Order of HPV/Chlamydia infections and cervical high-grade precancer risk: a case-cohort study.

Interactions of carcinogenic human papillomaviruses (most notably HPV types 16/18/31/33/45), and HPV6 or Chlamydia trachomatis are not well understood. We have used seroconversions to study effects the order of these infections has on the risk of high-grade cervical precancer. In a cohort of 94,349 Finnish women with paired sera from consecutive pregnancies within an average of 2.4 years, 490 were diagnosed with cervical CIN3/AIS. Serum antibodies to HPV6/16/18/31/33/45 and C. trachomatis were measured in paired sera of the cases and a subcohort of 2,796 women with a minimum of two pregnancies. HPV16-adjusted rate ratios (RR) and confidence intervals were estimated by stratified Cox model. Compared to dual seropositivity already at the first serum sampling, RRs related to HPV6 seropositivity before and after HPV31 seroconversion were 0.4 (95% CI 0.0, 4.4) and 10 (95% CI 1.8, 57). Furthermore, RR related to seroconversions of both HPV18/45 and C.trachomatis between the consecutive pregnancies was 28 (95% CI 4.3, 190). Virtually concomitant HPV18/45 and C.trachomatis infections are associated with very high CIN3 risk.

Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer.

Pregnancy reduces maternal risk of breast cancer in the long term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case-control study (536 cases and 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (± 6 months) and date of sampling (± 3 months) were selected. Estradiol, estrone and progesterone in first-trimester serum were measured by high-performance liquid chromatography tandem mass spectrometry and sex-hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.08-3.06), but inversely associated with risk in women who were diagnosed ≥ age 40 (upper quartile OR, 0.64; CI, 0.40-1.04), p(interaction) 0.004. Risk estimates for estrone mirrored those for estradiol but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40.

Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer.

BACKGROUND: Several sexually transmitted infections (STI) have been reported to interact with human papillomavirus (HPV) in the etiology of cervical cancer. A large cohort study is required to obtain a both unbiased and stable estimate of their effects. METHODS: Four major biobanks in the Nordic Countries containing samples from about 1,000,000 subjects were linked with nation-wide cancer registries. Serum samples from 604 women with invasive cervical cancer (ICC) diagnosed on average 10 years after sampling and 2,980 matched control women were retrieved and analyzed with serology for key STI. RESULTS: Exposure to HPV16 was the strongest risk factor for cervical cancer [OR = 2.4; 95% confidence interval (CI), 2.0-3.0], particularly for squamous cell carcinoma (OR = 2.9; 95% CI, 2.2-3.7). HPV18 was strongly associated with increased risk for adenocarcinoma (OR = 2.3; 95% CI, 1.3-4.1). Baseline seropositivity for HPV16 did not confer any increased risk for HPV18 DNA-positive cancer and conversely HPV18 seropositivity had no association with HPV16 DNA-positive cancers. HPV6 had no effect on its own (OR = 1.1; 95% CI, 0.9-1.3), but had an antagonistic effect on the risk conferred by HPV16 (P < 0.01). Herpes simplex virus 2 had little or no association (OR = 1.1; 95% CI, 0.8-1.4). Previous exposure to Chlamydia trachomatis, as indicated by serum antibodies, had a strongly increased risk for cervical cancer (OR = 1.9; 95% CI, 1.5-2.3). CONCLUSIONS: A large prospective study has assessed the role of different STIs in cervical cancer. IMPACT: Prospective evidence supports cofactor role of some STI in cervical cancer.

Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer.

