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103. Maxillary sinus carcinoma: a retrospective study

Author

CARLO GOBITTI, Barzan L, Franchin G, De Paoli A, Frustaci S, Caruso G, Sacilotto C, Minatel E, Comoretto R, and Grigoletto E

Subjects
Male, Radiotherapy, High-Energy, Maxillary Sinus Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Squamous Cell, Humans, Female, Middle Aged, Combined Modality Therapy, Paranasal Sinus Neoplasms, Retrospective Studies

109. Association between BMI, Change in BMI over a Lifetime, and Upper Aerodigestive Tract (UADT) Cancers in the ARCAGE Study

Author

Park, S. L., Lee, Y. C., Marron, M., Agudo, A., Ahrens, W., Barzan, L., Vladimir Bencko, Benhamou, S., Black, R., Bouchardy, C., Canova, C., Castellsague, X., Conway, D., Healy, C. M., Holcatova, I., Kjaerheim, K., Lagiou, P., Lowry, R. J., Macfarlane, T., Macfarlane, G. J., Mccartan, B. E., Merletti, F., Pohlabeln, H., Richiardi, L., Simonato, L., Sneddon, L., Talamini, R., Trichopoulos, D., Znaor, A., Brennan, P., and Hashibe, M.

113. Head and neck cancer survivors patients and late effects related to oncologic treatment: Update of literature

Author

Taibi, R., Lleshi, A., Barzan, L., Fiorica, F., Leghissa, M., Vaccher, E., Paoli, P., Giovanni Franchin, Berretta, M., and Tirelli, U.

Subjects
Radiation therapy, Postoperative Complications, Head and Neck Neoplasms, Humans, Chemotherapy, Antineoplastic Agents, Chemoradiotherapy, Survivors, Head and neck cancer survivors, Cancer
Abstract

Cancer survivorship represents a new challenge in the third Millennium. In Europe the number of cancer survivors was estimated to be 17,8 million in 2008 and this number is growing. Recent improvements in cancer survival are largely due to earlier diagnosis and advancements in treatment. Despite having favorable effects on cancer survival, radiation therapy, surgery treatment and combination chemotherapy regimens can also cause long-term organ damage and functional disabilities. In this paper we review the most important aspects of long-term toxicities in otolaryngology cancer survivors patients.

118. Head and neck manifestations during HIV infection

Author

Barzan, L., Tavio, M., Tirelli, U., and Comoretto, R.

Subjects
HIV infection -- Diagnosis, Oral manifestations of general diseases -- Diagnosis, Otolaryngology -- Usage
Abstract

AUTHORS: L. Barzan, M. Tavio, U. Tirelli and R. Comoretto. Division of Otolaryncology, Ospedale Civile of Pordenone and Centro di Riferimento Oncologico, Aviano, Italy; Division of Medical Oncology and AIDS [...]

Published
1992

120. A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Author

J. Ramón Quirós, Eva Ardanaz, Stefania Boccia, Wilbert H.M. Peters, Dimitrios Trichopoulos, Mario Foglio, Luigi Barzan, Lenka Foretova, Joshua E. Muscat, Françoise Clavel-Chapelon, Elio Riboli, Diana Zelenika, Paul Brennan, Salvatore Panico, Eleonora Fabianova, Lars J. Vatten, Kay-Tee Khaw, David I. Conway, Pilar Galan, Doris Lechner, Erich M. Sturgis, Shilong Zhong, Shama Buch, Jolanta Lissowska, Franco Merletti, Carmen Enid Martínez, Li E. Wang, H. Bas Bueno-de-Mesquita, Vittorio Krogh, Andres Metspalu, Anne Tjønneland, Shen Chih Chang, Rayjean J. Hung, Silvia Franceschi, Amelie Chabrier, Kristina Kjærheim, Gabriella Cadoni, Sergio Koifman, Ariana Znaor, Chu Chen, Pagona Lagiou, Ivana Holcatova, Richard B. Hayes, James McKay, Graham Byrnes, Philip Lazarus, Christine Bouchardy, Ray Lowry, Vladimir Bencko, Merethe Kumle, Jingchun Luo, Antonio Agudo, Mark Lathrop, David R. Doody, Victor Wünsch-Filho, Joanna Trubicka, Lorenzo Simonato, Martin Lacko, Cristina Canova, John K. Field, Sherianne Fish, Valerie Gaborieau, Xavier Castellsagué, Mary Toner, Thérèse Truong, Tomoko Nukui, Carla J. Gallagher, Wolfgang Ahrens, Triantafillos Liloglou, Kim Overvad, Vladimir Janout, Ivo Gut, Paolo Boffetta, Shu Chun Chuang, Göran Hallmans, Jakob Linseisen, Marjorie Romkes, David Zaridze, Mark C. Weissler, Simone Benhamou, Antonia Trichopoulou, Nerea Larrañaga, José Eluf Neto, Neonila Szeszenia-Dabrowska, Jan Lubinski, Stephen M. Schwartz, Peter Rudnai, Hélène Blanché, Mia Hashibe, William K. Funkhouser, Paolo Vineis, Maria Paula Curado, Gary J. Macfarlane, Marcin Lener, Claire M. Healy, Michael D. McClean, Domenico Palli, Marc Delepine, Tõnu Voodern, Carmen J. Marsit, Zuo-Feng Zhang, Kristjan Välk, Dorota Oszutowska, Heiner Boeing, Ana M. B. Menezes, Rolando Herrero, Leticia Fernández Garrote, Heather H. Nelson, Renato Talamini, Anne Boland, Alexandru Bucur, Qingyi Wei, Gary E. Goodman, Lorenzo Richiardi, Carmen Navarro, Karl T. Kelsey, Rosario Tumino, Inger Njølstad, Johannes J. Manni, Carlos A. González, Oxana Shangina, John R. McLaughlin, Patricia A. McKinney, Timothy J. Key, Andrew F. Olshan, Dario Arzani, Tatiana V. Macfarlane, Simon Heath, Petra H.M. Peeters, International Agency for Research on Cancer (IARC), Russian Academy of Medical Sciences, Department of Epidemiology, Institute of Occupational Medicine, Maria Skłodowska Curie Memorial Cancer Center, National Institute for Environment, Partenaires INRAE, Regional Authority of Public Health, Institute of Public Health, Charles University [Prague] (CU), Palacky University Olomouc, Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute (RECAMO), National and Kapodistrian University of Athens (NKUA), The Netherlands Cancer Institute, Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Université de Genève (UNIGE), Bremen Institute for Prevention Research and Social Medicine (BIPS), University of Bremen, Universita di Torino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), General Hospital, Cancer Registry of Norway, School of Medicine and Dentistry, Universita di Padova, Imperial College London, Catalan Institute of Oncology, CIBER de Epidemiología y Salud Pública (CIBERESP), Newcastle University [Newcastle], Dental School, Centre for Epidemiology and Biostatistics, University of Leeds, NHS NSS ISD, School of Dental Science, University of Liverpool, National Institute of Public Health, National School of Public Health, Universidade Federal de Pelotas = Federal University of Pelotas (UFPel), Universidade de São Paulo (USP), Institute of Oncology and Radiobiology, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Institute of Hygiene, Università cattolica del Sacro Cuore [Milano] (Unicatt), University of North Carolina, Pomeranian Medical University, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Penn State College of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, University of California [Los Angeles] (UCLA), University of California, Anderson Cancer Center, The University of Texas Health Science Center at Houston (UTHealth), Instituto de Investigación Epidemiológica, Brown University, School of public health, The University of Hong Kong (HKU), Masonic Cancer Center, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, University of Pittsburgh (DEPARTMENT OF MATHEMATICS), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Maastricht University [Maastricht], Radboud University Medical Center [Nijmegen], Mount Sinai Hospital [Toronto, Canada] (MSH), Cancer Care Ontario, Norwegian University of Science and Technology (NTNU), University of Tromsø (UiT), Piedmont Reference Center for Epidemiology and Cancer Prevention, Department of Epidemiology and Public Health, Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto per lo Studio e la Prevezione Oncologica, Civile - M.P.Arezzo Hospital, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), INCa, France, US NCI [R01 CA092039 05/05S1], Benhamou, Simone, Bouchardy Magnin, Christine, Charles University in Prague, Università cattolica del Sacro Cuore [Roma] (Unicatt), Penn State System-Pennsylvania Commonwealth System of Higher Education (PCSHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), [McKay, JD, Truong, T, Gaborieau, V, Chabrier, A, Chuang, SC, Byrnes, G, Curado, MP, Franceschi, S, Hashibe, M, Boffetta, P, Brennan, P] IARC, Lyon, France. [Zaridze, D, Shangina, O] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Szeszenia-Dabrowska, N] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Lissowska, J] M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. [Lissowska, J] Inst Oncol, Warsaw, Poland. [Rudnai, P] Natl Inst Environm Hlth, Budapest, Hungary. [Fabianova, E] Reg Author Publ Hlth, Banska Bystrica, Slovakia. [Bucur, A] Inst Publ Hlth, Bucharest, Romania. [Bencko, V, Holcatova, I] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague, Czech Republic. [Janout, V] Palacky Univ, CR-77147 Olomouc, Czech Republic. [Foretova, L] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Trichopoulos, D] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Benhamou, S] INSERM U946, Paris, France. [Benhamou, S] Inst Gustave Roussy, CNRS UMR8200, Villejuif, France. [Bouchardy, C] Univ Geneva, Geneva Canc Registry, Inst Social & Prevent Med, Geneva, Switzerland. [Ahrens, W] Univ Bremen, Bremen Inst Prevent Res & Social Med BIPS, Bremen, Germany. [Merletti, F, Richiardi, L] Univ Turin, Canc Epidemiol Unit, Turin, Italy. [Talamini, R] IRCCS, Natl Canc Inst, Aviano, Italy. [Barzan, L] Gen Hosp Pordenone, Pordenone, Italy. [Kjaerheim, K] Canc Registry Norway, Oslo, Norway. [Macfarlane, GJ, Macfarlane, TV] Univ Aberdeen, Sch Med & Dent, Aberdeen, Scotland. [Simonato, L, Canova, C] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy. [Canova, C] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Agudo, A, Castellsague, X] ICO, Barcelona, Spain. [Castellsague, X, Navarro, C, Ardanaz, E] CIBERESP, Madrid, Spain. [Lowry, R] Univ Newcastle Dent Sch, Newcastle Upon Tyne, Tyne & Wear, England. [Conway, DI] Univ Glasgow Dent Sch, Glasgow, Lanark, Scotland. [McKinney, PA] Univ Leeds Ctr Epidemiol & Biostat, Leeds, W Yorkshire, England. [McKinney, PA] NHS NSS ISD, Edinburgh, Midlothian, Scotland. [Healy, CM, Toner, ME] Trinity Coll Sch Dent Sci, Dublin, Ireland. [Znaor, A] Croatian Natl Inst Publ Hlth, Croatian Natl Canc Registry, Zagreb, Croatia. [Koifman, S] Natl Sch Publ Hlth FIOCRUZ, Rio De Janeiro, Brazil. [Menezes, A] Univ Fed Pelotas, Pelotas, Brazil. [Wuensch, V, Neto, JE] Univ Sao Paulo, Sao Paulo, Brazil. [Garrote, LF] Inst Oncol & Radiobiol, Havana, Cuba. [Boccia, S, Cadoni, G, Arzani, D] Univ Cattolica Sacro Cuore, Inst Hyg, Rome, Italy. [Boccia, S] IRCCS San Raffaele Pisana, Rome, Italy. [Olshan, AF] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Weissler, MC, Funkhouser, WK, Luo, JC] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Lubinski, J, Trubicka, J, Lener, M, Oszutowska, D] Pomeranian Med Univ, Dept Genet & Pathomorphol, Int Hereditary Canc Ctr, Szczecin, Poland. [Oszutowska, D] Pomeranian Med Univ, Dept Hyg Epidemiol & Publ Hlth, Szczecin, Poland. [Schwartz, SM, Chen, C, Fish, S, Doody, DR, Goodman, GE] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Muscat, JE, Lazarus, P, Gallagher, CJ] Penn State Coll Med, Hershey, PA USA. [Chang, SC, Zhang, ZF] Univ Calif Los Angeles Sch Publ Hlth, Los Angeles, CA USA. [Wei, QY, Sturgis, EM, Wang, LE] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Herrero, R] Inst Invest Epidemiol, San Jose, Costa Rica. [Kelsey, KT, Marsit, CJ] Brown Univ, Providence, RI 02912 USA. [McClean, MD] Boston Univ Sch Publ Hlth, Boston, MA USA. [Nelson, HH] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Romkes, M, Buch, S, Nukui, T, Zhong, SL] Univ Pittsburgh, Pittsburgh, PA USA. [Lacko, M, Manni, JJ] Maastricht Univ Med Ctr, Dept Otorhinolaryngol & Head & Neck Surg, Maastricht, Netherlands. [Peters, WHM] St Radboud Univ Nijmegen Med Ctr, Dept Gastroenterol, Nijmegen, Netherlands. [Hung, RJ] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [McLaughlin, J] Canc Care Ontario, Toronto, ON, Canada. [Vatten, L] Norwegian Univ Sci & Technol, N-7034 Trondheim, Norway. [Njolstad, I] Univ Tromso, Dept Community Med, Fac Hlth Sci, Tromso, Norway. [Field, JK, Liloglou, T] Univ Liverpool Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool, Merseyside, England. [Vineis, P] Univ Turin, Serv Epidemiol Tumori, Turin, Italy. [Vineis, P] CPO Piemonte, Turin, Italy. [Vineis, P, Riboli, E] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. [Clavel-Chapelon, F] E3N EPIC Grp Inst Gustave Roussy, INSERM, Villejuif, France. [Palli, D] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy. [Tumino, R] Azienda Osped Civile MP Arezzo, Canc Registry, Ragusa, Italy. [Tumino, R] Azienda Osped Civile MP Arezzo, Histopathol Unit, Ragusa, Italy. [Krogh, V] Fdn IRCCS, Ist Nazl Tumori, Milan, Italy. [Panico, S] Univ Naples Federico 2, Dipartimento Med Clin & Sperimentale, Naples, Italy. [Gonzalez, CA] ICO, RETICC DR06 0020, IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain. [Quiros, JR] Principado Asturias, Consejeria Serv Sociales, Jefe Secc Informac Sanitaria, Oviedo, Spain. [Martinez, C] Escuela Andaluza Salud Publ, Granada, Spain. [Navarro, C] Murcia Hlth Council, Dept Epidemiol, Murcia, Spain. [Ardanaz, E] Navarra Publ Hlth Inst, Pamplona, Spain. [Larranaga, N] Gobierno Vasco, Subdirecc Salud Publ Gipuzkoa, San Sebastian, Spain. [Khaw, KT] Univ Cambridge, Sch Clin Med, Cambridge, England. [Key, T] Univ Oxford, Canc Res UK, Oxford, England. [Bueno-de-Mesquita, HB] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Peeters, PHM] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands. [Trichopoulou, A] Univ Athens Sch Med, WHO Collaborating Ctr Nutr, Dept Hyg Epidemiol & Med Stat, Athens, Greece. [Linseisen, J] Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany. [Linseisen, J] German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. [Boeing, H] Deutsch Inst Ernahrungsforsch, Dept Epidemiol, Potsdam, Germany. [Hallmans, G] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Overvad, K] Aarhus Univ, Dept Epidemiol & Social Med, Aarhus, Denmark. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Kumle, M] Univ Hosp No Norway, Tromso, Norway. [Valk, K, Voodern, T, Metspalu, A] Univ Tartu, EE-50090 Tartu, Estonia. [Zelenika, D, Boland, A, Delepine, M, Foglio, M, Lechner, D, Gut, IG, Heath, S, Lathrop, M] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, Evry, France. [Blanche, H, Lathrop, M] Fdn Jean Dausset CEPH, Paris, France. [Galan, P] Univ Paris 13, INSERM INRA CNAM U557 U1125, Bobigny, France. [Hayes, RB] New York Univ Langone Med Ctr, New York, NY USA, Support for the central Europe and ARCAGE genome-wide studies and follow-up genotyping was provided by INCa, France. Additional funding for study coordination, genotyping of replication studies, and statistical analysis was provided by the US NCI (R01 CA092039 05/05S1)., Norges teknisk-naturvitenskapelige universitet, Det medisinske fakultet, Institutt for samfunnsmedisin, McKay, J.D., Truong, T., Gaborieau, V., Chabrier, A., Chuang, S.-C., Byrnes, G., Zaridze, D., Shangina, O., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Bucur, A., Bencko, V., Holcatova, I., Janout, V., Foretova, L., Lagiou, P., Trichopoulos, D., Benhamou, S., Bouchardy, C., Ahrens, W., Merletti, F., Richiardi, L., Talamini, R., Barzan, L., Kjaerheim, K., Macfarlane, G.J., Macfarlane, T.V., Simonato, L., Canova, C., Agudo, A., Castellsagué, X., Lowry, R., Conway, D.I., McKinney, P.A., Healy, C.M., Toner, M.E., Znaor, A., Curado, M.P., Koifman, S., Menezes, A., Wünsch-Filho, V., Neto, J.E., Garrote, L.F., Boccia, S., Cadoni, G., Arzani, D., Olshan, A.F., Weissler, M.C., Funkhouser, W.K., Luo, J., Lubinski, J., Trubicka, J., Lener, M., Oszutowska, D., Schwartz, S.M., Chen, C., Fish, S., Doody, D.R., Muscat, J.E., Lazarus, P., Gallagher, C.J., Chang, S.-C., Zhang, Z.-F., Wei, Q., Sturgis, E.M., Wang, L.-E., Franceschi, S., Herrero, R., Kelsey, K.T., McClean, M.D., Marsit, C.J., Nelson, H.H., Romkes, M., Buch, S., Nukui, T., Zhong, S., Lacko, M., Manni, J.J., Peters, W.H.M., Hung, R.J., McLaughlin, J., Vatten, L., Njølstad, I., Goodman, G.E., Field, J.K., Liloglou, T., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., González, C.A., Quirós, J.R., Martínez, C., Navarro, C., Ardanaz, E., Larrañaga, N., Khaw, K.-T., Key, T., Bueno-de-Mesquita, H.B., Peeters, P.H.M., Trichopoulou, A., Linseisen, J., Boeing, H., Hallmans, G., Overvad, K., Tjønneland, A., Kumle, M., Riboli, E., Välk, K., Voodern, T., Metspalu, A., Zelenika, D., Boland, A., Delepine, M., Foglio, M., Lechner, D., Blanché, H., Gut, I.G., Galan, P., Heath, S., Hashibe, M., Hayes, R.B., Boffetta, P., Lathrop, M., Brennan, P., Promovendi PHPC, Metamedica, KNO, RS: MHeNs School for Mental Health and Neuroscience, and RS: GROW - School for Oncology and Reproduction

