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 (original) (raw)
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Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia
BMC cancer, 2003
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). We 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). p53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors wi...
A pilot study on risk factors and p53 gene expression in colorectal cancer
British journal of cancer, 1996
Of 311 colorectal cancers diagnosed in 1984-86 in the county of Ostergotland, Sweden, 179 were included in a case-control study, and, of these, 70 were investigated using immunohistochemical staining for p53 gene mutations. Alcohol use as well as medication with hydralazine-containing antihypertensive drugs, but not heredity were associated with p53 staining. The study is offered to illustrate the possible value of investigating molecularly defined tumour subtypes in relation to specific risk factors.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2015
Background: Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer (CRC) risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor beta (ESR2) has been associated with CRC stage and survival. Methods: In this prospective cohort study, we examined smoking, MHT, and folate -associated CRC risks by ESR2protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded CRC tissue specimens were collected and evaluated for ESR2protein expression by immunohistochemistry. Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between smoking, MHT, or folate and ESR2-defined CRC subtypes. Results: Informative environmental exposure and protein expression data were available for 491 incident ...
American Journal of Medical Genetics, 2001
Most studies demonstrate increased risk of colorectal cancer (CRC) and adenomas in folate-de®cient subjects or that high folate intake may afford some protection. Smoking increases such risk in some but not all studies. We investigated whether smoking, folate status and methylenetetrahydrofolate reductase (MTHFR) genotype predict the risk of adenomatous and hyperplastic polyps of colorectum. By colonoscopy, the type, number, size and extent of dysplasia of colorectal polyps were assessed in 443 subjects aged 63±72 years. We also determined RBC folate and the C667T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Smoking, folate status and the C677T MTHFR polymorphism were strong, interactive determinants of highrisk adenomas (HRAs, de®ned as adenomas !10 mm in diameter, adenomas with villous components or with severe dysplasia). The risk was particularly high in smokers with low folate and the CT/TT genotype (risk category T) and in smokers with high folate and the CC genotype (risk category C). With non-smokers with low folate and the CC genotype as reference, the odds ratios (OR, 95% CI) were 8.7 (2.5±29.7) in category T and 9.9 (2.6±38.4) in category C. Notably, this risk pattern was also observed for hyperplastic polyps. In conclusion, in smokers, high folate status may confer increased or decreased risk for HRAs, depending on the MTHFR genotype. These data demonstrate the strong gene-nutrition interaction involving the C677T MTHFR polymorphism.
Cigarette Smoking and Colorectal Cancer Risk: A Burning Issue
Gastroenterology, 2008
Cigarette smoking is an established risk factor for colorectal cancer. Because colorectal carcinogenesis is a heterogeneous process, we investigated whether cigarette smoking is differentially associated with molecularly defined subtypes of colorectal cancer.
Cancer Epidemiology Biomarkers & Prevention, 2009
Background: Many studies have reported a 20% to 60% increase in risk of colorectal cancer associated with active smoking. However, neither the U.S. Surgeon General nor the IARC have classified the relationship as causal because of concern about residual confounding. Methods: In a prospective study of 184,187 people followed from 1992 to 2005, we used Cox proportional hazard models to examine the relationship of cigarette smoking to incident colorectal cancer, controlling for screening and multiple known and putative risk factors. Information on smoking and time-varying covariates was updated in 1997, 1999, 2001, and 2003. Results: The incidence of colorectal cancer was significantly higher in current [hazard ratios (HR), 1.27; 95% confidence intervals (CI), 1.06-1.52] and former smokers (HR, 1.23; 95% CI, 1.11-1.36) compared with lifelong nonsmokers in analyses that controlled for 13 covariates, including screening. The relative risk was greatest among current smokers with at least 50 years of smoking (HR, 1.38; 95% CI, 1.04-1.84). Among former smokers, risk of colorectal cancer decreased with greater time since cessation (P trend = 0.0003), and also decreased with earlier age at cessation (P trend = 0.0014). No association was seen among former smokers who had quit before age of 40 years or abstained for 31 years or more. Conclusions: Long-term cigarette smoking is associated with colorectal cancer, even after controlling for screening and multiple other risk factors. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3362-7)
Cancer Epidemiology, Biomarkers & Prevention, 2005
Epidemiologic evidence indicates an inverse association of folate intake with risk of colorectal cancer, but whether this association is modified by intake of caffeine (in coffee and tea) or cigarette smoking—factors that possibly interfere with folate—has not been studied. Thus, we examined whether the association between dietary folate intake and incidence of colorectal cancer is modified by caffeine intake and smoking. Cox proportional hazards modeling was used to estimate rate ratios relating dietary folate intake to colorectal cancer incidence among 61,433 women ages 40 to 75 years at recruitment into the Swedish Mammography Cohort in 1987 to 1990. From March 1987 through June 2004, a total of 805 incident cases of colorectal cancer were diagnosed. After controlling for age and other potential confounders, we observed an inverse association between dietary folate intake and risk of colon cancer (rate ratio for the highest versus the lowest quintile, 0.61; 95% confidence interva...
