Is male gynaecomastia associated with an increased risk of death? A nationwide register-based cohort study.

OBJECTIVE: Recent evidence supports that gynaecomastia may predict long-term morbidity, but evidence on the association with death and causes of death in males with gynaecomastia is lacking. The objective of this work is to estimate the risk of death in men diagnosed with gynaecomastia and evaluate whether this was conditional on underlying aetiologies of gynaecomastia. DESIGN: A nationwide register-based cohort study. SETTING: Nationwide Danish national health registries. PARTICIPANTS: Males were diagnosed with incident gynaecomastia (n=23 429) from 1 January 1995 to 30 June 2021, and each was age and calendar matched to five randomly population-based males without gynaecomastia (n=117 145). INTERVENTIONS: Not applicable. PRIMARY AND SECONDARY OUTCOMES: Gynaecomastia was distinguished between males without (idiopathic) and males with a known pre-existing risk factor. Cox regression models and Kaplan-Meier analyses estimated associations between gynaecomastia and death (all cause/cause specific). RESULTS: We identified a total of 16 253 males with idiopathic gynaecomastia and 7176 with gynaecomastia and a known pre-existing risk factor. Of these, 1093 (6.7%) and 1501 (20.9%) died during follow-up, respectively. We detected a 37% increased risk of all-cause death in males with gynaecomastia in the entire cohort (HR 1.37; 95% CI 1.31 to 1.43). Death risk was highest in males diagnosed with gynaecomastia and a known pre-existing risk factor (HR 1.75; 95% CI 1.64 to 1.86) compared with males with idiopathic gynaecomastia (HR 1.05; 95% CI 0.98 to 1.13). Specific causes of increased death were malignant neoplasms and circulatory, pulmonary and gastrointestinal diseases. Of the latter, an over fivefold risk of death from liver disease was detected (HR 5.05; 95% CI 3.97 to 6.42). CONCLUSIONS: Males diagnosed with gynaecomastia are at higher risk of death, observed mainly in males with a known pre-existing risk factor of gynaecomastia. These findings will hopefully stimulate more awareness among healthcare providers to potentially apply interventions that aid in alleviating underlying risk factors in males with this condition.

Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case-control study.

Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.

Risk of Fracture After Bilateral Oophorectomy.

Fragility fractures, resulting from low-energy trauma, occur in approximately 1 in 10 Danish women aged 50 years or older. Bilateral oophorectomy (surgical removal of both ovaries) may increase the risk of fragility fractures due to loss of ovarian sex steroids, particularly estrogen. We investigated the association between bilateral oophorectomy and risk of fragility fracture and whether this was conditional on age at time of bilateral oophorectomy, hormone therapy (HT) use, hysterectomy, physical activity level, body mass index (BMI), or smoking. We performed a cohort study of 25,853 female nurses (≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from age 50 years or entry into the cohort, whichever came last, until date of first fragility fracture, death, emigration, or end of follow-up on December 31, 2018, whichever came first. Cox regression models with age as the underlying time scale were used to estimate the association between time-varying bilateral oophorectomy (all ages, <51/≥51 years) and incident fragility fracture (any and site-specific [forearm, hip, spine, and other]). Exposure and outcome were ascertained from nationwide patient registries. During 491,626 person-years of follow-up, 6600 nurses (25.5%) with incident fragility fractures were identified, and 1938 (7.5%) nurses had a bilateral oophorectomy. The frequency of fragility fractures was 24.1% in nurses who were <51 years at time of bilateral oophorectomy and 18.1% in nurses who were ≥51 years. No statistically significant associations were observed between bilateral oophorectomy at any age and fragility fractures at any site. Neither HT use, hysterectomy, physical activity level, BMI, nor smoking altered the results. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Maternal Exposure to Cigarette Smoke during Pregnancy and Testicular Cancer in Offspring: A Systematic Review and Meta-Analysis.

BACKGROUND: Maternal exposure to cigarette smoke in pregnancy may play a role in the development of testicular cancer in offspring. An updated and comprehensive systematic review of the available evidence is needed. OBJECTIVE: To identify and evaluate current evidence on maternal exposure to cigarette smoke during pregnancy and testicular cancer in offspring. METHODS: A systematic search of English peer-reviewed original literature in PubMed through a block search approach. Publications were considered if assessing maternal exposure to cigarette smoke and the risk of testicular cancer in offspring. RESULTS: Among the 636 identified records, 14 publications were eligible for review and 10 for meta-analysis. Quality assessment of the publications was conducted. Most included publications were case-control studies (n = 11, 79%), while the remaining were ecological studies (n = 3, 21%). Completeness of reporting was high, but more than half were considered subject to potential bias. The trend synthesis showed that half (n = 7) of the included publications demonstrated a higher risk of testicular cancer in the sons of mothers exposed to cigarette smoke during pregnancy. The meta-analysis generated an overall summary risk estimate of 1.00 (95% CI: 0.88; 1.15) (n = 10 publications), with a lower risk for seminoma (0.79, 95% CI: 0.59; 1.04) and nonseminoma (0.96, 95% CI: 0.74; 1.26) (n = 4 publications). CONCLUSIONS: This systematic review did not provide evidence of an association between maternal exposure to cigarette smoke and risk of testicular cancer in offspring. An overall positive trend was suggested, but it had low statistical precision. The methodological limitations across publications encourage further research based on valid exposure data.

Increased Morbidity in Males Diagnosed With Gynecomastia: A Nationwide Register-based Cohort Study.

CONTEXT: Evidence on the long-term and general health of males with gynecomastia is lacking. OBJECTIVES: To assess health before and following a diagnosis of gynecomastia. METHODS: A register-based cohort study of 140 574 males, of which 23 429 were diagnosed with incident gynecomastia and age- and calendar-matched (1:5) to 117 145 males without gynecomastia from the background population. Males with gynecomastia were stratified into males without (idiopathic) or with a known preexisting risk factor (disease/medication). Cox and logistic regression models investigated associations of disease risk according to International Classification of Diseases 10th revision sections following and before gynecomastia diagnosis. RESULTS: A total of 16 253 (69.4%) males in the cohort were identified with idiopathic gynecomastia. These males had a statistically significant higher risk of future disease across all included disease chapters (hazard ratio [HR], 1.19-1.89), with endocrine diseases representing the greatest disease risk (HR, 1.89; 95% CI, 1.76-2.03). The highest subchapter disease risk was observed for disorders of the endocrine glands (odds ratio [OR], 7.27; 95% CI, 6.19-8.54). Similarly, the ORs of comorbidities were higher across all included disease sections (OR, 1.05-1.51), except for psychiatric disease (OR, 0.72; 95% CI, 0.68-0.78), with the highest association with musculoskeletal/connective tissue (OR, 1.51; 95% CI, 1.46-1.57) and circulatory (OR, 1.36; 95% CI, 1.29-1.43) diseases. CONCLUSIONS: The presence of idiopathic gynecomastia is an important first clinical symptom of an underlying disease and a significant predictor of future disease risk. These findings should stimulate more awareness among health care providers to increase identification of gynecomastia and its causes in males.

Maternal Serum α-Fetoprotein Levels during Pregnancy and Testicular Cancer in Male Offspring: A Cohort Study within a Danish Pregnancy Screening Registry.

