Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

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 lympho...

Source: Human Molecular Genetics - March 22, 2016 Category: Genetics & Stem Cells Authors: Machiela, M. J., Lan, Q., Slager, S. L., Vermeulen, R. C. H., Teras, L. R., Camp, N. J., Cerhan, J. R., Spinelli, J. J., Wang, S. S., Nieters, A., Vijai, J., Yeager, M., Wang, Z., Ghesquieres, H., McKay, J., Conde, L., de Bakker, P. I. W., Cox, D. G., Bur Tags: ASSOCIATION STUDIES ARTICLE Source Type: research