Racial differences in prostate cancer: does timing of puberty play a role?


The burden of prostate cancer has a remarkably disproportionate distribution across racial groups. For example, in the USA, African Americans are twice as likely as individuals of European ancestry to develop or die from prostate cancer, and have a more aggressive disease nature at diagnosis. In contrast, Asian American men have the lowest incidence and mortality rates of prostate cancer. That considerable racial disparities exist even in the subclinical stage of prostate cancer among young men in their 20–30s suggests that patterns of prostate carcinogenesis start to diverge even earlier, perhaps during puberty, when the prostate matures at its most rapid rate. Mendelian randomisation studies have provided strong population-based evidence supporting the hypothesis that earlier onset of puberty increases the risk of prostate cancer—particularly of high grade—and prostate cancer-specific mortality later in life, observations which correspond to the epidemiology of the disease in African Americans. Notably, African American boys initiate genital development ~1 year earlier and thus go through longer periods of pubertal maturation compared with European American boys. In this perspective, bringing together existing evidence, we point to puberty as a potential critical window of increased susceptibility to prostate carcinogenesis that could account for the marked prevailing racial differences in the burden of prostate cancer.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Puberty as a potential window of susceptibility for prostate cancer development.


  1. 1.

    Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 70, 7–30 (2020).

  2. 2.

    Chornokur, G., Dalton, K., Borysova, M. E. & Kumar, N. B. Disparities at presentation, diagnosis, treatment, and survival in African American men, affected by prostate cancer. Prostate 71, 985–997 (2011).

  3. 3.

    Morrison, B. F., Aiken, W. D. & Mayhew, R. Current state of prostate cancer treatment in Jamaica. Ecancermedicalscience 8, 456 (2014).

  4. 4.

    Morrison, B. F., Aiken, W. D., Mayhew, R., Gordon, Y. & Odedina, F. T. Prostate cancer knowledge, prevention, and screening behaviors in Jamaican men. J. Cancer Educ. 32, 352–356 (2017).

  5. 5.

    Hoffman, R. M., Gilliland, F. D., Eley, J. W., Harlan, L. C., Stephenson, R. A., Stanford, J. L. et al. Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study. J. Natl Cancer Inst. 93, 388–395 (2001).

  6. 6.

    Howlader, N., Noone, A. M., Krapcho, M., Miller, D., Brest, A., Yu, M. et al. SEER cancer statistics review, 1975–2016. (National Cancer Institute, 2019).

  7. 7.

    Jahn, J. L., Giovannucci, E. L. & Stampfer, M. J. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the prostate-specific antigen-era. Int J. Cancer 137, 2795–2802 (2015).

  8. 8.

    Sutcliffe, S. & Colditz, G. A. Prostate cancer: is it time to expand the research focus to early-life exposures? Nat. Rev. Cancer 13, 208–518 (2013).

  9. 9.

    Clarke, M. A. & Joshu, C. E. Early life exposures and adult cancer risk. Epidemiol. Rev. 39, 11–27 (2017).

  10. 10.

    Cousminer, D. L., Stergiakouli, E., Berry, D. J., Ang, W., Groen-Blokhuis, M. M., Korner, A. et al. Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Hum. Mol. Genet 23, 4452–4464 (2014).

  11. 11.

    Day, F. R., Bulik-Sullivan, B., Hinds, D. A., Finucane, H. K., Murabito, J. M., Tung, J. Y. et al. Shared genetic aetiology of puberty timing between sexes and with health-related outcomes. Nat. Commun. 6, 8842 (2015).

  12. 12.

    Tanner, J. M. Foetus into man: physical growth from conception to maturity. (Harvard University Press, Cambridge, 1990) .

  13. 13.

    Spear, B. A. Adolescent growth and development. J. Am. Diet. Assoc. 102, S23–S29 (2002).

  14. 14.

    Marshall, W. A. & Tanner, J. M. Variations in the pattern of pubertal changes in boys. Arch. Dis. Child 45, 13–23 (1970).

  15. 15.

    Abreu, A. P. & Kaiser, U. B. Pubertal development and regulation. Lancet Diabetes Endocrinol. 4, 254–264 (2016).

  16. 16.

    Day, F. R., Thompson, D. J., Helgason, H., Chasman, D. I., Finucane, H., Sulem, P. et al. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. Nat. Genet 49, 834–841 (2017).

  17. 17.

    Parent, A. S., Teilmann, G., Juul, A., Skakkebaek, N. E., Toppari, J. & Bourguignon, J. P. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr. Rev. 24, 668–693 (2003).

  18. 18.

    Villamor, E. & Jansen, E. C. Nutritional determinants of the timing of puberty. Annu Rev. Public Health 37, 33–46 (2016).

  19. 19.

    Lee, J. M., Wasserman, R., Kaciroti, N., Gebremariam, A., Steffes, J., Dowshen, S. et al. Timing of puberty in overweight versus obese boys. Pediatrics 137, e20150164 (2016).

  20. 20.

