Spitz M R, Wu X, Jiang H, Hsu T C
Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Cell Biochem Suppl. 1996;25:80-4.
Modulation of environmental exposures by host genetic factors may explain interindividual variation in susceptibility to carcinogenesis. One determinant of susceptibility is mutagen sensitivity measured by the frequency of bleomycin-induced breaks in an in vitro lymphocyte assay. Mutagen sensitivity is a significant predictor of aerodigestive tract cancer risk. In this case-control study of lung-cancer susceptibility markers, 54% of 132 lung-cancer cases had mutagen-sensitivity scores greater than or equal to 1 break/cell, compared with only 22% of 232 controls. The mean breaks/cell value (+/-SE) for the 88 African-American cases was 1.11 (+/-0.60), compared with 0.82 (+/-0.49) for the 121 controls (P < 0.001). For the 44 Mexican-American cases and 111 controls, the comparable values were 1.11 (+/-0.52) and 0.76 (+/-0.38), respectively. The overall odds ratio (OR) for mutagen sensitivity (dichotomized at > or = 1 break/cell), after adjusting for ethnicity and smoking status, was 3.62 (95% confidence limits [CL] = 2.2, 5.9). For current smokers the adjusted risk associated with mutagen sensitivity was 2.52 (1.2, 5.3). For former smokers, the comparable OR (95% CL) was 6.19 (2.7, 14.1). The risk estimate for those under 61 years of age was 4.85 (2.3, 10.4), compared with 2.85 (1.5, 5.6) for older subjects. The risk also appeared to be higher for lighter smokers (< 20 cigarettes daily) than heavier smokers (ORs = 5.72 and 3.20, respectively). The ethnicity-adjusted ORs by quartile of breaks/cell were 1.0, 1.40, 2.46, and 4.80; the trend test was significant at P < 0.001. The joint effects of mutagen sensitivity and former smoking, current smoking, or heavy smoking were greater than additive, although the interaction terms were not statistically significant in the logistic model. Mutagen sensitivity may therefore be a useful member of a panel of susceptibility markers for defining high-risk subgroups for chemoprevention trials.
宿主遗传因素对环境暴露的调节作用可能解释个体间致癌易感性的差异。易感性的一个决定因素是通过体外淋巴细胞试验中博来霉素诱导的断裂频率来衡量的诱变敏感性。诱变敏感性是气消化道癌症风险的重要预测指标。在这项关于肺癌易感性标志物的病例对照研究中，132例肺癌患者中有54%的诱变敏感性评分大于或等于1次断裂/细胞，而232例对照中只有22%。88例非裔美国病例的平均断裂/细胞值（±标准误）为1.11（±0.60），121例对照为0.82（±0.49）（P<0.001）。44例墨西哥裔美国病例和111例对照的相应值分别为1.11（±0.52）和0.76（±0.38）。在调整种族和吸烟状况后，诱变敏感性（以≥1次断裂/细胞进行二分法划分）的总体优势比（OR）为3.62（95%置信区间[CL]=2.2，5.9）。对于当前吸烟者，与诱变敏感性相关的调整后风险为2.52（1.2，5.3）。对于既往吸烟者，相应的OR（95%CL）为6.19（2.7，14.1）。61岁以下人群的风险估计值为4.85（2.3，10.4），而年龄较大者为2.85（1.5，5.6）。轻度吸烟者（每天<20支香烟）的风险似乎也高于重度吸烟者（OR分别为5.72和3.20）。按断裂/细胞四分位数调整种族后的OR分别为1.0、1.40、2.46和4.80；趋势检验在P<0.001时具有显著性。诱变敏感性与既往吸烟、当前吸烟或重度吸烟的联合效应大于相加效应，尽管在逻辑模型中交互项无统计学显著性。因此，诱变敏感性可能是用于确定化学预防试验高危亚组的一组易感性标志物中的一个有用成员。
