Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia

Abstract

Background: 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, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma).

Moderate Alcohol Consumption Protects Against Colorectal Adenomas in Smokers

“…Additionally, both smoking and alcohol have been associated with expression of the tumor suppressor gene p53. Terry et al demonstrated that alcohol intake was associated with p53 over-expression while smoking may be inversely related to p53 expression (30). In our study, the finding of decreased odds of having an adenoma with increased alcohol consumption among those who had smoked for 15 years or more could be related to the independent effects of both agents on the various oncogenes or tumor suppressors that play a role in colorectal carcinogenesis.…”

Associations between Cigarette Smoking, Hormone Therapy, and Folate Intake with Incident Colorectal Cancer by TP53 Protein Expression Level in a Population-Based Cohort of Older Women

“…Terry et al found that heavy cigarette smoking was associated with CRC cases that did not overexpress TP53 (OR = 1.7 for current smokers and OR = 1.8 for 30 or more years of smoking) (12). While data from our study appear to be consistent with those reported by Terry et al, our relative risk estimates for CS-related variables were generally lower, and not statistically significant.…”

“…With respect to CRC risk assessment, our group and others have observed differential associations between common environmental exposures, including cigarette smoking (CS), hormone therapy (HT) and folate intake (FI), and incident CRCs defined by microsatellite instability (MSI), CpG island methylator phenotype (CIMP), KRAS mutation, or BRAF mutation status (5-10). However, to date, relatively fewer studies have examined subtype-specific CRC risks by TP53 expression levels (11-12). …”

APC and KRAS mutations in distal colorectal polyps are related to smoking habits in men: results of a cross-sectional study

“…Thus far, to the best of our knowledge, few studies have examined associations between smoking and genetic alterations present in precancerous lesions, focusing on APC [36] and KRAS [37,38] mutations and p53 expression [39]. Therefore, further studies are necessary to establish the genetic profi le of the polyps related to smoking.…”