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Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma.

Abstract

We found that regular use of aspirin may reduce the risk of Hodgkin lymphoma (HL), a common cancer of adolescents and young adults in the United States. To explore possible biological mechanisms underlying this association, we investigated whether polymorphic variation in genes involved in nuclear factor-kappaB (NF-kappaB) activation and inhibition, other inflammatory pathways, and aspirin metabolism influences HL risk. Twenty single nucleotide polymorphisms (SNP) in seven genes were genotyped in DNA from 473 classical HL cases and 373 controls enrolled between 1997 and 2000 in a population-based case-control study in the Boston, Massachusetts, metropolitan area and the state of Connecticut. We selected target genes and SNPs primarily using a candidate-SNP approach and estimated haplotypes using the expectation-maximization algorithm. We used multivariable logistic regression to estimate odds ratios (OR) for associations with HL risk. HL risk was significantly associated with rs1585215 in NFKB1 (AG versus AA: OR, 2.1; 95% confidence interval, 1.5-2.9; GG versus AA: OR, 3.5; 95% confidence interval, 2.2-5.7, Ptrend=1.7x10(-8)) and with NFKB1 haplotypes (Pglobal=6.0x10(-21)). Similar associations were apparent across categories of age, sex, tumor EBV status, tumor histology, and regular aspirin use, although statistical power was limited for stratified analyses. Nominally significant associations with HL risk were detected for SNPs in NFKBIA and CYP2C9. HL risk was not associated with SNPs in IKKA/CHUK, PTGS2/COX2, UDP1A6, or LTC4S. In conclusion, genetic variation in the NF-kappaB pathway seems to influence risk of HL. Pooled studies are needed to detect any heterogeneity in the association with NF-kappaB across HL subgroups, including aspirin users and nonusers.

Authors+Show Affiliations

Northern California Cancer Center, Fremont, CA 94538, USA. ellen@nccc.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19223558

Citation

Chang, Ellen T., et al. "Polymorphic Variation in NFKB1 and Other Aspirin-related Genes and Risk of Hodgkin Lymphoma." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 18, no. 3, 2009, pp. 976-86.
Chang ET, Birmann BM, Kasperzyk JL, et al. Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2009;18(3):976-86.
Chang, E. T., Birmann, B. M., Kasperzyk, J. L., Conti, D. V., Kraft, P., Ambinder, R. F., ... Mueller, N. E. (2009). Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 18(3), pp. 976-86. doi:10.1158/1055-9965.EPI-08-1130.
Chang ET, et al. Polymorphic Variation in NFKB1 and Other Aspirin-related Genes and Risk of Hodgkin Lymphoma. Cancer Epidemiol Biomarkers Prev. 2009;18(3):976-86. PubMed PMID: 19223558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma. AU - Chang,Ellen T, AU - Birmann,Brenda M, AU - Kasperzyk,Julie L, AU - Conti,David V, AU - Kraft,Peter, AU - Ambinder,Richard F, AU - Zheng,Tongzhang, AU - Mueller,Nancy E, Y1 - 2009/02/17/ PY - 2009/2/19/entrez PY - 2009/2/19/pubmed PY - 2009/4/17/medline SP - 976 EP - 86 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 18 IS - 3 N2 - We found that regular use of aspirin may reduce the risk of Hodgkin lymphoma (HL), a common cancer of adolescents and young adults in the United States. To explore possible biological mechanisms underlying this association, we investigated whether polymorphic variation in genes involved in nuclear factor-kappaB (NF-kappaB) activation and inhibition, other inflammatory pathways, and aspirin metabolism influences HL risk. Twenty single nucleotide polymorphisms (SNP) in seven genes were genotyped in DNA from 473 classical HL cases and 373 controls enrolled between 1997 and 2000 in a population-based case-control study in the Boston, Massachusetts, metropolitan area and the state of Connecticut. We selected target genes and SNPs primarily using a candidate-SNP approach and estimated haplotypes using the expectation-maximization algorithm. We used multivariable logistic regression to estimate odds ratios (OR) for associations with HL risk. HL risk was significantly associated with rs1585215 in NFKB1 (AG versus AA: OR, 2.1; 95% confidence interval, 1.5-2.9; GG versus AA: OR, 3.5; 95% confidence interval, 2.2-5.7, Ptrend=1.7x10(-8)) and with NFKB1 haplotypes (Pglobal=6.0x10(-21)). Similar associations were apparent across categories of age, sex, tumor EBV status, tumor histology, and regular aspirin use, although statistical power was limited for stratified analyses. Nominally significant associations with HL risk were detected for SNPs in NFKBIA and CYP2C9. HL risk was not associated with SNPs in IKKA/CHUK, PTGS2/COX2, UDP1A6, or LTC4S. In conclusion, genetic variation in the NF-kappaB pathway seems to influence risk of HL. Pooled studies are needed to detect any heterogeneity in the association with NF-kappaB across HL subgroups, including aspirin users and nonusers. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/19223558/Polymorphic_variation_in_NFKB1_and_other_aspirin_related_genes_and_risk_of_Hodgkin_lymphoma_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=19223558 DB - PRIME DP - Unbound Medicine ER -