Testicular cancer is believed to originate from disruptions of normal androgen-estrogen balance in-utero. α-fetoprotein (AFP) may modify fetal response to estrogens via estrogen interaction. In a cohort study, we investigated the association between circulating maternal pregnancy AFP and testicular cancer risk in offspring. Of the 56,709 live-born males from a pregnancy screening registry in 1980-1995, our study included 50,519 singleton males with available second trimester blood samples from their mothers and complete covariate ascertainment. Testicular cancer diagnoses and covariate data were obtained from nationwide Danish health registries. Cox regression and Kaplan-Meier analyses estimated the prospective risk of testicular cancer (all, seminoma, nonseminoma) by AFP multiples of the median. During follow-up, 163 (0.3%) of the included males developed testicular cancer, of which 89 (54.6%) were nonseminomas. Maternal serum AFP levels greater than/equal to the median were associated with a relative risk of testicular cancer close to unity (RR 1.04, 95% CI 0.76; 1.41) compared to AFP below the median. Associations differed by type of testicular cancer (RRseminoma 0.81, 95% CI 0.51; 1.29, RRnonseminoma 1.31, 95% CI 0.85; 2.02). On balance, our findings do not support that serum AFP in pregnancy can be used as a predictor of testicular cancer in offspring.

Bilateral oophorectomy and rate of colorectal cancer: A prospective cohort study.

Worldwide, colorectal cancer is the second most common cancer and third cause of cancer death in women. Estrogen exposure has been inversely associated with colorectal cancer. Oophorectomy reduces circulating estrogen, but the effect on colorectal cancer remains uncertain. The aim of this study was to examine the association between unilateral and bilateral oophorectomy and subsequent risk of colorectal cancer, and whether this association varied by menopausal status at time of oophorectomy, use of hormone replacement therapy (HRT) at baseline, hysterectomy and baseline body mass index (BMI). The study included 25 698 female nurses (aged ≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from baseline until date of colorectal cancer, death, emigration or end of follow-up at December 31, 2018, whichever came first. We examined the association between oophorectomy and colorectal cancer (all ages and stratified by menopausal status). The potential modifying effects of hysterectomy, HRT use at baseline and BMI were investigated. During 542 140 person-years of follow-up, 863 (3.4%) nurses were diagnosed with colorectal cancer. Bilateral oophorectomy was associated with a 79% increased colorectal cancer rate, adjusted rate ratio (aRR) (95% confidence interval [CI]): 1.79 (1.33-2.42). Effect estimates following unilateral oophorectomy also showed higher rate of colorectal cancer, although less pronounced and nonstatistically significant (aRR) (95% CI): 1.25 (0.86-1.82). Similar results were seen when stratifying by menopausal status. The association was not modified by baseline HRT use, hysterectomy or BMI. Oophorectomy was associated with increased rate of colorectal cancer, with highest rates among women with bilateral oophorectomy.

Environmental factors in declining human fertility.

A severe decline in child births has occurred over the past half century, which will lead to considerable population declines, particularly in industrialized regions. A crucial question is whether this decline can be explained by economic and behavioural factors alone, as suggested by demographic reports, or to what degree biological factors are also involved. Here, we discuss data suggesting that human reproductive health is deteriorating in industrialized regions. Widespread infertility and the need for assisted reproduction due to poor semen quality and/or oocyte failure are now major health issues. Other indicators of declining reproductive health include a worldwide increasing incidence in testicular cancer among young men and alterations in twinning frequency. There is also evidence of a parallel decline in rates of legal abortions, revealing a deterioration in total conception rates. Subtle alterations in fertility rates were already visible around 1900, and most industrialized regions now have rates below levels required to sustain their populations. We hypothesize that these reproductive health problems are partially linked to increasing human exposures to chemicals originating directly or indirectly from fossil fuels. If the current infertility epidemic is indeed linked to such exposures, decisive regulatory action underpinned by unconventional, interdisciplinary research collaborations will be needed to reverse the trends.

Endocrine Disrupting Chemicals and Risk of Testicular Cancer: A Systematic Review and Meta-analysis.

