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Insulin-like growth factors (IGFs) have been associated with growth, body size, physical activity and colorectal cancer (CRC). We hypothesized that variants in IGF-related genes increase the CRC susceptibility associated with a larger body size and a lack of physical activity. We assessed this in The Netherlands Cohort Study. Participants (n = 120 852) completed a baseline questionnaire on diet and cancer. ~75% returned toenail clippings. Using a case-cohort approach and 16.3 years of follow-up, toenail DNA from 3768 subcohort members and 2580 CRC cases was genotyped. We aggregated unfavorable alleles (potentially increasing CRC risk) for 18 single nucleotide polymorphisms in 8 genes into a sum score. The sum score (in tertiles) and an IGF1 19-CA repeat polymorphism (19/19, 19/non-19 and non-19/non-19 repeats) in combination with body size (mostly in tertiles) and (non-)occupational physical activity (>12, 8-12 and <8 kJ/min in the job and >90, >60-90, >30-60 and =30 min/day) were analyzed by Cox regression. Increasingly higher hazard ratios (HRs) for CRC were observed for a larger adult body mass index, larger trouser size and tallness in the presence of more unfavorable alleles in men. HRs (95% confidence intervals) for joint effects were 1.55 (1.06-2.25), 1.78 (1.29-2.46) and 1.48 (1.01-2.17), respectively. In women, variant repeat alleles halved CRC risk irrespective of body size and physical activity. Almost no interactions tested significant. To conclude, a larger body size was a CRC risk factor in men in the presence of an accumulation of unfavorable alleles in IGF-related genes, but interactions were generally nonsignificant. [ABSTRACT FROM AUTHOR]

Since a KRAS oncogene mutation is an early event in colorectal cancer development and cigarette smoking is thought to have an effect on early stages of colorectal tumorigenesis, smoking, especially long-term smoking, may be associated with the risk for colorectal cancer with KRAS oncogene mutations. In the Netherlands Cohort Study on diet and cancer (n=120,852 men and women), using a case-cohort design, adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed for colorectal tumors with wild-type and with mutated KRAS gene, and with specific G:C-->T:A or G:C-->A:T point mutations in KRAS, according to cigarette smoking status, frequency, duration, pack years, age at first exposure, years since cessation, inhalation and filter usage. After 7.3 years and excluding the first 2.3 years, 648 cases and 4083 sub-cohort members were included in the analyses. Ex-smokers, but not current smokers, were at increased risk for colorectal cancer with wild-type KRAS gene tumors when compared with never smokers, albeit not statistically significant (RR 1.26, 95% CI 0.96-1.66). This was not observed for KRAS mutated tumors when comparing ex-smokers with never smokers (RR 1.15, 95% CI 0.79-1.66). The highest category of smoking frequency (>20 cigarettes/day) and inhalation of smoke were associated with an increased risk for colorectal cancer with wild-type KRAS gene tumors, though not statistically significant, when compared with never smoking (frequency: RR 1.24, 95% CI 0.90-1.71 and inhalation: RR 1.25, 95% CI 0.94-1.67). These associations were strongest in men (ex-smokers: RR 1.79, 95% CI 1.00-3.20; frequency: RR 1.91, 95% CI 1.03-3.52; inhalation: RR 1.69, 95% CI 0.94-3.04). No associations were observed between any of the smoking characteristics and the risk for colorectal cancer with mutated KRAS gene tumors, nor where there any clear associations with tumors with specific G:C-->A:T transitions or G:C-->T:A transversions. These results suggest that, in contrast to the hypothesis, smoking does not increase the risk for colorectal tumors with a mutated KRAS gene. Some smoking characteristics, i.e. being an ex-smoker, frequency and inhalation, may be associated with risk for colorectal cancer characterized by the wild-type KRAS gene, especially in men.

Background: Many observational studies have shown that alcohol consumption is associated with a reduced risk of ischaemic heart disease (IHD). IHD mortality has generally fallen in established market economies but not in some countries of Eastern Europe. Since the level of consumption of saturated fat does not explain these differences in trends, other associations with risk need to be explored. We investigated whether alcohol consumption also presents a U or J-shaped association with IHD risk in a case-control study in Bulgaria., Methods: Cases (n = 155) were admissions to the cardiology unit, Central Clinical Hospital, Sofia, aged 45 to 69, with confirmed diagnoses of ischaemic heart disease. Controls (n = 154) were concurrent admissions for minor elective surgery. Measurements were made of blood pressure, height and weight and a blood sample was taken around three days after admission. Subjects were interviewed before discharge and asked about the type and amount of alcohol they consumed., Results: Reported alcohol intake demonstrated a J-shaped association with the risk of IHD. The odds ratio (adjusted only for age and sex) was 0.67 (95% CI 0.34-1.28) for patients reporting 0.01-18 g/d of alcohol consumption daily, and 0.36 (95% CI 0.18-0.73) for 18.01-36 g/d, compared to patients reporting to be abstainers. The associations with alcohol intake remained statistically significant and unaltered after adjustment for established IHD risk factors: HDL cholesterol, body mass index, systolic blood pressure, family history, education, physical activity and risk factors significantly related with IHD: fruit and vegetables consumption, type of fat used in cooking, bread consumption., Conclusions: Our results are consistent with previous studies showing a J-shaped association between alcohol intake and IHD risk. The highest protective effect we observed for levels of alcohol intake 18.01-36 g/d, which corresponds to 100-200 ml wine or 1-2 beers, or little more than 50-100 ml spirits.

