The relationship between smoking exposure and p53 overexpression in colorectal cancer

Abstract

SummaryAlthough epidemiological studies of the relationship between cigarette smoking and colorectal cancer risk have been equivocal, a positive association is consistently found for colorectal adenoma development. We performed an epidemiological study to determine whether p53 protein overexpression, in tumours obtained at the time of resection, is associated with cigarette exposure in colorectal cancer. A total of 163 colorectal cancer cases and 326 healthy controls responded to a standardised questionnaire on colorectal cancer risk factors including detailed information on their history of cigarette smoking. All patients' tumours were analysed immunohistochemically for p53 overexpression using an avidin -biotin immunoperoxidase procedure and polyclonal anti-p53 antibody CM 1. Comparison of colorectal cases with controls revealed an elevated risk for ex-smokers (OR= 1.34, 95% CI 0.85 -2.12) and current smokers (OR= 1.13, 95% CI 0.63-2.02) when compared with non-smokers. No dose-response relationship was found for total pack-years of smoking (trend test: P=0.19). However, a trend for total pack -years of smoking was found when p53-positive cases were compared with p53-negative cases suggesting aetiological, heterogeneity (trend test: P = 0.06). Estimating the individual relative risk of developing a p53-positive tumour relative to controls showed no associations for smoking status or total pack -years of smoking. However, when p53-negative cases were compared with controls, an elevated risk was found for ex-smokers (OR= 1.84, 95% CI 1.00 -3.37) and current smokers (OR= 1.78, 95% CI 0.88-3.61). A significant trend of increasing risk was also found for total packyears of smoking (trend test: P =0.03). Colorectal tumours developing through p53-positive dependent pathways were not associated with smoking exposure. A significant increase in risk was observed for the p53-negative independent pathway with smoking. p53 overexpression appears to be associated with smoking exposure in colorectal cancer.

Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia

“…This association persisted when only examining CIS and IM cases compared to control and was robust to different definitions of p53 positivity. This finding also closely matches that of Freedman and colleagues in their case-control study of invasive colorectal cancer: OR = 1.84 (95% CI, 1.00–3.37) with heavy cigarette smoking (40+ pack years) for p53 negative colorectal cancer and no association with p53 positive colorectal cancer as determined by protein overexpression [26]. Our findings also lend support to recent findings by Slattery and colleagues on the association between cigarette smoking and microsatellite instability (MSI) positive invasive colon cancers (OR = 1.6, 95%CI = 1.0–2.5 for men, OR = 2.2, 95%CI = 1.4–3.5 for women) but not MSI negative cancers[27].…”

GSTM1 and GSTT1 Polymorphisms, Cigarette Smoking, and Risk of Colon Cancer: A Population-based Case-control Study in North Carolina (United States)

“…A recent meta-analysis reported no association between GSTM1 null genotype and colorectal cancer [35]. Only a few GSTM1 previous studies also investigated the relationship between the GST polymorphisms and the effect of cigarette smoking on colorectal cancer [36][37][38][39][40][41]. However, these studies have been inconclusive.…”

p53 over-expression andp53 mutations in colon carcinomas: Relation to dietary risk factors

“…Some dietary factors may be related to specific genetic alterations, such as mutations in the p53 tumor‐suppressor gene. Epidemiological studies have addressed risk‐factor patterns of colorectal carcinomas with and without p53 over‐expression (Zhang et al, 1995; Fredrikson et al, 1996; Freedman et al, 1996a,b,c). Interestingly, Freedman et al (1996 a ) found cruciferous vegetables to be protective among cases with p53‐positive tumors, but not in p53‐negative cases, as compared with controls.…”