Oncogene, 2004
We undertook a case-control study to examine the possible associations of the TP53 variants Arg4Pro at codon 72 and p53PIN3, a 16 bp insertion/duplication in intron 3, with the risk of colorectal cancer (CRC). The p53PIN3 A2 allele (16 bp duplication) was associated with an increased risk (OR 1.55, 95% CI 1.10À2.18, P ¼ 0.012), of the same order of magnitude as that observed in previous studies for other types of cancer. The Pro72 allele was weakly associated with CRC (OR ¼ 1.34, 95% CI 0.98À1.84, P ¼ 0.066). The possible functional role of p53PIN3 was investigated by examining the TP53 mRNA transcripts in 15 lymphoblastoid cell lines with different genotypes. The possibility that the insertion/deletion could lead to alternatively spliced mRNAs was excluded. However, we found reduced levels of TP53 mRNA associated with the A2 allele. In conclusion, the epidemiological study suggests a role for p53PIN3 in tumorigenesis, supported by the in vitro characterization of this variant.
Consumption of Cigarettes but not Betel Quid or Alcohol Increases Colorectal Cancer Risk
Journal of the Formosan Medical Association, 2009
Colorectal cancer (CRC), the fourth most common cancer worldwide, was the third leading cause of cancer death among men and women in Taiwan in 2006. 1 The incidence of CRC has been increasing in the past few years. 1 Previous studies have shown that the prevalence rate of advanced colorectal neoplasia is 1.3-3.0% among middle-aged Taiwanese. 2,3 Cumulative evidence has linked habitual cigarette smoking 4,5 and alcohol consumption 6 to the increased risk of colorectal neoplasia. Most risk factors of colon adenoma are also associated with CRC. 4,6 However, debate exists when investigating the influence of tobacco and alcohol on CRC risk. 7-11 In Taiwan, the prevalence of smoking among men is about 11 times (46.8%) more than that in women (4.3%). 12 Male drinkers also outnumber female drinkers. Because the incidence of CRC is similar among men and women,
Sex-Specific Differences in Colon Cancer Associated With p53 Mutations
Nutrition and Cancer, 2004
Introduction: Sex-specific differences in observed incidence rates, tumor subsite, and diet and lifestyle associations with colon cancer have been observed. We evaluate sex-specific associations with p53 mutations in colon cancer to add to understanding of these differences. Data from a large population-based incident case-control study of colon cancer were used to evaluate age and gender associations with p53 mutations. To obtain a better understanding of gender-specific associations, we evaluated the role of estrogen as a mediator of risk. For these analyses, women were classified as estrogen positive or negative, based on menopausal status and use of hormone replacement therapy (HRT). Results: There was a significant interaction between age and sex and risk of an acquired p53 mutation compared with p53 Wt. Among men, there was an increase in p53 mutations with age, whereas among women the opposite was observed. Associations with parity, oral contraceptive use, and total ovulatory months were not associated with p53 mutations. However, recent use of HRT reduced risk of all tumors, as did being estrogen positive. Women who were estrogen positive (either premenopausal or recent users of HRT) were at a significantly increased risk of an acquired p53 mutation if they consumed a diet with a high sugar index (odds ratio = 2.94; 95% confidence interval = 1. 47-5.89); similar increases in risk of p53 mutations were not observed for men or women who were estrogen negative. Conclusions: Although sex-specific associations were detected for acquired p53 mutations, they do not indicate a unique role of estrogens in the mutation of p53. These data are consistent with a role for estrogen in altering susceptibility to diet and lifestyle factors possibly via an insulin-related mechanism.