26.11.2007

Chen, Y. C., Kraft, P., Bretsky, P., Ketkar, S., Hunter, D. J., Albanes, D., Altshuler, D., Andriole, G., Berg, C. D., Boeing, H., Burtt, N., Bueno-De-Mesquita, B., Cann, H., Canzian, F., Chanock, S., Dunning, A., Feigelson, H. S., Freedman, M., Gaziano, J. M., Giovannucci, E., Sanchez, M. J., Haiman, C. A., Hallmans, G., Hayes, R. B., Henderson, B. E., Hirschhorn, J., Kaaks, R., Key, T. J., Kolonel, L. N., LeMarchand, L., Ma, J., Overvad, K., Palli, D., Pharaoh, P., Pike, M., Riboli, E., Rodriguez, C., Setiawan, V. W., Stampfer, M., Stram, D. O., Thomas, G., Thun, M. J., Travis, R. C., Virtamo, J., Trichopouiou, A., Wacholder, S. and Weinstein, S. J.

Cancer Epidemiology Biomarkers & Prevention. 2007; 16(10): 1973-1981. Article. IF 4.289

Background: Estrogen receptor beta (ESR2) may play a role in modulating prostate carcirtogenesis through the regulation of genes related to cell proliferation and apoptosis.

Methods: We conducted nested case-control studies in the Breast and Prostate Cancer Cohort Consortium (BPC3) that pooled 8,323 prostate cancer cases and 9,412 controls from seven cohorts. Whites were the predominant ethnic group. We characterized genetic variation in ESR2 by resequencing exons in 190 breast and prostate cancer cases and genotyping a dense set of single nucleotide polymorphisms (SNP) spanning the locus in a multiethnic panel of 349 cancer-free subjects. We selected four haplotype-tagging SNPs (htSNP) to capture common ESR2 variation in Whites; these htSNPs were then genotyped in all cohorts. Conditional logistic regression models were used to assess the association between sequence variants of ESR2 and the risk of prostate cancer. We also investigated the effect modification by age, body mass index, and family history, as well as the association between sequence variants of ESR2 and advanced-stage (>= T3b, N-1, or M-1) and high-grade (Gleason sum >= 8) prostate cancer, respectively.

Results: The four tag SNPs in ESR2 were not significantly associated with prostate cancer risk, individually. The global test for the influence of any haplotype on the risk of prostate cancer was not significant (P = 0.31). However, we observed that men carrying two copies of one of the variant haplotypes (TACC) had a 1.46-fold increased risk of prostate cancer (99% confidence interval, 1.06-2.01) compared with men carrying zero copies of this variant haplotype. No SNPs or haplotypes were associated with advanced stage or high grade of prostate cancer.

Conclusion: In our analysis focused on genetic variation common in Whites, we observed little evidence for any substantial association of inherited variation in ESR2 with risk of prostate cancer. A nominally significant (P < 0.01) association between the TACC haplotype and prostate cancer risk under the recessive model could be a chance finding and, in any event, would seem to contribute only slightly to the overall burden of prostate cancer.

Physical inactivity, depression, and risk of cardiovascular mortality

Kamphuis, M. H., Geerlings, M. I., Tijhuis, M. A. R., Giampaoli, S., Nissinen, A., Grobbee, D. E. and Kromhout, D.

Medicine and Science in Sports and Exercise. 2007; 39(10): 1693-1699. Article. IF 2.909

Purpose: Studies indicate that depression may increase risk of cardiovascular disease (CVD) in addition to classical risk factors. One of the hypotheses to explain this relation is that depressed subjects become physically inactive. We set out to determine the role of physical inactivity in the relation between depressive symptoms and cardiovascular mortality. Methods: Data were used from the population-based prospective Finland, Italy, and the Netherlands Elderly (FINE) Study. Depressive symptoms were measured with the Zung Self-Rating Depression Scale in 909 elderly men, aged 70-90 yr, free of CVD and diabetes at baseline in 1990. Physical activity was assessed with a questionnaire for retired men. Hazard ratios (HR) for 10-yr cardiovascular mortality were calculated, adjusting for demographics and cardiovascular risk factors.

