European Journal of Epidemiology

, Volume 27, Issue 3, pp 187–196

Enigmatic sex disparities in cancer incidence

  • Gustaf Edgren
  • Liming Liang
  • Hans-Olov Adami
  • Ellen T. Chang


In this study we aimed to identify cancers where there is a consistent sex disparity, with the goal of identifying unexplained sex disparities that may offer promising opportunities for etiologic research. Age- and sex-specific cancer incidence data from Cancer Incidence in Five Continents, provided by the International Agency for Research on Cancer, were used to calculate incidence rate ratios for 35 cancer sites, comparing men to women, adjusting for attained age, gross domestic product (GDP), and geographical region. Genital cancers and breast cancer were excluded. The consistency of relative risks was examined by GDP and geographical region and, in a subset of longstanding cancer registers, by calendar year. For each cancer site, the sex disparity was broadly classified as plausibly explained by established environmental risk factors, partly explained, or unexplained. Cancer incidence was statistically significantly higher in men than women at 32 of 35 sites, with disparities >2-fold for 15 sites and >4-fold for 5 sites. For nearly all sites, the sex disparity was consistent across GDP groups and geographical regions. However, the incidence rate ratios varied considerably by age at diagnosis. The sex disparity for 13 cancer sites was considered to be entirely unexplained by known risk factors; these sites showed strikingly little variation in the incidence rate ratios over decades. Thus, the basis of many of the largest sex disparities in cancer incidence seems mostly unknown, highlighting the need for intensified research into its origins.


Cancer Gender Environmental risk factors Genetic risk factors Occupational risk factors Gender inequality 

Supplementary material

10654_2011_9647_MOESM1_ESM.pdf (12.4 mb)
Supplementary material 1 (PDF 12,662 kb)


