OBJECTIVE: Using a nested case-referent design we evaluated the relationship between plasma levels of six carotenoids, alpha-tocopherol, and retinol, sampled before diagnosis, and later breast cancer risk. METHODS: In total, 201 cases and 290 referents were selected from three population-based cohorts in northern Sweden, where all subjects donated blood samples at enrolment. All blood samples were stored at -80 degrees C. Cases and referents were matched for age, age of blood sample, and sampling centre. Breast cancer cases were identified through the regional and national cancer registries. RESULTS: Plasma concentrations of carotenoids were positively intercorrelated. In analysis of three cohorts as a group none of the carotenoids was found to be significantly related to the risk of developing breast cancer. Similarly, no significant associations between breast cancer risk and plasma levels of alpha-tocopherol or retinol were found. However, in postmenopausal women from a mammography cohort with a high number of prevalent cases, lycopene was significantly associated with a decreased risk of breast cancer. A significant trend of an inverse association between lutein and breast cancer risk was seen in premenopausal women from two combined population-based cohorts with only incident cases. A non-significant reduced risk with higher plasma alpha-carotene was apparent throughout all the sub-analyses. CONCLUSION: In conclusion, no significant associations were found between plasma levels of carotenoids, alpha-tocopherol or retinol and breast cancer risk in analysis of three combined cohorts. However, results from stratified analysis by cohort membership and menopausal status suggest that lycopene and other plasma-carotenoids may reduce the risk of developing breast cancer and that menopausal status has an impact on the mechanisms involved.
The carcinogenicity of cigar and pipe smoking is established but the effect of detailed smoking characteristics is less well defined. We examined the effects on cancer incidence of exclusive cigar and pipe smoking, and in combination with cigarettes, among 102395 men from Denmark, Germany, Spain, Sweden and UK in the EPIC cohort. Hazard ratios (HR) and their 95% confidence intervals (CI) for cancer during a median 9 year follow-up from ages 35-70 years were estimated using proportional hazards models. Compared to never smokers, HR of cancers of lung, upper aero-digestive tract and bladder combined was 2.2 (95% CI: 1.3, 3.8) for exclusive cigar smokers (16 cases), 3.0 (2.1, 4.5) for exclusive pipe smokers (33 cases) and 5.3 (4.4, 6.4) for exclusive cigarette smokers (1069 cases). For each smoking type, effects were stronger in current than in ex-smokers, and in inhalers than in non-inhalers. Ever smokers of both cigarettes and cigars (HR 5.7 (4.4, 7.3), 120 cases) and cigarettes and pipes (5.1 (4.1, 6.4), 247 cases) had as high a raised risk as had exclusive cigarette smokers. In these smokers, the magnitude of the raised risk was smaller if they had switched to cigars or pipes only (i.e. quit cigarettes) and had not compensated with greater smoking intensity. Cigar and pipe smoking is not a safe alternative to cigarette smoking. The lower cancer risk of cigar and pipe smokers as compared to cigarette smokers is explained by lesser degree of inhalation and lower smoking intensity. (c) 2010 UICC.
OBJECTIVE: The aim of this study was to investigate the role of insulin-like growth factor-I (IGF-I), a strongly mitogenic and anti-apoptotic factor, in the development of benign prostatic hyperplasia (BPH). The bioactivity of IGF-I within tissues depends on circulating levels, as well as on the local production of IGF-I and the presence of IGF-binding proteins (IGFBPs). The IGFBPs regulate the efflux of IGF-I to the extravascular space and the bioavailability of IGF-I within tissues. MATERIAL AND METHODS: Within the Northern Sweden Health and Disease Study, 60 cases of BPH defined by a history of prostate resection were identified, and two controls per case were selected. IGF-I, IGFBP-1, IGFBP-3 and insulin were measured by immuno-radiometric assays in stored plasma samples drawn a mean of 3.2 years before surgery. RESULTS: The risk of BPH increased with increasing quartile levels of IGF-I adjusted for IGFBP-3 (p(trend) = 0.10) up to a relative risk of 2.16 (95% confidence interval 0.83-5.64) for the highest quartile. The risk decreased with increasing levels of IGFBP-1 (p(trend) = 0.10). CONCLUSIONS: Our results suggest that elevated IGF-I bioactivity may stimulate the development of BPH; however, they were not statistically significant and require confirmation from larger studies.
We conducted a first pilot study on healthy women living in two countries with different dietary habits, Granada in the south of Spain and Malmö in the south of Sweden, in order to compare their levels of plasma phospholipid fatty acids, and to examine the relationship between the differences in food consumption. This study is part of a pilot study which is nested in the European Prospective Investigation into Cancer and Nutrition, a multi-centre prospective cohort study on diet, plasma concentrations of antioxidants and fatty acids, and markers of oxidative stress. Thirty-nine women in Granada and thirty-eight women in Malmö, aged 45-50 years (all pre-menopausal) were selected among the female participants in the cohorts from these two countries. Individual measurements of the women's habitual diet were obtained by a food frequency questionnaire. 24-hour diet recalls were used for the standardised measurement of diet at group level. Plasma phospholipid fatty acid composition was determined by capillary gas chromatography. We found a different fatty acid profile in plasma between the two populations, with higher mean levels of palmitic acid (16:0), palmitoleic acid (16:1) (n-7), oleic acid (18:1), alpha-linolenic acid (18:3) (n-3) and eicosapentaenoic acid (20:5) (n-3), and lower mean levels of stearic acid (18:0) in Malmö compared to Granada. Women in Malmö consumed more meat, alcoholic beverages and sugar, and less fish and shellfish than women in Granada. We conclude that the fatty acid composition in plasma phospholipids is different between women from the two European centres. For polyunsaturated fatty acids, differences were observed for (n-3) fatty acids. In relation to these differences, we observed that specific food intakes, particularly meat and fish, varied between the two centres.