Results: At baseline, men with more depressive symptoms were less physically active (722 min.wk(-1); 95% confidence interval (CI), 642-802) than men with few depressive symptoms (919 min.wk(-1); 95% CI, 823-1015). During 10 yr of follow-up, 256 (28%) men died from CVD. The adjusted HR of cardiovascular mortality for a decrease of 30 min.d(-1) in physical activity was 1.09 (95% CI, 1.04-1.14). An increase in depressive symptoms with one standard deviation was associated with a higher cardiovascular mortality risk (HR = 1.42; 95% CI, 1.26-1.60). After additional adjustment for physical activity the risk decreased (9%), but an independent risk remained (HR = 1.37; 95% CI, 1.21-1.56). The excess risk on cardiovascular mortality attributable to the combined effect of depressive symptoms with inactivity was 1.47 (95% CI, -0.17 to 3.11).

Conclusions: In the present study, the increased risk of depressive symptoms on cardiovascular mortality could not be explained by physical inactivity. However, our results suggest that depressive symptoms and physical inactivity may interact to increase cardiovascular mortality risk.

Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes

Kilpelainen, T. O., Lakka, T. A., Laaksonen, D. E., Laukkanen, O., Lindstroem, J., Eriksson, J. G., Valle, T. T., Hamalainen, H., Aunola, S., Ilanne-Parikka, P., Keinanen-Kiukaanniemi, S., Tuomilehto, J., Uusitupa, M. and Laakso, M.

Physiological Genomics. 2007; 31(2): 264-272. Article. IF 3.789

Single nucleotide polymorphisms ( SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes ( T2D) in the Finnish Diabetes Prevention Study (DPS).

We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT ( N = 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention ( dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate- to- vigorous PA during the follow-up had a 2.6- to 3.7- fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate- to- vigorous PA ( for the interaction of genotype with change in PA, P = 0.022 - 0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947).

We conclude that moderate- to- vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT.

Field trial of timed bright light exposure for jet lag among airline cabin crew

Lahti, T. J., Terttunen, J., Leppamäki, S., Lönnqvist, J. and Partonen, T.

Int J Circumpolar Health. 2007; 66(4): 365-9. IF

OBJECTIVES: Commercial airlines' flight crew members on transmeridian long-haul flights are constantly exposed to rapid changes in external time. Following rapid changes in circadian rhythm may lead to several symptoms known as jet lag. Our aim was to alleviate jet-lag symptoms by timed exposure to bright light (natural sunlight if present, otherwise artificial bright light).

STUDY DESIGN: Observational field trial with bright light against jet lag.

METHODS: Information on the effects of bright lights on health was delivered through corporate level wellness programs. Volunteer study subjects were cabin crew members on long-haul flights. Subjects filled in a 16-Item Columbia Jet Lag Scale (maximum score 64) before the flight (expected symptoms based on previous flights), on the third day at the destination and again on the third day after returning home. Changes in scores were compared relative to the timed exposure to bright light, and to flights eastwards or westwards, and in summer or winter.

RESULTS: Out of 75 subjects, 15 returned the questionnaires for a total of 28 flights. The mean estimated effect of bright light was a decrease of 5.3 points on the symptom scale. The difference was not significant (SE = 3.4, df = 11, t = -1.6, p = 0.15). The flight had no influence on the estimate.

CONCLUSIONS: The results do not give support to the hypothesis that timed exposure to bright light would alleviate jet lag symptoms, although the small sample size was a problem. More field studies are needed to establish the feasibility of bright light for reducing jet lag.

Increasing prevalence of coeliac disease over time

Lohi, S., Mustalahti, K., Kaukinen, K., Laurila, K., Collin, P., Rissanen, H., Lohi, O., Bravi, E., Gasparin, M., Reunanen, A. and Maki, M.

Alimentary Pharmacology & Therapeutics. 2007; 26(9): 1217-1225. Article. IF 3.287

Background The number of coeliac disease diagnoses has increased in the recent past and according to screening studies, the total prevalence of the disorder is around 1%. Aim To establish whether the increased number of coeliac disease cases reflects a true rise in disease frequency.

