Free testosterone drives cancer aggressiveness: evidence from US population studies

PLoS One. 2013 Apr 24;8(4):e61955. doi: 10.1371/journal.pone.0061955. Print 2013.

Abstract

Cancer incidence and mortality are higher in males than in females, suggesting that some gender-related factors are behind such a difference. To analyze this phenomenon the most recent Surveillance, Epidemiology and End Results (SEER) database served to access cancer survival data for the US population. Patients with gender-specific cancer and with limited information were excluded and this fact limited the sample size to 1,194,490 patients. NHANES III provided the distribution of physiologic variables in US population (n = 29,314). Cox model and Kaplan-Meier method were used to test the impact of gender on survival across age, and to calculate the gender-specific hazard ratio of dying from cancer five years following diagnosis. The distribution of the hazard ratio across age was then compared with the distribution of 65 physiological variables assessed in NHANES III. Spearman and Kolmogorov-Smirnov test assessed the homology. Cancer survival was lower in males than in females in the age range 17 to 61 years. The risk of death from cancer in males was about 30% higher than that of females of the same age. This effect was present only in sarcomas and epithelial solid tumors with distant disease and the effect was more prominent in African-Americans than Caucasians. When compared to the variables assessed in the NHANES III study, the hazard ratio almost exactly matched the distribution of free testosterone in males; none of the other analyzed variables exhibited a similar homology. Our findings suggest that male sex hormones give rise to cancer aggressiveness in patients younger than 61 years.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms / epidemiology
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Population Surveillance
  • SEER Program
  • Sex Factors
  • Testosterone / metabolism*
  • United States / epidemiology
  • Young Adult

Substances

  • Testosterone

Grant support

This work was partially supported by the Ruth C. Donovan Cancer Research Program and by a generous donation from Mr. and Mrs. Ruggles and by a grant from Associazione Italiana Ricerca sul Cancro (IG11975). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.