The study of the relationship between dietary intake of fatty acids and the risk of breast cancer has not yielded definite conclusions with respect to causality, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis of possible protection of n-3 polyunsaturated fatty acids (PUFA) against breast cancer in women, we examined the fatty-acid composition of phospholipids in pre-diagnostic sera of 196 women who developed breast cancer, and of 388 controls matched for age at recruitment and duration of follow-up, in a prospective cohort study in Umeâ, northern Sweden. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Conditional logistic-regression models showed no significant association between n-3 PUFA and breast-cancer risk. In contrast, women in the highest quartile of stearic acid had a relative risk of 0.49 (95% confidence interval, 0.22-1.08) compared with women in the lowest quartile (trend p = 0.047), suggesting a protective role of stearic acid in breast-cancer risk. Besides stearic acid, women in the highest quartile of the 18:0/18:1 n-9c ratio had a relative risk of 0.50 (95% confidence interval, 0.23-1.10) compared with women in the lowest quartile (trend p = 0.064), suggesting a decrease in breast-cancer risk in women with low activity of the enzyme delta 9-desaturase (stearoyl CoA desaturase), which may reflect an underlying metabolic profile characterized by insulin resistance and chronic hyper-insulinemia.
Despite strong indirect evidence that androgens stimulate prostate cancer development, data from most analytical studies on this association have been negative. To further investigate this issue, we studied the interrelationships between androgenicity and insulin-like growth factor I (IGF-I), insulin and leptin. Within a prospective cohort study, we measured testosterone, sex hormone-binding globulin (SHBG) and IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, insulin and leptin, in plasma from 149 cases and 298 controls. Testosterone correlated positively with SHBG, whereas testosterone and SHBG correlated inversely with IGF-I, IGFBP-3, insulin, leptin and body mass index (BMI). Indices of free testosterone showed an inverse linear correlation with leptin (P
In a cross-sectional study of 115 premenopausal non-smoking women, we examined the relationship between lymphocyte levels of 8-hydroxy-2'-deoxyguanosine (8-oxodGuo) and habitual alcohol consumption. The study was conducted in four different regions of Europe, including Potsdam (Germany), Turin (Italy), Malmö (Sweden) and Granada (Spain). Mean 8-oxodGuo levels differed significantly across study centres (P = 0.001), with the highest levels in Granada [2.17 8-oxodGuox10(-6) 2'-deoxyguanosine (95% confidence interval 1.27-4.40)] and lowest levels in Turin [1.19 (0.36-4.29)]. Mean levels of total alcohol intake and of types of alcoholic beverages consumed (wine, fortified wines, beer and cider) also differed across the study centres (P
A Western lifestyle has been implicated in the pathogenesis of prostate cancer. However, no clear association between obesity and prostate cancer has been shown. Leptin may stimulate prostate growth and angiogenesis, and receptors for leptin are present in the prostate. Leptin may, thus, be associated with increased risk of prostate cancer. One hundred forty-nine men with prostate cancer were identified (together with 298 matched referents) who, before diagnosis, had participated in population-based health surveys in Northern Sweden. Blood pressure, body mass index, and use of tobacco were recorded. Leptin, insulin, insulin-like growth factor I (IGF-I), IGF-I-binding proteins 1-3, testosterone, and sex hormone-binding globulin were analyzed in stored samples. Their influences on prostate cancer were estimated by conditional logistic regression analysis. Prostate cancer specimens were investigated for immunoreactivity for the leptin receptor. Relative risk (95% confidence intervals) estimates of prostate cancer over the quintiles of leptin were 1.0, 2.1 (1.1-4.1), 2.6 (1.4-4.8), 1.4 (0.7-2.7), and 1.6 (0.8-3.2). Adjustments for metabolic variables, testosterone, and IGF-I and its binding proteins did not attenuate this increased risk. Immunoreactivity for the leptin receptor was detected in normal, high-grade prostatic intraepithelial neoplasia lesions and malignant prostatic epithelium. Moderately elevated plasma leptin concentrations are associated with later development of prostate cancer. This may be due to direct effects of leptin on prostatic intraepithelial neoplasia lesions, or to indirect actions through other mechanisms. A critical fat mass related to an interior milieu favorable for prostate cancer development seems to exist, because intermediate but not high leptin levels are related to prostate cancer risk.
This review summarizes data on the occurrence, the trends, and the life-style, environmental, occupational and genetic determinants of pancreatic cancer. Epidemiologic evidence implicates tobacco smoking as one cause. The evidence regarding alcohol consumption is inconsistent. Although both positive and inconclusive findings are encountered, the bulk of the evidence on coffee consumption is negative. Fat intake is linked with obesity and diabetes mellitus, which are risk factors for pancreatic cancer. Fruit and vegetable consumption appears to be protective. No occupational or environmental agent has been confirmed to increase the risk, but epidemiologic evidence is inconsistent, Little is known about the role of genetic polymorphisms of metabolic enzymes in pancreas carcinogenesis. Pancreatic cancer shows high rates of mutations of Ki-ras and losses or mutations of tumor suppressor genes (p53, p16INK4A, and SMAD4/DPC-4). Ki-ras mutations have been associated with life-style factors in relation to pancreatic cancer, but the evidence is still scant and inconsistent.
Comment In: Scand J Work Environ Health. 1998 Jun;24(3):161-49710367