Environmental and heritable factors in the causation of cancer - Analyses of cohorts of twins from Sweden, Denmark, and Finland.

Background: The contribution of hereditary factors to the causation of spor adic cancer is unclear. Studies of twins make it possible to estimate the o verall contribution of inherited genes to the development of malignant dise ases. Methods: We combined data on 44,788 pairs of twins listed in the Swedish, D anish, and Finnish twin registries in order to assess the risks of cancer a t 28 anatomical sites for the twins of persons with cancer. Statistical mod eling was used to estimate the relative importance of heritable and environ mental factors in causing cancer at 11 of those sites. Results: At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically sign ificant effects of heritable factors were observed for prostate cancer (42 percent of the risk may be explained by heritable factors; 95 percent confi dence interval, 29 to 50 percent), colorectal cancer (35 percent; 95 percen t confidence interval, 10 to 48 percent), and breast cancer (27 percent; 95 percent confidence interval, 4 to 41 percent). Conclusions: Inherited genetic factors make a minor contribution to suscept ibility to most types of neoplasms. This finding indicates that the environ ment has the principal role in causing sporadic cancer. The relatively larg e effect of heritability in cancer at a few sites (such as prostate and col orectal cancer) suggests major gaps in our knowledge of the genetics of can cer. (N Engl J Med 2000;343:78-85.) (C) 2000, Massachusetts Medical Society .