Less efficient g2-m checkpoint is associated with an increased risk of lung cancer in African Americans.
Less efficient g2-m checkpoint is associated with an increased risk of lung cancer in African Americans.
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效率较低的 g2-m 检查点与非裔美国人患肺癌的风险增加有关。
DOI：
10.1158/0008-5472.can-05-1003
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发表时间：
2005
期刊：
影响因子：
11.2
通讯作者：
Harris,CurtisC
中科院分区：
文献类型：
--
作者：
Zheng,Yun-Ling;Loffredo,ChristopherA;Alberg,AnthonyJ;Yu,Zhipeng;Jones,RaymondT;Perlmutter,Donna;Enewold,Lindsey;Krasna,MarkJ;Yung,Rex;Shields,PeterG;Harris,CurtisC
细胞周期检查点在维持基因组完整性方面起着关键作用。遗传和表观遗传机制导致的检查点基因失活在所有癌症类型中都很常见，因为效率较低的细胞周期控制可能导致遗传不稳定和肿瘤发生。在一项正在进行的病例对照研究中，包括216例非小细胞肺癌患者，226例基于人群的对照和114例基于医院的对照，我们研究了γ辐射诱导的G2-M期阻滞与肺癌风险的关系。将外周血淋巴细胞培养90 h，照射剂量为1.0戈伊，照射后3 h收集淋巴细胞。γ-辐射诱导的G2-M期阻滞测量为未处理培养物中有丝分裂细胞的百分比减去来自同一受试者的γ-辐射处理培养物中有丝分裂细胞的百分比。病例组γ射线诱发G2-M期阻滞的平均百分比显著低于人群对照组（1.18vs1.44，P < 0.01）和医院对照组（1.18vs1.40，P = 0.01）。当在联合对照中的第50百分位值处二分时（人群和医院对照），在校正基线有丝分裂指数、年龄、性别和吸烟包年数后，较低水平的γ辐射诱导的G2-M期阻滞与非裔美国人肺癌风险增加相关[校正比值比（OR），2.25; 95%置信区间（95% CI），0.97-5.20]。在非裔美国人中观察到肺癌风险增加的显著趋势，G2-M期阻滞水平降低（Ptrend= 0.02），最低与最高四分位数校正OR为3.74（95%CI，0.98-14.3）。这种趋势在非裔美国女性中最为明显（P趋势< 0.01），最低与最高四分位数调整后的OR为11.75（95%CI，1.47-94.04）。结果表明，DNA损伤诱导的G2-M检查点效率较低与非裔美国人肺癌风险增加有关。有趣的是，我们观察到与高加索人相比，非裔美国人中DNA损伤诱导的G2-M期阻滞与肺癌之间存在更强的关联。如果重复，这些结果可能会为非洲裔美国人经历的极高肺癌发病率提供线索。
Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non–small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of γ-radiation-induced G2-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 Gy γ-radiation, and harvested at 3 hours after γ-radiation treatment. γ-Radiation-induced G2-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in γ-radiation-treated cultures from the same subject. The mean percentage of γ-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44,P< 0.01) and hospital controls (1.18 versus 1.40,P= 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of γ-radiation-induced G2-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97-5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G2-M arrest was observed (Ptrend= 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% CI, 0.98-14.3). This trend was most apparent among African American females (Ptrend< 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% CI, 1.47-94.04). The results suggest that a less-efficient DNA damage–induced G2-M checkpoint is associated with an increased risk of lung cancer among African Americans. Interestingly, we observed a stronger association of DNA damage–induced G2-M arrest and lung cancer among African Americans when compared with Caucasians. If replicated, these results may provide clues to the exceedingly high lung cancer incidence experienced by African Americans.
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家族性癌症患者皮肤成纤维细胞 G2 细胞周期期间的染色体放射敏感性。
DOI：
--
发表时间：
1985
影响因子：
11.1
作者：
R. Parshad;K. Sanford;G. Jones
通讯作者：
G. Jones
在病例对照研究中，诱变剂敏感性表现出剂量-反应关系。
DOI：
--
发表时间：
1996
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
影响因子：
--
作者：
Wu,X;Hsu,TC;Spitz,MR
通讯作者：
Spitz,MR
诱变剂敏感性作为非裔美国人肺癌风险的生物标志物。
DOI：
--
发表时间：
1995
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
影响因子：
--
作者：
Spitz,MR;Hsu,TC;Wu,X;Fueger,JJ;Amos,CI;Roth,JA
通讯作者：
Roth,JA
影响因子：
10.3
作者：
SCHANTZ, SP;SPITZ, MR;HSU, TC
通讯作者：
HSU, TC
影响因子：
11.2
作者：
Xifeng Wu;J. Roth;Hua Zhao;S. Luo;Yun-Ling Zheng;Silvia S Chiang;M. Spitz
通讯作者：
Xifeng Wu;J. Roth;Hua Zhao;S. Luo;Yun-Ling Zheng;Silvia S Chiang;M. Spitz