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Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings.Prevention relevanceUnderstanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

Marine omega-3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Multivariable hazard ratios and 95% confidence intervals (CIs) were calculated for the association between MO3PUFA and disease-free survival (DFS) and overall survival according to KRAS and BRAFV600E mutations and DNA mismatch repair (MMR) status. Higher MO3PUFA intake was associated with improved 3-year DFS for KRAS wild-type tumors (77% vs. 73%; HR: 0.84; 95% CI: 0.67-1.05) but not KRAS-mutant tumors (64% vs. 70%; HR: 1.30; 95% CI: 0.97-1.73; Pinteraction = 0.02). Similar heterogeneity was found by MMR (Pinteraction = 0.14): higher MO3PUFA was associated with better 3-year DFS for tumors with deficient MMR (72% vs. 67%) but not proficient MMR (72% vs. 72%). No heterogeneity was found by BRAFV600E mutation. Similar findings were obtained for overall survival. In conclusion, we found a suggestive beneficial association between higher MO3PUFA intake and improved survival among stage III colon cancer patients with wild-type KRAS and deficient MMR. Given the relatively small number of cases with tumor molecular assessments, further studies, preferably through pooled analyses of multiples cohorts, are needed to validate our findings.

Background: Stool-based screening with fecal immunochemical (FIT) or multitarget-stool DNA (mt-sDNA) tests is associated with increased colonoscopy polyp yield. mt-sDNA includes methylated markers, which improve detection of serrated polyps (SP) versus FIT. We compared SP detection in colonoscopies performed for positive FIT or mt-sDNA tests, as well as in colonoscopies without a preceding stool test, using the New Hampshire Colonoscopy Registry, a comprehensive statewide population-based registry. Methods: Across the three groups, we compared the frequency of clinically relevant SPs (CRSP: sessile SPs, hyperplastic polyps =10 mm, and traditional serrated adenomas). We also compared SP size, histology, number, and bulk (combined sizes). Results: Our sample included 560 mt-sDNA+ (age ± SD: 66.5 ± 7.9), 414 FIT+ (age ± SD: 66.3 ± 8.8), and 59,438 colonoscopy-only patients (age ± SD: 61.7 ± 8.0). mt-sDNA+ patients were more likely to have a higher yield of CRSPs and CRSP bulk than FIT+ (P < 0.0001) or colonoscopy-only patients (P < 0.0001). More mt-sDNA+ patients had CRSPs without large adenomas or colorectal cancers (17.9% vs. 9.9% of FIT+ and 8% of colonoscopy-only patients). After adjusting for synchronous large adenomas, colorectal cancers, and other risk factors, mt-sDNA+ patients were more likely (OR, 1.82; 95% CI, 1.18-2.85) than FIT+ patients to have CRSPs. Conclusions: mt-sDNA+ patients had a higher SP yield than FIT+ or colonoscopy-only patients, particularly in the absence of synchronous large adenomas or colorectal cancer. Impact: Our results suggest that screening with mt-sDNA tests could improve colorectal cancer screening by identifying more patients at increased risk from the serrated pathway. [ABSTRACT FROM AUTHOR]

Background: Emerging colorectal cancer trends demonstrate increased incidence and mortality in younger populations, prompting consideration of average-risk colorectal cancer screening initiation at age 45 versus 50 years. However, screening test performance characteristics in adults 45-49 years have been minimally described. To inform the biologic rationale for multi-target stool DNA (mt-sDNA) screening in younger patients, we analyzed and compared tissue levels of methylation (BMP3, NDRG4) and mutation (KRAS) markers included in the FDA-approved, mt-sDNA assay (Cologuard; Exact Sciences Corporation). Methods: Within 40-44, 45-49, and 50-64 year age groups, archived colorectal tissue specimens were identified for 211 sporadic colorectal cancer cases, 123 advanced precancerous lesions (APLs; adenomas >1 cm, high-grade dysplasia, =25% villous morphology, or sessile serrated polyp; 45-49 and 50-64 age groups only), and 204 histologically normal controls. Following DNA extraction, KRAS, BMP3, and NDRG4 were quantified using QuARTS assays, relative to ACTB (reference gene). Results: None of the molecular marker concentrations were significantly associated with age (P > 0.05 for all comparisons), with the exception of NDRG4 concentration in APL samples (higher in older vs. younger cases; P = 0.008). However, NDRG4 levels were also statistically higher in APL case versus normal control samples in both the 45-49 (P < 0.0001) and 50-64 (P < 0.0001) year age groups. Conclusions: Overall, these findings support the potential for earlier onset of average-risk colorectal cancer screening with the mt-sDNA assay. Impact: These novel data address an identified knowledge gap and strengthen the biologic basis for earlier-onset, average-risk screening with the mt-sDNA assay. [ABSTRACT FROM AUTHOR]

