TY - JOUR
T1 - Risk of non-Hodgkin lymphoma in association with germline variation in complement genes
AU - Cerhan, James R.
AU - Novak, Anne J.
AU - Fredericksen, Zachary S.
AU - Wang, Alice H.
AU - Liebow, Mark
AU - Call, Timothy G.
AU - Dogan, Ahmet
AU - Witzig, Thomas E.
AU - Ansell, Stephen M.
AU - Habermann, Thomas M.
AU - Kay, Neil E.
AU - Slager, Susan L.
PY - 2009/6
Y1 - 2009/6
N2 - Germline mutations in complement genes have been associated with susceptibility to infections and autoimmune diseases, conditions that are associated with non-Hodgkin lymphoma (NHL) risk. To test the hypothesis that common genetic variation in complement genes affect risk of NHL, we genotyped 167 single nucleotide polymorphisms (SNPs) from 31 genes in 441 NHL cases and 475 controls. Principal components (PC) and haplotype analyses were used for gene-level tests of NHL risk, while individual SNPs were modelled as having a log-additive effect. In gene level PC analyses, C2 (P = 0·023), C5 (P = 0·0032) and C9 (P = 0·020) were associated with NHL risk; haplotype analyses showed similar results, as well as a haplotype association for C7 (P = 0·046). When all four genes were considered simultaneously, only C5 and C9 remained significant (P < 0·05). In SNP level results from these genes, 10 SNPs had a P < 0·05. However, after correcting for multiple testing, only the C5 SNPs rs7026551 (q = 0·015; OR = 1·54, 95% CI 1·21-1·95) and rs2416810 (q = 0·015; OR = 1·57; 95% CI 1·22-2·01), and the C9 SNP rs187875 (q = 0·015; OR = 0·68; 95% 0·56-0·84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk.
AB - Germline mutations in complement genes have been associated with susceptibility to infections and autoimmune diseases, conditions that are associated with non-Hodgkin lymphoma (NHL) risk. To test the hypothesis that common genetic variation in complement genes affect risk of NHL, we genotyped 167 single nucleotide polymorphisms (SNPs) from 31 genes in 441 NHL cases and 475 controls. Principal components (PC) and haplotype analyses were used for gene-level tests of NHL risk, while individual SNPs were modelled as having a log-additive effect. In gene level PC analyses, C2 (P = 0·023), C5 (P = 0·0032) and C9 (P = 0·020) were associated with NHL risk; haplotype analyses showed similar results, as well as a haplotype association for C7 (P = 0·046). When all four genes were considered simultaneously, only C5 and C9 remained significant (P < 0·05). In SNP level results from these genes, 10 SNPs had a P < 0·05. However, after correcting for multiple testing, only the C5 SNPs rs7026551 (q = 0·015; OR = 1·54, 95% CI 1·21-1·95) and rs2416810 (q = 0·015; OR = 1·57; 95% CI 1·22-2·01), and the C9 SNP rs187875 (q = 0·015; OR = 0·68; 95% 0·56-0·84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk.
KW - Complement genes
KW - Epidemiology
KW - Genetic variation
KW - Non-Hodgkin lymphoma
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U2 - 10.1111/j.1365-2141.2009.07675.x
DO - 10.1111/j.1365-2141.2009.07675.x
M3 - Article
C2 - 19344414
AN - SCOPUS:66149167461
SN - 0007-1048
VL - 145
SP - 614
EP - 623
JO - British journal of haematology
JF - British journal of haematology
IS - 5
ER -