Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis.

BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by ß-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful.

Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption.

BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.

Moulds, bacteria and cancer among Finns: an occupational cohort study.

BACKGROUND: Some environmental moulds and bacteria produce carcinogenic toxins. AIM: To study associations between work-related exposure to moulds and bacteria and cancers in Finland. METHODS: A cohort of all economically active Finns in the population census in 1970 were followed-up for 30 million person-years. Subsequent cancer cases were identified through record linkage with the Finnish Cancer Registry. Observed and expected numbers of cancer cases were calculated by occupation, sex, birth cohort and period of observation. Exposures to moulds of agricultural and industrial origin and to bacteria of non-human origin were estimated with the Finnish Job-Exposure Matrix. RESULTS: Men with the highest mould and bacterial exposure had a reduced relative risk for lung cancer (RR 0.7, 95% CI 0.6 to 0.9 for moulds and RR 0.9, 95% CI 0.8 to 1.0 for bacteria). Women in the highest mould and bacterial exposure category had RRs of 3.1 (95% CI 1.0 to 9.2) and 2.6 (95% CI 1.5 to 4.7) for cervical cancer, respectively. The respective RRs for lip cancer were 2.4 (95% CI 1.2 to 5.1) and 1.6 (95% CI 1.2 to 2.2). CONCLUSIONS: Exposures at the investigated concentrations to either moulds or bacteria are unlikely to be major risk factors of cancer, although suggestions of risk increases were observed for some cancer types. It has been suggested previously that the decreased risk for lung cancer is due to the protective effect of endotoxins.

Lifestyle differences in twin pairs discordant for basal cell carcinoma of the skin.

BACKGROUND: Basal cell carcinoma (BCC) of the skin is a multifactorial disease with a complex interplay of genetic, environmental and lifestyle factors, including patterns of solar exposure, with childhood exposure being of particular relevance. Case-control studies in disease-discordant twin pairs adjust for familial factors and improve the power of conventional case-control studies. OBJECTIVES: To investigate the roles of sociodemographic, dietary, medication, hormonal and other lifestyle factors in the aetiology of BCC. METHODS: The study base comprised all same-sex twins who had answered the baseline health questionnaire of the Finnish Adult Twin Cohort Study in 1975. Information on all histologically confirmed cases of BCC was retrieved from the nationwide cancer registry. The first twin to have BCC was defined as the case and his/her co-twin (alive at the time of diagnosis) as the control. Only pairs with the first BCC between 1976 and 1999 were included in the study (n = 333). Conditional logistic regression analyses were used to assess BCC risk by study factors. RESULTS: A significantly increased risk was associated with smoking status in females but not in males. The risk was higher in dizygotic than in monozygotic females, possibly indicating the presence of a gene-smoking interaction. Suggestive but statistically nonsignificant increases in risk were observed for higher education, urticaria and atopic eczema, use of nonsteroidal anti-inflammatory drugs and coffee. A suggestive risk decrease was observed for outdoor work. No clear effects were observed for marital status, body mass index, use of alcohol, tea, fruit and vegetables or oral contraceptives. CONCLUSIONS: The results suggest a role for smoking and possibly also for other lifestyle factors in the risk of contracting BCC.

Malignant skin cancers in the Finnish Twin Cohort: a population-based study, 1976-97.

BACKGROUND: Both hereditary and environmental factors are implicated in the aetiology of cutaneous neoplasms. Studies of twins make it possible to estimate the contribution of inherited genes to the development of disease. OBJECTIVE: To assess the importance of hereditary and environmental factors (including physical environment and lifestyles) in malignant melanoma and malignant nonmelanoma of the skin. METHODS: The Finnish Twin Cohort, comprising 25 882 adult like-sexed twins with established zygosity, was linked with the Finnish Cancer Registry to identify malignant skin cancers in a prospective follow-up from 1976 to 1997. Standardized incidence ratios were computed based on national rates. RESULTS: Sixty twins were diagnosed with melanoma and 49 twins with nonmelanoma during the follow-up. The risks of these cancers did not differ from the risk in the population at large. There was only one pair where both twins had a malignant skin cancer (dizygotic male twins both with squamous cell carcinoma). CONCLUSIONS: The near-total lack of concordance for skin cancer in twin pairs suggests that environmental and not hereditary effects are most important in the causation of malignant skin cancers in a white population with low levels of sun exposure.