BACKGROUND: Sex steroid hormones have been proposed to play a role in the development of non-epithelial ovarian cancers (NEOC) but so far no direct epidemiologic data are available. METHODS: A case-control study was nested within the Finnish Maternity Cohort, the world's largest biorepository of serum specimens from pregnant women. Study subjects were selected among women who donated a blood sample during a singleton pregnancy that led to the birth of their last child preceding diagnosis of NEOC. Case subjects were 41 women with sex cord stromal tumors (SCST) and 21 with germ cell tumors (GCT). Three controls, matching the index case for age, parity at the index pregnancy, and date at blood donation were selected (n = 171). OR and 95% CI associated with concentrations of testosterone, androstenedione, 17-OH-progesterone, progesterone, estradiol, and sex hormone-binding globulin (SHBG) were estimated through conditional logistic regression. RESULTS: For SCST, doubling of testosterone, androstenedione, and 17-OH-progesterone concentrations were associated with about 2-fold higher risk of SCST [ORs and 95% CI of 2.16 (1.25-3.74), 2.16 (1.20-3.87), and 2.62 (1.27-5.38), respectively]. These associations remained largely unchanged after excluding women within 2-, 4-, or 6-year lag time between blood donation and cancer diagnosis. Sex steroid hormones concentrations were not related to maternal risk of GCT. CONCLUSIONS: This is the first prospective study providing initial evidence that elevated androgens play a role in the pathogenesis of SCST. IMPACT: Our study may note a particular need for larger confirmatory investigations on sex steroids and NEOC.

Lack of association between human papillomavirus type 16 and 18 infections and female lung cancer.

BACKGROUND: A carcinogenic role of human papillomavirus (HPV) in lung cancer development has been suggested through both clinical and laboratory research during the last two decades. METHODS: We did a population-based case-control study nested within the Finnish Maternity Cohort to assess the role of HPV16/18 infections in female lung carcinogenesis. The Finnish Maternity Cohort containing samples from more than 600,000 subjects were linked with nationwide cancer registries (1973-2006). Serum samples were retrieved from 311 women who developed lung cancer and 930 matched controls. The samples were analyzed for antibodies to HPV types 16 and 18 and cotinine (a biomarker of tobacco exposure). Conditional logistic regression-based estimates of odds ratios and 95% confidence intervals adjusted for cotinine levels were calculated. RESULTS: Overall, there was no evidence of increased risk of lung cancer associated with HPV 16 and 18 type-specific infections among nonsmokers and smokers, assessed via cotinine levels. CONCLUSIONS: The question of HPV etiologic effect on lung carcinoma deserves further longitudinal studies using different HPV detection methods. IMPACT: Our results bring new insights into female HPV lung cancer research.

Population fraction of cervical neoplasia attributable to high-risk human papillomaviruses.

AIMS: The efficacy of human papillomavirus (HPV) type 16 and 18 vaccines against cervical intraepithelial neoplasia grade II (CIN2+) has been verified, but the active follow-up of studies with invasive cervical cancer or cervical intraepithelial neoplasia grade III (CIN3) as primary end points are ethically not possible. Furthermore, ongoing registry-based passive follow-up studies with invasive cervical cancer as the end point will take time. MATERIALS & METHODS: To evaluate the feasibility of CIN3 as a surrogate end point, we compared high-risk (hr) HPV-associated relative risk and population attributable fraction (PAF) of CIN3 and/or squamous cell carcinoma (SCC) estimated in a large serological case-cohort HPV study. Our case-cohort comprised 83 SCC and 389 CIN3 cases and a subcohort of 7862 out of 230,998 Finnish women, who at baseline were under 32 years of age and had undergone a minimum of two pregnancies within 5 years during 1983-1997. RESULTS: PAFs of the case-cohort, approach-based, serologically defined and misclassification-corrected HPV16 and hrHPV (HPV types 16, 18, 31 and 33) exposures in the SCC samples were 61% (95% CI: 18-85) and 73% (95% CI: 13-93), respectively. Considerably lower HPV16 and hrHPV PAF estimates in CIN3 of 6% (95% CI: -19-35) and 36% (95% CI: -5-65), respectively, were obtained. A meta-analysis-derived, PCR-based, hrHPV-associated relative risk estimate of 20.3 in CIN2/3+ yielded a PAF estimate for hrHPV in CIN2/3+ of 86% (90% CI: 63-95) in our study population. The former, hrHPV serology-based CIN3 PAF estimates were biased owing to low sensitivity of HPV16 and/or HPV16/18/31/33 serology, most notably in cervical cancer precursor lesions, but the latter estimate overlapped with our hrHPV serology-based cervical cancer PAF estimate. CONCLUSION: CIN3 may be a valid surrogate efficacy end point for HPV vaccination studies, but the associated causality of multiple hrHPV exposures needs to be unambigously defined.

