Single nucleotide polymorphisms in the mitochondrial displacement loop and age at onset of non-Hodgkin lymphoma

Haiyan Fan,1 Cuiju Wang,2 Zhanjun Guo11Department of Gastroenterology and Hepatology, 2Department of Gynaecology Ultrasound, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of ChinaObjective: Single nucleotide polymorphisms (SNPs) accumulated frequently in the mitochondrial displacement loop (D-loop) in many cancers. We had identified cancer risk-associated SNPs in the D-loop of non-Hodgkin lymphoma (NHL) patients previously, in this study, we investigated the association of age at onset and D-loop SNPs in NHL patients.Materials and methods: The D-loop region of mtDNA was sequenced for 133 NHL patients recorded at the Fourth Hospital of Hebei Medical University. The Kaplan-Meier method was used to identify age at onset-associated SNPs in the D-loop of NHL patients. The Cox proportional hazards model was used to identify independent risk factors for age at onset.Results: The SNP sites of nucleotides 146C/T, 151T/C, 194T/C, 315C/C insert, 523Del/A, and 525Del/C were identified for their association with age at onset, by the logrank test. In an overall multivariate analysis, allele 146 (relative risk, 0.403; 95% confidence interval [CI]: 0.182-0.895) (P = 0.026), allele 151 (relative risk, 0.378; 95% CI: 0.165-0.868) (P = 0.022), and allele 315 (relative risk, 3.554; 95% CI: 1.344-9.400) (P = 0.011) were identified as independent predictors for age at onset in NHL patients.Conclusion: SNPs in the D-loop can predict age at onset in NHL patients. Analysis of the D-loop SNPs can help identify NHL patient subgroups at high risk of early onset.Keywords: Kaplan–Meier; Cox proportional hazards model, D-loop, single nucleotide polymorphisms