Background: Prior studies have supported an inverse association between physical activity and colon cancer risk and suggest that higher physical activity may also improve cancer survival. Among participants in a phase III adjuvant trial for stage III colon cancer, we assessed the association of physical activity around the time of cancer diagnosis with subsequent outcomes. Methods: Before treatment arm randomization (FOLFOX or FOLFOX + cetuximab), study participants completed a questionnaire including items regarding usual daily activity level and frequency of participation in recreational physical activity (N = 1,992). Using multivariable Cox models, we calculated HRs for associations of aspects of physical activity with disease-free (DFS) and overall survival (OS). Results: Over follow-up, 505 participants died and 541 experienced a recurrence. Overall, 75% of participants reported recreational physical activity at least several times a month; for participants who reported physical activity at least that often (vs. once a month or less), the HRs for DFS and OS were 0.82 [95% confidence interval (CI), 0.69-0.99] and 0.76 (95% CI, 0.63-0.93), respectively. There was no evidence of material effect modification in these associations by patient or tumor attributes, except that physical activity was more strongly inversely associated with OS in patients with stage T3 versus T4 tumors (Pinteraction = 0.03). Conclusions: These findings suggest that higher physical activity around the time of colon cancer diagnosis may be associated with more favorable colon cancer outcomes. [ABSTRACT FROM AUTHOR]

Background: Host immune response may predict the course of colorectal cancer. We examined the survival of 468 colorectal cancer patients associated with two tumor-infiltrating immune biomarkers, the number of cytotoxic T lymphocytes (CTLs), and the activated CTLs, as reflected by the number of cells expressing granzyme B (GZMB) in the prospective Iowa Women's Health Study. Methods: Using paraffin-embedded tissue samples, we constructed and immunostained tumor microarrays with CD8 (for CTL) and GZMB antibodies. We scored CTL and GZMB densities in tumor epithelial and stromal tissues and also created a composite score for each biomarker (sum of the scores across tissue compartments). Cox regression estimated the HR and 95% confidence intervals (CI) for all-cause and colorectal cancer-specific death associated with each composite score. Results: CTL and GZMB composite scores were positively correlated (r = 0.65) and each biomarker was inversely correlated with stage at diagnosis. Both composite scores were higher in proximal colon tumors and tumors characterized by MSI-high, CIMP-high, or BRAF mutation status. HRs (95% CI) were 0.53 (0.38-0.75; Ptrend = 0.0004) and 0.66 (0.51-0.86; Ptrend = 0.002) for all-cause death, respectively, and 0.30 (0.18-0.51; Ptrend < 0.0001) and 0.41 (0.27-0.63; Ptrend < 0.0001) for colorectal cancer-related death, respectively. Including CTL and GZMB scores simultaneously in the model significantly improved the predictive performance of the models for all-cause and colorectal cancer-related death. Conclusions: Higher tumor infiltration with CTL and GZMB cells is associated with improved all-cause and cancer-specific survival of colorectal cancer patients. [ABSTRACT FROM AUTHOR]

The article discusses a research related to association between environmental exposures and incident colorectal cancer. It mentions several risk factors for colorectal cancer which include cigarette smoking, folate intake, and hormone therapy. It also mentions association of expression of estrogen receptor beta (ESR2) with colorectal cancer stage and survival.

