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Type 2 diabetes and obesity in midlife and breast cancer risk in the Reykjavik cohort

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Abstract

Purpose

As obesity and type 2 diabetes (T2D) have been increasing worldwide, we investigated their association with breast cancer incidence in the Reykjavik Study.

Methods

During 1968–1996, approximately 10,000 women (mean age = 53 ± 9 years) completed questionnaires and donated blood samples. T2D status was classified according to self-report (n = 140) and glucose levels (n  = 154) at cohort entry. A linkage with the Icelandic Cancer Registry provided breast cancer incidence through 2015. Cox regression with age as time metric and adjusted for known confounders was applied to obtain hazard ratios (HR) and 95% confidence intervals (CI).

Results

Of 9,606 participants, 294 (3.1%) were classified as T2D cases at cohort entry while 728 (7.8%) women were diagnosed with breast cancer during 28.4 ± 11.6 years of follow-up. No significant association of T2D (HR 0.95; 95% CI 0.56–1.53) with breast cancer incidence was detected except among the small number of women with advanced breast cancer (HR 3.30; 95% CI 1.13–9.62). Breast cancer incidence was elevated among overweight/obese women without (HR 1.18; 95% CI 1.01–1.37) and with T2D (HR 1.35; 95% CI 0.79–2.31). Height also predicted higher breast cancer incidence (HR 1.03; 95% CI 1.02–1.05). All findings were confirmed in women of the AGES–Reykjavik sub-cohort (n  = 3,103) who returned for an exam during 2002–2006. With a 10% T2D prevalence and 93 incident breast cancer cases, the HR for T2D was 1.18 (95% CI 0.62–2.27).

Conclusions

These findings in a population with low T2D incidence suggest that the presence of T2D does not confer additional breast cancer risk and confirm the importance of height and excess body weight as breast cancer risk factors.

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References

  1. International Diabetes Federation (2017) IDF Diabetes Atlas 2017. https://www.diabetesatlas.org/. Accessed 21 Jun 2018.

  2. Maskarinec G, Grandinetti A, Matsuura G et al (2009) Diabetes prevalence and body mass index differ by ethnicity: the Multiethnic Cohort. Ethn Dis 19:49–55

    PubMed  Google Scholar 

  3. Barnes BB, Steindorf K, Hein R, Flesch-Janys D, Chang-Claude J (2011) Population attributable risk of invasive postmenopausal breast cancer and breast cancer subtypes for modifiable and non-modifiable risk factors. Cancer Epidemiol 35:345–352

    Article  PubMed  Google Scholar 

  4. Parkin DM, Boyd L, Walker LC (2011) The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Br J Cancer 105(Suppl 2): S77–S81

  5. Sprague BL, Trentham-Dietz A, Egan KM, Titus-Ernstoff L, Hampton JM, Newcomb PA (2008) Proportion of invasive breast cancer attributable to risk factors modifiable after menopause. Am J Epidemiol 168:404–411

    Article  PubMed  PubMed Central  Google Scholar 

  6. Bandera EV, Maskarinec G, Romieu I, John EM (2015) Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective. Adv Nutr 6:803–819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Boyle P, Boniol M, Koechlin A et al (2012) Diabetes and breast cancer risk: a meta-analysis. Br J Cancer 107:1608–1617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hsu WC, Boyko EJ, Fujimoto WY et al (2012) Pathophysiologic differences among Asians, native Hawaiians, and other Pacific Islanders and treatment implications. Diabetes Care 35:1189–1198

    Article  PubMed  PubMed Central  Google Scholar 

  9. Pearson-Stuttard J, Zhou B, Kontis V, Bentham J, Gunter MJ, Ezzati M (2018) Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment. Lancet Diabetes Endocrinol 6:e6–e15

    Article  PubMed  PubMed Central  Google Scholar 

  10. Larsson SC, Mantzoros CS, Wolk A (2007) Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 121:856–862

    Article  CAS  PubMed  Google Scholar 

  11. Maskarinec G, Jacobs S, Park SY et al (2017) Type II diabetes, obesity, and breast cancer risk: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev 26:854–861

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gunter MJ, Xie X, Xue X et al (2015) Breast cancer risk in metabolically healthy but overweight postmenopausal women. Cancer Res 75:270–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cust AE, Stocks T, Lukanova A et al (2009) The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis: a prospective study. Breast Cancer Res Treat 113:567–576

    Article  CAS  PubMed  Google Scholar 

  14. Vilbergsson S, Sigurdsson G, Sigvaldason H, Hreidarsson AB, Sigfusson N (1997) Prevalence and incidence of NIDDM in Iceland: evidence for stable incidence among males and females 1967–1991–the Reykjavik Study. Diabet Med 14:491–498

    Article  CAS  PubMed  Google Scholar 

  15. Harris TB, Launer LJ, Eiriksdottir G et al (2007) Age, Gene/environment susceptibility-Reykjavik Study: multidisciplinary applied phenomics. Am J Epidemiol 165:1076–1087

    Article  PubMed  Google Scholar 

  16. Jonsdottir LS, Sigfusson N, Gudnason V, Sigvaldason H, Thorgeirsson G (2002) Do lipids, blood pressure, diabetes, and smoking confer equal risk of myocardial infarction in women as in men? The Reykjavik Study. J Cardiovasc Risk 9:67–76

    Article  PubMed  Google Scholar 

  17. Thorbjarnardottir T, Olafsdottir EJ, Valdimarsdottir UA, Olafsson O, Tryggvadottir L (2014) Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort study of 16 928 women 48 years and older. Acta Oncol 53:752–758

