For many common cancers, first-degree relatives (i.e. parents, siblings, offspring) of patients are at increased risk for cancer at the same site.1-34 This has been recognized for many years but, for most cancers, there are still too few systematic studies to provide precise estimates of these familial risks, particularly for relatives of younger patients. Some cohort studies have been conducted but most estimates of familial cancer risks have been based on case-control studies. Table 17.1 provides summary estimates of risks to relatives of affected cases for a number of common cancers. Estimates from early case-control studies may be somewhat inflated by under-reporting of affected relatives by controls but, in most recent studies, this bias is minimized by systematic questioning about each relative. For first-degree relatives of patients with most common cancers, the risk of developing cancer at the same site is generally increased by 2-5-fold above that in the general population. Such apparently moderate increases in risk could be due to a shared environment or a polygenic mechanism, but Table 17.2 shows that, if they are caused by single genes, the genetic effect must be substantial. For a dominant gene to cause a rela-
individuals has to be at least ten times greater than in non-susceptible individuals, and, for a recessive gene, the risk ratio must be over 20. Table 17.2 also shows that a moderate familial risk is consistent with a wide range of gene frequencies and genetic mechanisms, so the underlying genetic model cannot be reliably inferred from relative risks in first-degree relatives.