Variants altering expression of GPC5 may affect susceptibility to disease in non-smokers-- Eric Metcalf
Thursday, March 25, 2010 (Last Updated: 03/26/2010)
THURSDAY, March 25 (HealthDay News) -- Genetic variants that affect the expression of the GPC5 gene may play a role in lung cancer in people who have never smoked, according to research published online March 22 in The Lancet Oncology.
Yafei Li, Ph.D., of the Mayo Clinic College of Medicine in Rochester, Minn., and colleagues analyzed data from a genome-wide association study of single nucleotide polymorphisms (SNPs) in a group of 754 cases and controls who were never smokers. Top candidate SNPs were validated in two more groups of never smokers, and the top SNP was further replicated in another group.
The researchers identified 44 top candidate SNPs. Using an additive genetic model in the four independent studies, they replicated rs2352028 at chromosome 13q31.3; there was a combined odds ratio of 1.46. Using a cis expression quantitative trait loci analysis, they found an association between the SNP genotypes and expression of GPC5 in normal lung tissue, with the high-risk allele linked to lower expression. The transcription level of GPC5 was twice as high in normal lung tissue than matched lung adenocarcinoma tissue.
"In summary, we have identified a genetic locus at 13q31.3 that regulates the expression of GPC5, which might contribute to the development of lung cancer in never smokers. Future studies are needed to investigate the regulatory effect of these SNPs (or tagged variants) and the functional role of GPC5 in lung tumorigenesis," the authors write.
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