    Gunther, A. L., Karaolis-Danckert, N., Kroke, A., Remer, T. & Buyken, A. E. Dietary protein intake throughout childhood is associated with the timing of puberty. J. Nutr. 140, 565–571 (2010).

  21. 21.

    Krieger, N., Kiang, M. V., Kosheleva, A., Waterman, P. D., Chen, J. T. & Beckfield, J. Age at menarche: 50-year socioeconomic trends among US-born black and white women. Am. J. Public Health 105, 388–397 (2015).

  22. 22.

    Mouritsen, A., Aksglaede, L., Sorensen, K., Mogensen, S. S., Leffers, H., Main, K. M. et al. Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty. Int J. Androl. 33, 346–359 (2010).

  23. 23.

    Burns, J. S., Lee, M. M., Williams, P. L., Korrick, S. A., Sergeyev, O., Lam, T. et al. Associations of peripubertal serum dioxin and polychlorinated biphenyl concentrations with pubertal timing among Russian boys. Environ. Health Perspect. 124, 1801–1807 (2016).

  24. 24.

    Wyshak, G. & Frisch, R. E. Evidence for a secular trend in age of menarche. N. Engl. J. Med. 306, 1033–1035 (1982).

  25. 25.

    Meng, X., Li, S., Duan, W., Sun, Y. & Jia, C. Secular trend of age at menarche in Chinese adolescents born from 1973 to 2004. Pediatrics 140, e20170085 (2017).

  26. 26.

    Bogaert, A. F. Age at puberty and father absence in a national probability sample. J. Adolesc. 28, 541–546 (2005).

  27. 27.

    Deardorff, J., Ekwaru, J. P., Kushi, L. H., Ellis, B. J., Greenspan, L. C., Mirabedi, A. et al. Father absence, body mass index, and pubertal timing in girls: differential effects by family income and ethnicity. J. Adolesc. Health 48, 441–447 (2011).

  28. 28.

    Swyer, G. I. Post-natal growth changes in the human prostate. J. Anat. 78, 130–145 (1944).

  29. 29.

    Wernert, N., Seitz, G. & Achtstatter, T. Immunohistochemical investigation of different cytokeratins and vimentin in the prostate from the fetal period up to adulthood and in prostate carcinoma. Pathol. Res Pract. 182, 617–626 (1987).

  30. 30.

    Kasper, S. Exploring the origins of the normal prostate and prostate cancer stem cell. Stem Cell Rev. 4, 193–201 (2008).

  31. 31.

    Diamandis, E. P. & Yu, H. Does prostate cancer start at puberty? J. Clin. Lab Anal. 10, 468–469 (1996).

  32. 32.

    Cole, T. J., Ahmed, M. L., Preece, M. A., Hindmarsh, P. & Dunger, D. B. The relationship between insulin-like growth factor 1, sex steroids and timing of the pubertal growth spurt. Clin. Endocrinol. 82, 862–869 (2015).

  33. 33.

    Casazza, K., Higgins, P. B., Fernandez, J. R., Goran, M. I. & Gower, B. A. Longitudinal analysis of the insulin-like growth factor system in African-American and European American children and adolescents. J. Clin. Endocrinol. Metab. 93, 4917–4923 (2008).

  34. 34.

    Rowlands, M. A., Gunnell, D., Harris, R., Vatten, L. J., Holly, J. M. & Martin, R. M. Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis. Int J. Cancer 124, 2416–2429 (2009).

  35. 35.

    Travis, R. C., Appleby, P. N., Martin, R. M., Holly, J. M. P., Albanes, D., Black, A. et al. A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk. Cancer Res 76, 2288–2300 (2016).

  36. 36.

    Sandhu, J., Davey Smith, G., Holly, J., Cole, T. J. & Ben-Shlomo, Y. Timing of puberty determines serum insulin-like growth factor-I in late adulthood. J. Clin. Endocrinol. Metab. 91, 3150–3157 (2006).

  37. 37.

    Platz, E. A., Pollak, M. N., Rimm, E. B., Majeed, N., Tao, Y., Willett, W. C. et al. Racial variation in insulin-like growth factor-1 and binding protein-3 concentrations in middle-aged men. Cancer Epidemiol. Biomark. Prev. 8, 1107–1110 (1999).

  38. 38.

    Chan, J. M., Stampfer, M. J., Giovannucci, E., Gann, P. H., Ma, J., Wilkinson, P. et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279, 563–566 (1998).

  39. 39.

    Chan, J. M., Stampfer, M. J., Ma, J., Gann, P., Gaziano, J. M., Pollak, M. et al. Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. J. Natl Cancer Inst. 94, 1099–1106 (2002).

  40. 40.

    Cheng, I., Stram, D. O., Penney, K. L., Pike, M., Le Marchand, L., Kolonel, L. N. et al. Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort. J. Natl Cancer Inst. 98, 123–134 (2006).

  41. 41.

    Kelsey, J. L., Gammon, M. D. & John, E. M. Reproductive factors and breast cancer. Epidemiol. Rev. 15, 36–47 (1993).

  42. 42.

    Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol. 13, 1141–1151 (2012).

  43. 43.

    Bertrand, K. A., Gerlovin, H., Bethea, T. N. & Palmer, J. R. Pubertal growth and adult height in relation to breast cancer risk in African American women. Int J. Cancer 141, 2462–2470 (2017).

  44. 44.

    Honda, G. D., Bernstein, L., Ross, R. K., Greenland, S., Gerkins, V. & Henderson, B. E. Vasectomy, cigarette smoking, and age at first sexual intercourse as risk factors for prostate cancer in middle-aged men. Br. J. Cancer 57, 326–331 (1988).

  45. 45.

    Dennis, L. K. & Dawson, D. V. Meta-analysis of measures of sexual activity and prostate cancer. Epidemiology 13, 72–79 (2002).

  46. 46.

    Habel, L. A., Van Den Eeden, S. K. & Friedman, G. D. Body size, age at shaving initiation, and prostate cancer in a large, multiracial cohort. Prostate 43, 136–143 (2000).

  47. 47.

    Barba, M., Terrenato, I., Schunemann, H. J., Fuhrman, B., Sperati, F., Teter, B. et al. Indicators of sexual and somatic development and adolescent body size in relation to prostate cancer risk: results from a case-control study. Urology 72, 183–187 (2008).

  48. 48.

    Nair-Shalliker, V., Yap, S., Nunez, C., Egger, S., Rodger, J., Patel, M. I. et al. Adult body size, sexual history and adolescent sexual development, may predict risk of developing prostate cancer: results from the New South Wales Lifestyle and Evaluation of Risk Study (CLEAR). Int J. Cancer 140, 565–574 (2017).

  49. 49.

    Bonilla, C., Lewis, S. J., Martin, R. M., Donovan, J. L., Hamdy, F. C., Neal, D. E. et al. Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort. BMC Med 14, 66 (2016).

  50. 50.

    Yarmolinsky, J., Wade, K. H., Richmond, R. C., Langdon, R. J., Bull, C. J., Tilling, K. M. et al. Causal inference in cancer epidemiology: what is the role of Mendelian randomization? Cancer Epidemiol. Biomark. Prev. 27, 995–1010 (2018).

  51. 51.

    Herman-Giddens, M. E., Steffes, J., Harris, D., Slora, E., Hussey, M., Dowshen, S. A. et al. Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings network. Pediatrics 130, e1058–e1068 (2012).

  52. 52.

    Susman, E. J., Houts, R. M., Steinberg, L., Belsky, J., Cauffman, E., Dehart, G. et al. Longitudinal development of secondary sexual characteristics in girls and boys between ages 91/2 and 151/2 years. Arch. Pediatr. Adolesc. Med. 164, 166–173 (2010).

  53. 53.

    Lopez, D. S., Peskoe, S. B., Joshu, C. E., Dobs, A., Feinleib, M., Kanarek, N. et al. Racial/ethnic differences in serum sex steroid hormone concentrations in US adolescent males. Cancer Causes Control 24, 817–826 (2013).

  54. 54.

    Biro, F. M., Greenspan, L. C., Galvez, M. P., Pinney, S. M., Teitelbaum, S., Windham, G. C. et al. Onset of breast development in a longitudinal cohort. Pediatrics 132, 1019–1027 (2013).

  55. 55.

    Biro, F. M., Pajak, A., Wolff, M. S., Pinney, S. M., Windham, G. C., Galvez, M. P. et al. Age of menarche in a longitudinal US cohort. J. Pediatr. Adolesc. Gynecol. 31, 339–345 (2018).

  56. 56.

    Mehta, H. H., Gao, Q., Galet, C., Paharkova, V., Wan, J., Said, J. et al. IGFBP-3 is a metastasis suppression gene in prostate cancer. Cancer Res 71, 5154–5163 (2011).

  57. 57.

    Ezzat, V. A., Duncan, E. R., Wheatcroft, S. B. & Kearney, M. T. The role of IGF-I and its binding proteins in the development of type 2 diabetes and cardiovascular disease. Diabetes Obes. Metab. 10, 198–211 (2008).

  58. 58.

    Farvid, M. S., Cho, E., Chen, W. Y., Eliassen, A. H. & Willett, W. C. Adolescent meat intake and breast cancer risk. Int J. Cancer 136, 1909–1920 (2015).

  59. 59.

    Farvid, M. S., Chen, W. Y., Michels, K. B., Cho, E., Willett, W. C. & Eliassen, A. H. Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study. BMJ 353, i2343 (2016).

Download references

Author information




Both authors contributed to researching data, discussion of content and drafting, reviewing and revising of the paper.

Corresponding authors

Correspondence to Jinhee Hur or Edward Giovannucci.

Ethics declarations

Ethical approval and consent to participate

Not applicable.

Consent to publish

Not applicable.

Data availability

Not applicable.

Competing interests

The authors declare no competing interests.

Funding information


Additional information

Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hur, J., Giovannucci, E. Racial differences in prostate cancer: does timing of puberty play a role?. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-0897-4

Download citation