title: Variations in chromosomes 9 and 6p21.3 with risk of non-Hodgkin lymphoma.
abstract: BACKGROUND
  There is growing evidence linking genetic variations to non-Hodgkin lymphoma (NHL) etiology. To complement ongoing agnostic approaches for identifying susceptibility genes, we evaluated 488 candidate gene regions and their relation to risk for NHL and NHL subtypes.
  
  
  METHODS
  We genotyped 6,679 tag single nucleotide polymorphisms (SNPs) in 947 cases and 826 population-based controls from a multicenter U.S. case-control study. Gene-level summary of associations were obtained by computing the minimum P value ("minP test") on the basis of 10,000 permutations. We used logistic regression to evaluate the association between genotypes and haplotypes with NHL. For NHL subtypes, we conducted polytomous multivariate unconditional logistic regression (adjusted for sex, race, age). We calculated P-trends under the codominant model for each SNP.
  
  
  RESULTS
  Fourteen gene regions were associated with NHL (P < 0.01). The most significant SNP associated with NHL maps to the SYK gene (rs2991216, P-trend = 0.00005). The three most significant gene regions were on chromosome 6p21.3 (RING1/RXRB; AIF1; BAT4). Accordingly, SNPs in RING1/RXRB (rs2855429), AIF1 (rs2857597), and BAT4 (rs3115667) were associated with NHL (P-trends ≤ 0.0002) and both diffuse large B-cell and follicular lymphomas (P-trends < 0.05).
  
  
  CONCLUSIONS
  Our results suggest potential importance for SYK on chromosome 9 with NHL etiology. Our results further implicate 6p21.3 gene variants, supporting the need for full characterization of this chromosomal region in relation to lymphomagenesis.
  
  
  CONCLUSIONS
  Gene variants on chromosome 9 may represent a new region of interesting for NHL etiology. The independence of the reported variants in 6p21.3 from implicated variants (TNF/HLA) supports the need to confirm causal variants in this region.
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute and City of Hope, 500 Duarte Road, Duarte, CA 9101, USA. sowang@coh.org
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Idan
authors.initials: I
authors.lastname: Menashe
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Richard K
authors.initials: RK
authors.lastname: Severson
authors.forename: Scott
authors.initials: S
authors.lastname: Davis
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult