Head and neck cancer in nonsmokers: A distinct clinical and molecular entity

Head and neck cancer in nonsmokers: A distinct clinical and molecular entity
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DOI:
10.1097/00005537-199910000-00002
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发表时间:
1999-10-01
期刊:
影响因子:
2.6
通讯作者:
Sidransky, D
Sidransky, D
中科院分区:
医学2区
文献类型:
--
作者:
Koch, WM;Lango, M;Sidransky, D

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目的/假设:非吸烟者和吸烟者的头颈鳞状细胞癌 (HNSCC) 的临床和分子模式可能不同,对这些模式的分析可以提高对该疾病的了解和治疗。研究设计:纳入了 305 名受试者(46 名非吸烟者、29 名戒烟者和 230 名吸烟者)。对子集的 10 个染色体位点的 p53 突变、人乳头瘤病毒 (HPV) 和杂合性丢失 (LOH) 进行了分析。方法:分析各组中常见疾病模式的临床信息。对p53基因进行测序,并使用聚合酶链式反应检测每个位点的两个微卫星标记处的HPV DNA和LOH。 chi(2) 检验用于评估组间遗传改变的差异,逻辑回归用于检查烟草暴露与每个改变之间关联的独立性,Kaplan Meier 估计和对数秩统计用于评估生存差异。结果:不吸烟者中女性、口腔(尤其是舌头)肿瘤以及非常年轻或年老的人的比例不成比例。吸烟者的喉部、下咽部和口底肿瘤较多。吸烟者的 p53 突变率要高得多; HPV 感染的比例略低。在非吸烟者的肿瘤中,3p、4q 和 11q13 处的 LOH 百分比以及染色体丢失的总体平均数显着较低。生存率不随吸烟或年龄而变化。结论:HNSCC 的临床和遗传特征在由烟草使用定义的群体之间是不同的,非吸烟者的肿瘤包含的常见遗传改变的频率较低,表明这些肿瘤的潜在变化可能仍未被发现。
Objectives/Hypothesis: Clinical and molecular patterns of head and neck squamous cell carcinoma (HNSCC) in nonsmokers and smokers may be differ ent, Analysis of these patterns may improve understanding and management of this disease. Study Design: three hundred five subjects were included (46 nonsmokers, 29 former smokers, and 230 smokers). Subsets were analyzed for p53 mutation, human papillomavirus (HPV), and loss of heterozygosity (LOH) at 10 chromosomal loci. Methods: Clinical information was analyzed for common patterns of disease among the groups. The p53 gene was sequenced, and polymerase chain reaction was used to detect HPV DNA and LOH at two microsatellite markers for each loci. The chi(2) test was used to assess differences in genetic alterations between groups, logistic regression to examine the independence of association of tobacco exposure with each alteration, and Kaplan Meier estimates and the log-rank statistic to assess differences in survival. Results: Nonsmokers included a disproportionate number of women, oral cavity (especially tongue) tumors, and very young or old individuals. Smokers had more tumors of the larynx, hypopharynx, and floor of mouth. The rate of p53 mutation was much greater in smokers; the percentage with HPV was marginally lower. The percentage of LOH at 3p, 4q, and 11q13, and the overall average number of chromosomal losses, was significantly lower in nonsmokers' tumors. Survival did not vary with smoking or age. Conclusions: The clinical and genetic features of HNSCC are distinct between groups defined by tobacco use, Tumors of nonsmokers contain a lower frequency of common genetic alterations, suggesting that the underlying changes in these tumors may remain undiscovered.