Browsing by Author "Skytthe, Axel"

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    Cancer and longevity--is there a trade-off? A study of cooccurrence in Danish twin pairs born 1900-1918.
    (J Gerontol A Biol Sci Med Sci, 2012-05) Christensen, Kaare; Pedersen, Jacob K; Hjelmborg, Jacob VB; Vaupel, James W; Stevnsner, Tinna; Holm, Niels V; Skytthe, Axel
    BACKGROUND: Animal models and a few human studies have suggested a complex interaction between cancer risk and longevity indicating a trade-off where low cancer risk is associated with accelerating aging phenotypes and, vice versa, that longevity potential comes with the cost of increased cancer risk. This hypothesis predicts that longevity in one twin is associated with increased cancer risk in the cotwin. METHODS: A total of 4,354 twin pairs born 1900-1918 in Denmark were followed for mortality in the Danish Civil Registration System through 2008 and for cancer incidence in the period 1943-2008 through the Danish Cancer Registry. RESULTS: The 8,139 twins who provided risk time for cancer occurrence entered the study between ages 24 and 43 (mean 33 years), and each participant was followed up to death, emigration, or at least 90 years of age. The total follow-up time was 353,410 person-years and, 2,524 cancers were diagnosed. A negative association between age at death of a twin and cancer incidence in the cotwin was found in the overall analyses as well as in the subanalysis stratified on sex, zygosity, and random selection of one twin from each twin pair. CONCLUSIONS: This study did not find evidence of a cancer-longevity trade-off in humans. On the contrary, it suggested that longevity in one twin is associated with lower cancer incidence in the cotwin, indicating familial factors associated with both low cancer occurrence and longevity.
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    Cohort Profile: The 1895, 1905, 1910 and 1915 Danish Birth Cohort Studies - secular trends in the health and functioning of the very old.
    (Int J Epidemiol, 2017-04-22) Rasmussen, Signe Høi; Andersen-Ranberg, Karen; Thinggaard, Mikael; Jeune, Bernard; Skytthe, Axel; Christiansen, Lene; Vaupel, James W; McGue, Matt; Christensen, Kaare
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    Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study.
    (Aging Cell, 2013-04) Beekman, Marian; Blanché, Hélène; Perola, Markus; Hervonen, Anti; Bezrukov, Vladyslav; Sikora, Ewa; Flachsbart, Friederike; Christiansen, Lene; De Craen, Anton JM; Kirkwood, Tom BL; Rea, Irene Maeve; Poulain, Michel; Robine, Jean-Marie; Valensin, Silvana; Stazi, Maria Antonietta; Passarino, Giuseppe; Deiana, Luca; Gonos, Efstathios S; Paternoster, Lavinia; Sørensen, Thorkild IA; Tan, Qihua; Helmer, Quinta; van den Akker, Erik B; Deelen, Joris; Martella, Francesca; Cordell, Heather J; Ayers, Kristin L; Vaupel, James W; Törnwall, Outi; Johnson, Thomas E; Schreiber, Stefan; Lathrop, Mark; Skytthe, Axel; Westendorp, Rudi GJ; Christensen, Kaare; Gampe, Jutta; Nebel, Almut; Houwing-Duistermaat, Jeanine J; Slagboom, Pieternella Eline; Franceschi, Claudio; GEHA consortium
    Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10(-8) ). By combined modeling of linkage and association, we showed that association of longevity with APOEε4 and APOEε2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10(-5) , respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.
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    Low tobacco-related cancer incidence in offspring of long-lived siblings: a comparison with Danish national cancer registry data.
    (Ann Epidemiol, 2015-08) Pedersen, Jacob K; Skytthe, Axel; McGue, Matt; Honig, Lawrence S; Franceschi, Claudio; Kirkwood, Thomas BL; Passarino, Giuseppe; Slagboom, P Eline; Vaupel, James W; Christensen, Kaare
    PURPOSE: Familial clustering of longevity is well documented and includes both genetic and other familial factors, but the specific underlying mechanisms are largely unknown. We examined whether low incidence of specific cancers is a mechanism for familial clustering of longevity. METHODS: The study population of individuals from longevity-enriched families consisted of 3267 offspring from 610 Danish long-lived families defined by two siblings attaining an age of 90 years or more. The offspring of the long-lived siblings were followed from 1968 to 2009. Using high-quality registry data, observed numbers of cancers were compared with expected numbers based on gender-, calendar period-, and age-specific incidence rates in the general population. RESULTS: During the 41-year-follow-up period, a total of 423 cancers occurred in 397 individuals. The standardized incidence ratios (95% confidence interval) for offspring of long-lived individuals were 0.78 (0.70-0.86) for overall cancer; 0.66 (0.56-0.77) for tobacco-related cancer; 0.34 (0.22-0.51) for lung cancer; 0.88 (0.71-1.10) for breast cancer; 0.91 (0.62-1.34) for colon cancer. CONCLUSIONS: The low incidence of tobacco-related cancers in long-lived families compared with non-tobacco-related cancers suggests that health behavior plays a central role in lower early cancer incidence in offspring of long-lived siblings in Denmark.
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    The Danish Twin Registry: linking surveys, national registers, and biological information.
    (Twin Res Hum Genet, 2013-02) Skytthe, Axel; Christiansen, Lene; Kyvik, Kirsten Ohm; Bødker, Frans L; Hvidberg, Lars; Petersen, Inge; Nielsen, Morten MF; Bingley, Paul; Hjelmborg, Jacob; Tan, Qihua; Holm, Niels V; Vaupel, James W; McGue, Matt; Christensen, Kaare
    Over the last 60 years, the resources and the research in the Danish Twin Registry (DTR) have periodically been summarized. Here, we give a short overview of the DTR and a more comprehensive description of new developments in the twenty-first century. First, we outline our experience over the last decade of combining questionnaire and survey data with national demographic, social, and health registers in Statistics Denmark. Second, we describe our most recent data collection effort, which was conducted during the period 2008-2011 and included both in-person assessments of 14,000+ twins born 1931-1969 and sampling of biological material, hereby expanding and consolidating the DTR biobank. Third, two examples of intensively studied twin cohorts are given. The new developments in the DTR in the last decade have facilitated the ongoing research and laid the groundwork for new research directions.