Soya intake and plasma concentrations of daidzein and genistein: validity of dietary assessment among eighty British women (Oxford arm of the European Prospective Investigation into Cancer and Nutrition).

Soya products contain high levels of the isoflavones genistein and daidzein, and their glucosides, and may lower the risk of cardiovascular disease, osteoporosis and cancer. The present cross-sectional study investigated plasma concentrations of daidzein and genistein and their correlations with dietary soya consumption in four groups of twenty premenopausal British women. The women were selected from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition using data from food-frequency questionnaires (FFQ) to guarantee a wide variation in soya consumption, and to investigate the utility of the question related to soya milk consumption compared with the utility of the question related to other soya foods. Dietary intakes of isoflavones were additionally assessed by 7 d food diaries. Plasma concentrations of daidzein and genistein were measured by time-resolved fluoroimmunoassay. Geometric mean plasma concentrations (nmol/l) were for the four groups, which were based on increasing soya intake, 4.9, 8.4, 39.2 and 132 for daidzein and 14.3, 16.5, 119 and 378 for genistein. The Spearman correlation coefficients for plasma isoflavone concentrations with estimated dietary intakes were between 0.66 and 0.80 for the diary-based estimates and between 0.24 and 0.74 for the FFQ-based estimates. The correlations for soya milk intakes were clearly higher than the correlations for intakes of other soya foods. We conclude that both the food diary and the FFQ estimate dietary soya isoflavone intakes sufficiently well to use them in epidemiological studies, and that plasma concentrations of daidzein and genistein in Western women who consumed soya products as a part of their regular diet were close to those in Asian populations.

Energy balance and cancer: the role of sex hormones.

Energy balance can affect the risk for hormone-related cancers by altering sex hormone levels. Energy intake and expenditure are difficult to measure in epidemiological studies, but a chronic excess of intake relative to expenditure leads to a high BMI, which can be accurately measured. In premenopausal women obesity has little effect on the serum concentration of oestradiol, but causes an increase in the frequency of anovular menstrual cycles and thus a reduction in progesterone levels; these changes lead to a large increase in the risk for endometrial cancer. but little change, or a small decrease, in the risk for breast cancer. In post-menopausal women oestradiol levels are not regulated by negative feedback, and obesity causes an increase in the serum concentration of bioavailable oestradiol; this factor causes increases in the risk for both endometrial cancer and breast cancer. The development of ovarian cancer appears to be related more strongly to the frequency of ovulation than to direct effects of circulating levels of sex hormones, and BMI is not clearly associated with the risk for ovarian cancer. In men, increasing BMI has little effect on bioavailable androgen levels, and any effect of obesity on prostate cancer risk is small.

Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom).

OBJECTIVE: To investigate the relationships between plasma concentrations of sex hormones and risk factors for breast cancer. METHODS: We investigated the relationship of plasma concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456 postmenopausal women. Risk factor data were obtained from questionnaires and hormone concentrations measured by immunoassays; variations in geometric means were compared using analysis of covariance. RESULTS: SHBG decreased with increasing body mass index and increasing waist-hip ratio both in pre- and postmenopausal women. In postmenopausal women only, estradiol increased with increasing body mass index. In premenopausal women, estradiol decreased with increasing physical activity, estradiol was higher in current than in ex- and non-smokers, and FSH decreased with increasing alcohol intake. No associations were observed between sex hormones and age at menarche, parity, age at menopause, and previous use of oral contraceptives in either pre- or postmenopausal women. CONCLUSIONS: Certain factors such as obesity and perhaps waist-hip ratio, physical activity and alcohol consumption, but probably not age at menarche and parity, may mediate their effects on breast cancer risk by changing circulating concentrations of sex hormones.

Stress of daily activities and risk of breast cancer: a prospective cohort study in Finland.

