (Baltim.) 16, 235–251 (1987).

  14. 14.

    Moore, L. L. et al. Weight loss in overweight adults and the long-term risk of hypertension the Framingham study. Arch. Intern. Med. 165, 1298–1303 (2005).

  15. 15.

    Romero-Corral, A. et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J. Obes. 32, 959–966 (2008).

  16. 16.

    Meigs, J. B. et al. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA 283, 221–228 (2000).

  17. 17.

    Schaefer, E. J. et al. Elevated remnant-like particle cholesterol and triglyceride levels in diabetic men and women in the Framingham Offspring Study. Diabetes Care 25, 989–994 (2002).

  18. 18.

    Garrison, R. et al. The association of total cholesterol, triglycerides and plasma lipoprotein cholesterol levels in first degree relatives and spouse pairs. Am. J. Epidemiol. 110, 313–321 (1979).

  19. 19.

    National Heart and Lung Institute. Lipid Research Clinics Program. Manual of Laboratory Operations, Lipid Research Clinics Program, Volume 1, Lipid and Lipoprotein Analysis, DHEW Publications No. (NIH) 75-628 (1974). (https://archive.org/details/manualoflaborato00nati).

  20. 20.

    McNamara, J. R. & Schaefer, E. J. Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin. Chim. Acta 166, 1–8 (1987).

  21. 21.

    Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106, 3143–3421 (2002). 

  22. 22.

    Moore, L. L., Chadid, S., Singer, M. R., Kreger, B. E. & Denis, G. V. Metabolic health reduces risk of obesity-related cancer in Framingham study adults. Cancer Epidemiol. Biomark. Prev. 23, 2057–2065 (2014).

  23. 23.

    Mainous, A. G., Wells, B. J., Koopman, R. J., Everett, C. J. & Gill, J. M. Iron lipids, and risk of cancer in the Framingham Offspring Cohort. Am. J. Epidemiol. 161, 1115–1122 (2005).

  24. 24.

    McMillan, D., Sattar, N., Lean, M. & McCardle, C. Obesity and cancer. BMJ 333, 1109 (2006).

  25. 25.

    Campisi, J. Aging, cellular senescence, and cancer. Annu Rev. Physiol. 75, 685–705 (2013).

  26. 26.

    Byers, T. & Sedjo, R. Does intentional weight loss reduce cancer risk? Diabetes Obes. Metab. 13, 1063–1072 (2011).

  27. 27.

    Fisher, G. et al. Markers of inflammation and fat distribution following weight loss in African-American and white women. Obesity (Silver Spring) 20, 715–720 (2012).

  28. 28.

    Feigelson, H. S., Jonas, C. R., Teras, L. R., Thun, M. J. & Calle, E. E. Weight gain, body mass index, hormone replacement therapy, and postmenopausal breast cancer in a large prospective study. Cancer Epidemiol. Biomark. Prev. 13, 220–224 (2004).

  29. 29.

    Huang, Z. et al. Dual effects of weight and weight gain on breast cancer risk. JAMA 278, 1407–1411 (1997).

  30. 30.

    Lahmann, P. H. et al. Long-term weight change and breast cancer risk: the European prospective investigation into cancer and nutrition (EPIC). Br. J. Cancer 93, 582–589 (2005).

  31. 31.

    Harvie, M. et al. Association of gain and loss of weight before and after menopause with risk of postmenopausal breast cancer in the Iowa women’s health study. Cancer Epidemiol. Biomark. Prev. 14, 656–661 (2005).

  32. 32.

    Eng, S. M. et al. Body size changes in relation to postmenopausal breast cancer among women on Long Island, New York. Am. J. Epidemiol. 162, 229–237 (2005).

  33. 33.

    Rosner, B. et al. Weight and weight changes in early adulthood and later breast cancer risk. Int. J. Cancer 140, 2003–2014 (2017).

  34. 34.

    Alsaker, M., Janszky, I., Opdahl, S., Vatten, L. & Romundstad, P. Weight change in adulthood and risk of postmenopausal breast cancer: the HUNT study of Norway. Br. J. Cancer 109, 1310–1317 (2013).

  35. 35.

    Radimer, K. L. et al. Weight change and the risk of late-onset breast cancer in the original Framingham cohort. Nutr. Cancer 49, 7–13 (2004).

  36. 36.

    Keum, N. et al. Adult weight gain and adiposity-related cancers: a dose–response meta-analysis of prospective observational studies. J. Natl. Cancer Inst. 107, 1–14 (2015).

  37. 37.

    Aleksandrova, K. et al. Adult weight change and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition. Eur. J. Cancer 49, 3526–3536 (2013).

  38. 38.

    Nock, N. L., Thompson, C. L., Tucker, T. C., Berger, N. A. & Li, L. Associations between obesity and changes in adult BMI over time and colon cancer risk. Obesity (Silver Spring) 16, 1099–1104 (2008).

  39. 39.

    Renehan, A. G. et al. Body mass index at different adult ages, weight change, and colorectal cancer risk in the National Institutes of Health-AARP cohort. Am. J. Epidemiol. 176, 1130–1140 (2012).

  40. 40.

    Bisschop, C. N. S. et al. Weight change later in life and colon and rectal cancer risk in participants in the EPIC-PANACEA study. Am. J. Clin. Nutr. 99, 139–147 (2014).

  41. 41.

    Aune, D. et al. Anthropometric factors and ovarian cancer risk: a systematic review and nonlinear dose–response meta-analysis of prospective studies. Int. J. Cancer 136, 1888–1898 (2015).

  42. 42.

    Kahn, R. Metabolic syndrome: is it a syndrome? Does it matter? Circulation 115, 1806–1810 (2007).

  43. 43.

    Simmons, R. K. et al. The metabolic syndrome: useful concept or clinical tool? Report of a WHO expert consultation. Diabetologia 53, 600–605 (2010).

  44. 44.

    Gale, E. Should we dump the metabolic syndrome? Yes. BMJ 336, 640 (2008).

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Acknowledgements

These data were collected with funding from the National Heart, Lung, and Blood Institute (Framingham Study Contract No. N01-HC-25195).

Author contributions

S.C. wrote proposal, oversaw analyses, interpreted results, wrote manuscript; M.R.S. created data set, conducted analyses, critically revised manuscript; B.E.K. directed cancer data collection, adjudicated cancer outcomes, provided analytical advice, critically revised manuscript; M.L.B. conducted background research, edited and critically revised manuscript; L.L.M. provided direction for study design and statistical analyses, interpreted results, edited and critically revised manuscript. All authors consented to manuscript submission and publication.

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Affiliations

  1. Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA

    • Susan Chadid
    • , Martha R. Singer
    • , M. Loring Bradlee
    •  & Lynn L. Moore
  2. General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA

    • Bernard E. Kreger
  3. Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA, 01702, USA

    • Bernard E. Kreger

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Competing interest

The authors declare no competing interests.

Ethical approval:

These analyses were approved by the Boston Medical Center and Boston University Medical Campus Institutional Review Board.

Corresponding author

Correspondence to Lynn L. Moore.

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DOI

https://doi.org/10.1038/s41416-018-0106-x