Variations in chromosomes 9 and 6p21.3 with risk of non-hodgkin lymphoma

S. S. Wang, Idan Menashe, James R. Cerhan, Wendy Cozen, Richard K. Severson, Scott Davis, Amy Hutchinson, Nathaniel Rothman, Stephen J. Chanock, Leslie Bernstein, Patricia Hartge, Lindsay M. Morton

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)42-49
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume20
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

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Chromosomes, Human, Pair 9
Non-Hodgkin's Lymphoma
Single Nucleotide Polymorphism
Genes
Logistic Models
Follicular Lymphoma
Population Control
Lymphoma, Large B-Cell, Diffuse
Haplotypes
Case-Control Studies
Chromosomes
Genotype

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Wang, S. S., Menashe, I., Cerhan, J. R., Cozen, W., Severson, R. K., Davis, S., ... Morton, L. M. (2011). Variations in chromosomes 9 and 6p21.3 with risk of non-hodgkin lymphoma. Cancer Epidemiology Biomarkers and Prevention, 20(1), 42-49. https://doi.org/10.1158/1055-9965.EPI-10-0638

Variations in chromosomes 9 and 6p21.3 with risk of non-hodgkin lymphoma. / Wang, S. S.; Menashe, Idan; Cerhan, James R.; Cozen, Wendy; Severson, Richard K.; Davis, Scott; Hutchinson, Amy; Rothman, Nathaniel; Chanock, Stephen J.; Bernstein, Leslie; Hartge, Patricia; Morton, Lindsay M.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 1, 01.2011, p. 42-49.

Research output: Contribution to journalArticle

Wang, SS, Menashe, I, Cerhan, JR, Cozen, W, Severson, RK, Davis, S, Hutchinson, A, Rothman, N, Chanock, SJ, Bernstein, L, Hartge, P & Morton, LM 2011, 'Variations in chromosomes 9 and 6p21.3 with risk of non-hodgkin lymphoma', Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 1, pp. 42-49. https://doi.org/10.1158/1055-9965.EPI-10-0638
Wang, S. S. ; Menashe, Idan ; Cerhan, James R. ; Cozen, Wendy ; Severson, Richard K. ; Davis, Scott ; Hutchinson, Amy ; Rothman, Nathaniel ; Chanock, Stephen J. ; Bernstein, Leslie ; Hartge, Patricia ; Morton, Lindsay M. / Variations in chromosomes 9 and 6p21.3 with risk of non-hodgkin lymphoma. In: Cancer Epidemiology Biomarkers and Prevention. 2011 ; Vol. 20, No. 1. pp. 42-49.
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AU - Wang, S. S.

AU - Menashe, Idan

AU - Cerhan, James R.

AU - Cozen, Wendy

AU - Severson, Richard K.

AU - Davis, Scott

AU - Hutchinson, Amy

AU - Rothman, Nathaniel

AU - Chanock, Stephen J.

AU - Bernstein, Leslie

AU - Hartge, Patricia

AU - Morton, Lindsay M.

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N2 - 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.

AB - 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.

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