Breast cancer risk in male twins: joint analyses of four twin cohorts in Denmark, Finland, Sweden and the United States

To test the hypothesis that in utero exposure to high levels of oestrogen increases the risk of male breast cancer, we followed 115 235 male twins for more than 3.5 million person-years at risk. We observed 11 cases of male breast cancer versus 16.16 expected based on national rates (standardized rate ratio 0.68, 95% confidence interval 0.34–1.22) and conclude that any adverse influence of in utero oestrogen exposure is likely to be small. © 2000 Cancer Research Campaig

Mechanisms underlying familial aggregation of exceptional health and survival: A three-generation cohort study

The familial resemblance in length of adult life is very modest. Studies of parent-offspring and twins suggest that exceptional health and survival have a stronger genetic component than lifespan generally. To shed light on the underlying mechanisms, we collected information on Danish long-lived siblings (born 1886-1938) from 659 families, their 5379 offspring (born 1917-1982), and 10,398 grandchildren (born 1950-2010) and matched background population controls through the Danish 1916 Census, the Civil Registration System, the National Patient Register, and the Register of Causes of Death. Comparison with the background, population revealed consistently lower occurrence of almost all disease groups and causes of death in the offspring and the grandchildren. The expected incidence of hospitalization for mental and behavioral disorders was reduced by half in the offspring (hazard ratio 0.53, 95% confidence interval 0.45-0.62) and by one-third in the grandchildren (0.69, 0.61-0.78), while the numbers for tobacco-related cancer were 0.60 (0.51-0.70) and 0.71 (0.48-1.05), respectively. Within-family analyses showed a general, as opposed to specific, lowering of disease risk. Early parenthood and divorce were markedly less frequent in the longevity-enriched families, while economic and educational differences were small to moderate. The longevity-enriched families in this study have a general health advantage spanning three generations. The particularly low occurrence of mental and behavioral disorders and tobacco-related cancers together with indicators of family stability and only modest socioeconomic advantage implicate behavior as a key mechanism underlying familial aggregation of exceptional health and survival

Twin Family Registries Worldwide : An Important Resource for Scientific Research

Much progress has been made in twin research since our last special issue on twin registries (Hur, Y.-M., & Craig, J. M. (2013). Twin Research and Human Genetics, 16, 1-12.). This special issue provides an update on the state of twin family registries around the world. This issue includes 61 papers on twin family registries from 25 countries, of which 3 describe consortia based on collaborations of several twin family registries. The articles included in this issue discuss the establishment and maintenance of twin registries, recruitment strategies, methods of zygosity assessment, research aims and major findings from twin family cohorts, as well as other important topics related to twin studies. The papers amount to approximately 1.3 million monozygotic, dizygotic twins and higher order multiples and their family members who participate in twin studies around the world. Nine new twin family registries have been established across the world since our last issue, which demonstrates that twin registers are increasingly important in studies of the determinants and correlates of complex traits from disease susceptibility to healthy development.Non peer reviewe

Increased Genetic Variance of BMI with a Higher Prevalence of Obesity

Peer reviewe

Lung cancer, genetic predisposition and smoking : the Nordic Twin Study of Cancer

Background We aimed to disentangle genetic and environmental causes in lung cancer while considering smoking status. Methods Four Nordic twin cohorts (43 512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had smoking data before cancer diagnosis. We used time-to-event analyses accounting for censoring and competing risk of death to estimate incidence, concordance risk and heritability of liability to develop lung cancer by smoking status. Results During a median of 28.5 years of follow-up, we recorded 1508 incident lung cancers. Of the 30 MZ and 28 DZ pairs concordant for lung cancer, nearly all were current smokers at baseline and only one concordant pair was seen among never smokers. Among ever smokers, the case-wise concordance of lung cancer, that is the risk before a certain age conditional on lung cancer in the co-twin before that age, was significantly increased compared with the cumulative incidence for both MZ and DZ pairs. This ratio, the relative recurrence risk, significantly decreased by age for MZ but was constant for DZ pairs. Heritability of lung cancer was 0.41 (95% CI 0.26 to 0.56) for currently smoking and 0.37 (95% CI 0.25 to 0.49) for ever smoking pairs. Among smoking discordant pairs, the pairwise HR for lung cancer of the ever smoker twin compared to the never smoker co-twin was 5.4 (95% CI 2.1 to 14.0) in MZ pairs and 5.0 (95% CI 3.2 to 7.9) in DZ pairs. Conclusions The contribution of familial effects appears to decrease by age. The discordant pair analysis confirms that smoking causes lung cancer.Peer reviewe

The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer

BACKGROUND: Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. METHODS: To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic and 30,054 dizygotic same sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability. RESULTS: The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability (heritability=58% (95% CI 52%–63%) of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary. CONCLUSIONS: Results from the population based twin cohort, indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age IMPACT: Findings impact the search for genetic and epigenetic markers and frame prevention efforts

Education Modifies Genetic and Environmental Influences on BMI

Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height2) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were −.13 in women, −.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity

Pain in the lumbar, thoracic or cervical regions: do age and gender matter? A population-based study of 34,902 Danish twins 20–71 years of age

Background. It is unclear to what extent spinal pain varies between genders and in relation to age. It was the purpose of this study to describe the self-reported prevalence of 1) pain ever and pain in the past year in each of the three spinal regions, 2) the duration of such pain over the past year, 3) pain radiating from these areas, and 4) pain in one, two or three areas. In addition, 5) to investigate if spinal pain reporting is affected by gender and 6) to see if it increases gradually with increasing age. Method. A cross-sectional survey was conducted in 2002 on 34,902 twin individuals, aged 20 to 71 years, representative of the general Danish population. Identical questions on pain were asked for the lumbar, thoracic and cervical regions. Results. Low back pain was most common, followed by neck pain with thoracic pain being least common. Pain for at least 30 days in the past year was reported by 12%, 10%, and 4%, respectively. The one-yr prevalence estimates of radiating pain were 22% (leg), 16% (arm), and 5% (chest). Pain in one area only last year was reported by 20%, followed by two (13%) and three areas (8%). Women were always more likely to report pain and they were also more likely to have had pain for longer periods. Lumbar and cervical pain peaked somewhat around the middle years but the curves were flatter for thoracic pain. Similar patterns were noted for radiating pain. Older people did not have pain in a larger number of areas but their pain lasted longer. Conclusion. Pain reported for and from the lumbar and cervical spines was found to be relatively common whereas pain in the thoracic spine and pain radiating into the chest was much less common. Women were, generally, more likely to report pain than men. The prevalence estimates changed surprisingly little over age and were certainly not more common in the oldest groups, although the pain was reported as more long-lasting in the older group