Germline variation in apoptosis pathway genes and risk of non-Hodgkin's lymphoma.
Germline variation in apoptosis pathway genes and risk of non-Hodgkin's lymphoma.
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DOI：
10.1158/1055-9965.epi-10-0581
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Cerhan JR
中科院分区：
文献类型：
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作者：
Kelly JL;Novak AJ;Fredericksen ZS;Liebow M;Ansell SM;Dogan A;Wang AH;Witzig TE;Call TG;Kay NE;Habermann TM;Slager SL;Cerhan JR
The t(14;18)(q32;q21) is the most commonly observed chromosomal translocation in non-Hodgkin lymphoma (NHL), resulting in constitutive Bcl-2 expression and apoptosis inhibition. In addition, germline variation in both BCL2L11 (BIM) and CASP9, known regulators of apoptosis, have recently been linked to NHL risk. We conducted a comprehensive evaluation of 36 apoptosis pathway genes with risk of NHL. We genotyped 226 single nucleotide polymorphisms (SNPs) from 36 candidate genes in a clinic-based study of 441 newly diagnosed NHL cases and 475 frequency matched controls. We used principal components analysis to assess gene-level associations, and logistic regression to assess SNP-level associations. MACH was used for imputation of SNPs in BCL2L11 and CASP9. In gene level analyses, BCL2L11 (p=0.0019), BCLAF1 (p=0.0097), BAG5 (p=0.026) and CASP9 (p=0.0022) were associated with NHL risk after accounting for multiple testing (tail strength 0.38; 95% CI 0.05, 0.70). Two of the 5 BCL2L11 tagSNPs (rs6746608 and rs12613243), both genotyped BCLAF1 tagSNPs (rs797558 and rs703193), the single genotyped BAG5 tagSNP (rs7693), and 3 of the 7 genotyped CASP9 tagSNPs (rs6685648, rs2020902, rs2042370) were significant at p<0.05. We successfully imputed BCL2L11 and CASP9 SNPs previously linked to NHL, and replicated all 4 BCL2L11 and 2 of 3 CASP9 SNPs. We replicated the association of BCL2L11 and CASP9 with NHL risk at the gene and SNP-level, and identified novel associations with BCLAF1 and BAG5. Closer evaluation of germline variation of genes in the apoptosis pathway with risk of NHL and its subtypes is warranted.