The article discusses a study which examined the role of cigarette smoking (CS), folate intake (FI) and hormone therapy (HT) on the development of colorectal cancer. Topics discussed include the analysis of TP53 protein expression level, an inverse association between longer HT duration and TP53 high colorectal cancer, and no statistically significant association found between TP53-specific colorectal cancer and CS and FI.

The article discusses a study which examined the effect of metformin, thiazolidinediones (TZD), sulfonylureas and insulin on the risk of developing colorectal cancer in diabetic patients. Particular focus is given to the inclusion criteria for the meta-analysis, as well as use of the Cochran Q statistical test. Also discussed are the association between metformin use and colorectal cancer risk in Western populations and effect of sulfonylureas on colorectal cancer risk in Asian subjects.

The article presents a study which investigates the risk in colorectal cancer and postmenopausal hormone therapy (PHM) in relation to the status of somatic Kirsten RNA Associated Rat Sarcoma 2 Virus Gene (KRAS) mutation in older women. The study has recorded data of PMH therapy and other exposure at the baseline. Study shows the statistical insignificance of risk estimates in PHM therapy.

The article presents a population-based study to evaluate adherence to average-risk colorectal cancer screening (CRCS) guidelines in Olmsted County, Minnesota from 1997 to 2008. It finds that CRCS increased from 22% to 65% for women and from 17% to 59% for men. The mean ages of screening initiation were found stable at 55 years among both men and women in 2008. It believes that there is still room for improvement although overall CRCS reportedly tripled during the study period.

Background & Aims: Direct germline analysis could be used to screen high-risk patients for mutations in DNA mismatch repair genes associated with Lynch Syndrome. We examined the prevalence of mutations in MLH1, MSH2, and MSH6 in a population-based sample of patients with young-onset (age <50 years) colorectal cancer (CRC). Methods: Young-onset CRC cases were randomly selected from 3 Colon Cancer Family Registry sites. DNA was extracted from peripheral blood leukocytes; MLH1, MSH2, and MSH6 were sequenced, and duplication and deletion analyses was performed for MLH1 and MSH2. Results were reported as deleterious or suspected deleterious, likely neutral, variant of uncertain significance, or no alteration detected. Germline data were compared to Amsterdam II criteria (ACII) and immunohistochemistry results in secondary analyses. Results: Among 195 subjects, 11 had deleterious/suspected deleterious mutations (5.6%; 95% confidence interval [CI], 2.8%–9.9%), 12 had likely neutral alterations (6.2%; 95% CI, 3.2%–10.5%), 14 had variants of uncertain significance (7.2%; 95% CI, 4.0%–11.8%), 2 had a likely neutral alteration and a variant of uncertain significance (1.0%; 95% CI, 0.1%–3.7%), and 156 had no alteration detected (80.0%; 95% CI, 73.7%–85.4%). Sensitivity, specificity, and positive and negative predictive values for detecting deleterious/suspected deleterious mutations, based on ACII, were 36.4% (4/11), 96.7% (178/184), 40.0% (4/10), and 96.2% (178/185), respectively; based on immunohistochemistry these values were 85.7% (6/7), 91.9% (136/148), 33.3% (6/18), and 99.3% (136/137), respectively. Conclusions: In a population-based sample of young-onset CRC cases, germline mutations in MLH1, MSH, and/or MSH6 were more prevalent than reported for CRC patients overall. Because only about 5% of young-onset CRC cases had confirmed deleterious or suspected deleterious mutations, further comparative effectiveness research is needed to determine the most appropriate screening strategy for Lynch Syndrome in this high-risk group. [Copyright &y& Elsevier]

The article presents the Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO) Trial done from November 1993-July 2001, which evaluated the relation of C-reactive protein (CRP) level, a clinical biomarker of inflammation, and colorectal adenoma development. The methods used in the study are described including a sigmoidoscopy and risk factor questionnaire. Results show that high CRP levels may be protective against colorectal adenoma development. Further study is suggested due to contrasting data on inflammation and colorectal tumorigenesis.