Subjects
Male, Cancer Research, Candidate gene, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Genome-wide association study, FAMILY-HISTORY, genome-wide, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [Medical Subject Headings], 0302 clinical medicine, Gene Frequency, NECK-CANCER, Risk Factors, Càncer, SUSCEPTIBILITY LOCUS, SENSITIVITY PROTEIN MUS308, Genetics (clinical), Cancer, Genetics & Heredity, Genetics, Publication Characteristics::Study Characteristics::Multicenter Study [Medical Subject Headings], 0303 health sciences, TOBACCO-RELATED CANCERS, Tumor, Continental Population Groups, Middle Aged, 3. Good health, LUNG-CANCER, POOLED ANALYSIS, EPIDEMIOLOGY CONSORTIUM, INTERNATIONAL HEAD, ALCOHOL-DRINKING, Head and Neck Neoplasms, Drinking of alcoholic beverages, 030220 oncology & carcinogenesis, NEOPLASIAS, Consum d'alcohol, Head and Neck Neoplasms/enzymology/epidemiology/genetics, Genetics and Genomics/Gene Discovery, Female, Settore MED/31 - OTORINOLARINGOIATRIA, Life Sciences & Biomedicine, Medical Genetics, Research Article, Adult, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, Diseases::Neoplasms::Neoplasms by Site::Head and Neck Neoplasms [Medical Subject Headings], lcsh:QH426-470, Neoplasias de Cabeza y Cuello, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, Genetics and Genomics/Complex Traits, Biology, association study, Estudio de Asociación del Genoma Completo, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], 03 medical and health sciences, upper aerodigestive tract, Genetic variation, Biomarkers, Tumor, medicine, cancers, cancer, Humans, Genetic Predisposition to Disease, ddc:610, Tumor Markers, Biological/genetics, Genetics and Genomics/Cancer Genetics, Molecular Biology, Genotyping, Allele frequency, Settore MED/42 - IGIENE GENERALE E APPLICATA, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, ddc:613, Aged, Medicinsk genetik, Estudio Multicéntrico, Science & Technology, Racial Groups, Genetic Variation, Aldehyde Dehydrogenase, medicine.disease, lcsh:Genetics, Aldehyde Dehydrogenase/genetics, Genome-Wide Association Study, Persons::Persons::Population Groups::Continental Population Groups [Medical Subject Headings], INHANCE consortium, sensitivity protein mus308, tobacco-related cancers, lung-cancer, pooled analysis, susceptibility locus, neck-cancer, epidemiology consortium, international head, alcohol-drinking, family-history, INHANCE Consortium, Biomarkers, Genètica
Abstract

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility., Author Summary We have used a two-phased study approach to identify common genetic variation involved in susceptibility to upper aero-digestive tract cancer. Using Illumina HumanHap300 beadchips, 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls, were genotyped for a panel 317,000 genetic variants that represent the majority of common genetic in the human genome. The 19 top-ranked variants were then studied in an additional series of 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies. Five variants were significantly associated with UADT cancer risk after the completion of both stages, including three residing within the alcohol dehydrogenase genes (ADH1B, ADH1C, ADH7) that have been previously described. Two additional variants were found, one near the ALDH2 gene and a second variant located in HEL308, a DNA repair gene. These results implicate two variants 4q21 and 12q24 and further highlight three ADH variants UADT cancer susceptibility.

Published
2011

121. Flavonoids and the risk of oral and pharyngeal cancer: a case-control study from Italy

Author

Luigi Barzan, Valerio Ramazzotti, Marta Rossi, Alessandra Tavani, Eva Negri, Carlo La Vecchia, Luigino Dal Maso, Pagona Lagiou, Werner Garavello, Jerry Polesel, Silvia Franceschi, Renato Talamini, Cristina Bosetti, Rossi M, Garavello W, Talamini R, Negri E, Bosetti C, Dal Maso L, Lagiou P, Tavani A, Polesel J, Barzan L, Ramazzotti V, Franceschi S, La Vecchia C, Rossi, M, Garavello, W, Talamini, R, Negri, E, Bosetti, C, Dal Maso, L, Lagiou, P, Tavani, A, Polesel, J, Barzan, L, Ramazzotti, V, Franceschi, S, and La Vecchia, C

Subjects
Anthocyanin, Male, Flavonols, Epidemiology, Physiology, Body Mass Index, Anthocyanins, Risk Factors, Mouth neoplasm, chemistry.chemical_classification, Smoking, Middle Aged, Isoflavone, Oncology, Italy, Flavanones, Educational Status, Female, Mouth Neoplasms, Flavonol, Flavanone, Human, Adult, medicine.medical_specialty, Alcohol Drinking, medicine, Humans, Pharyngeal Neoplasm, Risk factor, Aged, Flavonoids, business.industry, Risk Factor, Case-control study, Pharyngeal Neoplasms, Odds ratio, Educational Statu, Mouth Neoplasm, Isoflavones, Confidence interval, Surgery, Diet, chemistry, Case-Control Studies, Flavonoid, business, Energy Intake, Body mass index
Abstract

The intake of flavonoids has been inversely related to the risk of various common neoplasms, but scanty data exist on oral and pharyngeal cancer. We used data from a case-control study conducted in Italy between 1992 and 2005 to examine the relationship between flavonoid intake and oral and pharyngeal cancer risk. The study included 805 cases with incident, histologically confirmed oral and pharyngeal cancer, and 2,081 hospital controls admitted for acute, nonneoplastic conditions. We have applied data on food and beverage content of six major classes of flavonoids, on dietary information collected through a validated food-frequency questionnaire. The odds ratios (OR) were calculated using multiple logistic regression models, conditioned on study center, sex, and age. After adjustment for education, tobacco, alcohol, body mass index, and non–alcohol energy intake, ORs for the highest versus the lowest quintile of intake were 0.51 [95% confidence intervals (95% CI), 0.37-0.71] for flavanones, 0.62 (CI, 0.43-0.89) for flavonols, and 0.56 (95% CI, 0.40-0.78) for total flavonoids. No significant association emerged for isoflavones (OR, 0.90), anthocyanidins (OR, 0.86), flavan-3-ols (OR, 0.84), and flavones (OR, 0.75). The ORs were consistent across strata of age, sex, education, body mass index, tobacco, and alcohol. After allowance for vegetable and fruit consumption, the inverse relations with total flavonoids and flavanones remained significant, whereas that with flavonols became nonsignificant. None of the associations were significant after further allowance for vitamin C, probably on account of the high collinearity between these compounds. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1621–5)

Published
2007

122. Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area

Author

Damiana Antonia Faè, Riccardo Dolcetti, Debora Martorelli, Luigi Barzan, Carlo Gobitti, E. Comaro, F. Navarria, C. Furlan, Giuseppe Fanetti, Sandro Sulfaro, Elena Muraro, Agostino Steffan, Giovanni Franchin, Chiara Pratesi, Stefania Zanussi, Emanuela Vaccher, Valentina Lupato, Jerry Polesel, Michela Cangemi, Vittorio Giacomarra, Vincenzo Canzonieri, C. Scaini, Giuseppe Grando, Elisabetta Fratta, Muraro, E., Vaccher, E., Furlan, C., Fratta, E., Fanetti, G., Fae', D. A., Martorelli, D., Cangemi, M., Polesel, J., Navarria, F., Gobitti, C., Comaro, E., Scaini, C., Pratesi, C., Zanussi, S., Lupato, V., Grando, G., Giacomarra, V., Sulfaro, S., Barzan, L., Dolcetti, R., Steffan, A., Canzonieri, V., and Franchin, G.

