女性血细胞X染色体失活偏移与肺癌早期发生有关

X-chromosomal inactivation skewing in blood cells is associated with early development of lung cancer in females

目的研究X染色体失活偏移(SXCI)与女性肺癌发生的关系。方法采集148例女性肺癌患者与289例女性对照者的外周血标本,提取基因组DNA,经HpaⅡ消化后,PCR扩增雄激素受体(AR)基因,产物经变性聚丙烯酰胺凝胶电泳,银染显示结果,比较HpaⅡ消化前后AR基因扩增产物的强度差异,计算其校正比值(CR)。结果采用CR≥10作为SXCI标准时,50岁以下的肺癌患者SXCI发生率高于相同年龄段的对照者(分别为7．9％和1．2％,P=0．046);50岁以上肺癌患者和相同年龄段的对照者SXCI发生率无显著差别(分别为4．5％和5．4％,P=0．488)。无论采用CR≥3抑或≥10为标准,女性肺癌患者中发生SXCI者的平均年龄均比未发生SXCI者提前10岁以上(P<0．05)。结论女性血细胞SXCI与肺癌的早期发生有关。

Objective To observe the relationship between skewed X-chromosomal inactivation （SXCI） and development of lung cancer in females. Methods DNA was isolated from peripheral blood cells from patients with primary lung cancer （ n = 148 ） and control subjects （ n = 289 ）. Exon 1 of androgen receptor （AR） gene was amplified, with its products from different alleles resolved on denaturing polyacrylamide gels and visualized by silver staining. The corrected ratio （CR） between products from different AR alleles before and after Hpa Ⅱ pretreatment was calculated. All statistical tests were two-sided. Results With CR≥10 adopted as the criterion, SXCI was found more frequently in the younger patients （≤50 years; 7.9%） than in the controls of the same age group （1.2%; P = 0. 046）. The SXCI frequency, however, were not significantly different between the old patients （ 〉50 years; 4.5% ） and the controls of the same age group （5.4% ; P =0.488）. Whether taking CR≥3 or CR≥10 as the criteria, the average ages of the patients with SXCI were more than 10 years younger than those without SXCI （P 〈 0.05）. Conclusion SXCI in blood cells is associated with early development of lung cancer in females.