Risk of being seropositive for multiple human papillomavirus types among Finnish and Ugandan women.

Although infections with multiple human papillomavirus (HPV) types have been reported widely, more information is needed on the occurrence of the different types. We determined the distribution of seroprevalences to multiple HPV types in Finland and Uganda to compare the epidemiology of the different HPV types in the 2 populations. Serum samples were obtained from 2784 Finnish and 1964 Ugandan women (mean ages 22 y and 25 y, respectively) of whom 44% and 57%, respectively, had antibodies to at least 1 of the 7 HPV types (6, 11, 16, 18, 31, 33, 45) tested (p < 0.001). Multiple HPV antibody positivity was common. HPV45-seropositive Finns had a higher risk of having antibodies to other high-risk HPV types: HPV18 (odds ratio (OR) = 10.9), HPV31 (OR 6.1), HPV33 (OR 12.2), than their Ugandan counterparts: HPV18 (OR 3.4), HPV31 (OR 2.2), HPV33 (OR 3.3). Increased estimates for being double antibody-positive were also noted among HPV18- and HPV16-seropositive women, but there were no major differences between HPV16-seropositive Finns and Ugandans. In addition to biological and behavioural factors, iatrogenic and societal factors (screening vs no screening) may also result in the different occurrence of infections with the high-risk HPV types in Finland and Uganda.

Population dynamics of serologically identified coinfections with human papillomavirus types 11, 16, 18 and 31 in fertile-aged Finnish women.

Licensed human papillomavirus (HPV) vaccines are expected to prevent high-risk (hr) HPV-infections (most notably types 16 and 18). Whether HPV vaccination will change the distribution of hrHPVs at the population level is open, since competition between HPV types is not well understood. Two stratified random subcohorts (1983-1997 and 1995-2003) of 7,815 and 3,252 women with a minimum of 2 pregnancies (<32 years) were selected from the Finnish Maternity Cohort. Using ELISA based on virus-like particles (VLP), we determined antibodies to HPV11, 16, 18 and 31 in paired sera of the women and used Poisson regression models to estimate the risk of further infection with other HPV types in those positive for HPV16 or HPV18 at baseline. Baseline HPV16 seropositivity was associated with increased risk of later infections with HPV18 (3.1, 95% CI: 1.7, 5.6). HPV18 seropositivity was associated with increased risk of HPV16 (3.9, 95% CI: 2.5, 6.1). Our observations favor a coinfection rather than superinfection model for the different HPV types and are not suggestive for type-replacement following HPV vaccination.

Time trends in allergic sensitisation and Helicobacter pylori prevalence in Finnish pregnant women.

BACKGROUND: An increase in the prevalence of allergic conditions has been documented in Finland, correlating with the diminishing prevalence of Helicobacter pylori infections. We investigated whether the increase of allergic sensitisation still continues and correlates with the prevalence of H. pylori infections. METHODS: The sera from 958 pregnant women in 1983, 1989, 1995 and 2001 were analysed for the presence of antibodies against H. pylori. In addition, allergen-specific IgE antibodies and total levels of IgE antibodies were measured. RESULTS: A clear birth cohort effect was found in the prevalence of allergic sensitization: allergen-specific IgE was more frequent among recent birth cohorts than earlier ones (p = 0.001). The frequency of H. pylori antibodies followed the opposite trend (p < 0.001) and the increase in allergic sensitisation was only seen among H. pylori-negative women. A modest increase was also seen in allergic sensitisation between the 4 time series among the H. pylori-negative subjects (p = 0.04). Total IgE levels did not differ between birth cohorts or time series. CONCLUSION: The results suggest that hygiene-related environmental factors have played a role in the increase of allergic sensitisation during the last decades.

Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: a nested case-referent study.

According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring.

Maternal smoking during pregnancy and testicular cancer in the sons: a nested case-control study and a meta-analysis.

