Diet and epigenetics in colon cancer

Over the past few years, evidence has accumulated indicating that apart from genetic alterations, epigenetic alterations, through e.g. aberrant promoter methylation, play a major role in the initiation and progression of colorectal cancer （CRC）. Even in the hereditary colon cancer syndromes, in which the susceptibility is inherited dominantly, cancer develops only as the result of the progressive accumulation of genetic and epigenetic alterations. Diet can both prevent and induce colon carcinogenesis, for instance, through epigenetic changes, which regulate the homeostasis of the intestinal mucosa. Food-derived compounds are constantly present in the intestine and may shift cellular balance toward harmful outcomes, such as increased susceptibility to mutations. There is strong evidence that a major component of cancer risk may involve epigenetic changes in normal cells that increase the probability of cancer after genetic mutation. The recognition of epigenetic changes as a driving force in colorectal neoplasia would open new areas of research in disease epidemiology, risk assessment, and treatment, especially in mutation carriers who already have an inherited predisposition to cancer.     

Age-incidence relationships and time trends in cervical cancer in Sweden

Age-incidence relationships are informative of carcinogenic mechanisms. These have been previously assessed for cervical squamous cell carcinoma (SCC) but not for adenocarcinoma. The aim was to assess by means of age-, period- and cohort- specific analyses and Poisson regression modelling whether the two types of cervical cancer show an age-incidence maximum at a relatively young age, as shown in cross-sectional analyses. The Swedish Family-Cancer Database was used to analyse age-incidence relationships in cervical SCC and adenocarcinoma diagnosed in years 1958–1996, including a total of 15,118 and 1866 cases, respectively. Area of residence and socio-economic status were included in analyses because they were risk factors of cervical cancer. The analysis of cervical SCC confirmed an incidence maximum at ages 35–39 years. The data for adenocarcinoma also suggested a similar early age maximum but the curves differed extensively by birth cohort. The incidence of adenocarcinoma increased substantially at young age groups towards the end of follow-up. Endometrial adenocarcinoma and vaginal and vulvar SCC, which share some risk factors with cervical cancer, did not show an early age incidence maximum. The results also showed that there was a decrease in the incidence of cervical SCC around year 1960, almost 10 years before the organized population screening, probably due to introduced opportunistic pap testing. The benefits of the organized screening were observed as a further decline in the incidence rates. The unique age-incidence relationships in cervical cancer call for biological explanations.     

Smoking and the occurrence of congenital malformations and spontaneous abortions: multivariate analysis

A multivariate analysis was carried out with retrospective data on the effects of tobacco smoking on congenital malformations and spontaneous abortions. Congenital malformations were collected from the Finnish Register of Congenital Malformation. Tens of possible confounding variables, including maternal and family characteristics, obstetric history, medicine taking, and diseases during the pregnancy, were taken into consideration. In the final analysis 13 confounders were controlled. The odds ratios for the smoker's child to be born with central nervous system, oral cleft, or musculoskeletal malformations were 1.25, 1.25, and 0.75, respectively. All the differences were statistically nonsignificant. The effect of smoking on spontaneous abortions was analyzed by means of a questionnaire study on hospital personnel. The smokers of over 10 cigarettes per day had more spontaneous abortions than the nonsmokers, but the differences were not significantly statistically. The data were controlled for age, parity, and coffee and alcohol drinking.     

No effect on adenoma formation in Min mice after moderate amount of flaxseed

Summary Background & aim The mammalian lignan enterolactone (ENL) produced from plant lignans, e. g. secoisolariciresinol diglycoside (SDG), may protect against various cancers in humans. The present work aims to evaluate the effect of flaxseed on tumour formation in multiple intestinal neoplasia (Min) mice, a model for colon tumorigenesis. Design Male and female Min mice were fed either with a non–fibre control diet or the same diet supplemented with 0.5 % (w/w) defatted flaxseed meal. Conversion of SDG to the mammalian lignans enterodiol (END) and ENL in the gut, and plasma ENL, were measured by HPLC with coulometric electrode array detector (CEAD) and timeresolved fluoroimmunoassay, respectively. Wild–type mice were also fed with the experimental diets in order to see whether lignan metabolism is different in Min and wild–type mice. Results The total number of adenomas or their size in the small intestine was not different in the flaxseed and control groups. The flaxseed group had a tendency for a decreased number of colon adenomas in both genders. Gender and genotype based differences were found in the intestinal ENL levels. When compared to Min females, Min males in the flaxseed group had several fold higher ENL levels in the small intestine (Min males 125 ± 124.5 nmol/g vs. females 22.8 ± 16.0 nmol/g, P = 0.048) and caecum (47.6 ± 31.6 nmol/g vs. females 14.5 ± 6.6 nmol/g, P = 0.001). Presence of adenomas in the gut influences the intestinal lignan metabolism. Min mice had less intestinal END and ENL as compared with the wild–type mice (P < 0.05). Mean plasma ENL increased 7–fold during the flaxseed feeding (7 nmol/L in control vs. 50 nmol/L in flaxseed group) but no differences between gender and genotype were found. The plasma ENL level did not correlate with adenoma number in the small intestine and colon. Conclusion The number of intestinal adenomas in the Min mouse model is not related to ENL level in plasma nor is it associated with the levels of intestinal lignans. A gender difference in ENL lignan metabolism was found in the gut but not in the plasma.     