The incidence of many hormone-dependent diseases, including testicular cancer, has sharply increased in all high-income countries during the 20th century. This is not fully explained by established risk factors. Concurrent, increasing exposure to antiandrogenic environmental endocrine disrupting chemicals (EDCs) in fetal life may partially explain this trend. This systematic review assessed available evidence regarding the association between environmental EDC exposure and risk of testicular cancer (seminomas and nonseminomas). Following PRISMA guidelines, a search of English peer-reviewed literature published prior to December 14, 2020 in the databases PubMed and Embase® was performed. Among the 279 identified records, 19 were eligible for quality assessment and 10 for further meta-analysis. The completeness of reporting was high across papers, but over 50% were considered subject to potential risk of bias. Mean age at diagnosis was 31.9 years. None considered effects of EDC multipollutant mixtures. The meta-analyses showed that maternal exposure to combined EDCs was associated with a higher risk of testicular cancer in male offspring [summary risk ratios: 2.16, (95% CI:1.78-2.62), 1.93 (95% CI:1.49-2.48), and 2.78 (95% CI:2.27-3.41) for all, seminoma, and nonseminoma, respectively]. Similarly, high maternal exposures to grouped organochlorines and organohalogens were associated with higher risk of seminoma and nonseminoma in the offspring. Summary estimates related to postnatal adult male EDC exposures were inconsistent. Maternal, but not postnatal adult male, EDC exposures were consistently associated with a higher risk of testicular cancer, particularly risk of nonseminomas. However, the quality of studies was mixed, and considering the fields complexity, more prospective studies of prenatal EDC multipollutant mixture exposures and testicular cancer are needed.

Breast cancer rate after oophorectomy: A Prospective Danish Cohort Study.

The association between oophorectomy and risk of breast cancer in the general population is uncertain. The aim of our study was to determine the breast cancer rate in women from the general population after oophorectomy (performed before/after menopause), and whether this varies by use of hormone replacement therapy (HRT), hysterectomy, body mass index (BMI) and shift work. The study included 24 409 female nurses (aged ≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from cohort entry until date of breast cancer, death, emigration or end of follow-up at 31 December 2018, whichever came first. Poisson regression with log-transformed person-years as the offset examined the association between oophorectomy and breast cancer (all ages and stratified by menopausal status at time of oophorectomy). The potential modifying effect of HRT use, hysterectomy, BMI and shift work on the associations was estimated. During 502 463 person-years of follow-up, 1975 (8.1%) nurses were diagnosed with breast cancer. Bilateral oophorectomy was associated with a reduced breast cancer rate compared to nurses with preserved ovaries, adjusted rate ratio (95% confidence interval): 0.79 (0.64; 0.99). Similar associations (magnitude and direction) were detected for unilateral oophorectomy and when stratifying according to menopausal status at time of oophorectomy, but without statistical significance. Unilateral and bilateral oophorectomy is associated with a reduced breast cancer rate in women from the general population. This association is not modified by use of HRT, hysterectomy, BMI or shift work.

Sex-dependent associations between maternal prenatal stressful life events, BMI trajectories and obesity risk in offspring: The Raine Study.