Subjects
Male, 0301 basic medicine, Oncology, Epstein-Barr Virus Infections, Cancer Research, medicine.medical_treatment, Radiation Tolerance, 0302 clinical medicine, Tumor Microenvironment, CD8, Chemoradiotherapy, EBV-specific immunity, FoxP3, Immunosuppression, Nasopharyngeal carcinoma, ELISPOT, FOXP3, Forkhead Transcription Factors, General Medicine, Middle Aged, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, Adolescent, CD8 Antigens, T cell, Pathology and Forensic Medicine, Viral Proteins, Young Adult, 03 medical and health sciences, Immune system, Predictive Value of Tests, Internal medicine, medicine, Humans, Aged, Retrospective Studies, business.industry, Nasopharyngeal Neoplasms, DNA Methylation, medicine.disease, 030104 developmental biology, Drug Resistance, Neoplasm, business
Abstract

Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.

Published
2020

123. CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer

Author

Giovanni Franchin, Martina Cusan, Luigi Barzan, Giorgio Giorda, Samuele Massarut, Maura Sonego, Andrea Vecchione, Alessandra Dall'Acqua, Francesca Russo, Lorena Musco, Monica Schiappacassi, Gustavo Baldassarre, Lorenzo Gerratana, Tiziana Perin, Vincenzo Canzonieri, Fabio Puglisi, Roberto Sorio, Francesca Citron, Filippo Vit, Giorgia Mungo, Sandro Sulfaro, Jerry Polesel, Emilio Lucia, Vittorio Giacomarra, Sara D'Andrea, Milena S. Nicoloso, Maria Chiara Mattevi, Davide Viotto, Ilaria Anania, Ilenia Segatto, Barbara Belletti, Gian Luca Rampioni Vinciguerra, Federica Toffolutti, Riccardo Bomben, V. Gattei, Viotto, D., Russo, F., Anania, I., Segatto, I., Rampioni Vinciguerra, G. L., Dall'Acqua, A., Bomben, R., Perin, T., Cusan, M., Schiappacassi, M., Gerratana, L., D'Andrea, S., Citron, F., Vit, F., Musco, L., Mattevi, M. C., Mungo, G., Nicoloso, M. S., Sonego, M., Massarut, S., Sorio, R., Barzan, L., Franchin, G., Giorda, G., Lucia, E., Sulfaro, S., Giacomarra, V., Polesel, J., Toffolutti, F., Canzonieri, V., Puglisi, F., Gattei, V., Vecchione, A., Belletti, B., and Baldassarre, G.

Subjects
Male, 0301 basic medicine, DNA Copy Number Variations, CNV, Breast Neoplasms, Neuroendocrine tumors, medicine.disease_cause, head and neck squamous cell carcinoma, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, Intestinal Neoplasms, medicine, Humans, Copy-number variation, CDKN1B, copy number variation, liquid biopsy, mutation, ovarian cancer, p27, young breast cancer patients, Original Paper, Mutation, copy number variation, CNV, business.industry, Prostatic Neoplasms, medicine.disease, Original Papers, Head and neck squamous-cell carcinoma, Squamous carcinoma, Neuroendocrine Tumors, 030104 developmental biology, 030220 oncology & carcinogenesis, MCF-7 Cells, Cancer research, Female, business, Ovarian cancer, Cyclin-Dependent Kinase Inhibitor p27, CDK inhibitor
Abstract

The CDKN1B gene, encoding for the CDK inhibitor p27kip1, is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra‐deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor‐positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell‐free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27kip1 protein truncation, leading to loss of most of the protein or of its C‐terminal domain. Using a gene‐editing approach in a luminal breast cancer cell line, MCF‐7, we observed that the expression of p27kip1 truncating mutants that lose the C‐terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C‐terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Published
2020

124. Intensity-modulated radiotherapy (IMRT)/Tomotherapy following neoadjuvant chemotherapy in stage IIB-IVA/B undifferentiated nasopharyngeal carcinomas (UCNT): A mono-institutional experience.

Author

Franchin G, Vaccher E, Talamini R, Politi D, Gobitti C, Minatel E, Lleshi A, Sartor G, Mascarin M, Rumeileh IA, Trovò MG, and Barzan L

Abstract

To evaluate the outcome of Undifferentiated Nasopharyngeal Carcinomas (UCNT) treated with intensity-modulated radiation therapy with Simultaneous Integrated Boost (SIB), following induction chemotherapy. Between January 2006 and June 2009, 52 patients with stage II B-IVA/B UCNT were treated either with linac-IMRT or Tomotherapy. All patients were scheduled to receive three cycles of cisplatin based neoadjuvant chemotherapy. With a median follow-up of 38.5months (range 12.3-64.1), 3year overall survival (OS), disease-free survival (DFS), and DFS by T2a-2b and T3-T4-stage were 95.0%, 84.6%, 89.0%, and 78.0%, respectively. At multivariate analysis, none of the examined prognostic factors reported statistical significance. N-classification was not a significant predictive factor for either OS or development of distant metastases. T-stage alone had a borderline effect on DFS and development of metastases. No difference between Tomotherapy and linac-IMRT emerged in terms of loco-regional control and development of severe, acute, and late toxicities. The most significant severe, acute toxicities were grade 3 (32.7%) and grade 4 (7.7%) mucositis. No grades 3 and 4 late toxicities were observed. The most commonly observed late effect was xerostomia, 11.5% patients complained grade 2 xerostomia. The severity of grade 2 xerostomia diminished over time with only four patients not improving salivation. IMRT-SIB following neoadjuvant chemotherapy was very satisfactory in terms of local control, regional control, DFS and OS rates in patients with stage IIB to IVB UCNT. In our experience, adding concurrent chemotherapy to IMRT after neoadjuvant chemotherapy in loco-regional widespread disease resulted to be the indicated approach. [ABSTRACT FROM AUTHOR]

Published
2011
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125. Multidisciplinary treatment approach for primary thyroid spindle cell sarcoma: A case report

Author

F. Navarria, Fabrizio Italia, Angela Buonadonna, G. Bertola, Luigi Barzan, M. Gigante, Maurizio Mascarin, A. De Paoli, Vincenzo Canzonieri, Luca Barresi, Navarria, F., Gigante, M., Mascarin, M., Italia, F., Barresi, L., Barzan, L., Bertola, G., Buonadonna, A., Canzonieri, V., and De Paoli, A.

Subjects
Adult, Radiology, Nuclear Medicine and Imaging, medicine.medical_specialty, medicine.medical_treatment, IORT, Disease, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Nuclear Medicine and Imaging, medicine, Chemotherapy, Humans, Radiology, Nuclear Medicine and imaging, Thyroid Neoplasms, Thyroid Neoplasm, Neoadjuvant therapy, Adjuvant, Patient Care Team, Radiotherapy, business.industry, Thyroid, Thyroidectomy, Sarcoma, medicine.disease, Neoadjuvant Therapy, Surgery, Radiation therapy, medicine.anatomical_structure, Oncology, Chemotherapy, Adjuvant, Thyroid sarcoma, Female, Radiotherapy, Adjuvant, 030220 oncology & carcinogenesis, Spindle cell sarcoma, business, Radiology, Human
Abstract

A 25-year-old female with high-grade spindle cell sarcoma of the thyroid persistent after thyroidectomy performed at another hospital was referred to our institute. Chemotherapy followed by surgery with intraoperative radiotherapy and postoperative intensity-modulated radiotherapy were planned within the sarcoma board. Chemotherapy was discontinued after two cycles because of local disease progression and surgery with intraoperative radiotherapy, was anticipated. The treatment was completed with postoperative radiotherapy. After 36 months off-therapy, the patient was free of disease without significant late effects. Thyroid sarcomas are very rare and there is no consensus on their clinical management. Hence, case reports are useful to share treatment options. In this patient case, the histotype and the high-grade disease required a combined therapy program, managed in a multidisciplinary setting.

Published
2019

126. Dietary intakes of carotenoids and other nutrients in the risk of nasopharyngeal carcinoma: a case–control study in Italy

Author

Luigi Barzan, Werner Garavello, Massimo Libra, Diego Serraino, Eva Negri, Cristina Bosetti, Jerry Polesel, Maurizio Montella, C. La Vecchia, Maria Parpinel, R. Talamini, Silvia Franceschi, J. Polesel, E. Negri, D. Serraino, M. Parpinel, L. Barzan, M. Libra, C. Bosetti, W. Garavello, M. Montella, C. La Vecchia, S. Franceschi, R. Talamini, Polesel, J, Negri, E, Serraino, D, Parpinel, M, Barzan, L, Libra, M, Bosetti, C, Garavello, W, Montella, M, La Vecchia, C, Franceschi, S, and Talamini, R

Subjects
Male, Cancer Research, Logistic regression, Gastroenterology, α-carotene, β-carotene, carotenoids, nasopharyngeal carcinoma, nutrients, Risk Factors, Micronutrient, Micronutrients, α-carotene, β-carotene, carotenoids, nasopharyngeal carcinoma, nutrients, Nasopharyngeal Neoplasm, education.field_of_study, Middle Aged, carotenoid, Italy, Oncology, Quartile, Female, Case-Control Studie, Human, Adult, medicine.medical_specialty, Adolescent, Short Communication, Population, MED/31 - OTORINOLARINGOIATRIA, Young Adult, Internal medicine, medicine, Humans, education, Aged, business.industry, Risk Factor, Carcinoma, Case-control study, Nasopharyngeal Neoplasms, Feeding Behavior, Odds ratio, medicine.disease, Confidence interval, Diet, Endocrinology, Nasopharyngeal carcinoma, Case-Control Studies, Food Habit, business
Abstract

BACKGROUND: Dietary habits have been related to the risk of nasopharyngeal carcinoma (NPC), but information on a wide range of macro- and micronutrients is still lacking, particularly for low-incidence countries. METHODS: We conducted a hospital-based case-control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity of 18-76 years of age. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Nutrients intake was assessed through a validated food-frequency questionnaire. Adjusted odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression. RESULTS: Dietary intake of carotenoids were inversely related to NPC risk, notably carotene (OR for highest vs lowest quartile=0.46; 95% CI: 0.26-0.79), α-carotene (OR=0.57; 95% CI: 0.33-0.97), and β-carotene (OR=0.42; 95% CI: 0.24-0.75). Increased NPC risk was observed for elevate cholesterol intake (OR=1.85; 95% CI: 1.12-3.05). CONCLUSION: Study findings suggest a protective effect of carotenoids against NPC in a low-risk population, adding further support to a possible beneficial role of a diet rich in fruits and vegetables in cancers of the head and neck.