  1. 1.
    Adami HO, Hunter D, Trichopoulos D, editors. Textbook of cancer epidemiology. 2nd ed. New York: Oxford University Press; 2008.Google Scholar
  2. 2.
    Cook MB, Dawsey SM, Freedman ND, et al. Sex disparities in cancer incidence by period and age. Cancer Epidemiol Biomarkers Prev. 2009;18(4):1174–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Cook MB, McGlynn KA, Devesa SS, Freedman ND, Anderson WF. Sex disparities in cancer mortality and survival. Cancer Epidemiol Biomarkers Prev. 2011;20(8):1629–37.PubMedCrossRefGoogle Scholar
  4. 4.
    Fuchs CS, Mayer RJ. Gastric carcinoma. N Engl J Med. 1995;333(1):32–41.PubMedCrossRefGoogle Scholar
  5. 5.
    Czene K, Adami HO, Chang ET. Sex- and kindred-specific familial risk of non-Hodgkin’s lymphoma. Cancer Epidemiol Biomarkers Prev. 2007;16(11):2496–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Schwartz EE, Upton AC. Factors influencing the incidence of leukemia: special consideration of the role of ionizing radiation. Blood. 1958;13(9):845–64.PubMedGoogle Scholar
  7. 7.
    Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12(6):421–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Haselkorn T, Stewart SL, Horn-Ross PL. Why are thyroid cancer rates so high in southeast asian women living in the United States? The bay area thyroid cancer study. Cancer Epidemiol Biomarkers Prev. 2003;12(2):144–50.PubMedGoogle Scholar
  9. 9.
    Gitschier J, Wood WI, Goralka TM, et al. Characterization of the human factor VIII gene. Nature. 1984;312(5992):326–30.PubMedCrossRefGoogle Scholar
  10. 10.
    Camp PG, Goring SM. Gender and the diagnosis, management, and surveillance of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2007;4(8):686–91.PubMedCrossRefGoogle Scholar
  11. 11.
    Curado MP, Edwards B, Shin HR, et al., editors. Cancer incidence in five continents, vol. IX. Lyon: IARC Scientific Publications; 2007.Google Scholar
  12. 12.
    World Development Indicators [database on the Internet]. The World Bank. 2009. Available from:
  13. 13.
    Sasco AJ, Secretan MB, Straif K. Tobacco smoking and cancer: a brief review of recent epidemiological evidence. Lung Cancer. 2004;45(Suppl 2):S3–9.PubMedCrossRefGoogle Scholar
  14. 14.
    MacKay J, Eriksen M. The tobacco atlas. Geneva: World Health Organization; 2002.Google Scholar
  15. 15.
    IARC monographs on the evaluation of carcinogenic risks to humans: tobacco smoke and involuntary smoking. Lyon: International Agency for Research on Cancer; 2002.Google Scholar
  16. 16.
    Bagnardi V, Blangiardo M, La Vecchia C, Corrao G. A meta-analysis of alcohol drinking and cancer risk. Br J Cancer. 2001;85(11):1700–5.PubMedCrossRefGoogle Scholar
  17. 17.
    IARC monographs on the evaluation of carcinogenic risks to humans: alcohol drinking. Lyon: International Agency for Research on Cancer; 1988.Google Scholar
  18. 18.
    Driscoll T, Steenland K, Prüss-Üstun A, Imel Nelson D, Leigh J. Occupational carcinogens: assessing the environmental burden of disease at national and local levels. Prüss-Üstün A, Campbell-Lendrum D, Corvalán C, Woodward A, editors. Geneva: World Health Organization; 2004.Google Scholar
  19. 19.
    Black RJ, Bray F, Ferlay J, Parkin DM. Cancer incidence and mortality in the European Union: cancer registry data and estimates of national incidence for 1990. Eur J Cancer. 1997;33(7):1075–107.PubMedCrossRefGoogle Scholar
  20. 20.
    Whitacre CC. Sex differences in autoimmune disease. Nat Immunol. 2001;2(9):777–80.PubMedCrossRefGoogle Scholar
  21. 21.
    Schofield WN. Predicting basal metabolic rate, new standards and review of previous work. Hum Nutr Clin Nutr. 1985;39(Suppl 1):5–41.PubMedGoogle Scholar
  22. 22.
    Albanes D, Winick M. Are cell number and cell proliferation risk factors for cancer? J Natl Cancer Inst. 1988;80(10):772–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2010;61:301–16.PubMedCrossRefGoogle Scholar
  24. 24.
    IARC monographs on the evaluation of carcinogenic risks to humans: combined estrogen-progestogen contraceptives and combined estrogen-progestogen menopausal therapy. Lyon: International Agency for Research on Cancer; 2005.Google Scholar
  25. 25.
    Liu J, Morgan M, Hutchison K, Calhoun VD. A study of the influence of sex on genome wide methylation. PLoS One. 2010;5(4):e10028.PubMedCrossRefGoogle Scholar
  26. 26.
    Bjornsson HT, Sigurdsson MI, Fallin MD, et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA. 2008;299(24):2877–83.PubMedCrossRefGoogle Scholar
  27. 27.
    Kaminsky ZA, Tang T, Wang SC, et al. DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet. 2009;41(2):240–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Christensen BC, Houseman EA, Marsit CJ, et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009;5(8):e1000602.PubMedCrossRefGoogle Scholar
  29. 29.
    Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102(30):10604–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358(11):1148–59.PubMedCrossRefGoogle Scholar
  31. 31.
    Alexander DD, Mink PJ, Adami HO, et al. The non-Hodgkin lymphomas: a review of the epidemiologic literature. Int J Cancer. 2007;120(Suppl 12):1–39.PubMedCrossRefGoogle Scholar
  32. 32.
    Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345(11):784–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin’s lymphoma after infectious mononucleosis. N Engl J Med. 2003;349(14):1324–32.PubMedCrossRefGoogle Scholar
  34. 34.
    Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Henle G, Henle W. Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma. Int J Cancer. 1976;17(1):1–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981;2(8256):1129–33.Google Scholar
  37. 37.
    Bruix J, Barrera JM, Calvet X, et al. Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis. Lancet. 1989;2(8670):1004–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Lleo A, Battezzati PM, Selmi C, Gershwin ME, Podda M. Is autoimmunity a matter of sex? Autoimmun Rev. 2008;7(8):626–30.PubMedCrossRefGoogle Scholar
  39. 39.
    Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008;8(9):737–44.PubMedCrossRefGoogle Scholar
  40. 40.
    Inman RD. Immunologic sex differences and the female predominance in systemic lupus erythematosus. Arthr Rheum. 1978;21(7):849–52.CrossRefGoogle Scholar
  41. 41.
    Nelson RL, Davis FG, Sutter E, Sobin LH, Kikendall JW, Bowen P. Body iron stores and risk of colonic neoplasia. J Natl Cancer Inst. 1994;86(6):455–60.PubMedCrossRefGoogle Scholar
  42. 42.
    Stevens RG, Jones DY, Micozzi MS, Taylor PR. Body iron stores and the risk of cancer. N Engl J Med. 1988;319(16):1047–52.PubMedCrossRefGoogle Scholar
  43. 43.
    Hercberg S, Estaquio C, Czernichow S, et al. Iron status and risk of cancers in the SU.VI.MAX cohort. J Nutr. 2005;135(11):2664–8.Google Scholar
  44. 44.
    Edgren G, Nyren O, Melbye M. Cancer as a ferrotoxic disease: are we getting hard stainless evidence? J Natl Cancer Inst. 2008;100(14):976–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Edgren G, Reilly M, Hjalgrim H, et al. Donation frequency, iron loss, and risk of cancer among blood donors. J Natl Cancer Inst. 2008;100(8):572–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Beard JL, Dawson H, Pinero DJ. Iron metabolism: a comprehensive review. Nutr Rev. 1996;54(10):295–317.PubMedCrossRefGoogle Scholar
  47. 47.
    Stevens RG. Iron and the risk of cancer. Med Oncol Tumor Pharmacother. 1990;7(2–3):177–81.PubMedGoogle Scholar
  48. 48.
    Zacharski LR, Chow BK, Howes PS, et al. Reduction of iron stores and cardiovascular outcomes in patients with peripheral arterial disease: a randomized controlled trial. JAMA. 2007;297(6):603–10.PubMedCrossRefGoogle Scholar
  49. 49.
    Zacharski LR, Chow BK, Howes PS, et al. Decreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trial. J Natl Cancer Inst. 2008;100(14):996–1002.PubMedCrossRefGoogle Scholar
  50. 50.
    Frisch M, Glimelius B, van den Brule AJ, et al. Sexually transmitted infection as a cause of anal cancer. N Engl J Med. 1997;337(19):1350–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Edgren G, Sparen P. Risk of anogenital cancer after diagnosis of cervical intraepithelial neoplasia: a prospective population-based study. Lancet Oncol. 2007;8(4):311–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Fraumeni JF Jr. Cancers of the pancreas and biliary tract: epidemiological considerations. Cancer Res. 1975;35(11 Pt. 2):3437–46.Google Scholar
  53. 53.
    Tazuma S. Gallstone disease: epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic). Best Pract Res Clin Gastroenterol. 2006;20(6):1075–83.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Gustaf Edgren
    • 1
    • 2
  • Liming Liang
    • 2
  • Hans-Olov Adami
    • 1
    • 2
  • Ellen T. Chang
    • 3
    • 4
  1. 1.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  2. 2.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  3. 3.Cancer Prevention Institute of CaliforniaFremontUSA
  4. 4.Department of Health Research and PolicyStanford University School of MedicineStanfordUSA

Personalised recommendations