a comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma一个全面的候选基因方法识别与骨肉瘤相关遗传变异.pdfVIP
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a comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma一个全面的候选基因方法识别与骨肉瘤相关遗传变异
Mirabello et al. BMC Cancer 2011, 11:209
/1471-2407/11/209
RESEARCH ARTICLE Open Access
A comprehensive candidate gene approach
identifies genetic variation associated with
osteosarcoma
1* 1 1 2 2 2 2
Lisa Mirabello , Kai Yu , Sonja I Berndt , Laurie Burdett , Zhaoming Wang , Salma Chowdhury , Kedest Teshome ,
2 2 3 4 5 1
Arinze Uzoka , Amy Hutchinson , Tom Grotmol , Chester Douglass , Richard B Hayes , Robert N Hoover ,
Sharon A Savage1 and for the National Osteosarcoma Etiology Study Group
Abstract
Background: Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs
during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk.
Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain
the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from
growth/hormone, bone formation, DNA repair, and ribosomal pathways.
Methods: We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic
regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI).
Results: Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni
correction. Four SNPs in the DNA repair gene FANCM (ORs 1.9-2.0, P = 0.003-0.004) and 2 SNPs downstream of the
growth hormone gene GH1 (OR 1.6, P = 0.002; OR 0.5, P = 0.0009) were significantly associated with OS. One SNP
in the region of each of the following genes was signif
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