On the role of genes relative to the environment in carcinogenesis.
Age-specific incidence rates for cancers of the female breast, ovary, corpus uteri, testis, prostate and male and female cancers of the stomach, colon, rectum, lung, and male and female Hodgkin's disease in 51 worldwide populations in the 1990 era were obtained from a published source. For each cancer in each population, rates were summed over all age-intervals from birth to 84 years to give total incidence. The ages at 1/10th- and 1/2-this total were identified and found to vary among cancers, but, for each cancer except Hodgkin's disease, to be rather invariant with population. Except for Hodgkin's disease, the impact of this population-independent influence is far greater than the impact of the total population-dependent influence. The nature of this population-independent aging influence can be explained as the resultant of two opposing processes. On the one hand, DNA damage accumulates with advancing age and this predisposes to malignant transformation. On the other hand, cellular proliferation rates decline with advancing age and this inhibits malignant transformation. With advancing age, the second process becomes dominant suggesting that beyond some advanced age, the risk of cancer declines with advancing age.