Abstract
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.
Highlights
The p53 tumor suppressor gene is commonly mutated in colorectal cancer
P53 protein overexpression differed by type of case group (p < .01), univariate associations between risk factors and p53 status did not differ in magnitude or direction for the three types of cases, albeit numbers were small
We found similar associations between p53 status and polyp site, cigarette use, and alcohol consumption reported in several studies of invasive colorectal cancer
Summary
The 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, in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma). Of more common genes important to colorectal carcinogenesis (e.g., APC, K-ras, and p53), most data suggest that p53 is generally mutated later in the adenoma-carcinoma sequence [1,3,4,5,6,7,8,9]. The prevalence of p53 protein overexpression, which is highly correlated with p53 gene mutations [10,11,12], increases along the adenoma-carcinoma sequence with as little as 7.1 percent overexpression in adenomas with mild dysplasia to over sixty percent in those with severe dysplasia and invasive cancer [13,14,15]. Apart from pathologic characteristics such as larger size and villous histology, little is known about risk factors for intermediate steps along the adenoma-carcinoma sequence such as carcinoma in situ (CIS) and intramucosal carcinoma [18]
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