Nat2, Xrcc1 And Hogg1 Polymorphisms, Cigarette Smoking, Alcohol Consumption And Risk Of Upper Aerodigestive Tract Cancer

Aim: To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair crosscomplementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer. Patients and Methods: A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Results: Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among neverdrinkers (p=0.048). Conclusion: Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.34632173224Choong, N., Vokes, E., Expanding role of the medical oncologist in the management of head and neck cancer (2008) CA Cancer J, 58, pp. 32-53Kato, I., Nomura, A.M., Alcohol in the aetiology of upper aerodigestive tract cancer (1994) Eur J Cancer B Oral Oncol, 30 B, pp. 75-81Kato, I., Nomura, A.M., Stemmermann, G.N., Chyou, P.H., Prospective study of the association of alcohol with cancer of the upper aerodigestive tract and other sites (1992) Cancer Causes Control, 3, pp. 145-151Demokan, S., Suoglu, Y., Gozeler, M., Demir, D., Dalay, N., N-acetyltransferase 1 and 2 gene sequence variants and risk of head and neck cancer (2010) Mol Biol Rep, 37, pp. 3217-3226Hung, R.J., Hall, J., Brennan, P., Boffetta, P., Genetic polymorphisms in the base excision repair pathway and cancer risk: A HuGE review (2005) Am J Epidemiol, 162, pp. 925-942Badawi, A.F., Hirvonen, A., Bell, D.A., Lang, N.P., Kadlubar, F.F., Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder (1995) Cancer Res, 55, pp. 5230-5237Brockton, N., Little, J., Sharp, L., Cotton, S.C., N-acetyltransferase polymorphisms and colorectal cancer: A HuGE review (2000) Am J Epidemiol, 151, pp. 846-861Hein, D.W., Acetylator genotype and arylamine-induced carcinogenesis (1988) Biochim Biophys Acta, 948, pp. 37-66Hein, D.W., McQueen, C.A., Grant, D.M., Goodfellow, G.H., Kadlubar, F.F., Weber, W.W., Pharmacogenetics of the arylamine N-acetyltransferases: A symposium in honor of Wendell W (2000) Weber. Drug Metab Dispos, 28, pp. 1425-1432Cascorbi, I., Brockmoller, J., Mrozikiewicz, P.M., Bauer, S., Loddenkemper, R., Roots, I., Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer (1996) Cancer Res, 56, pp. 3961-3966Lu, A.L., Li, X., Gu, Y., Wright, P.M., Chang, D.Y., Repair of oxidative DNA damage: Mechanisms and functions (2001) Cell Biochem Biophys, 35, pp. 141-170Yi, L., Xiao-Feng, H., Yun-Tao, L., Hao, L., Ye, S., Song-Tao, Q., Association between the XRCC1 Arg399Gln polymorphism and risk of cancer: Evidence from 297 case-control studies (2013) PLoS One, 8, p. e78071Boiteux, S., Radicella, J.P., The human OGG1 gene: Structure, functions, and its implication in the process of carcinogenesis (2000) Arch Biochem Biophys, 377, pp. 1-8Kohno, T., Shinmura, K., Tosaka, M., Tani, M., Kim, S.R., Sugimura, H., Nohmi, T., Yokota, J., Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA (1998) Oncogene, 16, pp. 3219-3225Arizono, K., Osada, Y., Kuroda, Y., DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population (2008) Jpn J Clin Oncol, 38, pp. 186-191Bonilla, C., Shriver, M.D., Parra, E.J., Jones, A., Fernandez, J.R., Ancestral proportions and their association with skin pigmentation and bone mineral density in Puerto Rican women from New York city (2004) Hum Genet, 115, pp. 57-68(2008) R: R: A Language and Environment for Statistical Computing, , http://www.r-project.org/, Viena: R Development Core TeamExcoffier, L., Laval, G., Schneider, S., Arlequin (version 3.0): An integrated software package for population genetics data analysis (2005) Evol Bioinform Online, 1, pp. 47-50Talbot, J., Magno, L.A., Santana, C.V., Sousa, S.M., Melo, P.R., Correa, R.X., Di Pietro, G., Rios-Santos, F., Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations BMC Genetics, 11, p. 87Fuselli, S., Gilman, R.H., Chanock, S.J., Bonatto, S.L., De