Published
2012

127. Family history and the risk of oral and pharyngeal cancer

Author

Renato Talamini, Fabio Levi, Luigi Barzan, Alessandra Tavani, Valerio Ramazzotti, Silvia Franceschi, Marta Rossi, Luigino Dal Maso, Eva Negri, Carlo La Vecchia, Werner Garavello, Roberto Foschi, Garavello, W, Foschi, R, Talamini, R, La Vecchia, C, Rossi, M, Dal Maso, L, Tavani, A, Levi, F, Barzan, L, Ramazzotti, V, Franceschi, S, Negri, E, W. Garavello, R. Foschi, R. Talamini, C. La Vecchia, M. Rossi, L. Dal Maso, A. Tavani, F. Levi, L. Barzan, V. Ramazzotti, S. Franceschi, and E. Negri

Subjects
Male, Cancer Research, medicine.medical_specialty, Logistic Model, Alcohol Drinking, Risk Assessment, Risk Factors, Internal medicine, Tobacco, Confidence Intervals, Odds Ratio, Humans, Medicine, Family, Pharyngeal Neoplasm, Family history, Risk factor, Familial risk, Medical History Taking, Lung cancer, Laryngeal Neoplasms, Aged, Mouth neoplasm, Laryngeal Neoplasm, business.industry, Risk Factor, Smoking, Oral neoplasm, Cancer, Pharyngeal Neoplasms, Oral Neoplasm, Odds ratio, Middle Aged, medicine.disease, Mouth Neoplasm, Surgery, Logistic Models, Italy, Oncology, Case-Control Studies, Female, Mouth Neoplasms, business, Confidence Interval, Switzerland, Human
Abstract

Scanty data are available on familial risk in oral and pharyngeal cancer. The relationship between oral and pharyngeal cancer and family history of cancer in first-degree relatives was investigated using data from a multicentric case-control study conducted in Italy and Switzerland between 1992 and 2005 on 956 cases aged less than 79 years, with histologically confirmed incident oral and pharyngeal cancer, and 2362 controls admitted to hospital for acute, nonneoplastic conditions. Logistic regression models conditioned on sex, age, study centre, and including terms for education, tobacco smoking, alcohol drinking, and number of siblings were used to estimate the odds ratios (OR) of oral and pharyngeal cancer. The multivariate ORs were similar for a family history of oral and pharyngeal cancer (2.6, 95% confidence interval, CI, 1.5-4.5) and laryngeal cancer (3.8, 95% CI, 2.0-7.2). The OR was 3.1 (95% CI, 2.0-4.8) for oral and pharyngeal cancer and laryngeal cancer combined. The OR was 7.1 (95% CI, 1.3-37.2) for subjects with 2 or more first-degree relatives with oral and pharyngeal/laryngeal cancers. Significant increases in risk were also observed for a family history of melanoma (OR = 5.8; 95% CI, 1.3-26.4) and lung cancer (OR = 1.4; 95% CI, 1.0-2.0). Compared to subjects without family history, nonsmokers, and non or moderate drinkers, the OR was 42.6 for current smokers, heavy drinkers with family history. History of oral and pharyngeal cancer and laryngeal cancer is a strong determinant of oral and pharyngeal cancer risk, independent from tobacco and alcohol.

Published
2007

128. A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer

Author

Maria Paula Curado, Ioan Nicolae Mates, Pagona Lagiou, Kristina Kjærheim, Graham Byrnes, Jerry Polesel, Ariana Znaor, Lenka Foretová, James McKay, Valerie Gaborieau, Keitaro Matsuo, Manoj B. Mahimkar, Maxime Vallée, Stefania Boccia, Devasena Anantharaman, Wolfgang Ahrens, Antonio Agudo, Ana Paula de O. Menezes, Paolo Boffetta, Cristina Canova, Tatiana V. Macfarlane, Vladimir Bencko, Lorenzo Richiardi, Jolanta Lissowska, Manon Delahaye-Sourdeix, Jan Lubinski, David Zaridze, Ivana Holcatova, Silvia Franceschi, V. Wünsch-Filho, Amelie Chabrier, Nalin S. Thakker, Marcin Lener, Ewa Jaworowska, Maria Timofeeva, Leticia Fernández Garrote, Tanuja A. Samant, Claire M. Healy, Thangarajan Rajkumar, Vladimir Janout, Sergio Koifman, David I. Conway, Neonilia Szeszenia-Dabrowska, Paul Brennan, Eleonora Fabianova, Xavier Castellsagué, José Eluf-Neto, Luigi Barzan, International Prevention Research Institute (IPRI), The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Delahaye-Sourdeix, M., Anantharaman, D., Timofeeva, M.N., Gaborieau, V., Chabrier, A., Vallée, M.P., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T.V., Barzan, L., Canova, C., Thakker, N.S., Conway, D.I., Znaor, A., Healy, C.M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Fabianova, E., Mates, I.N., Bencko, V., Foretova, L., Janout, V., Curado, M.P., Koifman, S., Menezes, A., Wünsch-Filho, V., Eluf-Neto, J., Boffetta, P., Fernández Garrote, L., Polesel, J., Lener, M., Jaworowska, E., Lubinski, J., Boccia, S., Rajkumar, T., Samant, T.A., Mahimkar, M.B., Matsuo, K., Franceschi, S., Byrnes, G., Brennan, P., and Mckay, J.D.

Subjects
Oncology, Adult, Aged, Alcohol Drinking, BRCA2 Protein, Carcinoma, Squamous Cell, Case-Control Studies, Female, Genetic Predisposition to Disease, Head and Neck Neoplasms, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Risk Assessment, Risk Factors, Smoking, Polymorphism, Single Nucleotide, Cancer Research, Medicine (all), HOMOLOGOUS RECOMBINATION, Adult Aged Alcohol Drinking/adverse effects/epidemiology BRCA2 Protein/*genetics Carcinoma, BRCA2 genetic variants - Breast cancer - Lung squamous cell carcinoma, POPULATION, Single Nucleotide, 3. Good health, PREVALENCE, Single Nucleotide Risk Assessment Risk Factors Smoking/adverse effects/epidemiology, SQUAMOUS-CELL CARCINOMA, Risk assessment, medicine.medical_specialty, Single-nucleotide polymorphism, Biology, Brief Communication, Breast cancer, Internal medicine, medicine, Carcinoma, Genetic predisposition, SNP, GENOME-WIDE ASSOCIATION, Polymorphism, Settore MED/42 - IGIENE GENERALE E APPLICATA, POLYMORPHIC STOP CODON, cancer, Japanese, breast cancer, neoplasms, genetics, smoking, BRAC2 gene, single nucleotide polymorphism, squamous cell carcinoma of lung, breast cancer risk, squamous cell carcinoma, upper aerodigestive tract, upper aerodigestive tract neoplasms, genetic predisposition to disease, BRCA2 protein, mutation, cancer risk, Case-control study, Odds ratio, Squamous Cell/*genetics Case-Control Studies Female Genetic Predisposition to Disease Head and Neck Neoplasms/*genetics Humans Logistic Models Male Middle Aged Odds Ratio *Polymorphism, medicine.disease, Squamous Cell, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Delahaye-Sourdeix, Manon Anantharaman, Devasena Timofeeva, Maria N Gaborieau, Valerie Chabrier, Amelie Vallee, Maxime P Lagiou, Pagona Holcatova, Ivana Richiardi, Lorenzo Kjaerheim, Kristina Agudo, Antonio Castellsague, Xavier Macfarlane, Tatiana V Barzan, Luigi Canova, Cristina Thakker, Nalin S Conway, David I Znaor, Ariana Healy, Claire M Ahrens, Wolfgang Zaridze, David Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Fabianova, Eleonora Mates, Ioan Nicolae Bencko, Vladimir Foretova, Lenka Janout, Vladimir Curado, Maria Paula Koifman, Sergio Menezes, Ana Wunsch-Filho, Victor Eluf-Neto, Jose Boffetta, Paolo Fernandez Garrote, Leticia Polesel, Jerry Lener, Marcin Jaworowska, Ewa Lubinski, Jan Boccia, Stefania Rajkumar, Thangarajan Samant, Tanuja A Mahimkar, Manoj B Matsuo, Keitaro Franceschi, Silvia Byrnes, Graham Brennan, Paul McKay, James D eng 1R03DE020116/DE/NIDCR NIH HHS/ R01CA092039 05/05S1/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural 2015/04/04 06:00 J Natl Cancer Inst. 2015 Apr 2;107(5). pii: djv037. doi: 10.1093/jnci/djv037. Print 2015 May.; International audience; Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

Published
2015

129. Consumption of fruit, vegetables, and other food groups and the risk of nasopharyngeal carcinoma

Author

Renato Talamini, Diego Serraino, Carlo La Vecchia, Luigi Barzan, Jerry Polesel, Werner Garavello, Eva Negri, Emanuela Vaccher, Antonella Zucchetto, Maurizio Montella, Silvia Franceschi, J. Polesel, D. Serraino, E. Negri, L. Barzan, E. Vaccher, M. Montella, A. Zucchetto, W. Garavello, S. Franceschi, C. La Vecchia, R. Talamini, Polesel, J, Serraino, D, Negri, E, Barzan, L, Vaccher, E, Montella, M, Zucchetto, A, Garavello, W, Franceschi, S, La Vecchia, C, and Talamini, R

Subjects
Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Adolescent, Protective factor, MED/31 - OTORINOLARINGOIATRIA, Logistic regression, Dietary habit, Risk Assessment, Food group, Young Adult, Risk Factors, Surveys and Questionnaires, Environmental health, Epidemiology, Vegetables, Nasopharyngeal carcinoma, Humans, Medicine, Aged, business.industry, Carcinoma, Case-control study, Nasopharyngeal Neoplasms, Feeding Behavior, Odds ratio, Middle Aged, medicine.disease, Diet, fruit, vegetables, food groups, risk, nasopharyngeal carcinoma, Italy, Oncology, Case-Control Studies, Fruit, Female, business, Risk assessment
Abstract

PURPOSE: The role of dietary habits in the etiology of nasopharyngeal carcinoma (NPC) has been extensively investigated in high-incidence areas, but evidence is scanty in low-incidence populations. This study aimed to investigate the relationship between NPC risk and a wide range of food groups in the Italian population. METHODS: We conducted a hospital-based case-control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity, aged 18-76 years. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression, adjusting for socio-demographic characteristics, tobacco smoking, alcohol drinking, and energy intake. RESULTS: Elevated vegetable consumption was inversely related to NPC risk (OR for highest vs. lower quartile = 0.51; 95 % CI 0.29-0.90). The association was particularly strong for yellow- or red-pigmented vegetables (OR = 0.31; 95 % CI 0.18-0.54), and this effect was stronger among never smokers (OR = 0.18; 95 % CI 0.06-0.55) than among ever smokers (OR = 0.37; 95 % CI 0.19-0.71). Increased NPC risk emerged for elevated eggs consumption (OR = 2.50; 95 % CI 1.44-4.32; p-trend

Published
2013

130. Smoking addiction and the risk of upper-aerodigestive-tract cancer in a multicenter case-control study

Author

Lee, Y.C., Zugna, D., Richiardi, L., Merletti, F., Marron, M., Ahrens, W., Pohlabeln, H., Lagiou, P., Trichopoulos, D., Agudo, A., Castellsague, X., Betka, J., Holcatova, I., Kjaerheim, K., Macfarlane, G.J., Macfarlane, T.V., Talamini, R., Barzan, ., Canova, C., Simonato, L., Conway, D.I., McKinney, P.A., Thomson, P., Znaor, Ariana, Healy, C.M., McCartan, B.E., Boffetta, P., Brennan, P., Hashibe, M., Lee, Y.-C.A., Zugna, D., Richiardi, L., Merletti, F., Marron, M., Ahrens, W., Pohlabeln, H., Lagiou, P., Trichopoulos, D., Agudo, A., Castellsague, X., Betka, J., Holcatova, I., Kjaerheim, K., Macfarlane, G.J., Macfarlane, T.V., Talamini, R., Barzan, L., Canova, C., Simonato, L., Conway, D.I., McKinney, P.A., Thomson, P., Znaor, A., Healy, C.M., McCartan, B.E., Boffetta, P., Brennan, P., and Hashibe, M.

Subjects
Adult, Male, Alcohol Drinking, alcohol, Smoking, Middle Aged, tobacco, Europe, Logistic Models, smoking addiction, upper-aerodigestive-tract cancer, Head and Neck Neoplasms, Risk Factors, Case-Control Studies, Surveys and Questionnaires, Carcinoma, Squamous Cell, Humans, Female, Mouth Neoplasms, upper-aerodigestive-tract (UADT) cancers, Aged
Abstract

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables. What's new? Previous studies have clearly shown dose-response relationships between tobacco/alcohol use and the risk of upper-aerodigestive- tract (UADT) cancers, but these studies have focused only on the variables of frequency and duration of use. In this study, the authors asked whether addiction to smoking might be an independent risk factor. They found that addiction was indeed associated with UADT cancer risk among current smokers. This addiction-cancer association suggests that it is important to include questions that elicit information regarding smoking addiction when accounting for smoking effect through questionnaire information. Copyright © 2013 UICC.