Some large ecological studies have noted a significant association of testicular cancer (TC) with maternal smoking during pregnancy, while several more controlled studies have been negative. It has been difficult to obtain reliable data on exposure because of the long lag time to cancer diagnosis. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal smoking in the risk of TC in the offspring. After reviewing the literature, we also performed a meta-analysis of published studies. For each index mother of the TC patient, three to nine matched control mothers with a cancer-free son born at the same time as the TC case were identified within each cohort. First trimester sera were retrieved from the 70 index mothers and 519 control mothers and were tested for cotinine level by a novel HPLC-MS-MS method developed. No statistically significant association between maternal cotinine level and risk of TC in the offspring was found (OR 0.68; 95% CI 0.35, 1.34). This is the first study based on individual exposure measurements. Its results agree with our meta-analysis of seven previous epidemiological studies (total number of 2149 cases, 2762 controls) using indirect exposure assessment (OR 1.0; 95% CI 0.88, 1.12).

Is smoking an independent risk factor for invasive cervical cancer? A nested case-control study within Nordic biobanks.

The strong correlation between smoking and exposure to oncogenic human papillomaviruses (HPVs) has made it difficult to verify the independent role of smoking in cervical carcinogenesis. Thus, the authors evaluated this role. Five large Nordic serum banks containing samples from more than 1,000,000 subjects were linked with nationwide cancer registries (1973-2003). Serum samples were retrieved from 588 women who developed invasive cervical cancer and 2,861 matched controls. The samples were analyzed for cotinine (a biomarker of tobacco exposure) and antibodies to HPV types 16 and 18, herpes simplex virus type 2, and Chlamydia trachomatis. Smoking was associated with the risk of squamous cell carcinoma (SCC) among HPV16- and/or HPV18-seropositive heavy smokers (odds ratio=2.7, 95% confidence interval: 1.7, 4.3). A similar risk of SCC (odds ratio=3.2, 95% confidence interval: 2.6, 4.0) was found in heavy smokers after adjustment for HPV16/18 antibodies. The point estimates increased with increasing age at diagnosis and increasing cotinine level. This study confirms that smoking is an independent risk factor for cervical cancer/SCC in women infected with oncogenic HPVs. These findings emphasize the importance of cervical cancer prevention among women exposed to tobacco smoke.

Smoking impairs human papillomavirus (HPV) type 16 and 18 capsids antibody response following natural HPV infection.

The natural history of oncogenic human papillomavirus (HPV) infections results from interactions of the virus, the host, and multiple cofactors. We studied the association between humoral immune response to HPV and smoking in 191 HPV infected women prospectively. Two follow-up samples (first and last) were analysed for serum cotinine levels, IgA and IgG antibodies to HPV16 and 18, and Chlamydia trachomatis using ELISA methods. HPV DNA analyses were also performed, and HPV16/18 antibodies were detectable in 23 of 40 (57.5%) HPV DNA-positive women. We performed age-stratified analyses and found that young smokers were less likely to develop HPV16/18 antibodies than non-smokers (OR: 0.2, 95% CI 0.0-0.9). Furthermore, they had a significantly decreased tendency of maintaining constant HPV16/18 IgG antibody positivity by the end of the follow-up (OR: 0.1, 95% CI 0.0-0.8). Smoking did not affect the development of HPV antibody responses in women over 30 y of age. Our results suggest that smoking may induce impaired antibody response in HPV16/18-infected young women.

A discrepancy of Chlamydia trachomatis incidence and prevalence trends in Finland 1983-2003.

