Youichi Tanaka

RELAXATION OF INSULIN-LIKE GROWTH FACTOR 2 GENE IMPRINTING IN ESOPHAGEAL CANCER

Paternal allele‐specific expression is identified for the insulin‐like growth factor 2 (IGF2) gene. Relaxation or loss of IGF2 imprinting, however, has been reported in several neoplasms. We studied the expression of IGF2 mRNA in 35 squamous cancers of the esophagus and searched for the presence or absence of relaxation of IGF2 imprinting. In 28 (80%) cases, IGF2 mRNA was overexpressed in the tumor tissues (T) compared to the normal tissues (N). The patients whose tumor invaded the adventitia showed a higher T/N ratio than those whose tumor was restricted to the musculi propria layer. Heterozygosity was determined by using the Apa 1 polymorphism in exon 9. Thirteen of 35 cases showed heterozygosity. In these 13 cases, a similar analysis was performed on cDNA obtained by reverse transcriptase‐polymerase chain reaction. Consequently, 7 cases disclosed relaxation of IGF2 imprinting in the tumor tissue. The cases of esophageal cancer with relaxation of IGF2 imprinting showed a higher T/N ratio and deeper invasion than those without relaxation. The results suggest that overexpression of IGF2 mRNA plays an important role in esophageal cancer and, in certain cases, is associated with relaxation of IGF2 imprinting.

L‐myc Restriction Fragment Length Polymorphism in Japanese Patients with Esophageal Cancer

L‐myc polymorphism is a representative genetic trait related to an individuals susceptibility to several cancers. However, there have been no reports concerning the association between esophageal cancer and L‐myc polymorphism. To analyze the distribution of polymorphism in Japanese patients with esophageal cancer, a molecular genotyping method using a polymerase chain reaction‐based restriction fragment length polymorphism (PCR‐RFLP) was used. Based on an analysis of 65 Japanese patients with esophageal cancer and 107 healthy control subjects, a significant difference was observed in either the distribution of genotypes (P=0.012) or of allele frequencies between the two groups (P 0.004). The relative risk of esophageal cancer for genotypes including the shorter allele was 2.9 compared to the longer allele homozygote. Furthermore, the patients with S‐allele had a tendency for poor prognosis among those with three genotypes. A significant difference between the distribution of genotypes and the incidence of lymph node metastasis was found based on the clinicopathological features of the cancers. These results suggest that L‐myc polymorphism may be implicated as a genetic trait affecting an individuals susceptibility to esophageal cancer, at least among Japanese patients.