Published
2013

131. Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4 - the AdAPT Method

Author

Diana Zelenika, Pilar Galan, Luigi Barzan, Mattias Johansson, Kristina Kjærheim, James McKay, Antonio Agudo, Cristina Canova, Maria Paula Curado, Dan Chen, Xavier Castellsagué, Ioan Nicolae Mates, Renato Talamini, Jon Wakefield, Jolanta Lissowska, Rolando Herrero, Leticia Fernández Garrote, Ivana Holcatova, Graham Byrnes, Sergio Koifman, Simone Benhamou, Paolo Boffetta, Pagona Lagiou, Tatiana V. Macfarlane, Lenka Foretova, Yaoyong Li, Lorenzo Richiardi, Paul Brennan, Mark A. Greenwood, Vladimir Janout, Eleonora Fabianova, Stefania Boccia, Hamish Cunningham, Nalin Thakker, Angus Roberts, Niraj Aswani, Manon Delahaye-Sourdeix, Lars J. Vatten, David Zaridze, Vladimir Bencko, David I. Conway, Victor Wünsch-Filho, José Eluf-Neto, Ana M. B. Menezes, Silvia Franceschi, Mark Lathrop, Neonilia Szeszenia-Dabrowska, Peter Thomson, Ariana Znaor, Wolfgang Ahrens, Claire M. Healy, International Prevention Research Institute (IPRI), The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), EU-FP7 grant [LarKC, url: http://www.larkc.eu][FP7-215535], United States National Cancer Institute (R01 CA092039 05), National Institute of Dental and Craniofacial Research (1R03DE020116), Johansson, M., Roberts, A., Chen, D., Li, Y., Delahaye-Sourdeix, M., Aswani, N., Greenwood, M.A., Benhamou, S., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T.V., Barzan, L., Canova, C., Thakker, N.S., Conway, D.I., Znaor, A., Healy, C.M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Fabiánová, E., Mates, I.N., Bencko, V., Foretova, L., Janout, V., Curado, M.P., Koifman, S., Menezes, A., Wünsch-Filho, V., Eluf-Neto, J., Boffetta, P., Franceschi, S., Herrero, R., Garrote, L.F., Talamini, R., Boccia, S., Galan, P., Vatten, L., Thomson, P., Zelenika, D., Lathrop, M., Byrnes, G., Cunningham, H., Brennan, P., Wakefield, J., and Mckay, J.D.

Subjects
medical literature, Lung Neoplasms, Epidemiology, lcsh:Medicine, Genome-wide association study, Bioinformatics, Bayes' theorem, 0302 clinical medicine, Oral Diseases, lcsh:Science, Mouth neoplasm, Medicine(all), 0303 health sciences, Multidisciplinary, Agricultural and Biological Sciences(all), Cancer Risk Factors, Statistics, Single Nucleotide, Genomics, 3. Good health, Oncology, Pair 4, 030220 oncology & carcinogenesis, Genetic Epidemiology, Medicine, Mouth Neoplasms, Pair 4 Computational Biology/*methods Genetic Predisposition to Disease *Genome-Wide Association Study Humans Internet Lung Neoplasms/genetics Mouth Neoplasms/*genetics *Polymorphism, Chromosomes, Human, Pair 4, Lung cancer, Research Article, Human, Genetic Causes of Cancer, Oral Medicine, Locus (genetics), Single-nucleotide polymorphism, Biology, Biostatistics, Polymorphism, Single Nucleotide, Chromosomes, POOLED ANALYSIS, 03 medical and health sciences, Single Nucleotide Reproducibility of Results, Genome Analysis Tools, Genome-Wide Association Studies, Genetics, Cancer Genetics, SNP, cancer, Humans, Genetic Predisposition to Disease, Polymorphism, Statistical Methods, Settore MED/42 - IGIENE GENERALE E APPLICATA, 030304 developmental biology, Genetic association, Internet, Biochemistry, Genetics and Molecular Biology(all), génome, lcsh:R, Computational Biology, Reproducibility of Results, Bayes Theorem, Bayes Theorem *Chromosomes, oral cancer, Lung cancer susceptibility, Chromosome 4, Genòmica, Genetic Polymorphism, Càncer de pulmó, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Population Genetics, Mathematics, Genome-Wide Association Study
Abstract

Johansson, Mattias Roberts, Angus Chen, Dan Li, Yaoyong Delahaye-Sourdeix, Manon Aswani, Niraj Greenwood, Mark A Benhamou, Simone Lagiou, Pagona Holcatova, Ivana Richiardi, Lorenzo Kjaerheim, Kristina Agudo, Antonio Castellsague, Xavier Macfarlane, Tatiana V Barzan, Luigi Canova, Cristina Thakker, Nalin S Conway, David I Znaor, Ariana Healy, Claire M Ahrens, Wolfgang Zaridze, David Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Fabianova, Eleonora Mates, Ioan Nicolae Bencko, Vladimir Foretova, Lenka Janout, Vladimir Curado, Maria Paula Koifman, Sergio Menezes, Ana Wunsch-Filho, Victor Eluf-Neto, Jose Boffetta, Paolo Franceschi, Silvia Herrero, Rolando Fernandez Garrote, Leticia Talamini, Renato Boccia, Stefania Galan, Pilar Vatten, Lars Thomson, Peter Zelenika, Diana Lathrop, Mark Byrnes, Graham Cunningham, Hamish Brennan, Paul Wakefield, Jon McKay, James D eng 1R03DE020116/DE/NIDCR NIH HHS/ R01 CA092039 05/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2012/06/05 06:00 PLoS One. 2012;7(5):e36888. doi: 10.1371/journal.pone.0036888. Epub 2012 May 25.; International audience; BACKGROUND: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. METHODS: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest―the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. RESULTS: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5x10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. CONCLUSION: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).

Published
2012

132. Risk of upper aerodigestive tract cancer and type of alcoholic beverage: a European multicenter case-control study

Author

Renato Talamini, Kristina Kjærheim, Lorenzo Richiardi, Alena Slamova, Luigi Barzan, David I. Conway, Antonio Agudo, Lorenzo Simonato, Pagona Lagiou, Simone Benhamou, Cristina Canova, Wolfgang Ahrens, B. E. McCartan, Hermann Pohlabeln, Patricia McKinney, Peter Thomson, Anne Marie Biggs, Christine Bouchardy, Areti Lagiou, Henrik Møller, Tatiana V. Macfarlane, Xavier Castellsagué, Ariana Znaor, Mia Hashibe, Franco Merletti, Claire M. Healy, Manuela Marron, Paolo Boffetta, Paul Brennan, Gary J. Macfarlane, Miriam Schejbalova, Marron, M., Boffetta, P., Møller, H., Ahrens, W., Pohlabeln, H., Benhamou, S., Bouchardy, C., Lagiou, P., Lagiou, A., Slámová, A., Schejbalová, M., Merletti, F., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsague, X., Macfarlane, T.V., Macfarlane, G.J., Talamini, R., Barzan, L., Canova, C., Simonato, L., Biggs, A.-M., Thomson, P., Conway, D.I., McKinney, P.A., Znaor, A., Healy, C.M., McCartan, B.E., Brennan, P., and Hashibe, M.

Subjects
Adult, Male, medicine.medical_specialty, Gastrointestinal Neoplasms/epidemiology, Alcohol Drinking, Epidemiology, Beer/statistics & numerical data, Alcohol, Wine, Logistic regression, Europe/epidemiology, Alcohol Drinking/epidemiology, chemistry.chemical_compound, Age Distribution, Risk Factors, medicine, Odds Ratio, Humans, Sex Distribution, Wine/statistics & numerical data, ddc:613, Aged, Gastrointestinal Neoplasms, Alcoholic Beverages/classification/statistics & numerical data, business.industry, Alcoholic Beverages, Head and neck cancer, Carcinoma, Squamous Cell/epidemiology, Smoking, Case-control study, Cancer, Beer, Odds ratio, Smoking/epidemiology, Middle Aged, medicine.disease, Confidence interval, Surgery, Causality, Europe, chemistry, Case-Control Studies, Carcinoma, Squamous Cell, Female, Epidemiology Cancer Alcohol Wine Beer Liquor Head and neck cancer Upper aerodigestive tract cancer, business, Demography
Abstract

The general relationship between cancers of the upper aerodigestive tract (UADT) and alcohol drinking is established. Nevertheless, it is uncertain whether different types of alcoholic beverages (wine, beer and liquor) carry different UADT cancer risks. Our study included 2,001 UADT cancer cases and 2,125 controls from 14 centres in 10 European countries. All cases were histologically or cytologically confirmed squamous cell carcinomas. Controls were frequency matched by sex, age and centre. Logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (95 %CI) adjusted for age, sex, centre, education level, vegetable and fruit intake, tobacco smoking and alcohol drinking, where appropriate. Risk of beverage-specific alcohol consumption were calculated among 'pure drinker' who consumed one beverage type exclusively, among 'predominant drinkers' who consumed one beverage type to more than 66 % and among 'mixed drinkers' who consumed more than one beverage type to similar proportions. Compared to never drinkers and adjusted for cumulative alcohol consumption, the OR and 95 %CI for wine, beer and liquor drinking, respectively, were 1.24 (0.86, 1.78), 1.54 (1.05, 2.27) and 0.94 (0.53, 1.64) among 'pure drinkers' (p value for heterogeneity across beverage types = 0.306), 1.05 (0.76,1.47), 1.25 (0.87,1.79) and 1.43 (0.95, 2.16) among 'predominant drinkers' (p value = 0.456), and 1.09 (0.79, 1.50), 1.20 (0.88, 1.63) and 1.12 (0.82, 1.53) among 'mixed drinkers' (p value = 0.889). Risk of UADT cancer increased with increasing consumption of all three alcohol beverage types. Our findings underscore the strong and comparable carcinogenic effect of ethanol in wine, beer and liquor on organs of the UADT. © Springer Science+Business Media B.V. 2012.

Published
2012

133. A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers

Author

Vladimir Janout, Luigi Barzan, Jingchun Luo, Eleonora Fabianova, Joshua E. Muscat, Leticia Fernandez, Dan Chen, Shen Chih Chang, Shama Buch, Renato Talamini, Erich M. Sturgis, Claire M. Healy, Tomoko Nukui, Brock C. Christensen, Sergio Koifman, Jan Lubinski, Pagona Lagiou, Chu Chen, Alexandru Bucur, Jolanta Lissowska, Qingyi Wei, Nalin Thakker, Graham Byrnes, Philip Lazarus, Johannes J. Manni, Marcin Lener, Lorenzo Richiardi, Silvia Franceschi, Ivana Holcatova, Amelie Chabrier, Valerie Gaborieau, Paolo Boffetta, Simone Benhamou, Stefania Boccia, Wilbert H.M. Peters, Victor Wünsch-Filho, Joanna Trubicka, Ana M. B. Menezes, David I. Conway, Shu Chun Chuang, Ariana Znaor, Marjorie Romkes, Vladimir Bencko, Kristina Kjærheim, James McKay, Antonio Agudo, Martin Lacko, Cristina Canova, Andrew F. Olshan, Lenka Foretova, Tatiana V. Macfarlane, Rolando Herrero, Maria Paula Curado, Zuo-Feng Zhang, Xavier Castellsagué, Karl T. Kelsey, Wolfgang Ahrens, Mark C. Weissler, Mia Hashibe, José Eluf-Neto, Neonila Szeszenia-Dabrowska, Stephen M. Schwartz, Michael D. McClean, David Zaridze, Richard B. Hayes, Thérèse Truong, Renyi Wang, Paul Brennan, Chen, D., Truong, T., Gaborieau, V., Byrnes, G., Chabrier, A., Chuang, S.-C., Olshan, A.F., Weissler, M.C., Luo, J., Romkes, M., Buch, S., Nukui, T., Franceschi, S., Herrero, R., Talamini, R., Kelsey, K.T., Christensen, B., McClean, M.D., Lacko, M., Manni, J.J., Peters, W.H.M., Lubinski, J., Trubicka, J., Lener, M., Muscat, J.E., Lazarus, P., Wei, Q., Sturgis, E.M., Zhang, Z.-F., Chang, S.-C., Wang, R., Schwartz, S.M., Chen, C., Benhamou, S., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T.V., Barzan, L., Canova, C., Thakker, N.S., Conway, D.I., Znaor, A., Healy, C.M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Fabianova, E., Bucur, A., Bencko, V., Foretova, L., Janout, V., Curado, M.P., Koifman, S., Menezes, A., Wünsch-Filho, V., Eluf-Neto, J., Fernandez, L., Boccia, S., Hashibe, M., Hayes, R.B., Boffetta, P., Brennan, P., McKay, J.D., MUMC+: MA Keel Neus Oorheelkunde (9), Keel-, Neus- en Oorheelkunde, KNO, RS: MHeNs School for Mental Health and Neuroscience, and RS: GROW - School for Oncology and Reproduction

Subjects
Oncology, Male, Epidemiology, 0302 clinical medicine, Aged, Aged, 80 and over, Americas, Case-Control Studies, Europe, Female, Genotype, Head and Neck Neoplasms, Humans, Middle Aged, Sex Factors, Smoking, Chromosomes, Human, Pair 15, 80 and over, 15q25, 15q25 variant, 0303 health sciences, Head and Neck Cancer, 3. Good health, Case–control studies, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Molecular gastro-enterology and hepatology Translational research [IGMD 2], Human, medicine.medical_specialty, Chromosomes, Article, 03 medical and health sciences, Internal medicine, upper aerodigestive tract, cancers, medicine, otorhinolaryngologic diseases, Esophagus, Lung cancer, Settore MED/42 - IGIENE GENERALE E APPLICATA, 030304 developmental biology, Gynecology, business.industry, Head and neck cancer, association, Case-control study, Pair 15, Cancer, Odds ratio, medicine.disease, Confidence interval, sex-specific, stomatognathic diseases, variant, business
Abstract

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case–control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08–1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95–1.09, P = 0.66; P-heterogeneity (Phet) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12–1.34, P = 7 × 10−6) but not males (OR = 1.02, 95% CI = 0.97–1.08, P = 0.35; Phet = 6 × 10−4). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658–64. ©2011 AACR.