Background & Aims: Type 2 diabetes mellitus (DM) is associated with an increased risk of colorectal cancer (CRC); it is not clear if this association varies by sex or other factors. Insulin use might also be associated with CRC risk. We investigated associations of type 2 DM and insulin use with CRC risk. Methods: The Cancer Prevention Study II Nutrition Cohort is a prospective study of cancer incidence. In 1992 or 1993, adult participants (n = 184,194) completed a detailed, self-administered questionnaire. Follow-up questionnaires were sent in 1997 and every 2 years thereafter. Cox proportional hazards regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusting for covariates. Results: After exclusions, 73,312 men and 81,663 women remained in the final analytic cohort; 1567 men (227 with type 2 DM) and 1242 women (108 with type 2 DM) were diagnosed with colon or rectal cancer by 2007. Among men, type 2 DM was associated with increased risk of incident CRC compared to not having type 2 DM (RR: 1.24; 95% CI: 1.08−1.44); risk was higher for participants with type 2 DM using insulin (RR: 1.36; 95% CI: 1.05−1.78), and participants with type 2 DM not using insulin (RR: 1.22, 95% CI: 1.04−1.45). Among women, type 2 DM and insulin use were not associated with risk of incident CRC (RR: 1.01; 95% CI: 0.82−1.23 and RR: 0.95; 95% CI: 0.64−1.41, respectively). Conclusions: There is a modest association between type 2 DM and CRC among men, but not women. Insulin use is not associated with a substantially increased risk of CRC. [ABSTRACT FROM AUTHOR]

The article discusses a study which assessed the impact of folic acid-containing supplements (FAS) on the progression of colorectal cancer after diagnosis. Logistic regression models were used by the authors to investigate predictors of FAS use in 1,092 patients who were recruited through the Colon Cancer Family Registry. The authors found that the prevalence of FAS use was 35.4 percent before and 55.1 percent after diagnosis.

The article discusses a candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk. The study used data from 1,805 population-based colorectal cancer cases and 2,878 matched sibling controls from the Colon Cancer Family Registry. The study found only moderate evidence that genetic variation in 15 folate pathway genes could affect colorectal cancer risk except in non-multivitamin users.

The article reports on a population-based study which examined the association of change in the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme to the decreased risk of colorectal cancer. A tag single nucleotide polymorphism approach is used to determine the association of changes in the MTHFR gene to disease risk in a population-based study from the Colon Cancer Family Registry. The results proved that variability in the MTHFR gene did not change colorectal cancer risk.

The article offers a study which examines the possible role of susceptibility variants in tumor progression and evaluates association with commonly observed structural abnormalities. It mentions that the study intends to determine whether there are structural changes at chromosome 8q24 that could correlate with the variants. It investigates the significance of the susceptibility markers for colon cancer case-control status and survival.

The article focuses on a study which compared the rate and extent of absorption of sulindac from capsules versus tablets, each a the commonly prescribed dose of 150mg, to establish sulindac capsules as a pharmaceutical alternative for sulindac tablets. The study found that the bioavailability of sulindac appeared to be higher for the capsule compared with the tablet formulation based on test-to-reference pharmacokinetic ratios for sulindac sulfoxide.

This article discusses findings of a study, which determined the positive and negative predictive values of self-reported polyps, using colonoscopy and pathology reports as a gold standard for comparison. Colorectal adenomatous polyps or adenomas have the potential to progress to invasive colorectal cancer. The results of the study suggested that individuals with polyps are unable to accurately report polyp histology regardless of family history classification.