Objectives: Recent narrative reviews have concluded that there is no support for an association between alcohol consumption and urinary tract cancer. Many individual studies, however, have reported positive associations, although rarely statistically significant. The purpose of this meta-analysis is to summarize and quantify this relationship with more statistical power and to perform a sensitivity analysis on the study characteristics., Methods: We included 16 epidemiological studies published up to April 1999 and calculated summary odds ratios (SORs), both upgraded and adjusted for age, sex and smoking by meta-regression analyses. The age- and smoking-adjusted SORs (current alcohol drinking vs. non-drinking) were 1.3 (95% CI 0.9-2.0) for six studies with men and 1.0 (95% CI 0.4-2.6) for four studies with women., Results: The age-, sex- and smoking-adjusted SOR was 1.2 (95% CI 0.9-1.7) for seven studies with men and women combined., Conclusion: Even though studies differed in methodology, the results were rather consistent. Subgroup analyses by type or amount of alcohol were not possible due to sparse data. We conclude that the available data suggest a slightly increased risk of urinary tract cancer from alcohol consumption for men. The risk related to alcohol consumption for women and the influence of the amount and type of alcohol remain unclear.

The objective of this study was to identify risk factors for sudden cardiac arrest (SCA) in patients with coronary artery disease (CAD). A retrospective case-control study was performed consisting of a group of unselected patients who had suffered SCA and had a clinical history of CAD, and a group of unselected age- and gender-matched CAD control patients living in the region of Maastricht. Information about previous myocardial infarction (MI), left ventricular ejection fraction (LVEF), hypertension, hypercholesterolemia, diabetes mellitus, smoking, and coffee and alcohol consumption was collected. A logistic regression model was fitted to all mentioned variables including age and genders. Included were 117 SCA cases (84% men, mean age 65 years [+/-7]) and 144 control patients (83% men, mean age 63 years [+/-8]). Previous MI (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.7-9.3), hypertension (OR 2.9, 95% CI 1.5-6.1), heavy coffee consumption (>10 cups per day) (OR 55.7, 95% CI 6.4-483), and a LVEF <40% (OR 11.2, CI 4.4-28.5) were independent risk indicators for SCA in patients with CAD. Alcohol consumption (1-21 glasses per week) seemed to protect patients with CAD from SCA (OR 0.5, 95% CI 0.2-0.98). These observations suggest that changes in lifestyle factors can be of potential importance in protecting patients with CAD from dying suddenly.

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease in the middle-aged. We investigated whether a high serum homocysteine level is a risk factor for vascular disease in 878 elderly men (mean age at baseline, 71.5 years; range, 64 to 84 years) in a population-based, representative cohort followed up for 10 years in Zutphen, the Netherlands. Thirty-one percent had nonfasting homocysteine levels >/=17 micromol/L. After adjustment for other major risk factors, high homocysteine levels at baseline (the third compared with the first tertile) were associated with an increased baseline prevalence of myocardial infarction (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.07 to 3.08; P for trend, 0.03) and with a marginally significant increase in the risk of dying of coronary heart disease (relative risk [RR], 1.58; 95% CI, 0.93 to 2.69; P for trend, 0.09) but not with an increased risk of first-ever myocardial infarction. In addition, high homocysteine levels at baseline were associated with an increased baseline prevalence of stroke (OR, 4.61; 95% CI, 1.79 to 11.89; P for trend, 0.002) and with an increased risk of dying of cerebrovascular disease in subjects without hypertension (RR, 6.18; 95% CI, 2.28 to 16.76) but not in those with hypertension. High homocysteine levels were associated with an increased risk of first-ever stroke among normotensive subjects that was not statistically significant (RR, 1. 77 [95% CI, 0.83 to 3.75; P for trend, 0.14]). In a general population of elderly men, a high homocysteine level is common and is strongly associated with the prevalence of coronary heart disease and cerebrovascular disease. It is a strong predictive factor for fatal cerebrovascular disease in men without hypertension but less so for coronary heart disease.