Published
2011

134. Tobacco smoking, alcohol drinking, and the risk of different histological types of nasopharyngeal cancer in a low-risk population

Author

Renato Talamini, Diego Serraino, Massimo Libra, Giovanni Franchin, Carlo La Vecchia, Emanuela Vaccher, Jerry Polesel, Eva Negri, Maurizio Montella, Silvia Franceschi, Luigi Barzan, J. Polesel, S. Franceschi, R. Talamini, E. Negri, L. Barzan, M. Montella, M. Libra, E. Vaccher, G. Franchin, C. La Vecchia, D. Serraino, Polesel J, Franceschi S, Talamini R, Negri E, Barzan L, Montella M, Libra M, Vaccher E, Franchin G, La Vecchia C, and Serraino D

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Epstein-Barr Virus Infections, Adolescent, Alcohol drinking, Young Adult, Risk Factors, Internal medicine, medicine, otorhinolaryngologic diseases, Odds Ratio, Nasopharyngeal carcinoma, Humans, Young adult, Risk factor, Aged, Case-control study, Tobacco smoking, business.industry, Confounding, Smoking, Cancer, Nasopharyngeal Neoplasms, Odds ratio, Middle Aged, medicine.disease, Confidence interval, stomatognathic diseases, Endocrinology, Logistic Models, Oncology, Italy, Case-Control Studies, Carcinoma, Squamous Cell, Female, Oral Surgery, business
Abstract

Nasopharyngeal carcinoma (NPC) is rare in western Countries. Tobacco smoking is a well-recognised risk factor, whereas the role of alcohol drinking is still in debate. We conducted a hospital-based case-control study in Italy on 150, histologically-confirmed, NPC cases of Caucasian ethnicity, aged 18-76 years, including 118 undifferentiated NPCs and 22 differentiated squamous-cell NPC. Controls were 450 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Cases and controls were matched according to sex, age, and place of residence. Logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) while adjusting for known confounders. No significant association emerged between tobacco smoking and all NPCs (OR for current vs. never smokers = 1.52; 95% CI: 0.89-2.60). Conversely, for differentiated NPC only, statistically significant elevated OR were associated with increasing smoking intensity (OR for >= 15 cigarettes/day = 5.40; 95% CI: 1.34-21.76) and duration of the habit (OR for >= 32 years = 4.48; 95% CI: 1.11-18.04). Although alcohol drinking was not, per se, significantly associated to NPC risk, the combination of tobacco smoking and alcohol drinking accounted for 57% of differentiated NPCs, whereas it accounted for only 14% of undifferentiated carcinomas. Our findings suggest that, in western populations, NPC includes two separate entities: the differentiated NPC, associated with tobacco smoking like other cancers of head and neck, and the undifferentiated NPC, upon which tobacco smoking has little or no influence. (C) 2011 Elsevier Ltd. All rights reserved.

Published
2011

135. Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals

Author

James McKay, Jolanta Lissowska, Antonio Agudo, Valerie Gaborieau, Ivana Holcatova, Cristina Canova, George Xinarianos, Maria Paula Curado, Epic Study, John K. Field, Ray Lowry, Peter Rudnai, Pagona Lagiou, Paolo Boffetta, Luigi Barzan, Andres Metspalu, David Zaridze, David I. Conway, José Eluf-Neto, Vladimir Bencko, Dana Mates, Xavier Castellsagué, Elena Matos, Lenka Foretova, Neonilia Szeszenia-Dabrowska, Claire M. Healy, Ariana Znaor, Simone Benhamou, Kristian Hveem, Paul Brennan, Mia Hashibe, Vladimir Janout, Eleonora Fabianova, Maiken Bratt Elvestad, Triantafillos Liloglou, Tatiana V. Macfarlane, Frank Skorpen, Sergio Koifman, Geoffrey Liu, Simon Heath, Leticia Fernandez, John R. McLaughlin, Ana M. B. Menezes, Esther H. Lips, Amelie Chabrier, Mark Lathrop, Rayjean J. Hung, Franco Merletti, Lars J. Vatten, Kristina Kjærheim, Lips, E.H., Gaborieau, V., McKay, J.D., Chabrier, A., Hung, R.J., Boffetta, P., Hashibe, M., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Bencko, V., Foretova, L., Janout, V., Field, J.K., Liloglou, T., Xinarianos, G., McLaughlin, J., Liu, G., Skorpen, F., Elvestad, M.B., Hveem, K., Vatten, L., Benhamou, S., Lagiou, P., Holcátová, I., Merletti, F., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T.V., Barzan, L., Canova, C., Lowry, R., Conway, D.I., Znaor, A., Healy, C., Curado, M.P., Koifman, S., Eluf-Neto, J., Matos, E., Menezes, A., Fernandez, L., Metspalu, A., Heath, S., Lathrop, M., and Brennan, P.

Subjects
Male, medicine.medical_specialty, Pathology, Lung Neoplasms, Genotype, Epidemiology, upper aerodigestive tract cancers, smoking quantity, 15q25 gene variant, Single-nucleotide polymorphism, Genome-wide association study, Receptors, Nicotinic, Gastroenterology, Polymorphism, Single Nucleotide, tobacco, smoking, Internal medicine, medicine, Odds Ratio, Humans, cancer, Allele, 15q25 gene, Lung cancer, Aged, Chromosomes, Human, Pair 15, business.industry, Cancer, General Medicine, Odds ratio, Tobacco Use Disorder, Middle Aged, medicine.disease, Minor allele frequency, Genetic Epidemiology, Female, business, Genome-Wide Association Study
Abstract

Background: Genetic variants in 15q25 have been identified as potential risk markers for lung cancer (LC), but controversy exists as to whether this is a direct association, or whether the 15q variant is simply a proxy for increased exposure to tobacco carcinogens. Methods: We performed a detailed analysis of one 15q single nucleotide polymorphism (SNP) (rs16969968) with smoking behaviour and cancer risk in a total of 17 300 subjects from five LC studies and four upper aerodigestive tract (UADT) cancer studies. Results: Subjects with one minor allele smoked on average 0.3 cigarettes per day (CPD) more, whereas subjects with the homozygous minor AA genotype smoked on average 1.2 CPD more than subjects with a GG genotype (P20 CPD) [odds ratio (OR)=1.13, 95% confidence interval (CI) 0.96-1.34, P=0.13 for heterozygotes and 1.81, 95% CI 1.39-2.35 for homozygotes, P

Published
2010

136. Multiple ADH genes are associated with upper aerodigestive cancers

Author

José Eluf-Neto, Mia Hashibe, Juan Lence, Renato Talamini, Luigi Barzan, Jolanta Lissowska, David Zaridze, Ioan Nicolae Mates, José Carlos de Oliveira, Gary J Macfarlane, Dana Mates, Simone Benhamou, Ivana Holcatova, Neonilia Szeszenia-Dabrowska, Ana M. B. Menezes, Lorenzo Richiardi, Tatiana V. Macfarlane, Helena Kollárová, Areti Lagiou, Amelie Chabrier, Christine Bouchardy, Pagona Lagiou, Xavier Castellsagué, Kristina Kjærheim, Oxana Shangina, Valerie Gaborieau, James McKay, Vladimir Bencko, Antonio Agudo, Marinel Mór Dall'Agnol, Elena Matos, Rosalina Jorge Koifman, Franco Merletti, Cristina Canova, Ariana Znaor, Paul Brennan, Ray Lowry, Eleonora Fabianova, José Eduardo Levi, Paolo Boffetta, Rayjean J. Hung, Patricia A. McKinney, L Simonato, Sergio Koifman, Vladimir Janout, Maria Paula Curado, Victor Wünsch-Filho, Leticia Fernandez, David I. Conway, Hashibe, M., McKay, J.D., Curado, M.P., Oliveira, J.C., Koifman, S., Koifman, R., Zaridze, D., Shangina, O., Wünsch-Filho, V., Eluf-Neto, J., Levi, J.E., Matos, E., Lagiou, P., Lagiou, A., Benhamou, S., Bouchardy, C., Szeszenia-Dabrowska, N., Menezes, A., Dall'Agnol, M.M., Merletti, F., Richiardi, L., Fernandez, L., Lence, J., Talamini, R., Barzan, L., Mates, D., Mates, I.N., Kjaerheim, K., MacFarlane, G.J., MacFarlane, T.V., Simonato, L., Canova, C., Holcátová, I., Agudo, A., Castellsagué, X., Lowry, R., Janout, V., Kollarova, H., Conway, D.I., McKinney, P.A., Znaor, A., Fabianova, E., Bencko, V., Lissowska, J., Chabrier, A., Hung, R.J., Gaborieau, V., Boffetta, P., and Brennan, P.

Subjects
Adult, Male, Esophageal Neoplasms, Alcohol Drinking, Genotype, Alcohol Dehydrogenase/genetics, Models, Biological, Polymorphism, Single Nucleotide, Age Distribution, Risk Factors, Multiple ADH genes associated upper aerodigestive cancers, Genetics, medicine, Humans, chemoprevention, Genetic Predisposition to Disease, Risk factor, Laryngeal Neoplasms, Gene, Alcohol dehydrogenase, ddc:613, biology, Alcohol-Induced Disorders/epidemiology/genetics, Alcohol Dehydrogenase, Esophageal Neoplasms/epidemiology/genetics, ADH1B, Cancer, Genetic markers, Middle Aged, medicine.disease, Laryngeal Neoplasms/epidemiology/genetics, Alcohol-Induced Disorders, Oropharyngeal Neoplasms/epidemiology/genetics, Oropharyngeal Neoplasms, Genetic marker, ADH7, Case-Control Studies, Cancer research, biology.protein, Female, Cancer Etiology
Abstract

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10-10 and 10 -9, respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology. © 2008 Nature Publishing Group.

Published
2008

137. Interleukin-10 and interleukin-18 promoter polymorphisms in an Italian cohort of patients with undifferentiated carcinoma of nasopharyngeal type

Author

Ettore Bidoli, Stefania Zanussi, Maria Teresa Bortolin, Chiara Pratesi, Emanuela Vaccher, Riccardo Dolcetti, Rosamaria Tedeschi, Paolo De Paoli, Massimo Guidoboni, Luigi Barzan, Calogero Caruso, Gianni Franchin, PRATESI C, BORTOLIN MT, BIDOLI E, TEDESCHI R, VACCHER E, DOLCETTI R, GUIDOBONI M, FRANCHIN G, BARZAN L, ZANUSSI S, CARUSO C, and DE PAOLI P

Subjects
Male, Cancer Research, Epstein-Barr Virus Infections, Genotype, Immunology, Nasopharyngeal neoplasm, Single-nucleotide polymorphism, Biology, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Cohort Studies, Interleukin-10, Interleukin-18, Single nucleotide polymorphisms (SNPs), Undifferentiated carcinoma of nasopharyngeal type (UCNT), Epstein Barr virus (EBV), Risk Factors, Genetic predisposition, Immunology and Allergy, Humans, Genetic Predisposition to Disease, Genetic variability, Allele, Promoter Regions, Genetic, Allele frequency, Inflammation, Carcinoma, Interleukin-8, Case-control study, Nasopharyngeal Neoplasms, Middle Aged, Prognosis, Interleukin-10, Oncology, Italy, Case-Control Studies, Female
Abstract

Purpose: Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV). Methods: Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions –1082, −819, −592 by direct sequencing and IL-18 gene at position −607 and −137 by allele –specific PCR. EBV DNA serum viremia was evaluated by QC-PCR. Results: The distributions of the IL-10 and IL-18 genetic variants were not different between UCNT patients and healthy controls. The frequency of IL-10 –1082G allele, which is associated with high IL-10 expression, showed a nearly statistically significant increase in UCNT patients EBV DNA-negative as compared to healthy controls (OR=3.3 95% CI: 1.2–9.8). Subjects with C/C or C/G combined IL-18 genotypes showed an increased risk of being with Stages III-IV (OR=2.1 95% CI: 1.2–6.6). Conclusion: This study was performed to improve the definition of the pathogenetic factors implicated in UCNT by addressing the correlation between cytokine polymorphisms and clinical parameters. This is the first study investigating the possible role of the IL-18 and IL-10 polymorphisms in the development and outcome of UCNT. In our genetic analysis there is no evidence for involvement of IL-10 promoter polymorphisms alone in the genetic predisposition to this tumor. On the other hand, IL18 genetic variants may represent a genetic risk factor for tumor aggressiveness.

