Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia
Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia
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早期结直肠肿瘤中的烟草、酒精和 p53 过度表达
作者：
M. Terry;A. Neugut;M. Mansukhani;J. Waye;N. Harpaz;H. Hibshoosh
背景p53抑癌基因在结直肠癌中常见突变。虽然 p53 突变对结直肠癌预后的影响已得到深入研究，但人们对流行病学危险因素与 p53 状态之间的关系知之甚少，特别是在临床侵袭性结直肠癌之前的早期结直肠肿瘤（包括腺瘤、原位癌 (CIS) 和粘膜内癌）中。 方法我们在选自纽约市三项结肠镜检查的 157 例早期结直肠肿瘤病例中检查了 p53 状态，通过蛋白质过度表达来测量诊所。收集石蜡包埋的组织块后，使用抗 p53 单克隆小鼠 IgG2a [BP53-12-1] 抗体进行免疫组织化学分析。我们分析了相对于无息肉对照组 (n = 508)，结直肠肿瘤危险因素中 p53 的状态是否不同。结果在腺瘤性息肉、CIS 和粘膜内病例中，sp53 过表达率分别为 10.3%、21.7% 和 34.9%。超过 90% 的 p53 过表达肿瘤位于远端结肠和直肠。大量吸烟（30岁以上）与p53不过度表达的病例相关（OR = 1.8，95% CI = 1.1–2.9），但与p53过度表达的病例无关（OR = 1.0，95% CI = 0.4–2.6）。大量啤酒消费（每周 8 瓶以上）与 p53 过度表达病例相关（OR = 4.0，95% CI = 1.3–12.0），但与没有 p53 过度表达的病例无关（OR = 1.6，95% CI = 0.7–3.7）。一些关于 p53 表达和浸润性癌症的研究结果表明，在腺瘤到癌序列的早期，吸烟和饮酒可能与 p53 存在关系。
BackgroundThe p53 tumor suppressor gene is commonly mutated in colorectal cancer. While the effect of p53 mutations on colorectal cancer prognosis has been heavily studied, less is known about how epidemiologic risk factors relate to p53 status, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma).MethodsWe examined p53 status, as measured by protein overexpression, in 157 cases with early colorectal neoplasia selected from three New York City colonoscopy clinics. After collecting paraffin-embedded tissue blocks, immunohistochemistry was performed using an anti-p53 monoclonal mouse IgG2a [BP53-12-1] antibody. We analyzed whether p53 status was different for risk factors for colorectal neoplasia relative to a polyp-free control group (n = 508).Resultsp53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors with p53 overexpression were located in the distal colon and rectum. Heavy cigarette smoking (30+ years) was associated with cases not overexpressing p53 (OR = 1.8, 95% CI = 1.1–2.9) but not with those cases overexpressing p53 (OR = 1.0, 95% CI = 0.4–2.6). Heavy beer consumption (8+ bottles per week) was associated with cases overexpressing p53 (OR = 4.0, 95% CI = 1.3–12.0) but not with cases without p53 overexpression (OR = 1.6, 95% CI = 0.7–3.7).ConclusionOur findings that p53 overexpression in early colorectal neoplasia may be positively associated with alcohol intake and inversely associated with cigarette smoking are consistent with those of several studies of p53 expression and invasive cancer, and suggest that there may be relationships of smoking and alcohol with p53 early in the adenoma to carcinoma sequence.
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吸烟和结直肠腺瘤-癌序列：解释悖论的假设。
影响因子：
5
作者：
Terry,MB;Neugut,AI
通讯作者：
Neugut,AI
影响因子：
56.9
作者：
HOLLSTEIN, M;SIDRANSKY, D;HARRIS, CC
通讯作者：
HARRIS, CC
DOI：
10.1093/jnci/92.22.1831
发表时间：
2000-11-15
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Slattery, ML;Curtin, K;Samowitz, WS
通讯作者：
Samowitz, WS
结直肠腺瘤性息肉的流行病学。
DOI：
--
发表时间：
1993
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Neugut,AI;Jacobson,JS;DeVivo,I
通讯作者：
DeVivo,I
影响因子：
8.8
作者：
Freedman, AN;Michalek, AM;Marshall, JR;Mettlin, CJ;Petrelli, NJ;Zhang, ZF;Black, JD;Satchidanand, S;Asirwatham, JE
通讯作者：
Asirwatham, JE