Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumors
Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumors
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DOI：
10.1093/jnci/92.22.1831
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发表时间：
2000-11-15
期刊：
影响因子：
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通讯作者：
Samowitz, WS
中科院分区：
文献类型：
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作者：
Slattery, ML;Curtin, K;Samowitz, WS
背景：据报道，约 10%-15% 的结肠肿瘤发生微卫星不稳定性 (MSI)。 MSI 的特征是串联重复 DNA 序列（称为微卫星）中存在突变。一些患有不稳定肿瘤的个体遗传了错配修复基因突变，但在散发性结肠癌中也观察到了 MSI。目前尚不清楚与结肠癌相关的生活方式因素，例如体力活动、体型、吸烟或使用阿司匹林和/或非甾体类抗炎药是否会导致散发性肿瘤的 MSI。方法：使用基于人群的结肠癌病例对照研究的数据。病例受试者诊断时年龄在 30 岁至 79 岁之间，包括男性和女性。问卷数据用于获取有关生活方式因素的信息。使用一组 10 个四核苷酸重复和两个单核苷酸重复来确定肿瘤 MSI。共有 1510 名病例受试者拥有有效的问卷数据和肿瘤 DNA，我们可以从中获得 MSI 状态。将问卷数据与 2410 名基于人群的对照受试者报告的生活方式因素进行比较。所有统计检验都是双面的。结果：MSI 阳性 (MSI+) 肿瘤最常见于老年人和女性以及近端结肠。与 MSI 阴性 (MSI-) 肿瘤患者相比，MSI+ 肿瘤患者更有可能每天吸 20 支或更多香烟（男性吸烟者的优势比 = 1.6 [95% 置信区间 = 1.0-2.5]，女性吸烟者的优势比为 2.2 [95% 置信区间 = 1.4-3.5]）。 MSI+肿瘤与吸烟之间的关联在年轻时开始吸烟、吸烟时间达到或超过35年、目前吸烟或在诊断前已戒烟不到15年的病例受试者中最为明显。随着吸烟量的增加，观察到 MSI+ 肿瘤风险增加的统计显着线性趋势（P
Background: Microsatellite instability (MSI) has been reported to occur in approximately 10%-15% of colon tumors. MSI is characterized by the presence of mutations in tandemly repeated DNA sequences known as microsatellites. Some individuals with unstable tumors have inherited mutations in mismatch repair genes, but MSI is also observed in sporadic colon cancer. It is unknown whether lifestyle factors associated with colon cancer, such as physical activity, body size, cigarette smoking, or use of aspirin and/or nonsteroidal anti-inflammatory drugs, contribute to MSI in sporadic tumors. Methods: Data from a population-based, case-control study of colon cancer were used. Case subjects were between 30 and 79 years of age at the time of diagnosis and included both men and women. Questionnaire data were used to obtain information on lifestyle factors. Tumor MSI was determined with the use of a panel of 10 tetranucleotide repeats and two mononucleotide repeats. A total of 1510 case subjects had valid questionnaire data and tumor DNA from which we were able to obtain MSI status. Questionnaire data were compared with lifestyle factors reported by 2410 population-based control subjects. All statistical tests were two-sided. Results: MSI-positive (MSI+) tumors were most common in older people and women and in the proximal colon. Patients with MSI+ tumors were more likely to smoke 20 or more cigarettes a day than case subjects with MSI-negative (MSI-) tumors (odds ratio for being a smoker = 1.6 [95% confidence interval = 1.0-2.5] for men and 2.2 [95% confidence interval = 1.4-3.5] for women). The association between MSI+ tumors and cigarette smoking was strongest among case subjects who started to smoke at a young age, smoked for 35 or more years, and were either current smokers or had stopped fewer than 15 years before diagnosis. A statistically significant linear trend of increased risk of MSI+ tumors was observed with increasing amount smoked (P