Sonja Lumme

Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: A longitudinal, nested case-control study in the Nordic countries

Vitamin D inhibits the development and growth of prostate cancer cells. Epidemiologic results on serum vitamin D levels and prostate cancer risk have, however, been inconsistent. We conducted a longitudinal nested case‐control study on Nordic men (Norway, Finland and Sweden) using serum banks of 200,000 samples. We studied serum 25(OH)‐vitamin D levels of 622 prostate cancer cases and 1,451 matched controls and found that both low (≤19 nmol/l) and high (≥80 nmol/l) 25(OH)‐vitamin D serum concentrations are associated with higher prostate cancer risk. The normal average serum concentration of 25(OH)‐vitamin D (40–60 nmol/l) comprises the lowest risk of prostate cancer. The U‐shaped risk of prostate cancer might be due to similar 1,25‐dihydroxyvitamin D3 availability within the prostate: low vitamin D serum concentration apparently leads to a low tissue concentration and to weakened mitotic control of target cells, whereas a high vitamin D level might lead to vitamin D resistance through increased inactivation by enhanced expression of 24‐hydroxylase. It is recommended that vitamin D deficiency be supplemented, but too high vitamin D serum level might also enhance cancer development.

High levels of circulating testosterone are not associated with increased prostate cancer risk: A pooled prospective study

Androgens stimulate prostate cancer in vitro and in vivo. However, evidence from epidemiologic studies of an association between circulating levels of androgens and prostate cancer risk has been inconsistent. We investigated the association of serum levels of testosterone, the principal androgen in circulation, and sex hormone‐binding globulin (SHBG) with risk in a case‐control study nested in cohorts in Finland, Norway and Sweden of 708 men who were diagnosed with prostate cancer after blood collection and among 2,242 men who were not. In conditional logistic regression analyses, modest but significant decreases in risk were seen for increasing levels of total testosterone down to odds ratio for top vs. bottom quintile of 0.80 (95% CI = 0.59–1.06; ptrend = 0.05); for SHBG, the corresponding odds ratio was 0.76 (95% CI = 0.57–1.01; ptrend = 0.07). For free testosterone, calculated from total testosterone and SHBG, a bell‐shaped risk pattern was seen with a decrease in odds ratio for top vs. bottom quintile of 0.82 (95% CI = 0.60–1.14; ptrend = 0.44). No support was found for the hypothesis that high levels of circulating androgens within a physiologic range stimulate development and growth of prostate cancer.

Circulating enterolactone and prostate cancer risk: A Nordic nested case‐control study

Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by the intestinal microflora from precursors in plant foods and has been implicated in protection against cancer. We study the effect of enterolactone on the risk of a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested case‐control study by linkage of 3 biobanks to the cancer registries in Finland, Norway and Sweden, respectively. Enterolactone concentrations were measured by time‐resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of prostate cancer at a mean follow‐up time of 14.2 years after blood collection and among 2,550 control men matched within each cohort for age (±2 years), date of blood collection (±2 months) and county. The median enterolactone concentrations did not differ between case and control subjects in the full study group (8.4 nmol/L [25th–75th percentile = 4.5–15.0] vs. 8.5 nmol/L [25th–75th percentile = 4.3–15.9]), nor in the national groups. Odds ratios of prostate cancer risk estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles in the full study group were 1.00 (referent), 1.21 (95% confidence interval [CI] = 0.96–1.52), 1.16 (95% CI = 0.91–1.47) and 1.08 (95% CI = 0.83–1.39). The OR estimate for the highest vs. the lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish and Swedish cohort was 1.21 (95% CI = 0.91–1.60), 1.02 (95% CI = 0.59–1.76) and 0.87 (95% CI = 0.45–1.67), respectively. No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found.

Interaction of Factors Related to the Metabolic Syndrome and Vitamin D on Risk of Prostate Cancer

