title: Genome-wide homozygosity signature and risk of Hodgkin lymphoma.
abstract: Recent studies have reported that regions of homozygosity (ROH) in the genome are detectable in outbred populations and can be associated with an increased risk of malignancy. To examine whether homozygosity is associated with an increased risk of developing Hodgkin lymphoma (HL) we analysed 589 HL cases and 5,199 controls genotyped for 484,072 tag single nucleotide polymorphisms (SNPs). Across the genome the cumulative distribution of ROH was not significantly different between cases and controls. Seven ROH at 4q22.3, 4q32.2, 7p12.3-14.1, 7p22.2, 10p11.22-23, 19q13.12-2 and 19p13.2 were associated with HL risk at P < 0.01. Intriguingly 4q22.3 harbours an ROH to which the nuclear factor NF-kappa-B p105 subunit (NFKB1) maps (P = 0.002). The ROH at 19q13.12-2 has previously been implicated in B-cell precursor acute lymphoblastic leukaemia. Aside from these observations which require validation, it is unlikely that levels of measured homozygosity caused by autozygosity, uniparental isodisomy or hemizygosity play a major role in defining HL risk in predominantly outbred populations.
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
authors.forename: Amit
authors.initials: A
authors.lastname: Sud
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
authors.forename: Rosie
authors.initials: R
authors.lastname: Cooke
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.|Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D005808:Genes, Recessive; D055106:Genome-Wide Association Study; D005838:Genotype; D006689:Hodgkin Disease / Q000453:epidemiology* / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology