Association of E-cadherin germ-line alterations with prostate cancer

In our recent cancer registry-based study, the incidence of gastric carcino ma was increased up to 5-fold in male relatives of early-onset prostate can cer (PCA) patients. This association may reflect the influence of genetic f actors predisposing individuals to both tumor types. Germ-line mutations of the CDH1 gene at 16q have recently been associated with familial gastric c ancer. Furthermore, two genome-wide linkage studies of PCA recently reporte d positivity at 16q. We therefore identified families and individual patien ts with both gastric and PCA and investigated whether the CDH1 gene mutatio ns were involved in cancer predisposition in these cases. Fifteen of the 18 0 Finnish hereditary PCA families (8.3%) bad one or more gastric cancer cas es. No truncating or splice site CDH1 mutations were identified by PCR sing le-strand conformational polymorphism in these families or in eight individ ual patients who had both prostate and gastric cancer. However, a novel S27 0A missense mutation in exon 6 of the CDH1 gene was seen in a single family with four prostate and two gastric cancers. A large-scale population-based survey indicated a higher prevalence of S270A among both familial PCA case s (3.3%; n = 120; P = 0.01) and unselected PCA patients (1.5%; n = 472; P = 0.12) as compared with blood donors serving as population controls (0.5%; n = 923). We conclude that individual rare mutations and polymorphisms in t he CDH1 gene, such as S270A, may contribute to the onset of PCA and warrant further investigations in other populations. However, the CDH1 gene does n ot appear to explain the link between prostate and gastric cancer.