Hras1 VNTR alleles as susceptibility markers for lung cancer: relationship to microsatellite instability in tumors.

PURPOSE

To further evaluate lung cancer risk associated with rare Hras1 VNTR alleles and possible biological mechanisms.

MATERIALS AND METHODS

The Hras1 VNTR was genotyped in 295 lung cancer patients and 500 healthy controls by PCR and high resolution electrophoresis. Microsatellite alterations were examined in 168 tumors by PCR and capillary electrophoresis.

RESULTS

35 Hras1 VNTR alleles were found, of which 24 were defined as rare. A relative risk of 3.3 (95% CI; 1.9-6.0) associated with rare alleles was obtained using the total groups. Increased risk was significant both for males and females. When a matched control group was used, a relative risk of 12.7 (95% CI; 1.7-93.9) was calculated for individuals with rare alleles at the Hras1 VNTR locus. A low frequency of microsatellite alterations was observed (4.7%) in lung tumors. The frequency of altered microsatellite loci was higher among patients with rare Hras1 VNTR alleles than among patients with common alleles.

CONCLUSION

Rare Hras1 VNTR alleles are associated with lung cancer risk, and a genetic mechanism which increases allelic diversity may be involved.