Background & Aims: Recent studies showed that endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a low-risk procedure for causing bacteremia and infectious complications when sampling solid lesions of the upper gastrointestinal (GI) tract. As a result, antibiotics are not recommended for prophylaxis against endocarditis. Our aim was to prospectively evaluate the risk of bacteremia and other infectious complications in patients undergoing EUS FNA of lower GI tract lesions. Methods: Patients referred for EUS FNA of lower GI tract lesions were considered for enrollment. Patients were excluded if there was an indication for preprocedure antibiotic administration based on American Society for Gastrointestinal Endoscopy guidelines, had taken antibiotics within the prior 7 days, or if they had a cystic lesion. Blood cultures were obtained immediately before the procedure, after flexible sigmoidoscopy/radial EUS, and 15 minutes after EUS FNA. Results: One hundred patients underwent a total of 471 FNAs (mean, 4.7 FNAs/patient; range, 1–10 FNAs/patient). Blood cultures were positive in 6 patients. Cultures from 4 patients (4.0%, 95% confidence interval, 1.6%–9.8%) grew coagulase-negative Staphylococcus (n = 2), Peptostreptococcus stomatis (n = 1), or Moraxella (n = 1), which were considered contaminants. Two patients (2.0%, 95% confidence interval, 0.6%–7%) developed bacteremia: Bacteroides fragilis (n = 1) and Gemella morbillorum (n = 1). No signs or symptoms of infection developed in any patient. Conclusions: EUS FNA of solid lesions in the lower GI tract should be considered a low-risk procedure for infectious complications that does not warrant prophylactic administration of antibiotics for the prevention of bacterial endocarditis. [Copyright &y& Elsevier]

Background & Aims: Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment–insulin resistance (HOMA-IR) index. To date, few studies have directly examined serum insulin as an indicator of CRC risk, and none have reported associations on the basis of HOMA-IR. Methods: We performed a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (n = 29,133). Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects. HOMA-IR was derived as fasting insulin × fasting glucose/22.5. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models. Results: Median (interquartile range) values for serum insulin, glucose, and HOMA-IR were 4.1 (2.9–7.2) mIU/L, 101 (94–108) mg/dL, and 0.99 (0.69–1.98) for case subjects and 4.1 (2.7–6.1) mIU/L, 99 (93–107) mg/dL, and 1.02 (0.69–1.53) for non-case subjects, respectively. On the basis of comparison of the highest versus lowest quartiles for each biomarker, insulin (HR, 1.84; 95% CI, 1.03–3.30) and HOMA-IR (HR, 1.85; 95% CI, 1.06–3.24) were significantly associated with incident CRC, whereas glucose was marginally associated with incident CRC (HR, 1.70; 95% CI, 0.92–3.13) in age-adjusted risk models. However, trends across biomarker quartiles were somewhat inconsistent (P trend = .12, .04, and .12, respectively), and multivariable adjustment generally attenuated the observed risk estimates. Conclusions: Data from this prospective study of male smokers provide limited support for hyperinsulinemia, hyperglycemia, and/or insulin resistance as CRC risk factors. [Copyright &y& Elsevier]

Rationale and Objectives: Obesity is associated with increased risks for colorectal neoplasia. Few studies have examined quantitative body fat measurements as predictors of colorectal polyps. The objective is to determine whether visceral fat is associated with colorectal polyps at computed tomography (CT) colonography. Materials and Methods: Case (n = 25) and control (n = 25) subjects with proven large (>1 cm) colorectal adenomas or normal colons respectively were randomly selected from among an established CT colonography research study cohort. Using supine CT colonography data, the body wall was traced at three levels: top of the right kidney, iliac crest, and superior acetabulum. Total area from the three slices and each slice area were determined within the visceral fat range (-170 to -45 Hounsfield units) and recorded within the selected region. Visceral fat measures were compared between patient groups with and without polyps. Results: None of the single slice visceral fat area measures or summed measures predicted case or control status. The most informative visceral fat measure was obtained at the top of the right kidney with a maximum area under the received operator characteristic curve of 0.77 (0.05 SE). For a selected sensitivity of 75%, the maximum specificity for a large (>or=1 cm) polyp was 64%. Conclusion: In this pilot study, visceral fat measures at CT colonography were not significantly associated with the presence of large colorectal adenomas. However, odd ratios were elevated by a factor of 2. This suggests that a larger study may be justified. [ABSTRACT FROM AUTHOR]

