P. van 't Veer

Plasma Enterolignans Are Associated with Lower Colorectal Adenoma Risk

Lignans are biphenolic compounds that occur in foods of plant origin such as whole grains, seeds, fruits and vegetables, and beverages, such as coffee and tea. Plant lignans are converted by intestinal bacteria into the enterolignans, enterodiol and enterolactone. Enterolignans possess several biological activities, whereby they may influence carcinogenesis. We studied the associations between plasma enterolignans and the risk of colorectal adenomas in a Dutch case-control study. Colorectal adenomas are considered to be precursors of colorectal cancer. Cases (n = 532) with at least one histologically confirmed colorectal adenoma and controls (n = 503) with no history of any type of adenoma were included. Plasma enterodiol and enterolactone concentrations were measured by liquid chromatography with tandem mass spectrometry. Associations were stronger for incident than for prevalent cases. When only incident cases (n = 262) were included, high compared to low plasma concentrations of enterodiol were associated with a reduction in colorectal adenoma risk after adjustment for confounding variables. Enterodiol odds ratios (95% confidence intervals) were 1.00, 0.69 (0.42-1.13), 0.60 (0.37-0.99), and 0.53 (0.32-0.88) with a significant trend (P = 0.01) through the quartiles. Although enterolactone plasma concentrations were 10-fold higher, enterolactones reduction in risk was not statistically significant (P for trend = 0.09). Use of oral antibiotic therapy could decrease the plasma concentrations of enterolactone. Exclusion of antibiotic users resulted in similar odds ratios for both enterolignans, but the association for enterolactone became somewhat stronger (P = 0.05 versus P = 0.09). We observed a substantial reduction in colorectal adenoma risk among subjects with high plasma concentrations of enterolignans, in particular, enterodiol. These findings could be important in the prevention of colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1132–6)

Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: a prospective cohort study (The Netherlands)

Objective:The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer.Methods:The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer patients on whom case-cohort analyses (subcohort nxa0=xa02948) were performed.Results:Total meat consumption was not associated with the endpoints studied. Meat product (i.e. processed meat) consumption showed a positive association with colon tumours harbouring a truncating APC mutation, whereas beef consumption was associated with an increased risk of colon tumours without a truncating APC mutation (incidence rate ratio (RR) highest versus lowest quartile of intake 1.61, 95% confidence interval (CI) 0.96–2.71, p-trendxa0=xa00.04 and 1.58, 95% CI 1.10–2.25, p-trendxa0=xa00.01, respectively). Consumption of other meat (horsemeat, lamb, mutton, frankfurters and deep-fried meat rolls) was associated with an increased risk of rectal cancer without a truncating APC mutation (RR intake versus no intake 1.79, 95% CI 1.10–2.90). No associations were observed for meat consumption and tumours lacking hMLH1 expression.Conclusions:Our data indicate that several types of meat may contribute differently to the aetiology of colon and rectal cancer, depending on APC mutation status but not hMLH1 expression of the tumour.

Meat consumption and meat preparation in relation to colorectal adenomas among sporadic and HNPCC family patients in The Netherlands.

Meat consumption and meat preparation methods are thought to be associated with the risk of sporadic colorectal cancer, and possibly adenomas. As the same somatic mutations occur in sporadic adenomas and hereditary non-polyposis colorectal cancer (HNPCC)-related adenomas, similar exogenous factors may play a role in the development of both types of adenoma. In a case control study among 57 sporadic colorectal adenoma cases and 62 adenoma cases from HNPCC families (and 148 adenoma-free controls) from the Netherlands, we examined whether meat consumption and preparation are similarly associated with sporadic and suspected HNPCC colorectal adenomas. Frequency of meat consumption was not significantly associated with adenoma risk in our population of sporadic and HNPCC family cases and controls (Odds Ratios (OR) for high versus low consumption were 1.0 and 0.6, respectively). Interestingly, consumption of red meat and specific preparation methods (i.e., not adding any water and closed lid with most meat types) slightly, but non-significantly, increased the risk of adenomas in the sporadic group only (OR, 95% Confidence Interval (CI): 4.1, 0.7-23.0, 2.0, 0.6-6.5 and 2.6, 0.9-7.2, respectively). This is the first study to examine possible differences or similarities in risk factors for sporadic and HNPCC colorectal carcinogenesis. Our results do not provide support for meat consumption as a risk factor for adenoma formation in HNPCC family members. Some characteristics of habitual meat preparation in the Netherlands may, however, increase the risk of sporadic adenomas.

Fruits, vegetables, and hMLH1 protein-deficient and -proficient colon cancer: The Netherlands cohort study.

Background: Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes. Methods: Associations between consumption of fruits and vegetables and hMLH1 protein–deficient and –proficient colon cancer were evaluated in the Netherlands Cohort Study on diet and cancer using a case-cohort approach. A self-administered food frequency questionnaire was completed, in 1986, by 120,852 individuals ages 55 to 69 years. Using immunohistochemistry, hMLH1 protein expression was assessed in colon cancer tissue obtained from 441 patients who were identified over 7.3 years of follow-up excluding the initial 2.3 years. Incidence rate ratios (RR) were estimated for hMLH1 protein–deficient and –proficient colon cancer. Results: hMLH1 protein expression was absent in 54 tumors (12.2%) and present in 387 tumors. Fruit consumption was associated with hMLH1 protein–deficient colon cancer [highest versus lowest tertile, RR, 0.46; 95% confidence interval (95% CI), 0.23-0.90; Ptrend = 0.029] but not with hMLH1 protein–proficient tumors (highest versus lowest tertile, RR, 1.03; 95% CI, 0.78-1.35; Ptrend = 0.81). Total consumption of vegetables was not associated with either type of tumor (hMLH1 protein deficient: RR, 0.86; 95% CI, 0.45-1.65; Ptrend = 0.67; hMLH1 protein proficient: RR, 0.94; 95% CI, 0.72-1.23; Ptrend = 0.72). No associations were observed for folate, fiber, antioxidants, or subgroups of vegetables. Conclusion: These analyses indicate that an inverse association between consumption of fruits and colon cancer may be confined to the subgroup of tumors with a deficient mismatch repair system.

Meat consumption and preparation, and genetic susceptibility in relation to colorectal adenomas.

Epidemiological evidence suggests that a high meat consumption and/or animal fat intake may increase the risk of colorectal cancer. The objective of this study is to examine the role of dietary factors, in particular meat preparation and consumption, in relation to colorectal adenomas, the pattern of DNA-mutations (e.g. K-ras and p53), and genetic susceptibility (NAT2, HNPCC). In a case control study on diet and colorectal adenomas (sporadic and HNPCC), acetylator status (NAT2) of cases and controls as well as K-ras and p53 mutations in adenomas will be assessed. Consumption and preparation of meat, the primary interest of this study, will be assessed by a food frequency questionnaire designed especially for this purpose.