BACKGROUND: Reported rates of Chlamydia trachomatis are on the rise contradicting the declining rates of C. trachomatis associated reproductive sequelae in Western countries. Population based evaluation of the real trend of C. trachomatis infection is important to contemplate prevention efforts. We studied C. trachomatis occurrence during the past 20 years in Finland comparing incidence rate data based on serology and reported C. trachomatis laboratory notifications. METHODS: A random sample of 7999 women with two consecutive pregnancies within five years was selected from the population of the Finnish Maternity Cohort (FMC) serum bank stratified by calendar year and age. C. trachomatis IgG antibodies were determined by a standard peptide-ELISA. The reported incidence rates of C. trachomatis infections based on case notifications were obtained from the National Registry of Infectious Diseases (NIDR). RESULTS: C. trachomatis seroprevalence rates decreased significantly from 1983 to 2003 both in women under 23 years of age (23.3% to 9.2%) and in women between 23-28-years of age (22.2% to 12.6%). However, seroconversion rates increased from 31 per 10000 person years in 1983-85 to 97 per 10000 person years in 2001-2003 (incidence rate ratio 3.2, 95% CI, 1.1-8.7) among the older age group. Seroconversion rate was highest (264) in 1983-1985 in the younger age-group, then declined and subsequently increased again (188) in 2001-2003. The incidence based on seroconversions was in agreement with the reported incidence rates in both age groups. CONCLUSION: C. trachomatis seroprevalence rate decreased during 1983-2003 among fertile-aged women in Finland. During the same time period incidence rates based both on seroconversions and reported laboratory notifications of diagnosed C. trachomatis infections increased. The discrepancy between the C. trachomatis incidence and seroprevalence trends warrants further studies.

Maternal Epstein-Barr virus and cytomegalovirus infections and risk of testicular cancer in the offspring: a nested case-control study.

During recent decades the incidence of testicular cancer (TC) has increased rapidly around the world. Associated exogenous etiological factors might therefore be identifiable. We performed a case-control study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of congenital or neonatal infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) as risk factors of TC in the offspring. For each case-index mother pair, three or four matched control-control mother pairs were identified using national population registries. First trimester sera were retrieved from the index mothers of 66 TC cases and 258 matched control mothers, and were tested for antibodies to EBV and CMV. High level of maternal EBV IgG antibodies was associated with significantly increased risk of TC in the offspring (odds ratio (OR), 2.50; 95% confidence interval (CI), 1.15, 5.40), especially with risk of non-seminoma TC (OR, 2.73; 950% CI, 1.25, 5.99) and non-seminoma TC diagnosed under 8 years of age (OR, 2.72; 95% CI, 1.05, 7.04). In contrast, offspring of CMV IgG-seropositive mothers had a decreased risk of TC diagnosed under 8 years of age (OR, 0.35; 95% CI, 0.14, 0.89). Our results suggest that EBV and CMV infections may be associated with TC.

Maternal serum Chlamydia pneumoniae antibodies and CRP levels in women with preeclampsia and gestational hypertension.

OBJECTIVE: To determine whether Chlamydia pneumoniae antibodies and highly sensitive C-reactive protein (hsCRP) levels in maternal sera are associated with preeclampsia or gestational hypertension. METHODS: C. pneumoniae antibodies and hsCRP levels were measured in maternal serum during first trimester (mean, 10.4 weeks of gestation) using the microimmunofluorescence (MIF) test and a highly sensitive immunoenzymometric assay, respectively. RESULTS: No differences in the IgG antibody levels against C. pneumoniae or hsCRP levels were seen between the women with preeclampsia or gestational hypertension and those in the reference group. However, the women with preeclampsia and preterm delivery had serum IgG antibodies to C. pneumoniae (IgG titre > or =32) significantly more often in their first trimester sera compared with women having preeclampsia and full-term deliveries (p = 0.03). In addition, the proportion of subjects with C. pneumoniae IgG antibodies (IgG titre > or =32) and/or elevated CRP levels (> or =3.8 mg/L, upper quartile) was double among the women with preeclampsia and elective preterm delivery compared with the women with preeclampsia who delivered at term (p = 0.01). CONCLUSION: Our results suggest that chronic C. pneumoniae infection and systemic low-grade inflammation may be associated with preeclampsia requiring elective delivery before 37 weeks gestation.

Effect of long-term storage on hormone measurements in samples from pregnant women: the experience of the Finnish Maternity Cohort.

