Environmental and Heritable Factors in the Causation of Cancer -- Analyses of Cohorts of Twins from Sweden, Denmark, and Finland

doi:10.1056/NEJM200007133430201

Volume 343:78-85		July 13, 2000		Number 2

Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland

Paul Lichtenstein, Ph.D., Niels V. Holm, M.D., Ph.D., Pia K. Verkasalo, M.D., Ph.D., Anastasia Iliadou, M.Sc., Jaakko Kaprio, M.D., Ph.D., Markku Koskenvuo, M.D., Ph.D., Eero Pukkala, Ph.D., Axel Skytthe, M.Sc., and Kari Hemminki, M.D., Ph.D.

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by Hoover, R. N.

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ABSTRACT

Background The contribution of hereditary factors to the causationof sporadic cancer is unclear. Studies of twins make it possibleto estimate the overall contribution of inherited genes to thedevelopment of malignant diseases.

Methods We combined data on 44,788 pairs of twins listed inthe Swedish, Danish, and Finnish twin registries in order toassess the risks of cancer at 28 anatomical sites for the twinsof persons with cancer. Statistical modeling was used to estimatethe relative importance of heritable and environmental factorsin causing cancer at 11 of those sites.

Results At least one cancer occurred in 10,803 persons among9512 pairs of twins. An increased risk was found among the twinsof affected persons for stomach, colorectal, lung, breast, andprostate cancer. Statistically significant effects of heritablefactors were observed for prostate cancer (42 percent of therisk may be explained by heritable factors; 95 percent confidenceinterval, 29 to 50 percent), colorectal cancer (35 percent;95 percent confidence interval, 10 to 48 percent), and breastcancer (27 percent; 95 percent confidence interval, 4 to 41percent).

Conclusions Inherited genetic factors make a minor contributionto susceptibility to most types of neoplasms. This finding indicatesthat the environment has the principal role in causing sporadiccancer. The relatively large effect of heritability in cancerat a few sites (such as prostate and colorectal cancer) suggestsmajor gaps in our knowledge of the genetics of cancer.

Source Information

From the Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden (P.L., A.I.); the Institute of Public Health (Epidemiology) and the Danish Twin Registry, University of Southern Denmark, Odense (N.V.H., A.S.); the Department of Public Health, University of Helsinki, Helsinki, Finland (P.K.V., J.K., M.K.); the Department of Public Health and General Practice, University of Oulu, Oulu, Finland (J.K.); the Department of Public Health, University of Turku, Turku, Finland (M.K.); the Finnish Cancer Registry, Helsinki, Finland (E.P.); and the Department of Biosciences at Novum, Karolinska Institute, Stockholm, Sweden (K.H.).

Address reprint requests to Dr. Lichtenstein at the Department of Medical Epidemiology, Karolinska Institute, Box 281, SE-171 77 Stockholm, Sweden, or at paul.lichtenstein{at}mep.ki.se.

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Cancer, Genes, and the Environment
Spector N., Shapiro B. L., Peto R., Begg C. B., Lichtenstein P., Kaprio J., Hemminki K.
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N Engl J Med 2000; 343:1494-1496, Nov 16, 2000. Correspondence

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