RE: "PARENTAL AGE AT CHILD'S BIRTH AND SON'S RISK OF PROSTATE CANCER: THE FRAMINGHAM STUDY"

William H. James

Galton Laboratory Department of Biology University College London London, United Kingdom NW1 2HE

Zhang et al. (1Go) reported that paternal age, but not maternal age, is significantly and positively associated with the risk of prostatic cancer. These authors suggested that this effect may operate through increased germ cell mutation or by "mechanisms not yet defined" (1Go, p. 1208). I should like to suggest such a possible mechanism.

Both prostatic cancer and coital rates are reportedly associated with androgen levels. In particular, the androgen most closely related to coital rates is dihydrotestosterone (DHT) (2Go), which is also strongly suspected of being causally related to prostatic cancer. This suspicion is based on the findings that the well-established racial variation in the incidence of prostatic cancer is paralleled by racial variation in rates of activity of 5-alpha-reductase (which metabolizes testosterone to DHT) (3GoGo–5Go).

If it were correct that DHT is causally implicated in prostatic cancer, one might suggest that the association with elderly fathers is mediated by coital rate and hence fecundability (6Go) and hence fertility; even (perhaps especially) at advanced parental ages, many pregnancies are unplanned. In other words, men who sire children at advanced ages do not constitute a random sample of fathers. Instead, one would expect them to be self-selected for high levels of androgens. High androgen levels are associated with the psychological trait of sensation seeking—and, in particular, varied sexual experience and risk taking (7Go). Ex hypothesi, elderly fathers have higher DHT levels (when age is controlled) than other fathers do. Moreover, testosterone, at any level, shows substantial heritability (8Go). Thus, if I am correct, the finding of a paternal age effect in prostatic cancer can be reconciled with the hypothesis that the disease is caused by androgens.

Editor's note: In accordance with Journal policy, Dr. Zhang and colleagues were asked whether they wanted to respond to this letter but chose not to do so.

REFERENCES

  1. Zhang Y, Kreger BE, Dorgan JF, et al. Parental age at child's birth and son's risk of prostate cancer: the Framingham Study. Am J Epidemiol 1999;150:1208–12.[Abstract]
  2. Mantzoros CS, Georgiadis EI, Trichopoulos D. Contribution of dihydrotestosterone to male sexual behaviour. BMJ 1995;310:1289–91.[Abstract/Free Full Text]
  3. Ross RK, Bernstein L. Lobo RA, et al. 5-alpha-reductase activity and risk of prostate cancer among Japanese and U.S. white and black males. Lancet 1992;239:887–9.
  4. Reichardt JKV, Makridakis N, Henderson BE, et al. Genetic variability of the human SRD5A2 gene: implications for prostate cancer risk. Cancer Res 1995;55:3973–5.[Abstract]
  5. McIntosh H. Who do African-American men suffer more prostate cancer? J Natl Cancer Inst 1997;89:188–9.[Free Full Text]
  6. Potter RG, Millman SR. Fecundability and the frequency of marital intercourse: new models incorporating the aging of gametes. Popul Studies 1986;40:159–70.[ISI]
  7. Daitzman R, Zuckerman M. Disinhibitory sensation seeking and gonadal hormones. Personal Individ Diff 1980;1:103–10.[ISI]
  8. Harris JA, Vernon PA, Boomsma DI. The heritability of testosterone: a study of Dutch adolescent twins and their parents. Behav Genet 1998;28:165–71.[ISI][Medline]




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