Methods The total prevalence of coeliac disease was determined in two population-based samples representing the Finnish adult population in 1978-80 and 2000-01 and comprising 8000 and 8028 individuals, respectively. Both clinically-diagnosed coeliac disease patients and previously unrecognized cases identified by serum endomysial antibodies were taken into account.

Results Only two (clinical prevalence of 0.03%) patients had been diagnosed on clinical grounds in 1978-80, in contrast to 32 (0.52%) in 2000-01. The prevalence of earlier unrecognized cases increased statistically significantly from 1.03% to 1.47% during the same period. This yields a total prevalence of coeliac disease of 1.05% in 1978-80 and 1.99% in 2000-01.

Conclusions The total prevalence of coeliac disease seems to have doubled in Finland during the last two decades, and the increase cannot be attributed to the better detection rate. The environmental factors responsible for the increasing prevalence of the disorder are issues for further studies.

Prevalence and incidence of primary biliary cirrhosis are increasing in Finland

Rautiainen, H., Salomaa, V., Niemelä, S., Karvonen, A. L., Nurmi, H., Isoniemi, H. and Farkkila, M.

Scandinavian Journal of Gastroenterology. 2007; 42(11): 1347-1353. Article. IF 1.869

Objective. To examine the epidemiology of primary biliary cirrhosis (PBC) in Finland and to evaluate whether the possible increase in prevalence was attributable to the increasing incidence, better survival, or both.

Material and methods. The Hospital Discharge Register, pathology registers, and death certificates for the years 1988-99 were scrutinized, and the patients identified were followed-up for survival until 31 October 2004. The study area covered four university hospital districts: a total of 25 hospitals. The diagnosis of PBC was regarded as definite ( or probable) if three ( or two) of the following criteria were fulfilled: positive antimitochondrial antibodies, constantly elevated alkaline phosphatase, and compatible liver histology.

Results. In the total population of the study areas, the age-standardized prevalence of PBC increased during the study period from 103 (95% CI: 97-110) to 180 ( 172-189) per million inhabitants. Incidence increased from 12 ( 10-14) to 17 ( 15-20) per million inhabitants per year. The annual average increase in prevalence was 5.1% (4.2-5.9%, p < 0.0001) and in incidence 3.5% (0.9%-6.0%, p = 0.008). In gender-specific analyses among women, the prevalence of PBC increased from 161 ( 151-171) to 292 (277-207) per million during the study period and the incidence from 20 (16-24) to 27 (23-32) per million per year. The death rate was 4% per year and half the deaths were from liver-related causes. Survival after diagnosis during the study period lengthened.

Conclusions. The prevalence of PBC increased in Finland during 1988-99, owing to both the increased incidence and the prolonged survival.

Prevalence and Psychiatric Comorbidity of Attention-Deficit/Hyperactivity Disorder in an Adolescent Finnish Population

Smalley, S. L., McGough, J. J., Moilanen, I. K., Loo, S. K., Taanila, A., Ebeling, H., Hurtig, T., Kaakinen, M., Humphrey, L. A., McCracken, J. T., Varilo, T., Yang, M. H., Nelson, S. F., Peltonen, L. and Jarvelin, M. R.

J Am Acad Child Adolesc Psychiatry. 2007; 46(12): 1575-1583. IF 4.767

OBJECTIVE:: The purpose of the study was to estimate the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its clinical characteristics in the Northern Finland Birth Cohort 1986.

METHOD:: A general population Northern Finland Birth Cohort 1986 of 9,432 children followed prospectively from the early fetal period was surveyed at adolescence (ages 16-18) for ADHD behaviors. Among 6,622 respondents to the survey, a subset of 457 likely cases and controls were evaluated for ADHD and other psychiatric disorders. Chi-square and descriptive statistics were used to examine clinical characteristics of ADHD in the subset, and logistic regression was used to estimate prevalence by weighted extrapolation in the larger cohort.

