研究动态
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线粒体DNA断裂与非霍奇金淋巴瘤风险的关联。

Mitochondrial DNA Fragmentation and Risk of Non-Hodgkin Lymphoma.

发表日期:2023 Aug 01
作者: H Dean Hosgood, Meghan Davitt, Richard Cawthon, Stephanie J Weinstein, Batel Blechter, Jason Y Y Wong, Mohammad L Rahman, Wei Hu, Satu Männistö, Demetrius Albanes, Nathaniel Rothman, Qing Lan
来源: JAMA Network Open

摘要:

研究表明,线粒体DNA拷贝数(mtDNAcn)的增加与非何杰金淋巴瘤(NHL)的风险增加相关;然而,迄今为止没有研究评估线粒体DNA断裂部分(mtDNAfb)是否与NHL的风险相关。为了评估mtDNAfb与NHL风险的关联,本嵌套病例对照研究收集了1985年至1988年期间参与芬兰西南部进行的α-生育酚、β-胡萝卜素癌症预防(ATBC)研究的29,133名吸烟男性的前瞻性样本。该研究包括107例NHL患者和107名对照者(根据出生日期匹配,误差±5岁)。分析时间为2022年1月至9月。 采用高通量实时聚合酶链式反应测定mtDNAfb。通过芬兰癌症登记处和死因登记处,识别ATBC研究中的NHL病例截至2002年4月30日。根据对照组中位数、三分位数和四分位数分布对mtDNAfb进行定量并分类。使用条件 logistic 回归模型估计比值比和95%置信区间,以评估分类的mtDNAfb与未来NHL风险之间的关联,调整年龄、体重指数、每日吸烟量、吸烟年数以及mtDNAcn。 共有29,133名男性(年龄中位数[IQR]为57.2 [52.6-62.5]岁)参与了ATBC研究。mtDNAfb升高与NHL风险增加相关(中位数比值比为2.89,95%置信区间为1.40-5.93),且呈剂量依赖关系(四分位数2 vs 1比值比为1.24,95%置信区间为0.43-3.40;四分位数3 vs 1比值比为3.58,95%置信区间为1.39-9.24;四分位数4 vs 1比值比为3.42,95%置信区间为1.30-8.99;P = .004,趋势分析)。该研究的结果表明,mtDNAfb的增加与未来NHL的风险增加相关。需要进行更多的研究来证实这些发现,特别是对于女性和非吸烟者而言。
Research suggests that increased mitochondrial DNA copy number (mtDNAcn) is associated with increased risk of non-Hodgkin lymphoma (NHL); however, no studies to date have evaluated whether the mitochondrial DNA fraction with breaks (mtDNAfb) is associated with risk of NHL.To evaluate the association of mtDNAfb with NHL risk.This nested case-control study, which used prospectively collected samples as part of baseline enrollment (from 1985 through 1988) of 29 133 men who smoked for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study conducted in southwest Finland, included 107 incident NHL cases and 107 controls (matched on date of birth ±5 years). Analyses were conducted from January to September 2022.High-throughput real-time polymerase chain reaction assays quantifying mtDNAfb.Incident NHL cases were identified in the ATBC Study through April 30, 2002, using the Finnish Cancer Registry and the Register of Causes of Death. The mtDNAfb was quantified and categorized based on the median, tertile, and quartile distributions among controls. Odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression models to assess the associations between categorized mtDNAfb and future risk of NHL, controlling for age, body mass index, number of cigarettes smoked per day, number of pack-years, and mtDNAcn.A total of 29 133 men (median [IQR] age, 57.2 [52.6-62.5] years) participated in ATBC Study. Higher mtDNAfb was associated with an increased risk of NHL (median OR, 2.89; 95% CI, 1.40-5.93) in a dose-dependent manner (quartile 2 vs 1 OR, 1.24; 95% CI, 0.43-3.40; quartile 3 vs 1 OR, 3.58; 95% CI, 1.39-9.24; quartile 4 vs 1 OR, 3.42; 95% CI, 1.30- 8.99; P = .004 for trend).This study's findings suggest that increased mtDNAfb is associated with an increased future risk of NHL. Additional studies are needed to confirm these findings, particularly among women and nonsmokers.