title: N-acetyltransferase polymorphisms are associated with risk of lymphoma subtypes.
abstract: Genes encoding for arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) have been investigated with alternate findings in relation to risk of non-Hodgkin lymphoma (NHL). We tested functional haplotype-based NAT1 and NAT2 gene polymorphisms in relation to risk of lymphoma overall and its major B cell subtypes, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). We used allele specific primers and multiplex PCR to detect NAT1 and NAT2 haplotypes in 248 patients with incident lymphoma and 208 population controls. We inferred the NAT1 rapid and slow acetylator and the NAT2 rapid, intermediate or slow acetylator phenotype, based on published functional data on the respective genotypes. Odds ratios and 95% confidence intervals (95% CIs) for lymphoma, B-NHL, DLBCL, FL, CLL, and other B-NHL combined associated with the inferred rapid NAT1 acetylator and with the intermediate and slow NAT2 acetylator phenotypes were estimated with unconditional and polytomous logistic regression analysis, adjusting for age, gender and education. NAT1 rapid acetylators showed a 2.8-fold excess risk (95% CI 1.5-5.2) for lymphoma (all subtypes combined). Risk was highest for CLL and FL, with significant heterogeneity detected across subtypes. Risk also increased with decreasing NAT2 acetylating capacity with no heterogeneity detected across B cell lymphoma subtypes. Risks did not vary by gender. Although poor statistical power was a major limitation in our study, larger studies and pooled analyses are warranted to test whether NAT1 and NAT2 gene polymorphisms might modulate risk of specific lymphoma subtypes through the varying metabolic activity of their products. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, Occupational Health Section, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Pierluigi
authors.identifier: http://orcid.org/0000-0001-8256-7614
authors.initials: P
authors.lastname: Cocco
authors.affiliation: Department of Biomedical Sciences, Cytomorphology Section, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Zucca
authors.affiliation: Department of Biomedical Sciences, Cytomorphology Section, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Sanna
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, Occupational Health Section, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Giannina
authors.initials: G
authors.lastname: Satta
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, Occupational Health Section, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Tinucia
authors.initials: T
authors.lastname: Nonne
authors.affiliation: Unit of Haematology, A. Businco Oncology Hospital, Cagliari, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Angelucci
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, Occupational Health Section, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Gabbas
authors.affiliation: Cagliari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rais
authors.affiliation: ARC-NET Research Centre and Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Malpeli
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, Occupational Health Section, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Campagna
authors.affiliation: ARC-NET Research Centre and Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Department of Biomedical Sciences, Cytomorphology Section, University of Cagliari, Monserrato, Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: G Ennas
mesh_terms: D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000201:enzymology / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D007527:Isoenzymes; D009363:Neoplasm Proteins; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human
keywords: N-acetyltransferase; gene-environment interaction; lymphomas; molecular epidemiology