Importance of Heritable and Nonheritable Variation in Cancer Susceptibility: Evidence From a Twin Study

Extract

Cancer results from a process of genetic changes—some inherited from a parent, some induced by environmental exposures, and some occurring by chance. Statistical modeling and laboratory data suggest that 5%–10% of specific cancers can be attributed to inheriting very high risk genes, often characterized as tumor suppressor genes [e.g., female breast cancer and an abnormal BRCA1 gene ( 1 ) or BRCA2 gene ( 2 )]. An abnormal tumor suppressor gene is inherited from one parent; the normal gene, inherited from the other parent, either acquires a mutation or is lost in a cell, allowing the malignant process to begin (or proceed). Thus, something has to happen to the normal gene for cancer to develop. Genes may also affect an individual's sensitivity to certain exposures, through metabolic efficiency (in activating or detoxifying carcinogens) or DNA-damage repair efficiency, and an individual's ability to recognize abnormal cells (immune surveillance). It is in this context that epidemiologists and geneticists study familial clustering of cancer—trying to dissect out heritable genetic from nongenetic variation in risk using family information. The Swedish twin study by Ahlbom et al. ( 3 ), reported in this issue of the Journal, is an example of such a study.