Validity of biobank studies on hormone associated cancers depend on the extent the sample preservation is affecting the hormone measurements. We investigated the effect of long-term storage (up to 22 years) on immunoassay measurements of three groups of hormones and associated proteins: sex-steroids [estradiol, progesterone, testosterone, dihydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG)], pregnancy-specific hormones [human chorionic gonadotropin (hCG), placental growth hormone (pGH), alpha-fetoprotein (AFP)], and insulin-like growth factor (IGF) family hormones exploiting the world largest serum bank, the Finnish Maternity Cohort (FMC). Hormones of interest were analyzed in a random sample of 154 Finnish women in the median age (29.5 years, range 25 to 34 years) of their first pregnancy with serum samples drawn during the first trimester. All hormone measurements were performed using commercial enzyme-linked- or radio-immunoassays. Storage time did not correlate with serum levels of testosterone, DHEAS, hCG, pGH and total IGFBP-1. It had a weak or moderate negative correlation with serum levels of progesterone (Spearman's ranked correlation coefficient (r(s))=- 0.36), IGF-I (r(s)=-0.23) and IGF binding protein (BP)-3 (r(s)=-0.38), and weak positive correlation with estradiol (r(s)=0.23), SHBG (r(s)=0.16), AFP (r(s)=0.20) and non-phosphorylated IGF binding protein (BP)-1 (r(s)=0.27). The variation of all hormone levels studied followed the kinetics reported for early pregnancy. Bench-lag time (the time between sample collection and freezing for storage) did not materially affect the serum hormone levels. In conclusion, the stored FMC serum samples can be used to study hormone-disease associations, but close matching for storage time and gestational day are necessary design components of all related biobank studies.

Insulin resistance and depressive symptoms in young adult males: findings from Finnish military conscripts.

OBJECTIVE: To investigate whether the association between insulin resistance (IR) and depressive symptoms is present already in young adult males. The association between IR and depression has been poorly studied, although the existence of a connection of Type II diabetes with depression is well established. We previously demonstrated at epidemiological level in two groups of men aged 31 years and 61 to 63 years that IR is linked with depressive symptoms. METHODS: In a cross-sectional study, involving 1054 healthy Finnish male military conscripts of about 19 years of age, IR was defined through homeostasis model assessment (HOMA-IR). The severity of the depressive symptoms was evaluated through a Finnish modification of the 13-item Beck Depression Inventory (R-BDI). Moderate-to-severe depressive symptoms were said to be present, if the R-BDI score was > or = 8, and mild depressive symptoms were present if the R-BDI score was 5 to 7. RESULTS: After adjusting for confounders, moderate-to-severe depressive symptoms increased the risk for IR, as defined by the highest decile of the HOMA-IR, up to 2.8-fold (odds ratio = 2.8; 1.2-6.5). Mild depressive symptoms were not significantly associated with IR. CONCLUSIONS: In young adult males, co-occurring strictly defined IR seems to be positively associated with current moderate-to-severe depressive symptoms.

Maternal antibodies in breast milk protect the child from enterovirus infections.

OBJECTIVE: Enterovirus infections are frequent in infants and may cause severe complications. We set out to assess whether breastfeeding can protect against these infections and whether such an effect is related to maternal antibodies in breast milk or in the peripheral circulation of the infant. METHODS: One hundred fifty infants who were prospectively followed up from birth were monitored for enterovirus infections. The duration of breastfeeding was recorded, and maternal breast milk and blood samples were regularly taken at 3-month intervals for the detection of enterovirus antibodies and RNA. Maternal serum was available from early pregnancy, delivery, and 3 months postpartum. RESULTS: Enterovirus infections were frequent and were diagnosed in 43% of infants before the age of 1 year and in 15% of the mothers during pregnancy. Infants exclusively breastfed for >2 weeks had fewer enterovirus infections by the age of 1 year compared with those exclusively breastfed for < or =2 weeks (0.38 vs 0.59 infections per child). High maternal antibody levels in serum and in breast milk were associated with a reduced frequency of infections. This effect was seen only in those infants breastfed >2 weeks, indicating that breast milk antibodies mediate this effect. Enterovirus RNA was not found in any of the breast milk samples. CONCLUSIONS: These results suggest that breastfeeding has a protective effect against enterovirus infections in infancy. This effect seems to be mediated primarily by maternal antibodies in breast milk.

Nordic biological specimen banks as basis for studies of cancer causes and control--more than 2 million sample donors, 25 million person years and 100,000 prospective cancers.

The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at -20 degrees C to -135 degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.