Promotion of intestinal tumor formation by inulin is associated with an accumulation of cytosolic beta-catenin in Min mice

Inulin, polydisperse beta (2-1) fructan, has been suggested to protect against colon carcinogenesis and is currently used in a number of food applications. However, the data regarding the role of inulin in intestinal carcinogenesis remains controversial since the results of our previous study suggested that inulin promotes intestinal tumor formation in Min mice, an animal model for intestinal cancer with a mutation in the Apc tumor suppressor gene (Carcinogenesis 2000;21:1167-73). In our present study, we further examined the effects of inulin on intestinal tumor formation in Min mice by carefully analyzing beta-catenin expression and cellular localization at 3 different time points during the tumorigenic process. Min mice were fed a high-fat inulin-enriched (10% w/w) diet or the high-fat diet without any added fiber from the age of 6 weeks to the ages of 9, 12 or 15 weeks. The results showed that inulin significantly increased the number (by 20%) and especially the size (by 44%) of adenomas in the small intestine. At week 15, the promotion of tumor development was accompanied by an accumulation of cytosolic beta-catenin in the adenoma tissue. In the normal appearing mucosa, levels of membrane beta-catenin and PCNA were reduced in the inulin-fed mice, possibly indicating impaired enterocyte migration. These data do not support the earlier suggestions on the cancer preventive effects of inulin and emphasize the need for further research and evaluation where health claims for inulin are concerned.     

Inpatient hospital care for back disorders in relation to industry and occupation in Finland

OBJECTIVES: The variation in hospital admission rates was studied for back disorders by industry and occupational title among gainfully employed Finns. METHODS: Admissions to Finnish hospitals in 1996 among 25- to 64-year-olds, based on the Hospital Discharge Register, were linked with sociodemographic data from the 1995 population census for the following primary diagnoses [International Classification of Diseases, 10th revision (ICD-10)]: all back disorders (M40.0-54.9; N (individual patients) 7,253), lumbar intevertebral disc disorders (M51.0-M51.9, N = 3,863), and other common back disorders (ICD-10: M47.1-47.2, M47.8-47.9, M48.0, M54.1, M54.3-54.5, M54.8-54.9; N = 2,433), with the total occupationally active workforce (same age range and gender) as reference. Age-standardized hospitalization rate ratios (SRR) were calculated. RESULTS: The highest SRR values for hospitalization for any back disorder were found for fishing (SRR 195), "other" mining and carrying (SRR 168), and sewage and refuse disposal (SRR 152) among the men and water transport (SRR 158), wood product (SRR 149) and pulp, paper and paper product (SRR 145) manufacturing among the women. Computer activities (SRR 44) among the men and insurance and pension funding (SRR49) among the women had the lowest SRR values. The occupations reindeer breeders and herders (SRR 495), agricultural workers (SRR 232), and paper product workers (SRR 205) among the men and plastic product (SRR 233), laundry (SRR 224), and agricultural (SRR 219) workers among the women had the highest SRR values. The lowest SRR values were observed for upper white-collar employees in public administration [men (SRR 40) and women (SRR 61)]. CONCLUSIONS: Hospitalization rates for back disorders were high for several physically strenuous industries and occupations.     

Inpatient hospital care for lumbar intervertebral disc disorders in Finland in relation to education,occupational class,income, and employment

The object of the study was to describe socioeconomic and demographic determinants of inpatient hospital care for lumbar intervertebral disc disorders (LIDD) in Finland. Information from the 1996 Finnish Hospital Discharge Register was linked with the 1995 Population Census. Poisson regression analyses were made with the total and the gainfully employed workforce aged 20-64 y as reference. All 48 public and seven private acute care general hospitals treating LIDD patients in Finland. In the workforce, 4643 patients aged 20-64 y (3692 among the gainfully employed) were admitted to the hospital due to LIDD (ICD-10: M51.1-M51.9) in 1996. About one-half were treated surgically. The duration of unemployment in 1995 was inversely associated with hospitalisation for LIDD in 1996, allowing for age, sex, education and personal income (unemployed for 12 months vs 0 months: rate ratio 0.66; 95% CI 0.57-0.77). Among those employed for 12 months in 1995, the level of education was inversely associated with the hospital admission rate. The rate was also higher in manual occupations as compared with the upper white-collar employees. The associations were clearer among the medically than the surgically treated patients. Hospitalisation for back disorder was, however, less common in the lowest income group as compared with the highest (0.65; 0.57-0.77) allowing for education, occupational class, age and sex. Women were less often admitted to the hospital than men, allowing for the socioeconomic factors (0.83; 0.77-0.90). When indicated by education or occupation, low socioeconomic status was associated with a relatively high rate of inpatient hospital care for LIDD. When indicated by personal income, the situation was the reverse. Unemployment and female gender predicted a relatively low rate of hospitalisation.     

Factors predictive of ischemic heart disease mortality in foundry workers exposed to carbon monoxide

The potential predictors of ischemic heart disease mortality were studied for 931 male foundry workers in Finland who participated in a health examination in 1973. These workers were followed up to 1993 through registers and by using a questionnaire. In 1973, the systolic and diastolic blood pressures of workers exposed to carbon monoxide (CO) were slightly higher than those of unexposed workers. The prevalence of angina pectoris showed a clear dose-response relation to CO exposure. Electrocardiogram (ECG) findings indicating past myocardial infarction or suggesting coronary artery disease as a function of smoking and/or CO exposure were not evident. In the 1987 follow-up, the rate ratio for ischemic heart disease mortality was estimated as 4.4 for CO-exposed smokers compared with unexposed nonsmokers. Ischemic heart disease mortality in 1973-1993 was analyzed by using the Cox proportional hazards model. The statistically significant predictors were age, pathologic ECG findings in 1973, regular CO exposure, and abundant alcohol drinking. Of the ECG findings, changes in Q or QS and ST-J or ST waves and in ventricular extrasystoles were statistically significant. The risk of mortality from ischemic heart disease was increased by working in iron foundries, by hypertension, and by smoking.