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||Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma.
||Bassig BA, Zheng T, Zhang Y, Berndt SI, Holford TR, Hosgood HD 3rd, Hu W, Leaderer B, Yeager M, Menashe I, Boyle P, Xu J, Zou K, Zhu Y, Chanock S, Rothman N, Lan Q
||Environ Mol Mutagen
||CGR, LTG, OEEB
||The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency-matched controls. A gene-based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B-cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP-based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR)(CT) = 0.60, 95% confidence interval (CI) = 0.42-0.87, P(trend) = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (OR(CT) = 0.39, 95% CI = 0.20-0.73; P(trend) = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings.