Abstract

Background The role of mutations in proto-oncogenes and their regulatory sequences in the pathogenesis of cancer is under close scrutiny. Minisatellites are unstable repetitive sequences of DNA that are present throughout the human genome. The highly polymorphic HRAS1 minisatellite locus just downstream from the proto-oncogene H-ras-1 consists of four common progenitor alleles and several dozen rare alleles, which apparently derive from mutations of the progenitors. We previously observed an association of the rare mutant alleles with many forms of cancer, and we undertook the present study to pursue this observation further. Methods We conducted a case-control study, typing 736 HRAS1 alleles from patients with cancer and 652 from controls by Southern blotting of leukocyte DNA. We also carried out a meta-analysis of this study and 22 other published studies, estimating the relative risk of cancer (such as bladder, breast, or colorectal cancer) when one of the rare HRAS1 alleles was present. Results Both t...

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