Published
2006

138. Food groups, oils and butter, and cancer of the oral cavity and pharynx

Author

E. Conti, Silvia Franceschi, R. Talamini, A Favero, Eva Negri, C. La Vecchia, Roberto Volpe, Luigi Barzan, Franceschi S, Favero A, Conti E, Talamini R, Volpe R, Negri E, Barzan L, and La Vecchia C

Subjects
Adult, Male, Cancer Research, Alcohol Drinking, Dentistry, cancer of the oral cavity, oil, Oral cavity, Food group, Eating, Risk Factors, Humans, Medicine, Food science, Risk factor, Aged, Mouth neoplasm, business.industry, Smoking, Pharynx, Cancer, food and beverages, Pharyngeal Neoplasms, Regular Article, Middle Aged, medicine.disease, Dietary Fats, cancer of the pharynx, Diet, butter, medicine.anatomical_structure, Italy, Oncology, Epidermoid carcinoma, Case-Control Studies, Female, Mouth Neoplasms, business, Oils, Citrus fruit
Abstract

To elucidate the role of dietary habits, a study was carried out in 1992–1997 in the province of Pordenone in Northeastern Italy, and those of Rome and Latina in central Italy. Cases were 512 men and 86 women with cancer of the oral cavity and pharynx (lip, salivary glands and nasopharynx excluded) and controls were 1008 men and 483 women who had been admitted to local hospitals for a broad range of acute non-neoplastic conditions. The validated dietary section of the questionnaire included 78 foods or recipes and ten questions on fat intake patterns. After allowance for education, smoking, alcohol and total energy intake, significant trends of increasing risk with increasing intake emerged for soups, eggs, processed meats, cakes and desserts, and butter. Risk was approximately halved in the highest compared to the lowest intake quintile for coffee and tea, white bread, poultry, fish, raw and cooked vegetables, citrus fruit, and olive oil. The inverse association with oils, especially olive oil, was only slightly attenuated by allowance for vegetable intake. Thus, frequent consumption of vegetables, citrus fruit, fish and vegetable oils were the major features of a low-risk diet for cancer of the oral cavity and pharynx. © 1999 Cancer Research Campaign

Published
1999

139. A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers.

Author

Budhathoki S, Diergaarde B, Liu G, Olshan A, Ness A, Waterboer T, Virani S, Basta P, Bender N, Brenner N, Dudding T, Hayes N, Hope A, Huang SH, Hueniken K, Kanterewicz B, McKay JD, Pring M, Thomas S, Wisniewski K, Thomas S, Brhane Y, Agudo A, Alemany L, Lagiou A, Barzan L, Canova C, Conway DI, Healy CM, Holcatova I, Lagiou P, Macfarlane GJ, Macfarlane TV, Polesel J, Richiardi L, Robinson M, Znaor A, Brennan P, and Hung RJ

Subjects
Male, Humans, Female, Middle Aged, Human Papillomavirus Viruses, Genetic Markers, Risk Factors, Human papillomavirus 16 genetics, Antibodies, Viral, Transcription Factors genetics, Papillomavirus Infections, Head and Neck Neoplasms, Oropharyngeal Neoplasms, Oncogene Proteins, Viral genetics
Abstract

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer., (© 2023 UICC.)

Published
2023
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140. Multicentre study on resection margins in carcinoma of the oral cavity, oro-hypopharynx and larynx.

Author

Barzan L, Montomoli C, Di Carlo R, Bertinazzi M, Colangeli R, Martini A, Nicolai P, Gaio E, Artico R, Lupato V, Giacomarra V, Boscolo Nata F, Tirelli G, Lora L, Politi D, Spinato R, Menegaldo A, Boscolo Rizzo P, Da Mosto MC, Fiorino F, Herman I, Benazzo M, La Boria A, Grandi C, Fanetti G, Franchin G, Canzonieri V, Sulfaro S, Mazzoleni G, and Vaccher E

Subjects
Humans, Hypopharynx pathology, Margins of Excision, Mouth, Neoplasm Recurrence, Local surgery, Prognosis, Prospective Studies, Retrospective Studies, Carcinoma, Squamous Cell surgery, Larynx pathology
Abstract

Objective: The prognostic significance of the resection margins is still subject of conflicting opinions. The purpose of this paper is to report the results of a study on the margins in carcinoma of the oral cavity, oro-hypopharynx and larynx., Methods: A multicentre prospective study was carried out between 2015 and 2018 with the participation of 10 Italian reference hospitals. The primary objective was to evaluate local control in patients with well-defined clinical characteristics and comprehensive histopathological information., Results: During the study period, 455 patients were enrolled; the minimum follow-up was 2 years. Previous treatment, grading and fresh specimen examination were identified as risk factors for local control in multivariate analysis. On the basis of these results, it seems possible to delineate "risk profiles" for different oncological outcomes., Discussion: The prognostic significance of the margins is reduced, and other risk factors emerge, which require diversified treatment and follow-up., Conclusions: Multidisciplinary treatment with adjuvant therapy, if indicated, reduces the prognostic importance of margins. Collaboration with a pathologist is an additional favourable prognostic factor and quality indicator., An appendix with literature review is present in the online version., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Published
2022
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141. miR-9 modulates and predicts the response to radiotherapy and EGFR inhibition in HNSCC.

Author

Citron F, Segatto I, Musco L, Pellarin I, Rampioni Vinciguerra GL, Franchin G, Fanetti G, Miccichè F, Giacomarra V, Lupato V, Favero A, Concina I, Srinivasan S, Avanzo M, Castiglioni I, Barzan L, Sulfaro S, Petrone G, Viale A, Draetta GF, Vecchione A, Belletti B, and Baldassarre G

Subjects
Cell Line, Tumor, Cetuximab pharmacology, ErbB Receptors genetics, Humans, Squamous Cell Carcinoma of Head and Neck drug therapy, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck radiotherapy, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms genetics, Head and Neck Neoplasms radiotherapy, MicroRNAs genetics
Abstract

Radiotherapy (RT) plus the anti-EGFR monoclonal antibody Cetuximab (CTX) is an effective combination therapy for a subset of head and neck squamous cell carcinoma (HNSCC) patients. However, predictive markers of efficacy are missing, resulting in many patients treated with disappointing results and unnecessary toxicities. Here, we report that activation of EGFR upregulates miR-9 expression, which sustains the aggressiveness of HNSCC cells and protects from RT-induced cell death. Mechanistically, by targeting KLF5, miR-9 regulates the expression of the transcription factor Sp1 that, in turn, stimulates tumor growth and confers resistance to RT+CTX in vitro and in vivo. Intriguingly, high miR-9 levels have no effect on the sensitivity of HNSCC cells to cisplatin. In primary HNSCC, miR-9 expression correlated with Sp1 mRNA levels and high miR-9 expression predicted poor prognosis in patients treated with RT+CTX. Overall, we have discovered a new signaling axis linking EGFR activation to Sp1 expression that dictates the response to combination treatments in HNSCC. We propose that miR-9 may represent a valuable biomarker to select which HNSCC patients might benefit from RT+CTX therapy., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Published
2021
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142. CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer.

Author

Viotto D, Russo F, Anania I, Segatto I, Rampioni Vinciguerra GL, Dall'Acqua A, Bomben R, Perin T, Cusan M, Schiappacassi M, Gerratana L, D'Andrea S, Citron F, Vit F, Musco L, Mattevi MC, Mungo G, Nicoloso MS, Sonego M, Massarut S, Sorio R, Barzan L, Franchin G, Giorda G, Lucia E, Sulfaro S, Giacomarra V, Polesel J, Toffolutti F, Canzonieri V, Puglisi F, Gattei V, Vecchione A, Belletti B, and Baldassarre G

Subjects
Breast Neoplasms pathology, Cyclin-Dependent Kinase Inhibitor p27 genetics, Female, Humans, Intestinal Neoplasms pathology, MCF-7 Cells, Male, Mutation, Neuroendocrine Tumors pathology, Prostatic Neoplasms pathology, Breast Neoplasms genetics, Cyclin-Dependent Kinase Inhibitor p27 metabolism, DNA Copy Number Variations, Intestinal Neoplasms genetics, Neuroendocrine Tumors genetics, Prostatic Neoplasms genetics
Abstract

The CDKN1B gene, encoding for the CDK inhibitor p27 kip1 , is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra-deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor-positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27 kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell-free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27 kip1 protein truncation, leading to loss of most of the protein or of its C-terminal domain. Using a gene-editing approach in a luminal breast cancer cell line, MCF-7, we observed that the expression of p27 kip1 truncating mutants that lose the C-terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C-terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland., (© 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)

Published
2021
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143. Genetic Contributions to The Association Between Adult Height and Head and Neck Cancer: A Mendelian Randomization Analysis.

Author

Pastorino R, Puggina A, Carreras-Torres R, Lagiou P, Holcátová I, Richiardi L, Kjaerheim K, Agudo A, Castellsagué X, Macfarlane TV, Barzan L, Canova C, Thakker NS, Conway DI, Znaor A, Healy CM, Ahrens W, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Fabianova E, Mates IN, Bencko V, Foretova L, Janout V, Brennan P, Gaborieau V, McKay JD, and Boccia S

Subjects
Aged, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Body Height genetics, Head and Neck Neoplasms genetics, Mendelian Randomization Analysis methods, Polymorphism, Single Nucleotide
Abstract

With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.

Published
2018
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144. An Integrated Approach Identifies Mediators of Local Recurrence in Head and Neck Squamous Carcinoma.

Author

Citron F, Armenia J, Franchin G, Polesel J, Talamini R, D'Andrea S, Sulfaro S, Croce CM, Klement W, Otasek D, Pastrello C, Tokar T, Jurisica I, French D, Bomben R, Vaccher E, Serraino D, Belletti B, Vecchione A, Barzan L, and Baldassarre G

Subjects
Adult, Aged, Animals, Biomarkers, Tumor genetics, Carcinoma, Squamous Cell pathology, Cell Line, Tumor, Epithelial-Mesenchymal Transition genetics, Female, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms pathology, Humans, Keratin-13 genetics, Male, Mice, Middle Aged, Neoplasm Recurrence, Local pathology, Signal Transduction, Sp1 Transcription Factor genetics, Squamous Cell Carcinoma of Head and Neck, Transforming Growth Factor beta genetics, Tumor Suppressor Proteins genetics, Xenograft Model Antitumor Assays, Carcinoma, Squamous Cell genetics, Head and Neck Neoplasms genetics, MicroRNAs genetics, Neoplasm Recurrence, Local genetics
Abstract

Purpose: Head and neck squamous cell carcinomas (HNSCCs) cause more than 300,000 deaths worldwide each year. Locoregional and distant recurrences represent worse prognostic events and accepted surrogate markers of patients' overall survival. No valid biomarker and salvage therapy exist to identify and treat patients at high-risk of recurrence. We aimed to verify if selected miRNAs could be used as biomarkers of recurrence in HNSCC. Experimental Design: A NanoString array was used to identify miRNAs associated with locoregional recurrence in 44 patients with HNSCC. Bioinformatic approaches validated the signature and identified potential miRNA targets. Validation experiments were performed using an independent cohort of primary HNSCC samples and a panel of HNSCC cell lines. In vivo experiments validated the in vitro results. Results: Our data identified a four-miRNA signature that classified HNSCC patients at high- or low-risk of recurrence. These miRNAs collectively impinge on the epithelial-mesenchymal transition process. In silico and wet lab approaches showed that miR-9, expressed at high levels in recurrent HNSCC, targets SASH1 and KRT13, whereas miR-1, miR-133, and miR-150, expressed at low levels in recurrent HNSCC, collectively target SP1 and TGFβ pathways. A six-gene signature comprising these targets identified patients at high risk of recurrences, as well. Combined pharmacological inhibition of SP1 and TGFβ pathways induced HNSCC cell death and, when timely administered, prevented recurrence formation in a preclinical model of HNSCC recurrence. Conclusions: By integrating different experimental approaches and competences, we identified critical mediators of recurrence formation in HNSCC that may merit to be considered for future clinical development. Clin Cancer Res; 23(14); 3769-80. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Published
2017
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145. Prognostic significance of LINE-1 hypomethylation in oropharyngeal squamous cell carcinoma.