The belief that life stress enhances breast cancer is common, but there are few prospective epidemiological studies on the relationship of life stress and breast cancer. We have investigated the association between stress of daily activities (SDA) and breast-cancer risk in a prospective cohort study of 10,519 Finnish women aged 18 years or more. SDA measures a subject's own appraisal of daily stress. It was assessed in 1975 and 1981 by a self-administered questionnaire, which also provided information on subject characteristics and other known breast-cancer risk factors. Follow-up data for breast cancer from 1976 to 1996 were attained through record linkage to the Finnish Cancer Registry. Study subjects were divided into 3 groups based on their SDA scores in 1975: no stress (23% of subjects), some stress (68%) and severe stress (9%). Hazard ratios (HRs) and respective 95% confidence intervals (CIs) for incidence of breast cancer by level of SDA were obtained from the Cox proportional hazards model. We identified 205 incident breast cancers in the cohort. Multivariable-adjusted HRs for breast-cancer risk were 1.00 (reference), 1.11 (95% CI 0.78-1.57) and 0.96 (95% CI 0.53-1.73) by increasing level of stress. Neither shifting of the SDA cut-off points nor restricting the analysis to women who reported the same level of SDA in 1975 and 1981 materially altered the results. We found no evidence of an association between self-perceived daily stress and breast-cancer risk.

Epidemiology of breast cancer.

Breast cancer is the commonest cause of cancer death in women worldwide. Rates vary about five-fold around the world, but they are increasing in regions that until recently had low rates of the disease. Many of the established risk factors are linked to oestrogens. Risk is increased by early menarche, late menopause, and obesity in postmenopausal women, and prospective studies have shown that high concentrations of endogenous oestradiol are associated with an increase in risk. Childbearing reduces risk, with greater protection for early first birth and a larger number of births; breastfeeding probably has a protective effect. Both oral contraceptives and hormonal therapy for menopause cause a small increase in breast-cancer risk, which appears to diminish once use stops. Alcohol increases risk, whereas physical activity is probably protective. Mutations in certain genes greatly increase breast-cancer risk, but these account for a minority of cases.

Soy milk intake and plasma sex hormones: a cross-sectional study in pre- and postmenopausal women (EPIC-Oxford).

Soy beans contain high levels of the isoflavones genistein and daidzein and their glucosides. We investigated the relationship between soy milk intake and plasma concentrations of estradiol, sex hormone-binding globulin, and, in premenopausal women, follicle-stimulating hormone, luteinizing hormone, and progesterone in a cross-sectional study of 636 premenopausal and 456 postmenopausal British women. Sixty-five percent of the women were vegetarians or vegans. Data on soy milk intake and other factors were obtained from a validated food frequency questionnaire, hormone concentrations were measured by immunoassays, and variations in geometric means were compared using analysis of covariance. We observed no statistically significant trends or meaningful associations between soy milk intake and circulating sex hormones. Adjusting for factors possibly affecting circulating hormone concentrations did not materially alter the results. We conclude that soy milk intake does not change plasma concentrations of sex hormones in pre- or postmenopausal British women who consume soy milk as a part of their regular diet.

Breast cancer risk in male twins: joint analyses of four twin cohorts in Denmark, Finland, Sweden and the United States.

To test the hypothesis that in utero exposure to high levels of oestrogen increases the risk of male breast cancer, we followed 115 235 male twins for more than 3.5 million person-years at risk. We observed 11 cases of male breast cancer versus 16.16 expected based on national rates (standardized rate ratio 0.68, 95% confidence interval 0.34-1.22) and conclude that any adverse influence of in utero oestrogen exposure is likely to be small.

A pooled analysis of magnetic fields and childhood leukaemia.

Previous studies have suggested an association between exposure to 50-60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 microT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures >/= 0.4 microT the estimated summary relative risk was 2.00 (1.27-3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82-1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 microT had estimates compatible with no increased risk, while the 0.8% of children with exposures >/= 0.4 microT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase.

Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland.

BACKGROUND: The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. METHODS: We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. RESULTS: At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 percent; 95 percent confidence interval, 10 to 48 percent), and breast cancer (27 percent; 95 percent confidence interval, 4 to 41 percent). CONCLUSIONS: Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms. This finding indicates that the environment has the principal role in causing sporadic cancer. The relatively large effect of heritability in cancer at a few sites suggests major gaps in our knowledge of the genetics of cancer.

