An avaII restriction fragment length polymorphism in the insulin-like growth factor II gene and the occurrence of smooth muscle tumors.

To detect a previously described AvaII restriction fragment length polymorphism (RFLP) in the human insulin-like growth factor II (IGF-II) gene we used the polymerase chain reaction (PCR) and genomic sequencing. The RFLP is located in exon 9 of the IGF-II gene at nucleotide 820 (GenBank accession number X07868) as a C-->T transition. Digestion with AvaII reveals a two-allele polymorphism, an a allele in which the AvaII site is not present, and a b allele. In healthy Dutch persons (n = 26), the frequency of the a allele was 62%. A similar a allele frequency was found in groups of Japanese (53%, n = 65) and Chinese (54%, n = 84), while in a French group the frequency was significantly lower (25%, n = 52). In Dutch individuals that had developed benign (n = 11; all women) and malignant (n = 9; 2 women and 7 men) smooth muscle tumors, a significantly higher frequency of 83% for the a allele was found. Since there was no difference between the presence of the a and b alleles in normal and tumor tissue of the same individual, the higher a allele frequency was not due to mutation in the IGF-II gene or loss of heterozygosity. There was no correlation between the presence of the a allele and expression of the IGF-II gene. The data reveal a correlation between homozygosity for the a allele and the occurrence of smooth muscle tumors. Women homozygous for the IGF-II a allele are more prone to develop a leiomyoma than women who are heterozygous or homozygous for the b allele. Furthermore, in both women and men the risk for leiomyosarcomas seems to be higher in a allele homozygotes.