Author

Furlan C, Polesel J, Barzan L, Franchin G, Sulfaro S, Romeo S, Colizzi F, Rizzo A, Baggio V, Giacomarra V, Dei Tos AP, Boscolo-Rizzo P, Vaccher E, Dolcetti R, Sigalotti L, and Fratta E

Subjects
Carcinoma, Squamous Cell pathology, Epigenesis, Genetic, Female, Humans, Logistic Models, Male, Mouth Neoplasms, Neoplasm Staging, Oropharyngeal Neoplasms pathology, Prognosis, Recurrence, Carcinoma, Squamous Cell genetics, DNA Methylation, Long Interspersed Nucleotide Elements, Oropharyngeal Neoplasms genetics
Abstract

Background: Inclusion of new biomarkers to improve a personalized treatment approach for oropharyngeal squamous cell carcinoma (OPSCC) is urgently needed. Hypomethylation of the Long interspersed nucleotide element-1 (LINE-1) repetitive elements, a widely accepted surrogate of overall genomic DNA methylation content, was found to be associated with a poor prognosis in several cancers. At present, no studies have investigated the influence of LINE-1 methylation levels on OPSCC relapse. The main goal of this study was the evaluation of the prognostic value of LINE-1 methylation status in predicting early tumor relapse in locally advanced OPSCC., Methods: We retrospectively reviewed a cohort of 77 patients with stage III-IVB OPSCC. Methylation of LINE-1 repetitive sequences was evaluated by real-time quantitative methylation-specific PCR in formalin-fixed paraffin-embedded tissues. The prognostic relevance of LINE-1 methylation was assessed by comparing patients who relapsed within 2 years from the end of treatment (cases) with those who did not (controls). Results were validated in an independent cohort of 33 patients with OPSCC., Results: With respect to early OPSCC relapse, the mean LINE-1 methylation level was significantly lower in relapsed cases than in control group ( p  < 0.01). Interestingly, LINE-1 methylation was lower in relapsed cases than in controls in both HPV16-negative and HPV16-positive OPSCC patients, even if statistical significance was reached only for the former group ( p  = 0.01). LINE-1 methylation levels were also significantly reduced in relapsed cases with respect to the controls in OPSCC current smokers ( p  = 0.02). Consistently, in HPV16-negative current smokers, OPSCC relapse was significantly associated with decreased levels of LINE-1 methylation ( p  = 0.02). Using logistic regression model, we found that patients with hypomethylated LINE-1 were associated with a 3.5 higher risk of early relapse than hypermethylated ones (OR = 3.51; 95% CI 1.03-12.00). Adjustment for potential confounders did not substantially change the risk magnitude. Results from the validation cohort confirmed the lower LINE-1 methylation in patients who early relapsed compared to relapse-free patients., Conclusions: LINE-1 hypomethylation is associated with higher risk of early relapse in stage III-IVB OPSCC. Further validation in a prospective study is needed for its application in daily clinical practice.

Published
2017
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146. The impact of time to treatment initiation on survival from head and neck cancer in north-eastern Italy.

Author

Polesel J, Furlan C, Birri S, Giacomarra V, Vaccher E, Grando G, Gobitti C, Navarria F, Schioppa O, Minatel E, Bidoli E, Barzan L, and Franchin G

Subjects
Adolescent, Adult, Aged, Carcinoma, Squamous Cell pathology, Female, Head and Neck Neoplasms pathology, Humans, Italy, Male, Middle Aged, Squamous Cell Carcinoma of Head and Neck, Survival Analysis, Young Adult, Carcinoma, Squamous Cell therapy, Head and Neck Neoplasms therapy
Abstract

Objectives: To evaluate the impact of time to treatment initiation (TTI) on overall survival in patients with head-and-neck squamous cell carcinoma (HNSCC)., Materials and Methods: In the period 2003-2009, 1616 HNSCC patients were diagnosed in Friuli Venezia Giulia Region, Northeastern Italy, including 462 oral, 346 oropharyngeal, 212 hypopharyngeal, and 596 laryngeal cancers. Clinical information, including date and type of first treatment, and follow-up were retrieved from the regional Cancer Registry and a population-based health database collecting comprehensive health information on people living in the Region. Multivariate hazard ratio (HR) and confidence intervals (CI) were calculated through Cox model., Results: Overall, the median TTI was 28days, (Q1-Q3: 13-45days), but significant variations emerged according to anatomical site, cancer stage, treatment approach, and care transition to specialized centers. Five-year overall survival decreased with increasing treatment delay from 62% for TTI<30days to 39% for TTI≥90days (p<0.01). HR of death was 1.13 (95% CI: 0.92-1.39) for TTI between 45-89days, and 1.47 (1.05-2.05) for TTI≥90days. The association between TTI and poor prognosis was stronger for laryngeal cancers and early-stage HNSCCs. Further, care transition from community hospitals to specialized centers was associated to a better prognosis (HR=0.73; 95% CI: 0.60-0.88)., Conclusion: Our study findings suggest that HNSCC patients treated within 45days from diagnosis have increased survival probabilities and that early-stage patients suffered the most from treatment delay. Furthermore, care transition to specialized centers -though competitive to timely treatment- improves survival by providing the most innovative technologies and treatment approaches., (Copyright © 2017. Published by Elsevier Ltd.)

Published
2017
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147. Long-term update of the 24954 EORTC phase III trial on larynx preservation.

Author

Henriques De Figueiredo B, Fortpied C, Menis J, Lefebvre JL, Barzan L, de Raucourt D, Geoffrois L, Giurgea L, Hupperets P, Leemans CR, Licitra L, Rolland F, Tesselaar M, Vermorken JB, and Grégoire V

Subjects
Adult, Aged, Carcinoma, Squamous Cell pathology, Cisplatin administration & dosage, Disease Progression, Dose Fractionation, Radiation, Female, Fluorouracil administration & dosage, Humans, Hypopharyngeal Neoplasms pathology, Laryngeal Neoplasms pathology, Laryngectomy, Male, Middle Aged, Survival Analysis, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Squamous Cell therapy, Chemoradiotherapy methods, Hypopharyngeal Neoplasms therapy, Laryngeal Neoplasms therapy, Larynx, Organ Sparing Treatments methods
Abstract

The long-term results of the EORTC 24954 trial comparing sequential versus alternating chemotherapy and radiotherapy (RT) for patients with locally advanced laryngeal and hypopharyngeal cancer are reported. From 1996 to 2004, 450 patients were randomly assigned (1-1) to a sequential arm (SA = induction cisplatin-5fluorouracil followed by a 70Gy-RT for the responders or a total laryngectomy and post-operative RT for the non-responders) and an alternating arm (AA = cisplatin-5fluorouracil alternated with three 2-week courses of 20 Gy-RT for a total dose of 60 Gy). Median follow-up was 10.2 years. Ten-year survival with functional larynx (primary end-point) and overall survival were similar in both arms (18.7% and 33.6% in SA versus 18.3% and 31.6% in AA). Late toxicity was also similar; however, a trend for higher larynx preservation and better laryngeal function was observed in AA., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Published
2016
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148. Broadening Specificity and Enhancing Cytotoxicity of Adoptive T Cells for Nasopharyngeal Carcinoma Immunotherapy.

Author

Faè DA, Martorelli D, Mastorci K, Muraro E, Dal Col J, Franchin G, Barzan L, Comaro E, Vaccher E, Rosato A, and Dolcetti R

Subjects
Antibiotics, Antineoplastic pharmacology, Antigen-Presenting Cells immunology, Carcinoma, Cell Differentiation immunology, Cell Line, Tumor, Cytotoxicity, Immunologic immunology, Doxorubicin pharmacology, Herpesvirus 4, Human immunology, Humans, Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms immunology, Nasopharyngeal Neoplasms pathology, Tumor Cells, Cultured, Up-Regulation drug effects, Viral Proteins biosynthesis, Viral Proteins genetics, Immunotherapy, Adoptive methods, Nasopharyngeal Neoplasms therapy, T-Lymphocytes, Cytotoxic immunology
Abstract

Although promising, clinical responses to adoptive immunotherapy for nasopharyngeal carcinoma (NPC) are still limited by the restricted number of Epstein-Barr virus (EBV) antigens that can be targeted and their poor immunogenicity. Our previous work indicated that the immunogenic features of the NPC-associated viral antigen BARF1 may be exploited for immunotherapeutic purposes. Nevertheless, T-cell lines obtained with current protocols include only negligible numbers of BARF1-specific cytotoxic T lymphocytes, pointing to the need to enrich these effectors in BARF1 specificities. Considering that in B lymphocytes BARF1 is mainly a lytic EBV antigen, we tested different EBV lytic-cycle inducers (TPA/butyric acid, doxorubicin, and cisplatin) used at suboptimal concentrations for their ability to upregulate BARF1 expression in lymphoblastoid B-cell lines (LCL), the commonly used antigen-presenting cells, without compromising their survival. The LCLs treated with doxorubicin (DX-LCL) can reproducibly and efficiently generate EBV-specific effectors enriched in BARF1 specificities from both healthy donors and NPC patients. These DX-LCLs also had more pronounced immunogenic properties, including HLA class I upregulation and expression of immunogenic cell death markers, such as enhanced calreticulin exposure and HMGB1 release. In particular, doxorubicin triggers an HMGB1 autocrine/paracrine loop with its receptor, TLR4, which is also upregulated in DX-LCLs and is responsible for NF-κB activation and a delayed apoptosis that allows a prolonged stimulation of EBV-specific T-cell precursors. This protocol may thus constitute a valid alternative to the use of engineered LCLs to generate EBV-specific T-cell lines for adoptive immunotherapy, being relatively simple, easily upgradable to Good Manufacturing Practice standards, and therefore more broadly applicable. Cancer Immunol Res; 4(5); 431-40. ©2016 AACR., (©2016 American Association for Cancer Research.)

Published
2016
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149. Lower platelet counts and antiplatelet therapy independently predict better outcomes in patients with head and neck squamous cell carcinoma: a retrospective analysis.

Author

Furlan C, Steffan A, Polesel J, Trovo M, Gobitti C, Vaccher E, Serraino D, Barzan L, and Franchin G

Abstract

The paper by Rachidi et al. suggests that antiplatelet drugs may play a role in ameliorating the clinical outcome in a large series of patients with head and neck cancer managed with either surgery or radiation. Our data, as well as confirming the results observed by the authors, enhance their clinical relevance pointing out the effect of antiplatelet drugs in terms of locoregional control in the setting of patients with advanced head and neck cancer managed with definitive chemo-radiotherapy.

Published
2015
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150. Effectiveness of selective neck dissection in head and neck cancer: the experience of two Italian centers.

Author

Barzan L, Talamini R, Franchin G, Pin M, Silvestrini M, Grando G, Galla S, Savignano MG, Armas G, Margiotta F, Vanoni V, Magri E, and Grandi C

Subjects
Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell epidemiology, Carcinoma, Squamous Cell surgery, Female, Follow-Up Studies, Head and Neck Neoplasms epidemiology, Head and Neck Neoplasms surgery, Humans, Italy epidemiology, Lymphatic Metastasis, Male, Middle Aged, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck, Treatment Outcome, Young Adult, Carcinoma, Squamous Cell secondary, Elective Surgical Procedures methods, Head and Neck Neoplasms secondary, Neck Dissection methods
Abstract

Objective: The aim of this study was to evaluate the oncologic outcomes after a selective neck dissection (SND), both in elective and therapeutic settings, with particular regard to regional recurrence rate., Methods: Retrospective analysis of 827 patients with head and neck primary tumors submitted to SND from 1999 to 2011 in two large hospital centers of northern Italy., Results: A total of 40 neck recurrences were found in the whole series, with the same incidence after primary or salvage surgery (4.4% and 5.2%, respectively), but only 22 neck recurrences occurred in the same side of the dissected neck (3.0%). Factors predicting an increase of ipsilateral neck relapse were pathologically positive nodes, number of positive nodes, and nodal ratio (ratio between positive nodes and total nodal removed), but the risk of regional relapse did not exceed 5.0% in any subgroups. A total of 320 patients (39%) had postoperative radiotherapy (52.0% and 22.0% after primary and salvage surgery, respectively). Considering the primary surgery group alone, postoperative radiotherapy produced only a light reduction of homolateral neck recurrence rate in patients with pathological positive nodes (2.4% vs. 5.0%), but it impacted significantly disease-specific survival, both in pathological classification of nodes (pN)1 and pN2-3 patients., Conclusion: The SND can be considered a safe and sound procedure both in primary surgery and in salvage setting. Postoperative radiotherapy adds minor advantage to regional control only in node-positive patients but may impact survival., Level of Evidence: 4., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Published
2015
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