Stefano, G., Evans, C.A., Labuda, D., Tarazona-Santos, E., Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity (2007) The Pharmacogenomics Journal, 7, pp. 144-152Hein, D.W., N-acetyltransferase SNPs: Emerging concepts serve as a paradigm for understanding complexities of personalized medicine (2009) Expert Opinion on Drug Metabolism & Toxicology, 5, pp. 353-366Bendjemana, K., Abdennebi, M., Gara, S., Jmal, A., Ghanem, A., Touati, S., Boussen, H., Guemira, F., Genetic polymorphism of gluthation-S transferases and N-acetyl transferases 2 and nasopharyngeal carcinoma: The Tunisia experience (2006) Bull Cancer, 93, pp. 297-302. , (in French)Gajecka, M., Rydzanicz, M., Jaskula-Sztul, R., Kujawski, M., Szyfter, W., Szyfter, K., CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma (2005) Mutat Res, 574, pp. 112-123Hou, Y.Y., Ou, H.L., Chu, S.T., Wu, P.C., Lu, P.J., Chi, C.C., Leung, K.W., Ger, L.P., NAT2 slow acetylation haplotypes are associated with the increased risk of betel quid-related oral and pharyngeal squamous cell carcinoma Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics, 112, pp. 484-492Ying, X.J., Dong, P., Shen, B., Wang, J., Wang, S., Wang, G., Possible association of NAT2 polymorphism with laryngeal cancer risk: An evidence-based meta-analysis Journal of Cancer Research and Clinical Oncology, 137, pp. 1661-1667Marques, C.F., Koifman, S., Koifman, R.J., Boffetta, P., Brennan, P., Hatagima, A., Influence of CYP1A1 CYP2E1 GSTM3 and NAT2 genetic polymorphisms in oral cancer susceptibility: Results from a case-control study in Rio de Janeiro (2006) Oral Oncology, 42, pp. 632-637Buch, S.C., Nazar-Stewart, V., Weissfeld, J.L., Romkes, M., Case-control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes (2008) Head Neck, 30, pp. 1139-1147Liu, J., Cao, X.L., Zhang, Z., Lei, D.P., Jin, T., Yu, X.M., Pan, X.L., HOGG1 Ser326Cys polymorphism and susceptibility to head and neck cancer: A meta-analysis (2011) Asian Pac J Cancer Prev, 12, pp. 2491-2494Wang, W., Wang, M., Chen, Y., Zhang, Z., Wang, S., Xu, M., Wang, B., Zhao, Q., The hOGG1 Ser326Cys polymorphism contributes to cancer susceptibility: Evidence from 83 case-control studies (2012) Mutagenesis, 27, pp. 329-336Vineis, P., Martone, T., The role of genetically-based metabolic polymorphisms in human cancer: An ecological study of bladder cancer and N-acetyltransferase in 23 populations (1998) Biotherapy, 11, pp. 201-204Nelson, H.H., Kelsey, K.T., Mott, L.A., Karagas, M.R., The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: Evidence of gene-environment interaction (2002) Cancer Res, 62, pp. 152-155Mitra, A.K., Singh, S.V., Garg, V.K., Sharma, M., Chaturvedi, R., Rath, S.K., Protective association exhibited by the single nucleotide polymorphism (SNP) rs1052133 in the gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of squamous cell carcinomas of the head & neck (SCCHN) among north Indians (2011) Indian J Med Res, 133, pp. 605-612Yuan, W., Xu, L., Feng, Y., Yang, Y., Chen, W., Wang, J., Pang, D., Li, D., The hOGG1 Ser326Cys polymorphism and breast cancer risk: A meta-analysis (2010) Breast Cancer Res Treat, 122, pp. 835-842Chen, C., Ricks, S., Doody, D.R., Fitzgibbons, E.D., Porter, P.L., Schwartz, S.M., N-Acetyltransferase 2 polymorphisms, cigarette smoking and alcohol consumption, and oral squamous cell cancer risk (2001) Carcinogenesis, 22, pp. 1993-199

Comparative Genomics Of Two Leptospira Interrogans Serovars Reveals Novel Insights Into Physiology And Pathogenesis

Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing of Leptospira interrogans serovar Copenhageni and comparative analysis with the available Leptospira interrogans serovar Lai genome reveal that despite overall genetic similarity there are significant structural differences, including a large chromosomal inversion and extensive variation in the number and distribution of insertion sequence elements. Genome sequence analysis elucidates many of the novel aspects of leptospiral physiology relating to energy metabolism, oxygen tolerance, two-component signal transduction systems, and mechanisms of pathogenesis. A broad array of transcriptional regulation proteins and two new families of afimbrial adhesins which contribute to host tissue colonization in the early steps of infection were identified. Differences in genes involved in the biosynthesis of lipopolysaccharide O side chains between the Copenhageni and Lai serovars were identified, offering an important starting point for the elucidation of the organism's complex polysaccharide surface antigens. Differences in adhesins and in lipopolysaccharide might be associated with the adaptation of serovars Copenhageni and Lai to different animal hosts. Hundreds of genes encoding surface-exposed lipoproteins and transmembrane outer membrane proteins were identified as candidates for development of vaccines for the prevention of leptospirosis.186721642172Barocchi, M.A., Ko, A.I., Ferrer, S.R., Faria, M.T., Reis, M.G., Riley, L.W., Identification of new repetitive element in Leptospira interrogans serovar Copenhageni and its application to PCR-based differentiation of Leptospira serogroups (2001) J. Clin. Microbiol., 39, pp. 191-195Barocchi, M.A., Ko, A.I., Reis, M.G., McDonald, K.L., Riley, L.W., Rapid translocation of polarized MDCK cell monolayers by Leptospira interrogans, an invasive but nonintracellular pathogen (2002) Infect. Immun., 70, pp. 6926-6932Boursaux-Eude, C., Saint Girons, I., Zuerner, R., IS1500, an IS3-like element from Leptospira interrogans (1995) Microbiology, 141, pp. 2165-2173Charon, N.W., Goldstein, S.F., Genetics of motility and chemotaxis of a fascinating group of bacteria: The spirochetes (2002) Annu. Rev. Genet., 36, pp. 47-73Chen, C.W., Huang, C.H., Lee, H.H., Tsai, H.H., Kirby, R., Once the circle has been broken: Dynamics and evolution of Streptomyces chromosomes (2002) Trends Genet., 18, pp. 522-529Colombatti, A., Bonaldo, P., Doliana, R., Type A modules: Interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins (1993) Matrix, 13, pp. 297-306De La Pena-Moctezuma, A., Bulach, D.M., Kalambaheti, T., Adler, B., Comparative analysis of the LPS biosynthetic loci of the genetic subtypes of serovar Hardjo: Leptospira interrogans subtype Hardjoprajitno and Leptospira borgpetersenii subtype Hardjobovis (1999) FEMS Microbiol. Lett., 177, pp. 319-326Delcher, A.L., Kasif, S., Fleischmann, R.D., Peterson, J., White, O., Salzberg, S.L., Alignment of whole genomes (1999) Nucleic Acids Res., 27, pp. 2369-2376Dimroth, P., Wang, H., Grabe, M., Oster, G., Energy transduction in the sodium F-ATPase of Propionigenium modestum (1999) Proc. Natl. Acad. Sci. USA, 96, pp. 4924-4929Dolata, M.M., Van Beeumen, J.J., Ambler, R.P., Meyer, T.E., Cusanovich, M.A., Nucleotide sequence of the heme subunit of flavocytochrome c from the purple phototrophic bacterium, Chromatium vinosum. A 2.6-kilobase pair DNA fragment contains two multiheme cytochromes, a flavoprotein, and a homolog of human ankyrin (1993) J. Biol. Chem., 268, pp. 14426-14431Dunne Jr., W.M., Bacterial adhesion: Seen any good biofilms lately? (2002) Clin. Microbiol. Rev., 15, pp. 155-166Durbin, R., Eddy, S.R., Krogh, A., Mitchison, G., (1998) Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids, , Cambridge University Press, Cambridge, United KingdomEisen, J.A., Heidelberg, J.F., White, O., Salzberg, S.L., Evidence for symmetric chromosomal inversions around the replication origin in bacteria (2000) Genome Biol., 1. , http://genomebiology.com/2000/1/6/RESEARCH/0011, 4 