Polymorphic variation of the ARP gene on 3p21 in Japanese esophageal cancer patients.

Allelic loss of the short arm of chromosome 3 is common in esophageal squamous cell carcinoma (ESC) and its premalignant lesions. The ARP gene (Arginine Rich Protein) was mapped to 3p21, and frequent variations of the triplet, AGG, repeat around codon 50 of the ARP gene were reported in a variety of human cancers. To examine the involvement of the ARP gene in esophageal cancer, we screened mutations around codon 50 in 35 ESC tumours and matched normal tissues. Sequence variants were observed in four ESC tumours; two (AGG)2 insertions, one ATG50-to-AGG substitution and one AGG deletion. However, they were also found in its corresponding normal tissues, suggesting that variation of the ARP gene found in ESC is polymorphic. We next analyzed sequence changes in 48 unrelated Japanese healthy individuals. They consist of 33 wild-type homozygotes, nine (AGG)2 insertion/wild-type heterozygotes, two (AGG)2 insertion homozygotes, one AGG deletion/wild-type heterozygote and three ATG50-to-AGG substitution/wild-type heterozygotes. Allele frequencies for wild-type, (AGG)2 insertion, ATG50-to-AGG substitution and AGG deletion are 0.82, 0.14, 0.03 and 0.01, respectively. Observed genotype frequencies fit well with the Hardy-Weinberg's law. Significant difference was not observed between allele distributions in normal and cancer patient populations.