Background: Factors related to the metabolic syndrome and low levels of vitamin D have been implicated as risk factors for prostate cancer. Insofar, no studies have assessed their joint effects on prostate cancer risk. Methods: We studied (a) the associations of vitamin D with the metabolic syndrome factors body mass index, systolic and diastolic blood pressure, and high-density lipoprotein cholesterol (HDL-C) and (b) the prostate cancer risk associated with these factors and especially their joint effects with vitamin D on risk of prostate cancer. We did a longitudinal nested case-control study on 132 prostate cancer cases and 456 matched controls from a cohort of 18,939 Finnish middle-aged men from the Helsinki Heart Study. The odds ratios (OR) of prostate cancer were assessed via conditional logistic regression analysis. Results: Apart from HDL-C, there was no linear association between the metabolic syndrome factors and vitamin D levels. In univariate analysis, men in the highest quartiles of body mass index (>28 kg/m2) and systolic blood pressure (>150 mmHg) showed a modest increase in risks of prostate cancer, with ORs of 1.37 (P = 0.16) and 1.53 (P = 0.05) when compared with the three lower quartiles, but low HDL-C entailed no prostate cancer risk. However, with all three factors present, the OR was 3.36 (P = 0.02), and jointly with low vitamin D (≤40 nmol/L), the OR was 8.03 (P = 0.005) compared with those with no metabolic syndrome factors and intermediate levels of vitamin D. There was an interaction between vitamin D and the metabolic syndrome factors so that a clustering of these factors entailed high risk of prostate cancer but only if vitamin D level was low (≤40 nmol/L). If it was at intermediate levels, the metabolic syndrome factors entailed no prostate cancer risk. Conclusions: We conclude that the prostate cancer risk associated with factors related to the metabolic syndrome is strongly conditioned by levels of vitamin D. (Cancer Epidemiol Biomarkers Prev 2007;16(2):302–7)

Human Papillomavirus 16, 18, and 33 Infections and Risk of Prostate Cancer: A Nordic Nested Case-Control Study

Epidemiologic evidence of sexual history has emerged as a consistently found risk factor for prostate cancer. Some studies have reported an association between human papillomavirus (HPV) infections and prostate cancer. We did a nested case-control study within cohorts of more than 200,000 men enrolled in three Nordic biobanking projects. Follow-up using cancer registry linkages identified 804 prospectively occurring prostate cancer cases. Four control subjects per case were randomly selected from eligible sets of matched subjects that were alive and free of cancer at the time of diagnosis of the corresponding case and were matched to cases on biobank cohort, age (±2 years), county of residence, and date of blood sampling (±2 months in the Finnish and Swedish cohorts, ±6 months in the Norwegian cohort). The serum samples were analyzed by standard ELISAs for the presence of immunoglobulin G antibodies against HPV types 16, 18, and 33. The joint HPV-16/HPV-18/HPV-33 seroprevalence in the joint cohort was 13.4% (107 of 799) among cases and 14.0% (363 of 2,596) among controls (odds ratio, 0.94; 95% confidence interval, 0.74-1.19). There were no noteworthy differences when the data were analyzed by different HPV type, country, or antibody levels. Our data do not support an association between serologic markers of HPV-16, HPV-18, and HPV-33 infections and risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2952–5)

Chlamydial Antibodies and Risk of Prostate Cancer

Objective: We assessed the risk of prostate cancer by exposure to Chlamydia trachomatis. Method: Seven hundred thirty eight cases of prostate cancer and 2,271 matched controls were identified from three serum sample banks in Finland, Norway, and Sweden by linkage to the population based cancer registries. Results: A statistically significant inverse association (odds ratio, 0.69; 95% confidence interval, 0.51-0.94) was found. It was consistent by different serotypes and there was a consistent dose-response relationship. Conclusion: C. trachomatis infection is not likely to increase the risk of prostate cancer. Whether the inverse relationship is true or due to difficulties in measuring the true exposure in prostatic tissue by serology, confounders or other sources of error remain open.

Socioeconomic equity in amenable mortality in Finland 1992–2008

This study presents an approach to assess socioeconomic equity in the effectiveness of health services. As an indicator of health system performance we use amenable mortality which captures premature deaths that should not occur in the presence of effective and timely health care. Data on amenable deaths by income groups in Finland in 1992-2008 came from the National Causes of Death Register which was linked to sociodemographic data in population registers. We evaluate the extent of and trends in socioeconomic differences with two widely used inequity indices, the concentration index and the slope index of inequality, and also for different categories of amenable mortality. By categorizing conditions according to the level of intervention associated with the conditions it is possible to evaluate the effect of types of health interventions. Causes of death attributable to specialized and primary care interventions comprise the main groups. By this approach of decomposing equity in amenable mortality in Finland we detected major and increasing socioeconomic inequities and also greater inequity among deaths amenable to specialized health care interventions. Moreover, we saw that inequity increased at a faster pace among deaths amenable to specialized health care interventions yet primary health care interventions made a greater contribution to overall inequity. Although the overall rate of amenable mortality decreased notably during the follow-up, the time trends of socioeconomic differences in amenable health care indicate a substantial increase in inequities in health care in Finland.

