The age distribution of cancer and a multi-stage theory of carcinogenesis

TLDR

Cancer mortality patterns over the past 75 years generally support the multi‑stage theory, with most sites aligning under constant carcinogenic factors, while others require varying factor strengths. The study tests the theory that human cancer results from successive cellular changes by examining age‑specific mortality rates for 17 cancer types. The authors analyze age‑specific mortality data for 17 cancers to evaluate the multi‑stage carcinogenesis model. The authors derived a weighting formula that shows the timing of carcinogenic factor strength is critical for each stage, and this explains why early circumcision protects against penile cancer.

Abstract

The theory that human cancer is the end-result of several successive cellular changes is tested by examining the age specific mortality rates for 17 types of cancer. On the supposition that the carcinogenic factors responsible have remained approximately constant over the past 75 years, the rates for cancer of the oesophagus, stomach, colon, rectum and pancreas in men and for cancer of the stomach, colon, rectum and pancreas in women accord, in general, with the theory. The mortality rates for cancer of the lung, bladder and prostate in men and for cancer of the lung, breast, ovary and cervix and corpus uteri in women also accord with the theory, if it is postulated that the carcinogenic factors responsible have varied in strength. A formula has been obtained which can be used to weight the strengths of the carcinogenic factors at different periods and it is shown that the time when the strength of the factors responsible for the individual changes is of greatest importance varies according to which change in the series is affected. The conclusion provides a possible explanation for the observation that circumcision exerts an important protective effect against the development of cancer of the penis only if it be carried out early in life.