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

      The New England journal of medicine
      Adult, Aged, Breast Neoplasms, genetics, Cohort Studies, Colorectal Neoplasms, Denmark, Diseases in Twins, etiology, Environment, Female, Finland, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Models, Statistical, Neoplasms, Prostatic Neoplasms, Registries, Risk, Sweden, Twins, Dizygotic, Twins, Monozygotic

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          Abstract

          The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. 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 significant effects of heritable factors were observed for prostate cancer (42 percent; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 percent; 95 percent confidence interval, 10 to 48 percent), and breast cancer (27 percent; 95 percent confidence interval, 4 to 41 percent). Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms. This finding indicates that the environment has the principal role in causing sporadic cancer. The relatively large effect of heritability in cancer at a few sites suggests major gaps in our knowledge of the genetics of cancer.

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          Genetic dissection of complex traits

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            The inheritance of liability to certain diseases, estimated from the incidence among relatives

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              Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands.

              Cancer has long been recognized to have a familial component. Elevated risks for cancers at the same site for relatives of cancer probands have been reported for both common cancers and a number of the rarer cancer sites. For a particular cancer site, however, the estimated risks to relatives have varied considerably depending on criteria for selection of probands, how cancers were determined in relatives, and overall study design. Not surprisingly, the estimated risks of other cancers in relatives of probands with cancer at a given site have been subject to even more variation. The aim of this study was to use the Utah Population Database resource to systematically study familial clustering of 28 distinct cancer site definitions among first-degree relatives (parents, siblings, and off-spring) of cancer probands. We estimated familial relative risks from the Utah Population Database by identifying all cases of cancer in these first-degree relatives. These observed values were compared with those expected based on cohort-specific internal rates calculated from 399,786 relatives of all individuals in the Utah Population Database known to have died in Utah. All sites showed an excess of cancers of the same site among relatives, with thyroid and colon cancers and lymphocytic leukemia showing the highest familial risks. When the analyses were restricted to cases with early ages at diagnosis, increased familial components for most cancer sites became evident. A significant difference in familial relative risk (FRR) between male (FRR = 4.04; 95% confidence interval [CI] = 3.13-5.07) and female (FRR = 2.24; 95% CI = 1.54-3.08) probands was found for colon cancer. Highly significant familial associations (one-sided; P < .001) were found among breast, colon, and prostate cancers and between breast and thyroid cancers. Statistically significant (one-sided, P < .01) associations were also found between tobacco-associated sites (lung, larynx, lip, and cervix). This study represents a unique comprehensive population-based study of familial cancer. The familial associations reported here will be useful in generating hypotheses about specific genetic and environmental factors that can be tested in genetic linkage and case-control studies.
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