Background: There is a high and growing prevalence of childhood obesity which increases the risk of adult obesity and adverse physical and mental health outcomes in adulthood. Experimental and clinical data suggest that the early life environment, particularly prenatal stress, may program development of obesity in the offspring. But few studies have assessed the associations between prenatal maternal stress and rapid (ascending) weight gain, which is the strongest predictor of adult obesity and metabolic disease. Experimental data indicate that the associations may be sex dependent, but the sex-dependent association between prenatal stress and growth in the human offspring during childhood and adolescence is largely unexplored. The aim of this study is to investigate the association between prenatal exposure to stressful life events and childhood obesity in the offspring and whether maternal smoking during pregnancy and breastfeeding mediate this. Method: Participants from a large prospective population-based Australian pregnancy cohort study (The Raine Study, n=2868) were closely and frequently followed from prenatal life (18 weeks gestation) through to adolescence. Maternal stressful life events were prospectively recorded at 18 and 34 weeks and childhood BMI (categorized into six z-score trajectories) was measured from 3 to age 14 years. We studied the prospective association between maternal exposure to stressful life events and BMI z-score trajectories in 2056 offspring (1082 boys). Mothers prospectively reported stressful life events at 18- and 34-weeks' gestation using a standardized and validated 10-point questionnaire. Age- and gender-specific z-scores for BMI were obtained from height and weight at age 3, 5, 8, 10 and 14 years using standardized methods. Latent class group analysis identified six distinct trajectory classes of BMI z-score. Multinomial logistic regression was used to examine the associations between maternal stressful life events and gender-specific BMI z-score trajectories as well as risk of overweight/obesity at each age point. Mediation analyses were also conducted to model the indirect associations through maternal smoking during pregnancy and breastfeeding. Results: Of the 2056-included offspring, 1322 (64.3%) were exposed to at least one maternal stressful life event during early gestation and 1203 (58.5%) were exposed in late gestation. In boys, exposure to stressful life events in early but not late gestation was significantly associated with ascending (accelerated) weight-gain (ages 3-14 years) (adjusted odds ratio (aOR): 1.25, 95% CI: 1.02, 1.52) and increased risk of overweight (aOR: 1.18, 95% CI: 1.00, 1.39) aged 10 years. No similar associations were observed in girls. We observed that 29.2% of the association between more maternal stressful life events and obesity in male offspring was mediated by breastfeeding for less than 6 months. Likewise, up to 35% of the association between more maternal stressful life events and obesity in male offspring was mediated by maternal smoking during the index pregnancy. Conclusion: Prenatal stress in early gestation is directly associated with accelerated childhood weight gain (assessed by childhood BMI z-score trajectories) and risk of obesity in adolescent boys, but not girls and breastfeeding and maternal smoking significantly mediates this association.

Marked Increase in Incident Gynecomastia: A 20-Year National Registry Study, 1998 to 2017.

CONTEXT: Gynecomastia, the proliferation of mammary glandular tissue in the male, is a frequent but little-studied condition. Available prevalence data are based on selected patient populations or autopsy cases with their inherent bias. OBJECTIVE: The objective of this work is to evaluate the age-related incidence and secular trends in gynecomastia in the general population. DESIGN: An observational, 20-year national registry study was conducted. SETTING: This population-based study used nationwide registry data. PARTICIPANTS: Participants included all Danish males (age 0-80 years) with a first-time diagnosis of gynecomastia. MAIN OUTCOME MEASURES: All Danish males (age 0-80 years) were followed up for incident diagnosis of gynecomastia in the Danish National Patient Registry from 1998 to 2017 using the International Codes of Diseases, 10th revision, and the Danish Health Care Classification System. Age-specific incidence rates were estimated. The hypothesis tested in this study was formulated prior to data collection. RESULTS: Overall, a total 17 601 males (age 0-80 years) were registered with an incident diagnosis of gynecomastia within the 20-year study period, corresponding to 880 new cases per year and an average 20-year incidence of 3.4 per 10 000 men (age 0-80 years). The average annual incidence was 6.5/10 000 in postpubertal males age 16 to 20 years and 4.6/10 000 in males age 61 to 80 years, with a respective 5- and 11-fold overall increase in these 2 age groups over the 20-year period. CONCLUSIONS: The incidence of gynecomastia has dramatically increased over the last 20 years, implying that the endogenous or exogenous sex-steroid environment has changed, which is associated with other adverse health consequences in men such as an increased risk of prostate cancer, metabolic syndrome, type 2 diabetes, or cardiovascular disorders.

Weight affects survival of primary total knee arthroplasty: study based on the Danish Knee Arthroplasty Register with 67,810 patients and a median follow-up time of 5 years.

