Samuel M. Lesko

Dietary Patterns and Colorectal Adenoma and Cancer Risk: A Review of the Epidemiological Evidence

A number of studies exploring associations between individual dietary components and colorectal adenoma or cancer risk have yielded conflicting results. The study of food-based dietary patterns in relation to chronic disease risk represents an alternative approach to the evaluation of single dietary exposures in epidemiological investigations. Results from prospective cohort and population-based case-control studies examining associations between dietary patterns and colorectal cancer or adenoma risk were evaluated and described in this review. Despite notable differences in population characteristics, study design, and methods used for characterizing dietary patterns across the different studies, two general dietary patterns were found to modestly predict colorectal adenoma and cancer risk. A healthier pattern consisting of greater intakes of fruits and vegetables, and lower intakes of red and processed meat, appeared protective against colorectal adenoma and cancer incidence. Findings also suggest that a less healthy pattern characterized by higher intakes of red and processed meat, as well as potatoes and refined carbohydrates, may increase risk. Continued research efforts are needed to evaluate the cumulative and interactive effects of numerous dietary exposures on colorectal cancer risk.

Diet Index-Based and Empirically Derived Dietary Patterns Are Associated with Colorectal Cancer Risk

Previous studies have derived patterns by measuring compliance with preestablished dietary guidance or empirical methods, such as principal components analysis (PCA). Our objective was to examine colorectal cancer risk associated with patterns identified by both methods. The study included 431 incident colorectal cancer cases (225 men, 206 women) and 726 healthy controls (330 men, 396 women) participating in a population-based, case-control study. PCA identified sex-specific dietary patterns and the Healthy Eating Index-2005 (HEI-05) assessed adherence to the 2005 Dietary Guidelines for Americans. A fruits and vegetables pattern and a meat, potatoes, and refined grains pattern were identified among men and women; a third pattern (alcohol and sweetened beverages) was identified in men. The fruits and vegetables pattern was inversely associated with risk among men [odds ratio (OR) = 0.38, 95% CI = 0.21-0.69 for the highest compared with the lowest quartile] and women (OR = 0.35, 95% CI = 0.19-0.65). The meat, potatoes, and refined grains pattern was positively associated with risk in women (OR = 2.20, 95% CI = 1.08-4.50) and there was a suggestion of a positive association among men (OR = 1.56, 95% CI = 0.84-2.90; P-trend = 0.070). Men and women with greater HEI-05 scores had a significantly reduced risk of colorectal cancer (OR = 0.56, 95% CI = 0.31-0.99; OR = 0.44, 95% CI = 0.24-0.77, respectively). Following the Dietary Guidelines or a dietary pattern lower in meat, potatoes, high fat, and refined foods and higher in fruits and vegetables may reduce colorectal cancer risk.

Meat-Related Compounds and Colorectal Cancer Risk by Anatomical Subsite

Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends < 0.05). For analyses by meat type, cooking method, and doneness preference, positive associations between red processed meat and proximal colon cancer and pan-fried red meat and colorectal cancer were found (P-trends < 0.05). Inverse associations were observed between unprocessed poultry and colorectal, colon, proximal colon, and rectal tumors; grilled/barbequed poultry and proximal colon cancer; and well-done/charred poultry and colorectal, colon, and proximal colon tumors (P-trends < 0.05). HCAs, PAHs, nitrites, and nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted.

The effect of copy number variation in the phase II detoxification genes UGT2B17 and UGT2B28 on colorectal cancer risk

Genetic polymorphisms in combination with the Western‐style diet, physical inactivity, smoking, excessive alcohol consumption, and obesity have been hypothesized to affect colorectal cancer (CRC) risk. Metabolizers of environmental carcinogenic and endogenous compounds affecting CRC risk include the phase II detoxification UDP‐glucuronosyltransferase (UGT) enzymes UGT2B17 and UGT2B28, which are 2 of the most commonly deleted genes in the genome.

