ASSOCIATION BETWEEN CIGARETTE-SMOKING AND MUTATION OF THE P53 GENE IN SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK
ASSOCIATION BETWEEN CIGARETTE-SMOKING AND MUTATION OF THE P53 GENE IN SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK
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DOI：
10.1056/nejm199503163321104
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发表时间：
1995-03-16
影响因子：
158.5
通讯作者：
SIDRANSKY, D
中科院分区：
文献类型：
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作者：
BRENNAN, JA;BOYLE, JO;SIDRANSKY, D
背景虽然流行病学研究长期以来将烟草和酒精的使用与头颈部鳞状细胞癌的发生联系起来，但这些致癌物质的分子靶点尚未确定。我们进行了一项分子分析，以确定肿瘤的p53基因突变的模式与鳞状细胞癌的头部和颈部和吸烟或饮酒的历史。对129例头颈部原发性鳞状细胞癌患者的肿瘤标本进行p53基因保守区的序列分析。然后，我们使用统计分析来确定与p53基因突变相关的任何患者特征。我们在42%的患者（129例中的54例）中发现了p53突变。58%的吸烟和饮酒的患者（64人中的37人; 95%置信区间，45%至70%），33%的吸烟但戒酒的患者（13/39）95%的置信区间，19%至50%），17%的患者既不吸烟也不喝酒（4/24，95%置信区间，5%至37%）有p53突变（P = 0.001）。(Two患者饮酒，但不吸烟，也没有p53突变。此外，在既不喝酒也不吸烟的患者中，100%的突变发生在含有胞苷磷酸鸟苷二核苷酸的位点上。（可能代表内源性突变）（5个突变中的5个; 95%置信区间，48%至100%），而吸烟者中只有23%的人发生了这种变化。（53个突变中的12个; 95%置信区间，12%至36%; P = 0.001）。在我们的研究中，吸烟和饮酒史与头颈部鳞状细胞癌患者中p53基因突变的高频率相关。初步证据表明，吸烟与非内源性突变位点的p53突变有关。我们的研究结果表明，烟草在头颈部鳞状细胞癌的分子进展中的作用，并支持戒烟对预防头颈部癌很重要的流行病学证据。
Background. Although epidemiologic studies have long associated tobacco and alcohol use with the development of squamous-cell carcinoma of the head and neck, the molecular targets of these carcinogens have yet to be identified. We performed a molecular analysis to determine the pattern of mutations in the p53 gene in neoplasms from patients with squamous-cell carcinoma of the head and neck and a history of tobacco or alcohol use.Methods. Sequence analysis of the conserved regions of the p53 gene was performed in tumor samples from 129 patients with primary squamous-cell carcinoma of the head and neck. We then used statistical analysis to identify any patient characteristics associated with mutation of the p53 gene.Results. We found p53 mutations in 42 percent of the patients (54 of 129). Fifty-eight percent of the patients who smoked cigarettes and used alcohol (37 of 64; 95 percent confidence interval, 45 to 70 percent), 33 percent of the patients who smoked but abstained from alcohol (13 of 39; 95 percent confidence interval, 19 to 50 percent), and 17 percent of the patients who neither smoked nor drank alcohol (4 of 24, 95 percent confidence interval, 5 to 37 percent) had p53 mutations (P = 0.001). (Two patients used alcohol but did not smoke, and neither had a p53 mutation.) Furthermore, 100 percent of the mutations in the patients who neither drank nor smoked occurred at sites containing cytidine phosphate guanosine dinucleotides (potentially representing endogenous mutations) within the p53 gene (5 of 5 mutations; 95 percent confidence interval, 48 to 100 percent), whereas only 23 percent of those in cigarette smokers consisted of such changes (12 of 53 mutations; 95 percent confidence interval, 12 to 36 percent; P = 0.001).Conclusions. In our study, a history of tobacco and alcohol use was associated with a high frequency of p53 mutations in patients with squamous-cell carcinoma of the head and neck. Preliminary evidence linked cigarette smoking to p53 mutations at nonendogenous mutation sites. Our findings suggest a role for tobacco in the molecular progression of squamous-cell carcinoma of the head and neck and support the epidemiologic evidence that abstinence from smoking is important to prevent head and neck cancer.