We investigated associations of serum albumin with the incidence and mortality of coronary heart disease among men from the Zutphen Elderly Study. In 1985, 820 men were randomly selected from a population age 64-84 years and were followed for 5 years. We adjusted relative risks for traditional risk factors (age, body mass index, diastolic blood pressure, total and high-density lipoprotein cholesterol, smoking, and alcohol consumption) and also for baseline health status indicators (white blood cell count, physician's health score, self-rated health, and history of relevant diseases). Albumin was inversely associated with the incidence of coronary heart disease only among men with elevated total cholesterol levels (> or = 6.5 mmol per liter). The relative risk for a 1-standard deviation increase (2.5 gm per liter) in albumin was 0.60 [95% confidence interval (CI) = 0.38-0.96] and was not altered after additional adjustment for baseline health status. In all men, the relative risk for death due to coronary heart disease was 0.67 (95% CI = 0.49-0.92), and the relative risk was reduced to 0.84 (95% CI = 0.61-1.15) after adjustment for health status. We found comparable health status-adjusted relative risks for mortality from cardiovascular diseases (relative risk = 0.83; 95% CI = 0.67-1.02) and for mortality from all causes (relative risk = 0.86; 0.73-0.99). Independent of traditional risk factors, moderately low serum albumin is predictive of coronary heart disease and all-cause mortality in elderly men. Only part of this relation could be explained by baseline health status.

Because the importance of established risk factors for coronary heart disease (CHD) is unclear in older people, the associations of white blood cell (WBC) count with the risk for CHD and all-cause mortality were investigated in an elderly cohort that was followed up for 5 years. In 1985, complete information on the risk factors of interest was available for 884 randomly selected men, aged 64 to 84 years, from the Dutch town of Zutphen (participation rate, 74%). Relative risks (RRs) for each 10(9)/L increase in WBC count were obtained for the 5-year incidence of and mortality from CHD and all causes. RRs were adjusted for age, body mass index, systolic blood pressure, total and high density lipoprotein cholesterol levels, and cigarette smoking habit. The WBC count was 6.7 +/- 1.8 X 10(9)/L (means +/- SD) at baseline. An increased WBC count was independently associated with mortality due to CHD, and the RR amounted to 1.32 (95% confidence interval [95% CI], 1.15 to 1.51). For the incidence of CHD the RR was 1.14 (95% CI, 0.98 to 1.32). These associations were observed regardless of cigarette smoking habit. Regarding all-cause mortality, the RR amounted to 1.25 (95% CI, 1.17 to 1.35). This association was especially noticeable among former smokers and those who had never smoked. In conclusion, during 5 years of follow-up WBC count predicted CHD and all-cause mortality in elderly men, independent of the conventional risk factors for CHD.

The associations of serum total and high density lipoprotein (HDL) cholesterol with coronary heart disease were investigated in men aged 64-84 years from the Dutch town of Zutphen during 5 years of follow-up. In 1985, 885 randomly selected men, 710 of whom did not have a history of clinical coronary heart disease, participated in the study. Associations were adjusted for age, body mass index, systolic blood pressure, cigarette smoking, and alcohol consumption. Total cholesterol was not significantly associated with the incidence of coronary heart disease, but for mortality the relative risk corresponding to a 1.00 mmol/liter increase was 1.40 (95 percent confidence interval (CI) 1.07-1.83). HDL cholesterol was not associated with mortality from coronary heart disease. The relative risk for the incidence of the disease, corresponding to a 0.26 mmol/liter increase, was 0.80 (95 percent CI 0.60-1.08). For the ratio of HDL cholesterol to total cholesterol, the relative risk for coronary heart disease incidence corresponding to a 0.05 increase amounted to 0.70 (95 percent CI 0.51-0.95). These results show that in elderly men followed for 5 years, both total and HDL cholesterol are important in predicting coronary heart disease. Total cholesterol seems to be a stronger risk factor for mortality from the disease, whereas HDL cholesterol is more strongly associated with the incidence of a first coronary heart disease event.

Body composition was assessed by means of densitometry, anthropometry and bioelectrical impedance in 28 healthy, elderly females, aged 67-78 years. Underwater weighing was used as the reference method. Mean body mass index (BMI) was 26.3 +/- 3.4 kg/m2. Body fat percentage from body density was 39.6 +/- 5.6%. The fat-free mass (FFM) from body density was 41.0 +/- 5.4 kg. Mean predicted FFM using different prediction formulas from the literature ranged from 38.8 +/- 4.2 to 46.3 +/- 5.3 kg. The differences between FFM from densitometry and FFM using either prediction equation were highly correlated, thus part of the difference is probably due to an error in the reference method. The different prediction equations revealed rather good relative validity, compared to the densitometric method, with the exception of equations based on skinfold measurements developed in younger reference populations. Age-specific prediction equations based on BMI and bioelectrical impedance measurement may be used to assess body composition in the elderly. Prediction equations using skinfold thickness measurements are less appropriate for this purpose.