Association of Dietary and Supplemental Iron and Colorectal Cancer in a Population-Based Study

We evaluated the role of dietary iron, heme iron, and supplemental iron on colorectal cancer (CRC) risk in a population-based case–control study in Pennsylvania, including 1005 incident cases and 1062 controls. Diet was assessed through a modified food frequency questionnaire that included supplement use and a meat-specific module. Cases reported intakes for the year before diagnosis, whereas controls reported intakes for the year before interview. Heme iron intake was calculated using a new heme database developed by the US National Cancer Institute. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. After multivariate adjustment, there were no significant associations between heme iron or total iron intake and CRC incidence. Dietary iron intake was inversely associated with CRC among women (OR Q5 vs. Q1=0.45; 95% CI=0.22–0.92), but not among men. Supplemental iron intake of more than 18 mg/day versus none was positively associated with CRC incidence (OR=2.31; 95% CI=1.48–3.59; P-trend<0.001), an effect that was observed in both men (OR=2.56; 95% CI=1.30–5.05) and women (OR=2.46; 95% CI=1.34–4.52). These findings suggest that consumption of more than 18 mg/day of supplemental iron may increase risk for CRC.

The effect of UGT1A and UGT2B polymorphisms on colorectal cancer risk: Haplotype associations and gene–environment interactions

UDP‐glucuronosyltransferases (UGTs) play an important role in the phase II metabolism of exogenous and endogenous compounds. As colorectal cancer (CRC) etiology is thought to involve the biotransformation of dietary factors, UGT polymorphisms may affect CRC risk by altering levels of exposure. Genotyping of over 1800 Caucasian subjects was completed to identify the role of genetic variation in nine UGT1A and five UGT2B genes on CRC risk. Unconditional logistic regression and haplotype analyses were conducted to identify associations with CRC risk and potential gene‐environment interactions. UGT1A haplotype analysis found that the T‐G haplotype in UGT1A10 exon 1 (block 2: rs17864678, rs10929251) decreased cancer risk for the colon [proximal (OR = 0.28, 95% CI = 0.11–0.69) and for the distal colon (OR = 0.32, 95% CI = 0.12–0.91)], and that the C‐T‐G haplotype in the 3′ region flanking the UGT1A shared exons (block 11: rs7578153, rs10203853, rs6728940) increased CRC risk in males (OR = 2.56, 95% CI = 1.10–5.95). A haplotype in UGT2B15 containing a functional variant (rs4148269, K523T) and an intronic SNP (rs6837575) was found to affect rectal cancer risk overall (OR = 2.57, 95% CI = 1.21–5.04) and in females (OR = 3.08, 95% CI = 1.08–8.74). An interaction was found between high NSAID use and the A‐G‐T haplotype (block 10: rs6717546, rs1500482, rs7586006) in the UGT1A shared exons that decreased CRC risk. This suggests that UGT genetic variation alters CRC risk differently by anatomical sub‐site and gender and that polymorphisms in the UGT1A shared exons may have a regulatory effect on gene expression that allows for the protective effect of NSAIDs on CRC risk.

Dietary Iron and Colorectal Cancer Risk: A Review of Human Population Studies.

Iron is an essential micronutrient that is involved in many redox processes and serves as an integral component in various physiological functions. However, excess iron can cause tissue damage through its pro-oxidative effects, potentiating the development of many diseases such as cancer through the generation of reactive oxidative species. The two major forms of iron in the diet are heme and nonheme iron, both of which are found in several different foods. In addition to natural food sources, intake of nonheme iron may also come from fortified foods or in supplement form. This review summarizes the results of human population studies that have examined the role of dietary iron (heme and nonheme), heme iron alone, and iron from supplements in colorectal carcinogenesis.