Multilevel modeling of regional variation in equity in health care

Background:The use of a concentration index is recommended to estimate socioeconomic equity in health and health services. Methods for the analysis of concentration indices have been developed in several studies. However, these methods do not take into consideration clustering within areas, which is necessary in a comprehensive study of regional variations in equity. Objectives:The study aims to develop a statistical method to assess variations in socioeconomic inequities in the use of health services in relation to need in different regions. Methods:Concentration index methods were developed further and the advantages of multilevel modeling were exploited. As an empirical example we analyzed revascularizations in 2001–2003 among the Finnish population. Results:The average inequity indices for the income distribution of revascularizations in Finland obtained with multilevel and standard regression modeling were comparable, but confidence intervals were smaller with multilevel modeling. Inequity indices for different areas estimated using multilevel modeling were more conservative and had smaller confidence intervals than indices estimated using the standard approach. Conclusions:The proposed approach is an efficient way of estimating regional variations in the socioeconomic equity of health care use. It enables the inclusion of need in the model and takes into account the varying need for services in different population groups and areas. In addition, the advantages of using multilevel modeling to estimate indices include the possibility to take into account dependence between observations within regions and to overcome the problems associated with random error in small regions.

Excess Mortality in Patients with Severe Mental Disorders in 1996-2010 in Finland.

Unselected population-based nationwide studies on the excess mortality of individuals with severe mental disorders are scarce with regard to several important causes of death. Using comprehensive register data, we set out to examine excess mortality and its trends among patients with severe mental disorders compared to the total population. Patients aged 25–74 and hospitalised with severe mental disorders in 1990–2010 in Finland were identified using the national hospital discharge register and linked individually to population register data on mortality and demographics. We studied mortality in the period 1996–2010 among patients with psychotic disorders, psychoactive substance use disorders, and mood disorders by several causes of death. In addition to all-cause mortality, we examined mortality amenable to health care interventions, ischaemic heart disease mortality, disease mortality, and alcohol-related mortality. Patients with severe mental disorders had a clearly higher mortality rate than the total population throughout the study period regardless of cause of death, with the exception of alcohol-related mortality among male patients with psychotic disorders without comorbidity with substance use disorders. The all-cause mortality rate ratio of patients with psychotic disorders compared to the total population was 3.48 (95% confidence interval 2.98–4.06) among men and 3.75 (95% CI 3.08–4.55) among women in the period 2008–10. The corresponding rate ratio of patients with psychoactive substance use disorders was 5.33 (95% CI 4.87–5.82) among men and 7.54 (95% CI 6.30–9.03) among women. Overall, the mortality of the total population and patients with severe mental disorders decreased between 1996 and 2010. However, the mortality rate ratio of patients with psychotic disorders and patients with psychoactive substance use disorders compared to the total population increased in general during the study period. Exceptions were alcohol-related mortality among patients with psychoactive substance use disorders and female patients with psychotic disorders, as well as amenable mortality among male patients with psychotic disorders. The mortality rate ratio of persons with mood disorders compared to the total population decreased. The markedly high mortality amenable to health care intervention among patients with severe mental disorders found in our study suggests indirectly that they may receive poorer quality somatic care. The results highlight the challenges in co-ordinating mental and somatic health services.

Are there socioeconomic differences in outcomes of coronary revascularizations--a register-based cohort study.

BACKGROUND Earlier studies have reported socioeconomic differences in coronary heart disease incidence and mortality and in coronary treatment, but less is known about outcomes of care. We examined trends in income group differences in outcomes of coronary revascularizations among Finnish residents in 1998-2010. METHODS First revascularizations for 45-84-year-old Finns were extracted from the Hospital Discharge Register in 1998-2009 and followed until 31 December 2010. Income was individually linked to them and adjusted for family size. We examined the risk of major adverse cardiac events (MACEs), coronary mortality and re-revascularization. We calculated age-standardized rates with direct method and Cox regression models. RESULTS Altogether 69 076 men and 27 498 women underwent revascularization during the study period. Among men [women] in the 1998 cohort, 41% [35%] suffered MACE during 29 days after the operation and 30% [28%] in the 2009 cohort. Myocardial infarction mortality within 1 year was 2% among both genders in both cohorts. Among men [women] 9% [14%] underwent revascularization within 1 year after the operation in 1998 and 12% [12%] in 2009. Controlling for age, co-morbidities, year, previous infarction and disease severity, an inverse income gradient was found in MACE incidence within 29 days and in coronary mortality. The excess MACE risk was 1.39 and excess mortality risk over 1.70 among both genders in the lowest income quintile. All income group differences remained stable from 1998 to 2010. CONCLUSIONS In health care, more attention should be paid to prevention of adverse outcomes among persons with low socioeconomic position undergoing revascularization.