Genetic predisposition, environment and cancer incidence: A nationwide twin study in Finland, 1976-1995

Twin studies integrate genetic and environmental (including physical enviro nment and life-style) information by comparing monozygotic and dizygotic tw ins for the occurrence of disease. Our objectives were to compare cancer in cidence in twins with national rates and to estimate both the probability t hat co-twins of affected twins may develop cancer and the importance of gen etic predisposition and environment in cancer development. The nationwide r ecord linkage of the Finnish Twin Cohort Study, the Finnish Cancer Registry and the Central Population Register allowed the follow-up of 12,941 same-s exed twin pairs for incident primary cancers from 1976 to 1995. Zygosity wa s determined by use of a validated questionnaire in 1975. Methods included calculation of standardized incidence ratios and concordances and fitting o f structural equation models. A total of 1,613 malignant neoplasms occurred in the cohort. The overall cancer incidence among twins resembled that amo ng the general population. Monozygotic co-twins of affected twins were at 5 0% higher risk than were dizygotic co-twins. Based on genetic modeling, inh erited genetic factors accounted for 18% (95% confidence interval 4-32%) of the liability in inter-individual variation in the risk of overall cancer, while non-genetic factors shaved by twins accounted for 7% (0-16%) and uni que environmental factors for 75% (65-85%). Our results appear to exclude a contribution greater than one-third for genetic predisposition in the deve lopment of cancer in the general population, thus pointing to the earlier c onfirmed substantial role of environment. (C) 1999 Wiley-Liss, Inc.