Background and purpose - Obesity is a rising issue worldwide and growing evidence supports poor outcome amongst obese patients following total knee arthroplasty (TKA). Using nationwide registries we investigated the association between bodyweight and risk of revision of primary TKA. Patients and methods - All primary TKA performed during 1997-2015, weight at time of primary TKA and subsequent TKA revisions were identified in the Danish Knee Arthroplasty Register (DKR). Data on comorbidities and a priori selected confounding variables were collected from nationwide registries. The association between weight and 1st time TKA revision was calculated as both crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) using Cox regression. Results - Of 67,810 identified primary TKAs, 4.8% were revised within a median follow-up time of 5.4 years. No association between weight and risk of any revision in patients aged 18-54 and 55-70 years was found. Increased risk of any revision was seen in patients >70 years, 80-89 kg (aHR =1.5, CI 1.2-1.8), 90-99 kg (aHR =1.7, CI 1.3-2.1) and patients >99 kg (aHR =1.6, CI 1.3-2.1), as well as those weighing 45-60 kg (aHR =1.4, CI 1.1-1.9) compared with same aged patients weighing 70-79 kg. Interpretation - We found a complex association between weight and knee arthroplasty survival. There was an increased risk of any revision in patients older than 70 years of age weighing <60 kg and >80 kg. Patients aged 18-55 years weighing 60-69 kg had a lower risk of revision compared with all other weight groups, whereas weight was not found to affect risk of any revision in patients aged 55-70 years.

The Danish National Database for Asthma: establishing clinical quality indicators.

Asthma is one of the most common chronic diseases worldwide affecting more than 300 million people. Symptoms are often non-specific and include coughing, wheezing, chest tightness, and shortness of breath. Asthma may be highly variable within the same individual over time. Although asthma results in death only in extreme cases, the disease is associated with significant morbidity, reduced quality of life, increased absenteeism, and large costs for society. Asthma can be diagnosed based on report of characteristic symptoms and/or the use of several different diagnostic tests. However, there is currently no gold standard for making a diagnosis, and some degree of misclassification and inter-observer variation can be expected. This may lead to local and regional differences in the treatment, monitoring, and follow-up of the patients. The Danish National Database for Asthma (DNDA) is slated to be established with the overall aim of collecting data on all patients treated for asthma in Denmark and systematically monitoring the treatment quality and disease management in both primary and secondary care facilities across the country. The DNDA links information from population-based disease registers in Denmark, including the National Patient Register, the National Prescription Registry, and the National Health Insurance Services register, and potentially includes all asthma patients in Denmark. The following quality indicators have been selected to monitor trends: first, conduction of annual asthma control visits, appropriate pharmacological treatment, measurement of lung function, and asthma challenge testing; second, tools used for diagnosis in new cases; and third, annual assessment of smoking status, height, and weight measurements, and the proportion of patients with acute hospital treatment. The DNDA will be launched in 2016 and will initially include patients treated in secondary care facilities in Denmark. In the nearby future, the database aims to include asthma diagnosis codes and clinical data registered by general practitioners and specialised practitioners as well.

Distance to high-voltage power lines and risk of childhood leukemia--an analysis of confounding by and interaction with other potential risk factors.

We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters the association between distance to nearest power line and childhood leukemia. We included 1024 cases aged <15, diagnosed with leukemia during 1968-1991, from the Danish Cancer Registry and 2048 controls randomly selected from the Danish childhood population and individually matched by gender and year of birth. We used geographical information systems to determine the distance between residence at birth and the nearest 132-400 kV overhead power line. Concentrations of domestic radon and traffic-related air pollution (NOx at the front door) were estimated using validated models. We found a statistically significant interaction between distance to nearest power line and domestic radon regarding risk of childhood leukemia (p = 0.01) when using the median radon level as cut-off point but not when using the 75th percentile (p = 0.90). We found no evidence of an interaction between distance to nearest power line and traffic-related air pollution (p = 0.73). We found almost no change in the estimated association between distance to power line and risk of childhood leukemia when adjusting for socioeconomic status of the municipality, urbanization, maternal age, birth order, domestic radon and traffic-related air pollution. The statistically significant interaction between distance to nearest power line and domestic radon was based on few exposed cases and controls and sensitive to the choice of exposure categorization and might, therefore, be due to chance.

Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women.

Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.

Residential radon and brain tumour incidence in a Danish cohort.

BACKGROUND: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. OBJECTIVE: To investigate the long-term effect of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. METHODS: During 1993-1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced residential addresses from 1 January 1971 until 31 December 2009 and calculated radon concentrations at each address using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and 95% confidence intervals (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed. RESULTS: Median estimated radon was 40.5 Bq/m(3). The adjusted IRR for primary brain tumour associated with each 100 Bq/m(3) increment in average residential radon levels was 1.96 (95% CI: 1.07; 3.58) and this was exposure-dependently higher over the four radon exposure quartiles. This association was not modified by air pollution. CONCLUSIONS: We found significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies.

Residential radon and lung cancer incidence in a Danish cohort.

High-level occupational radon exposure is an established risk factor for lung cancer. We assessed the long-term association between residential radon and lung cancer risk using a prospective Danish cohort using 57,053 persons recruited during 1993-1997. We followed each cohort member for cancer occurrence until 27 June 2006, identifying 589 lung cancer cases. We traced residential addresses from 1 January 1971 until 27 June 2006 and calculated radon at each of these addresses using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for lung cancer risk associated with residential radon exposure with and without adjustment for sex, smoking variables, education, socio-economic status, occupation, body mass index, air pollution and consumption of fruit and alcohol. Potential effect modification by sex, traffic-related air pollution and environmental tobacco smoke was assessed. Median estimated radon was 35.8 Bq/m(3). The adjusted IRR for lung cancer was 1.04 (95% CI: 0.69-1.56) in association with a 100 Bq/m(3) higher radon concentration and 1.67 (95% CI: 0.69-4.04) among non-smokers. We found no evidence of effect modification. We find a positive association between radon and lung cancer risk consistent with previous studies but the role of chance cannot be excluded as these associations were not statistically significant. Our results provide valuable information at the low-level radon dose range.

Predictors of adipose tissue concentrations of organochlorine pesticides in a general Danish population.

Organochlorine pesticides are ubiquitously present in the environment and suspected of carcinogenic, neurological and immunological effects. Our objective was to identify determinants of adipose tissue levels of organochlorine pesticides experienced by a general Danish population. Adipose tissue was collected upon enrolment of 245 randomly selected persons from a prospective cohort of 57,053 persons enrolled between 1993 and 1997. We examined geography, gender, age, lactation, body mass index (BMI) and intake of nine dietary groups and tap water drinks, as potential determinants of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene, hexachlorocyclohexane, dieldrin, hexachlorobenzene, cis-nonachlor, trans-nonachlor and oxychlordane. Living in Copenhagen city and age at enrolment showed positive associations with all compounds. BMI was positively associated with all compounds except cis-nonachlor. Fatty-fish consumption showed positive associations with cis-nonachlor, trans-nonachlor, DDT and dieldrin and fruit and vegetables were inversely associated with dieldrin. Determinant estimates of trans-nonachlor were similar to estimates of total chlordanes while cis-nonachlor and oxychlordane seemed to differ. This is one of the first studies of organochlorine pesticides predictors in adipose tissue and contributes to the ongoing debate about exposure sources of these compounds. Single determinants varied among the individual compounds, even within related chlordane residues, suggesting that organochlorine pesticides should not be treated as a homogenous group.

Occurrence of organochlorine pesticides in indoor dust.

Organochlorine pesticides are present in the environment and suspected of causing serious health effects. Diet has been the main exposure source, but indoor source release is gaining focus. Within a monitoring study of polychlorinated biphenyls of Danish buildings built during the 1960s and 1970s, we coincidently determined extreme levels of dichlorodiphenyltrichloroethane (DDT) levels in two of ten random samples. This raises concern and further large scale investigations are warranted to confirm this.