December, posting date. [Online.]Faine, S., Adler, B., Bolin, C., Perolat, P., (1999) Leptospira and Leptospirosis, , MediSci, Melbourne, AustraliaFarr, R.W., Leptospirosis (1995) Clin. Infect. Dis., 21, pp. 1-6Franklin, M.J., Obman, D.E., Mutant analysis and cellular localization of the AlgI, AlgJ, and AlgF proteins required for O acetylation of alginate in Pseudomonas aeruginosa (2002) J. Bacteriol., 184, pp. 3000-3007Fraser, C.M., Casjens, S., Huang, W.M., Sutton, G.G., Clayton, R., Lathigra, R., White, O., Venter, J.C., Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi (1997) Nature, 390, pp. 580-586Fraser, C.M., Norris, S.J., Weinstock, G.M., White, O., Sutton, G.G., Dodson, R., Gwinn, M., Venter, J.C., Complete genome sequence of Treponema pallidum, the syphilis spirochete (1998) Science, 281, pp. 375-388Fukunaga, M., Mifuchi, I., Unique organization of Leptospira interrogans rRNA genes (1989) J. Bacteriol., 171, pp. 5763-5767Fulop, V., Ridout, C.J., Greenwood, C., Hajdu, J., Crystal structure of the di-haem cytochrome c peroxidase from Pseudomonas aeruginosa (1995) Structure, 3, pp. 1225-1233Galperin, M.Y., Nikolskaya, A.N., Koonin, E.V., Novel domains of the prokaryotic two-component signal transduction systems (2001) FEMS Microbiol. Lett., 203, pp. 11-21Gilges, D., Vinit, M.A., Callebaut, I., Coulombel, L., Cacheux, V., Romeo, P.H., Vigon, I., Polydom: A secreted protein with pentraxin, complement control protein, epidermal growth factor and von Willebrand factor A domains (2000) Biochem. J., 352, pp. 49-59Godfroid, F., Taminiau, B., Danese, I., Denoel, P., Tibor, A., Weynants, V., Cloeckaert, A., Letesson, J.J., Identification of the perosamine synthetase gene of Brucella melitensis 16M and involvement of lipopolysaccharide O side chain in Brucella survival in mice and in macrophages (1998) Infect. Immun., 66, pp. 5485-5493Haake, D.A., Spirochaetal lipoproteins and pathogenesis (2000) Microbiology, 146, pp. 1491-1504Haake, D.A., Champion, C.I., Martinich, C., Shang, E.S., Blanco, D.R., Miller, J.N., Lovett, M.A., Molecular cloning and sequence analysis of the gene encoding OmpL1, a transmembrane outer membrane protein of pathogenic Leptospira spp (1993) J. Bacteriol., 175, pp. 4225-4234Henneberry, R.C., Cox, C.D., Beta-oxidation of fatty acids by Leptospira (1970) Can. J. Microbiol., 16, pp. 41-45Howell, M.L., Alsabbagh, E., Ma, J.F., Ochsner, U.A., Klotz, M.G., Beveridge, T.J., Blumenthal, K.M., Hassett, D.J., AnkB, a periplasmic ankyrin-like protein in Pseudomonas aeruginosa, is required for optimal catalase B (KatB) activity and resistance to hydrogen peroxide (2000) J. Bacteriol., 182, pp. 4545-4556Hunnicutt, D.W., Kempf, M.J., McBride, M.J., Mutations in Flavobacterium johnsoniae gldF and gldG disrupt gliding motility and interfere with membrane localization of GldA (2002) J. Bacteriol., 184, pp. 2370-2378Jovanovic, T., Ascenso, C., Hazlett, K.R., Sikkink, R., Krebs, C., Litwiller, R., Benson, L.M., Rusnak, F., Neelaredoxin, an iron-binding protein from the syphilis spirochete, Treponema pallidum, is a superoxide reductase (2000) J. Biol. Chem., 275, pp. 28439-28448Ko, A.I., Galvao Reis, M., Ribeiro Dourado, C.M., Johnson Jr., W.D., Riley, L.W., Urban epidemic of severe leptospirosis in Brazil (1999) Lancet, 354, pp. 820-825. , Salvador Leptospirosis Study GroupLamothe, G.T., Jolly, L., Mollet, B., Stingele, F., Genetic and biochemical characterization of exopolysaccharide biosynthesis by Lactobacillus delbrueckii subsp. bulgaricus (2002) Arch. Microbiol., 178, pp. 218-228Levett, P.N., Leptospirosis (2001) Clin. Microbiol. Rev., 14, pp. 296-326Lombard, M., Touati, D., Fontecave, M., Niviere, V., Superoxide reductase as a unique defense system against superoxide stress in the microaerophile Treponema pallidum (2000) J. Biol. Chem., 275, pp. 27021-27026Matsunaga, J., Barocchi, M.A., Croda, J., Young, T.A., Sanchez, Y., Siqueira, I., Bolin, C.A., Ko, A.I., Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily (2003) Mol. Microbiol., 49, pp. 929-945Meidanis, J., Braga, M.D., Verjovski-Almeida, S., Whole-genome analysis of transporters in the plant pathogen Xylella fastidiosa (2002) Microbiol. Mol. Biol. Rev., 66, pp. 272-299Missiakas, D., Raina, S., The extracytoplasmic function sigma factors: Role and regulation (1998) Mol. Microbiol., 28, pp. 1059-1066Palaniappan, R.U., Chang, Y.F., Jusuf, S.S., Artiushin, S., Timoney, J.F., McDonough, S.P., Barr, S.C., Mohammed, H.O., Cloning and molecular characterization of an immunogenic LigA protein of Leptospira interrogans (2002) Infect. Immun., 70, pp. 5924-5930Paton, A.W., Paton, J.C., Molecular characterization of the locus encoding biosynthesis of the lipopolysaccharide O antigen of Escherichia coli serotype O113 (1999) Infect. Immun., 67, pp. 5930-5937Paulsen, I.T., Nguyen, L., Sliwinski, M.K., Rabus, R., Saier Jr., M.H., Microbial genome analyses: Comparative transport capabilities in eighteen prokaryotes (2000) J. Mol. Biol., 301, pp. 75-100Pizza, M., Scarlato, V., Masignani, V., Giuliani, M.M., Arico, B., Comanducci, M., Jennings, G.T., Rappuoli, R., Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing (2000) Science, 287, pp. 1816-1820Rappuoli, R., Reverse vaccinology, a genome-based approach to vaccine development (2001) Vaccine, 19, pp. 2688-2691Ren, S.X., Fu, G., Jiang, X.G., Zeng, R., Miao, Y.G., Xu, H., Zhang, Y.X., Zhao, G.P., Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing (2003) Nature, 422, pp. 888-893Santos, J.M., Lobo, M., Matos, A.P., De Pedro, M.A., Arraiano, C.M., The gene bola regulates daca (PBP5), dacC (PBP6) and ampC (AmpC), promoting normal morphology in Escherichia coli (2002) Mol. Microbiol., 45, pp. 1729-1740Springer, T.A., Folding of the N-terminal, ligand-binding region of integrin alpha-subunits into a beta-propeller domain (1997) Proc. Natl. Acad. Sci. USA, 94, pp. 65-72Tang, Y.P., Dallas, M.M., Malamy, M.H., Characterization of the Batl (Bacteroides aerotolerance) operon in Bacteroides fragilis: Isolation of a B. fragilis mutant with reduced aerotolerance and impaired growth in in vivo model systems (1999) Mol. Microbiol., 32, p. 139149Van Sluys, M.A., De Oliveira, M.C., Monteiro-Vitorello, C.B., Miyaki, C.Y., Furlan, L.R., Camargo, L.E., Da Silva, A.C., Kitajima, J.P., Comparative analyses of the complete genome sequences of Pierce's disease and citrus variegated chlorosis strains of Xylella fastidiosa (2003) J. Bacteriol, 185, pp. 1018-1026Vujaskovic, Z., Batinic-Haberle, I., Rabbani, Z.N., Feng, Q.F., Kang, S.K., Spasojevic, I., Samulski, T.V., Anscher, M.S., A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury (2002) Free Radic. Biol. Med., 33, pp. 857-863Werts, C., Tapping, R.I., Mathison, J.C., Chuang, T.H., Kravchenko, V., Saint Girons, I., Haake, D.A., Ulevitch, R.J., Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism (2001) Nat. Immunol., 2, pp. 346-352Whitfield, C., Roberts, I.S., Structure, assembly and regulation of expression of capsules in Escherichia coli (1999) Mol. Microbiol., 31, pp. 1307-1319Wizemann, T.M., Heinrichs, J.H., Adamou, J.E., Erwin, A.L., Kunsch, C., Choi, G.H., Barash, S.C., Koenig, S., Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection (2001) Infect. Immun., 69, pp. 1593-1598Zuerner, R.L., Nucleotide sequence analysis of IS1533 from Leptospira borgpetersenii: Identification and expression of two IS-encoded proteins (1994) Plasmid, 31, pp. 1-11Zuerner, R.L., Huang, W.M., Analysis of a Leptospira interrogans locus containing DNA replication genes and a new IS, IS1502 (2002) FEMS Microbiol. Lett., 215, pp. 175-18