No Association Between Vitamin D Intake, VDR Polymorphisms, and Colorectal Cancer in a Population-Based Case–Control Study

Background: Epidemiologic evidence indicates that greater intakes of vitamin D may decrease the risk of colorectal cancer. Variants in the vitamin D receptor (VDR) gene have the potential to modify associations between vitamin D intake and colorectal cancer. Methods: Associations between intakes of vitamin D and colorectal cancer were studied in a large case–control study conducted in central and northeastern Pennsylvania including 1,012 cases with histologically confirmed colorectal cancer and 1,080 population-based controls. Associations between 35 tagSNPs encompassing the VDR gene and risk for colorectal cancer as well as gene–diet associations were also assessed among a subset of the population (770 controls, 710 cases). Results: No significant trends were observed between vitamin D intake and colorectal cancer risk. After adjustment for multiple comparisons, none of the SNPs or haplotypes within the VDR gene were associated with colorectal cancer. There were also no interactions between dietary factors and variants in the entire VDR gene. Conclusions: Overall, results from this study suggest that vitamin D intake and variants in the VDR gene have little effect on risk for colorectal cancer. Impact: Increasing vitamin D intake from the diet may not result in decreasing the incidence of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(10); 1635–7. ©2015 AACR.

Association of dietary and supplemental folate intake and polymorphisms in three FOCM pathway genes with colorectal cancer in a population-based case-control study

Previous research has shown that greater intakes of dietary folate are associated with reduced risk for colorectal cancer (CRC) and that single nucleotide polymorphisms (SNPs) in genes involved in folate‐mediated one‐carbon metabolism (FOCM) also may be involved in altering CRC risk. The objective of this study was to evaluate the role of folate intake (and intakes of related dietary components such as methionine), 35 SNPs in three FOCM pathway genes (MTHFD1, MTHFR, and TYMS), and their interactions on CRC risk in a population‐based case‐control study in Pennsylvania (686 cases, 740 controls). Diet and supplement use was assessed for the year before diagnosis or interview for cases and controls, respectively, with a modified Diet History Questionnaire from the National Cancer Institute. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. Using a dominant model for the variant allele, several SNPs were significantly associated with CRC including MTHFD1 rs8003379 (OR = 1.65; 95% CI = 1.00−2.73) and rs17824591 (OR = 1.98; 95% CI = 1.14−3.41) and the TYMS rs2853533 SNP (OR = 1.38; 95% CI = 1.05−1.80). Using a nondominant model, the AA genotype for MTHFR rs1476413 exhibited a marginally significant (OR = 1.56; 95% CI = 1.00−2.44) association with CRC. Two TYMS SNPs (rs16948305 and rs495139) exhibited significant (P = 0.024 and P = 0.040, respectively) gene‐diet interactions with folate intake. One MTHFD1 (P = 0.019) and one MTHFR (P = 0.042) SNP exhibited gene‐diet interactions with methionine intake. These findings suggest that allelic variants in genes involved in FOCM interact with dietary factors including folate and methionine to modify risk for CRC.

Evaluating the impacts of screening and smoking cessation programmes on lung cancer in a high-burden region of the USA: a simulation modelling study

Objective While the US Preventive Services Task Force has issued recommendations for lung cancer screening, its effectiveness at reducing lung cancer burden may vary at local levels due to regional variations in smoking behaviour. Our objective was to use an existing model to determine the impacts of lung cancer screening alone or in addition to increased smoking cessation in a US region with a relatively high smoking prevalence and lung cancer incidence. Setting Computer-based simulation model. Participants Simulated population of individuals 55 and older based on smoking prevalence and census data from Northeast Pennsylvania. Interventions Hypothetical lung cancer control from 2014 to 2050 through (1) screening with CT, (2) intensified smoking cessation or (3) a combination strategy. Primary and secondary outcome measures Primary outcomes were lung cancer mortality rates. Secondary outcomes included number of people eligible for screening and number of radiation-induced lung cancers. Results Combining lung cancer screening with increased smoking cessation would yield an estimated 8.1% reduction in cumulative lung cancer mortality by 2050. Our model estimated that the number of screening-eligible individuals would progressively decrease over time, indicating declining benefit of a screening-only programme. Lung cancer screening achieved a greater mortality reduction in earlier years, but was later surpassed by smoking cessation. Conclusions Combining smoking cessation programmes with lung cancer screening would provide the most benefit to a population, especially considering the growing proportion of patients ineligible for screening based on current recommendations.