RESULTS:: The estimated prevalence of ADHD among adolescents in the Northern Finland Birth Cohort 1986 is 8.5% with a male/female ratio of 5.7:1. The distribution of ADHD subtypes among the ADHD adolescents is 28% Combined, 64% Inattentive, and 8% Hyperactive-Impulsive. A lifetime diagnosis of a broadly defined ADHD (probable or definite) had a prevalence of 18.2% with a male/female odds ratio (OR) of 3.2. This lifetime diagnosis of ADHD is significantly associated with anxiety (OR 2.4), mood (OR 2.9), and disruptive behavioral disorders (OR 17.3) in the cohort.

CONCLUSIONS:: ADHD is a common neurobehavioral disorder among Northern Finnish adolescents and significantly associated with psychiatric comorbidity in adolescence. J. Am. Acad. Child Adolesc. Psychiatry, 2007;46(12):1575-1583.

Survival of Mycobacterium avium in drinking water biofilms as affected by water flow velocity, availability of phosphorus, and temperature

Torvinen, E., Lehtola, M. J., Martikainen, P. J. and Miettinen, I. T.

Applied and Environmental Microbiology. 2007; 73(19): 6201-6207. Article. IF 3.532

Mycobacterium avium is a potential pathogen occurring in drinking water systems. It is a slowly growing bacterium producing a thick cell wall containing mycolic acids, and it is known to resist chlorine better than many other microbes. Several studies have shown that pathogenic bacteria survive better in biofilms than in water. By using Propella biofilm reactors, we studied how factors generally influencing the growth of biofilms (flow rate, phosphorus concentration, and temperature) influence the survival of M. avium in drinking water biofilms. The growth of biofilms was followed by culture and DAPI (4',6'-diamidino-2-phenylindole) staining, and concentrations of M. avium were determined by culture and fluorescence in situ hybridization methods. The spiked M. aviam survived in biofilms for the 4-week study period without a dramatic decline in concentration. The addition of phosphorus (10 mu g/liter) increased the number of heterotrophic bacteria in biofilms but decreased the culturability of M. avium. The reason for this result is probably that phosphorus increased competition with other microbes. An increase in flow velocity had no effect on the survival of M. avium, although it increased the growth of biofilms. A higher temperature (20 degrees C versus 7 degrees C) increased both the number of heterotrophic bacteria and the survival of M. avium in biofilms.

In conclusion, the results show that in terms of affecting the survival of slowly growing M. avium in biofilms, temperature is a more important factor than the availability of nutrients like phosphorus.

Molecular analysis of the CHD7 gene in CHARGE syndrome: identification of 22 novel mutations and evidence for a low contribution of large CHD7 deletions

Vuorela, P., Ala-Mello, S., Saloranta, C., Penttinen, M., Poyhonen, M., Huoponen, K., Borozdin, W., Bausch, B., Botzenhart, E. M., Wilhelm, C., Kaariainen, H. and Kohlhase, J.

Genetics in Medicine. 2007; 9(10): 690-694. Article. IF 3.427

Purpose: Autosomal dominant CHARGE syndrome (OMIM no. 214800) is characterized by choanal atresia or cleft lip or palate, ocular colobomas, cardiovascular malformations, retardation of growth, ear anomalies, and deafness, and is caused by mutations in the CHD7 gene. Here, we describe the outcome of a molecular genetic analysis in 18 Finnish and 56 German patients referred for molecular confirmation of the clinical diagnosis of suspected CHARGE syndrome.

Methods: Quantitative real-time polymerase chain reaction or multiplex ligation-dependent probe amplification assays did not reveal deletions in mutation negative cases, suggesting that larger CHD7 deletions are not a major cause of CHARGE syndrome.

Results: In this group of 74 patients, we found mutations in 30 cases. 22 mutations were novel, including 11 frameshift, 5 nonsense, 3 splice-site, and 3 missense mutations. One de novo frameshift mutation was found in the last exon and is expected to result in a minimally shortened CHD7 polypepticle. Because the mutation is associated with a typical CHARGE syndrome phenotype, it may indicate the presence of an as yet unknown functional domain in the very carboxyterminal end of CHD7.

Conclusions: Our mutation detection rate of 40.5% is reflective of screening an unselected sample population referred for CHD7 testing based on suspected clinical diagnosis of CHARGE syndrome and not for having met strict clinical criteria for this disorder.