Sigurdson Alice J, Ha Mina, Hauptmann Michael, Bhatti Parveen, Sram Radim J, Beskid Olena, Tawn E Janet, Whitehouse Caroline A, Lindholm Carita, Nakano Mimako, Kodama Yoshiaki, Nakamura Nori, Vorobtsova Irena, Oestreicher Ursula, Stephan Günther, Yong Lee C, Bauchinger Manfred, Schmid Ernst, Chung Hai Won, Darroudi Firouz, Roy Laurence, Voisin Phillipe, Barquinero Joan F, Livingston Gordon, Blakey David, Hayata Isamu, Zhang Wei, Wang Chunyan, Bennett L Michelle, Littlefield L Gayle, Edwards Alan A, Kleinerman Ruth A, Tucker James D
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Mutat Res. 2008 Apr 30;652(2):112-21. doi: 10.1016/j.mrgentox.2008.01.005. Epub 2008 Feb 2.
Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p<0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR)=1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.
正常健康人的外周血淋巴细胞中的染色体易位会随年龄增长而增加，但性别、种族和吸烟对背景易位率的影响尚未得到系统研究。此外，年龄与易位频率（TF）之间关系的形态也尚未明确确定。我们收集了北美、欧洲和亚洲16个实验室的现有数据，这些数据来自1933名个体通过荧光原位杂交全染色体涂染在外周血淋巴细胞中测量的TF。在泊松回归模型中，年龄范围从新生儿（脐带血）到85岁，与TF密切相关，并且这种关系在老年时呈现出明显的向上弯曲，而非线性关系（p<0.001）。曾经吸烟者的TF显著高于不吸烟者（率比（RR）=1.19，95%置信区间（CI），1.09 - 1.30），并且吸烟改变了年龄对TF的影响，与不吸烟者相比，曾经吸烟者中与年龄相关的增加更为陡峭（p<0.001）。TF在性别上没有差异。由于实验室差异，很难解释种族的独立影响。我们的研究规模是迄今为止任何汇总研究的三倍，证实了TF与年龄之间疑似的曲线关系。之前关于人类TF的汇总研究未观察到吸烟的显著影响。我们的数据提供了按年龄、性别、种族和吸烟状况划分的背景TF的稳定估计，并表明在60岁以上以及有吸烟史的人群中染色体损伤加速。
