CANCER IN TWINS - GENETIC AND NONGENETIC FAMILIAL RISK-FACTORS

Background: Familial clustering has been observed for cancers that occ ur at specific sites, Most findings, which leave little doubt about th e involvement of a heritable (i.e., genetic) component in the developm ent of some cancers, are based on data from ''cancer-prone'' families or interviews with subjects who have cancer, The study of twins should be of value in cancer epidemiology because twins either are genetical ly identical or share half of their segregating genes, Purpose: We lin ked the Swedish Twin Registry to the Swedish Cancer Registry, thereby identifying cases of cancer diagnosed from 1959 through 1992 in twins born in the period from 1886 through 1958, to assess the importance of both genetic and nongenetic (i.e., environmental) familial factors in determining cancer risk, Methods: Same-sex twin pairs with both indiv iduals alive and living in Sweden in 1959-1961 or 1970-1972 were ident ified in the old cohort (born from 1886 through 1925) or the young coh ort (born from 1926 through 1958), respectively, of the Swedish Twin R egistry; pairs for whom zygosity (i.e., the number of eggs that gave r ise to the twins) could be determined were considered further, The ass ociation of cancer with combined genetic and nongenetic familial facto rs was tested by comparing all twin pairs (regardless of zygosity) in which at least one member of the pair had been diagnosed with cancer a t one of several specific sites with pairs in which neither twin had t hat cancer, Heritable effects alone were tested by comparing monozygot ic (one egg) and dizygotic (two eggs) twin pairs, Statistical methods used in quantitative genetics and standard methods for epidemiologic r esearch were used in parallel to analyze the data, Results and Conclus ions: In the 10 503 twin pairs from the old cohort, 3617 cases of mali gnant cancer were identified; 918 malignant cancers were identified in the 12 883 twin pairs from the young cohort, When cancer,sites with a total number of at least 200 cases and at least one twin pair concord ant (i.e., both twins affected) for the site were evaluated, namely, c ancers of the stomach, colon and rectum, lung, female breast, and pros tate, as well as total cancer, profound genetic and/or nongenetic fami lial effects were identified in twins from the old cohort, Similar fin dings mere obtained for twins in the young cohort for cancers of the p rostate and female breast, as well as for total cancer, Genetic and no n-genetic familial effects were also identified in twins from both coh orts for in situ cancer of the cervix, The increase in risk of colon a nd rectum, breast, cervical, and especially prostate cancer, but not s tomach or lung cancer, tended to be greater if a monozygotic rather th an a dizygotic twin were affected, Implications: The identification of familial effects for total cancer in this study is consistent with th e idea that individuals may possess a genetic susceptibility to cancer in general.