Background & Aims: Inflammatory bowel disease (IBD) is associated with an increased risk for colorectal cancer (CRC). However, the genetic, endoscopic, and histologic features of IBD-associated CRC differ from cancers that arise sporadically. The objectives of this study were to describe the clinicopathologic features of IBD-associated CRC and to compare survival rates between patients with IBD-associated CRC and patients with sporadic CRC. Methods: There were 290 patients with IBD-associated CRC (241 with chronic ulcerative colitis [CUC] and 49 with Crohn’s disease) and an equal number of age- and sex-matched sporadic CRC patients who were evaluated at the Mayo Clinic between 1976 and 1996. Medical records were reviewed retrospectively for demographic features, endoscopic and histologic characteristics, and vital status at the time of the last follow-up evaluation. The actuarial survival of each group was calculated by the Kaplan–Meier method. The influence of clinical features on survival was assessed using Cox proportional hazards regression modeling. Results: The median age at diagnosis of IBD-related CRC was 48 years. Fifty-five percent of IBD-related tumors were distal to the splenic flexure compared with 78% of sporadic tumors. During a median follow-up period of 5 years, 163 IBD-associated CRC patients died (56%), compared with 164 sporadic CRC patients (57%). The 5-year survival rates were 54% in the IBD–CRC subgroup vs 53% in the sporadic CRC subgroup (P = .94, log-rank). Conclusions: CUC-related CRC is diagnosed at a relatively young age, and IBD-related tumors tend to be distributed more evenly across the colorectum than sporadic tumors. The survival rates for IBD-associated and sporadic CRC were similar. [Copyright &y& Elsevier]

Background & Aims: Esophageal squamous cell carcinoma remains a leading cause of cancer death worldwide. Squamous dysplasia, the accepted histological precursor for esophageal squamous cell carcinoma, represents a potentially modifiable intermediate end point for chemoprevention trials in high-risk populations. Methods: We conducted a randomized, controlled trial of selenomethionine 200 μg daily and/or celecoxib 200 mg twice daily (2 × 2 factorial design) among residents of Linxian, People’s Republic of China. Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline. Esophagogastroduodenoscopy was performed before and after a 10-month intervention. Per-subject change (regression, stable, or progression) in the worst dysplasia grade was defined as the primary end point. Results were compared by agent group (selenomethionine vs placebo; celecoxib vs placebo). Results: Two hundred sixty-seven subjects fulfilled all eligibility criteria, and 238 (89%) completed the trial. Overall, selenomethionine resulted in a trend toward increased dysplasia regression (43% vs 32%) and decreased dysplasia progression (14% vs 19%) compared with no selenomethionine (P = .08). In unplanned stratified analyses, selenomethionine favorably affected a change in dysplasia grade among 115 subjects with mild esophageal squamous dysplasia at baseline (P = .02), but not among 123 subjects with moderate esophageal squamous dysplasia at baseline (P = 1.00). Celecoxib status did not influence changes in dysplasia grade overall (P = .78) or by baseline histology subgroup. Conclusions: After a 10-month intervention, neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for all high-risk subjects. However, among subjects with mild esophageal squamous dysplasia at baseline, selenomethionine did have a protective effect. Although it is based on unplanned stratified analyses, this finding is the first report of a possible beneficial effect for any candidate esophageal squamous cell carcinoma chemopreventive agent in a randomized controlled trial. [Copyright &y& Elsevier]

In a prospective cohort of 41,836 Iowa women aged 55–69 years with 13 years of follow-up from 1986 through 1998, the authors examined the association between cigarette smoking history and three common histologic subtypes of lung cancer (123 small cell, 115 squamous cell, and 234 adenocarcinoma). Using Cox proportional hazards and additive Poisson regression analysis, they estimated four epidemiologic measures of effect: age-adjusted incidence rate, relative risk, excess risk (or risk difference), and population attributable risk. Of the three major lung cancer subtypes, the excess risk for heavy smokers compared with never smokers was higher for adenocarcinoma (excess risk = 206) than for squamous cell (excess risk = 122) and small cell (excess risk = 104) carcinomas. Adenocarcinoma of the lung is more strongly associated with tobacco smoke exposure than previously recognized. [ABSTRACT FROM PUBLISHER]

The article describes the association between fasting serum insulin-like growth factor (IGF) -I, IGF binding protein-3 (IGFBP-3) and IGF-I/IGFBP-3 molar ratio and colorectal cancer (CRC) risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. According to the authors, the serum-based biomarkers were not significantly associated with incident CRC. The authors add that body mass index, total energy intake, alcohol intake and physical activity level did not modify the risk estimates.