Subsequent primary cancers after basal-cell carcinoma: A nationwide study in Finland from 1953 to 1995.

The aim of this study was to investigate whether patients with basal-cell carcinoma (BCC) of the skin have an increased risk of developing other cancers. A total of 71,924 patients diagnosed with BCC between 1953 and 1995 were identified from the Finnish Cancer Registry. They were followed up for subsequent primary cancers from the date of the first BCC diagnosis to the end of 1995. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated based on national rates. Altogether 11,042 subsequent primary cancers occurred among the study cohort during 625,000 person-years of follow-up. Risk increases were observed for non-melanoma skin cancer (SIR 3.79, 95% CI 3.59-4.00) and skin melanoma (SIR 2.34, 95% CI 2.08-2.61). The five other primary sites presenting the highest SIRs were salivary glands (SIR 3.30), lip (2. 19), small intestine (1.85), nose (1.73) and pharynx (1.71). Patients who were less than 40 years of age at the time of BCC diagnosis had a significantly higher relative risk for a subsequent new cancer than the older patients (ratio of the SIRs 1.29, 95% CI 1. 10-1.51). Time since BCC diagnosis did not materially influence the overall relative risk of subsequent cancers. Part of the increase in the risk of skin cancer is likely to be due to enhanced diagnostic activity after an initial diagnosis of BCC. However, the increases in the risk of several non-cutaneous cancers suggest a generalized carcinogenic role of some factors in the BCC pathogenic pathways.

Plastic wall materials in the home and respiratory health in young children.

OBJECTIVES: The relation between the presence of plastic wall materials in the home and respiratory health in children was assessed. METHODS: This population-based cross-sectional study involved 2568 Finnish children aged 1 to 7 years. RESULTS: In logistic regression models, lower respiratory tract symptoms--persistent wheezing (adjusted odds ratio [OR] = 3.42, 95% confidence interval [CI] = 1.13, 10.36), cough (OR = 2.41, 95% CI = 1.04, 5.63), and phlegm (OR = 2.76, 95% CI = 1.03, 7.41)--were strongly related to the presence of plastic wall materials, whereas upper respiratory symptoms were not. The risk of asthma (OR = 1.52, 95% CI = 0.35, 6.71) and pneumonia (OR = 1.81, 95% CI = 0.62, 5.29) was also increased in children exposed to such materials. CONCLUSIONS: Emissions from plastic materials indoors may have adverse effects on the lower respiratory tracts of small children.

Genetic predisposition, environment and cancer incidence: a nationwide twin study in Finland, 1976-1995.

Twin studies integrate genetic and environmental (including physical environment and life-style) information by comparing monozygotic and dizygotic twins for the occurrence of disease. Our objectives were to compare cancer incidence in twins with national rates and to estimate both the probability that co-twins of affected twins may develop cancer and the importance of genetic predisposition and environment in cancer development. The nationwide record linkage of the Finnish Twin Cohort Study, the Finnish Cancer Registry and the Central Population Register allowed the follow-up of 12,941 same-sexed twin pairs for incident primary cancers from 1976 to 1995. Zygosity was determined by use of a validated questionnaire in 1975. Methods included calculation of standardized incidence ratios and concordances and fitting of structural equation models. A total of 1,613 malignant neoplasms occurred in the cohort. The overall cancer incidence among twins resembled that among the general population. Monozygotic co-twins of affected twins were at 50% higher risk than were dizygotic co-twins. Based on genetic modeling, inherited genetic factors accounted for 18% (95% confidence interval 4-32%) of the liability in inter-individual variation in the risk of overall cancer, while non-genetic factors shared by twins accounted for 7% (0-16%) and unique environmental factors for 75% (65-85%). Our results appear to exclude a contribution greater than one-third for genetic predisposition in the development of cancer in the general population, thus pointing to the earlier confirmed substantial role of environment.

Inverse association between breast cancer incidence and degree of visual impairment in Finland.

A total of 10935 women with visual impairment were identified from the Finnish Register of Visual Impairment and followed up for cancer through the Finnish Cancer Registry for years 1983-1996. Breast cancer risk decreased by degree of visual impairment (P for trend 0.04) which suggests a dose-response relationship between visible light and breast cancer risk.