Genetic susceptibility to head and neck squamous cell carcinoma.
Genetic susceptibility to head and neck squamous cell carcinoma.
复制标题
头颈鳞状细胞癌的遗传易感性。
DOI：
10.1093/jnci/88.8.530
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Snow,GB
中科院分区：
文献类型：
--
作者：
Cloos,J;Spitz,MR;Schantz,SP;Hsu,TC;Zhang,ZF;Tobi,H;Braakhuis,BJ;Snow,GB
背景除了暴露于致癌化合物的影响外，癌症的发展可能取决于个体内在的癌症易感性。癌症易感性的生物标志物可以有力地补充流行病学analysis.PurposeThis多中心，病例对照分析结合了以前发表的数据和新的数据，以证实诱变剂敏感性作为头颈部鳞状细胞癌易感性的生物标志物的价值，更重要的是，了解易感性和致癌物暴露之间的相互作用。方法诱变剂敏感性在两个主要的美国医疗机构和一个欧洲机构中，在313名头颈癌患者和334名对照受试者中测定了（在细胞周期的晚期S-G2期用博来霉素处理的培养淋巴细胞的每个细胞的染色单体断裂的平均数），产生了独特的研究人群。病例组和对照组受试者的年龄，以及他们的吸烟和饮酒史也被记录下来。变量之间的关系采用Student t检验、斯皮尔曼等级相关和多元线性回归进行分析。为了估计癌症风险，测量粗比值比（OR）并进行多元logistic回归。AllPvalues是基于双侧tests.ResultsThere的突变敏感性（Kruskal-Wallis检验）的情况下，受试者和对照组的分布机构之间没有差异。在总体分析中，病例受试者的值始终显著（P<.0001）高于对照受试者的值。无论是病例组还是对照组，年龄和吸烟或饮酒均不影响诱变剂敏感性结果。发现在1.0处二分的每个细胞的平均断裂数是超敏表型的最佳预测因子。对于不敏感的重度吸烟者，OR为11.5（95%置信区间[CI] = 5.0-26.6）。在致突变剂过敏、重度吸烟者中，该风险显著增加至44.6（95% CI = 17.4-114.0）。多元逻辑回归分析证实了这些结果，并发现吸烟导致癌症风险呈剂量依赖性增加的显著趋势（P<0.01）。酒精的消费增强了吸烟的影响，导致OR为57.5（95%CI = 17.5-188.0）在过敏persons.ConclusionsMutagen敏感性被发现是癌症易感性的生物标志物。这项研究强调了利用易感性标志物和暴露数据的重要性，用于识别的人在高风险的发展cancer.ImplicationsMore准确的风险估计可以定义易感亚组可能有针对性的密集的行为干预，通过筛选监测，并登记在chemoprevention programmes。[J Natl Cancer Inst 1996;88：530-5]
BackgroundIn addition to influences of exposure to carcinogenic compounds, the development of cancer may depend on an individual intrinsic cancer susceptibility. Biomarkers for cancer susceptibility can be powerful additions to epidemiologic analyses.PurposeThis multicenter, case—control analysis combines previously published data and new data to substantiate the value of mutagen sensitivity as a biomarker of susceptibility to head and neck squamous cell carcinoma and, more importantly, to gain insight into the interaction between susceptibility and exposure to carcinogens.MethodsMutagen sensitivity (mean number of chromatid breaks per cell of cultured lymphocytes treated with bleomycin in the late S-G2 phase of the cell cycle) was determined in 313 patients with head and neck cancer and in 334 control subjects at two major U.S. medical institutions and one European institution, yielding a unique study population. The ages of the case and control subjects, as well as their history of use of tobacco and alcohol, were also recorded. The relationships between variables were analyzed by use of Student'sttests, Spearman's rank correlations, and multiple linear regression. For estimation of cancer risk, crude odds ratios (ORs) were measured and multiple logistic regression was performed. AllPvalues were based on two-sided tests.ResultsThere were no differences across institutions in the distribution of mutagen sensitivity (Kruskal-Wallis test) for both case subjects and control subjects. Values for case subjects were consistently and significantly (P<.0001) higher than values for control subjects in the overall analyses. Age and tobacco or alcohol use did not influence the outcome in terms of mutagen-sensitivity values for either the case or the control subjects. A mean number of breaks per cell dichotomized at 1.0 was found to be the best predictor of a hypersensitive phenotype. For nonsensitive, heavy smokers, the OR was 11.5 (95% confidence interval [CI] = 5.0–26.6). This risk increased dramatically in mutagen-hypersensitive, heavy smokers to 44.6 (95% CI = 17.4–114.0). Multiple logistic regression analysis confirmed these results, and a significant trend was found (P<.01) for the dose-dependent increase in cancer risk by smoking. The consumption of alcohol potentiated the effects of smoking, resulting in an OR of 57.5 (95% CI = 17.5-188.0) in hypersensitive persons.ConclusionsMutagen sensitivity was found to be a biomarker of cancer susceptibility. This study underscores the importance of utilizing both susceptibility markers and exposure data for the identification of persons at high risk of developing cancer.ImplicationsMore accurate risk estimation can define susceptible subgroups who might be targeted for intensive behavioral interventions, surveillance through screening, and enrollment in chemoprevention programs. [J Natl Cancer Inst 1996;88:530–5]