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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA..
Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA..
Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
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2016 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, no 8, 1663-1676 p.Article in journal (Refereed) PublishedText
Abstract [en]

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

Place, publisher, year, edition, pages
2016. Vol. 25, no 8, 1663-1676 p.
National Category
Cancer and Oncology Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-297914DOI: 10.1093/hmg/ddw027ISI: 000374231400016PubMedID: 27008888OAI: oai:DiVA.org:uu-297914DiVA: diva2:944251
Funder
NIH (National Institute of Health)EU, European Research Council, QLK4-CT-2000-00422EU, European Research Council, FOOD-CT-2006-023103NIH (National Institute of Health), NO1-CO-12400NIH (National Institute of Health), K08CA134919 CA167552 CA149445 CA098122 CA098566 K07 CA115687 CA186107 CA87969 CA49449NIH (National Institute of Health), CA1046282 CA154643NIH (National Institute of Health), HHSN261201000026C
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De fem första författarna delar på förstaförfattarskapet.

De åtta sista författarna samarbetade kring ledning av arbetet.

Available from: 2016-06-29 Created: 2016-06-28 Last updated: 2016-06-29Bibliographically approved

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