    Article  CAS  PubMed  Google Scholar 

  18. Steingrimsdottir L, Halldorsson TI, Siggeirsdottir K et al (2014) Hip fractures and bone mineral density in the elderly–importance of serum 25-hydroxyvitamin D. PLoS ONE 9:e91122

    Article  PubMed  PubMed Central  Google Scholar 

  19. Olafsdottir E, Aspelund T, Sigurdsson G et al (2009) Unfavourable risk factors for type 2 diabetes mellitus are already apparent more than a decade before onset in a population-based study of older persons: from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik). Eur J Epidemiol 24:307–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Genuth S, Alberti KG, Bennett P et al (2003) Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160–3167

    Article  PubMed  Google Scholar 

  21. World Health Organization (1999) Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. https://apps.who.int/iris/bitstream/10665/66040/1/WHO_NCD_NCS_99.2.pdf. Accessed 6 Mar 2018

  22. Sigurdardottir LG, Jonasson JG, Stefansdottir S et al (2012) Data quality at the Icelandic cancer registry: comparability, validity, timeliness and completeness. Acta Oncol 51:880–889

    Article  PubMed  Google Scholar 

  23. Haraldsdottir A, Steingrimsdottir L, Valdimarsdottir UA et al (2017) Early life residence, fish consumption, and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 26:346–354

    Article  CAS  PubMed  Google Scholar 

  24. Knol MJ, VanderWeele TJ (2012) Recommendations for presenting analyses of effect modification and interaction. Int J Epidemiol 41:514–520

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  26. van den Brandt PA, Spiegelman D, Yaun SS et al (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152:514–527

    Article  PubMed  Google Scholar 

  27. Boyle P, Koechlin A, Pizot C et al (2013) Blood glucose concentrations and breast cancer risk in women without diabetes: a meta-analysis. Eur J Nutr 52:1533–1540

    Article  CAS  PubMed  Google Scholar 

  28. Phillips CM (2017) Metabolically healthy obesity across the life course: epidemiology, determinants, and implications. Ann N Y Acad Sci 1391:85–100

    Article  PubMed  Google Scholar 

  29. Stefan N, Haring HU, Schulze MB (2018) Metabolically healthy obesity: the low-hanging fruit in obesity treatment? Lancet Diabetes Endocrinol 6:249–258

    Article  PubMed  Google Scholar 

  30. Neeland IJ, Poirier P, Despres JP (2018) Cardiovascular and metabolic heterogeneity of obesity: clinical challenges and implications for management. Circulation 137:1391–1406

    Article  PubMed  PubMed Central  Google Scholar 

  31. Olafsdottir E, Aspelund T, Sigurdsson G et al (2013) Similar decline in mortality rate of older persons with and without type 2 diabetes between 1993 and 2004 the Icelandic population-based Reykjavik and AGES-Reykjavik cohort studies. BMC Public Health 13:36

    Article  PubMed  PubMed Central  Google Scholar 

  32. Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990–2015: a novel analysis from the Global Burden of Disease Study 2015 (2017) Lancet 390: 231–266

  33. Barry E, Roberts S, Oke J, Vijayaraghavan S, Normansell R, Greenhalgh T (2017) Efficacy and effectiveness of screen and treat policies in prevention of type 2 diabetes: systematic review and meta-analysis of screening tests and interventions. BMJ 356:i6538

    Article  PubMed  Google Scholar 

  34. Walker JJ, Johnson JA, Wild SH (2013) Diabetes treatments and cancer risk: the importance of considering aspects of drug exposure. Lancet Diabetes Endocrinol 1:132–139

    Article  PubMed  Google Scholar 

  35. Bergsveinsson J, Aspelund T, Gudnason V, Benediktsson R (2007) Prevalence of type 2 diabetes mellitus in Iceland 1967–2002. Laeknabladid 93:397–402

    PubMed  Google Scholar 

Download references

Acknowledgments

The AGES–Reykjavik Study was funded by NIH contract N01-AG-12100, the Intramural Research Program of the National Institute on Aging, the Icelandic Heart Association, and the Icelandic Parliament. This work was also supported by the Icelandic Centre for Research, RANNIS Grant Number: 152495051, https://en.rannis.is/ (to AH), and the Public Health Fund of the Icelandic Directorate of Health (to AH). GM was funded by a Fulbright Global Scholar Award (2017–2018).

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Authors and Affiliations

  1. University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA

    Gertraud Maskarinec

  2. Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    Álfheiður Haraldsdóttir, Kristjana Einarsdóttir, Thor Aspelund & Jóhanna E. Torfadóttir

  3. Faculty of Food Science and Human Nutrition, University of Iceland, Reykjavik, Iceland

    Álfheiður Haraldsdóttir

  4. The Icelandic Cancer Registry, Reykjavik, Iceland

    Laufey Tryggvadóttir

  5. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    Laufey Tryggvadóttir

  6. Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

    Tamara B. Harris

  7. The Icelandic Heart Association, Kopavogur, Iceland

    Vilmundur Gudnason

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  1. Gertraud Maskarinec
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  2. Álfheiður Haraldsdóttir
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  3. Kristjana Einarsdóttir
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  4. Thor Aspelund
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  8. Jóhanna E. Torfadóttir
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Correspondence to Gertraud Maskarinec.

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Maskarinec, G., Haraldsdóttir, Á., Einarsdóttir, K. et al. Type 2 diabetes and obesity in midlife and breast cancer risk in the Reykjavik cohort. Cancer Causes Control 30, 1057–1065 (2019). https://doi.org/10.1007/s10552-019-01213-y

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