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102. Prognostic significance of the Ca2+ binding protein S100A2 in laryngeal squamous-cell carcinoma

Author

Lauriola, Libero, Michetti, Fabrizio, Maggiano, N., Galli, Jacopo, Cadoni, Gabriella, Scḧafer, B., Heizmann, C., Ranelletti, F., Lauriola L. (ORCID:0000-0003-0481-5138), Michetti F. (ORCID:0000-0003-2546-0532), Galli J. (ORCID:0000-0001-6353-6249), Cadoni G. (ORCID:0000-0001-8244-784X), Lauriola, Libero, Michetti, Fabrizio, Maggiano, N., Galli, Jacopo, Cadoni, Gabriella, Scḧafer, B., Heizmann, C., Ranelletti, F., Lauriola L. (ORCID:0000-0003-0481-5138), Michetti F. (ORCID:0000-0003-2546-0532), Galli J. (ORCID:0000-0001-6353-6249), and Cadoni G. (ORCID:0000-0001-8244-784X)

Abstract

We investigated by immunocytochemistry the expression of the Ca(2+) binding protein S100A2 in 62 cases of laryngeal squamous-cell carcinoma (SCC). S100A2 was detected in 18/19 (95%) low-grade tumors and in 22/43 (51%) high-grade tumors, which were partially keratinizing. The remaining 21/43 (49%) high-grade tumors were non-keratinizing, anaplastic tumors and clearly S100A2-negative. In normal laryngeal squamous epithelium and in laryngeal SCC, S100A2 expression was strictly associated with that of cytokeratins 14 (P = 0.0002) and 17 (P = 0.0021), suggesting an association of S100A2 expression and cell commitment to squamous differentiation. A correlation was found between S100A2 tumor positivity and longer relapse-free (P = 0.0005) and overall (P = 0.0095) survival.

Published
2000

103. Prospects and therapeutic decisions in the light of biological findings in laryngeal cancer

Author

Almadori, Giovanni, Galli, Jacopo, Cadoni, Gabriella, Bussu, Francesco, Scarano, E., Maurizi, Maurizio, Almadori G. (ORCID:0000-0002-4605-2442), Galli J. (ORCID:0000-0001-6353-6249), Cadoni G. (ORCID:0000-0001-8244-784X), Bussu F. (ORCID:0000-0001-6261-2772), Maurizi M., Almadori, Giovanni, Galli, Jacopo, Cadoni, Gabriella, Bussu, Francesco, Scarano, E., Maurizi, Maurizio, Almadori G. (ORCID:0000-0002-4605-2442), Galli J. (ORCID:0000-0001-6353-6249), Cadoni G. (ORCID:0000-0001-8244-784X), Bussu F. (ORCID:0000-0001-6261-2772), and Maurizi M.

Abstract

head and neck

Published
2000

107. Tc99m-sestamibi SPECT and head and neck tumors: preliminary data

Author

Galli, Jacopo, Giordano, Alessandro, Corina, Luigi, Maccafeo, S., Cadoni, Gabriella, D'Andrea, G., Almadori, Giovanni, Galli J. (ORCID:0000-0001-6353-6249), Giordano A. (ORCID:0000-0002-6978-0880), Corina L., Cadoni G. (ORCID:0000-0001-8244-784X), Almadori G. (ORCID:0000-0002-4605-2442), Galli, Jacopo, Giordano, Alessandro, Corina, Luigi, Maccafeo, S., Cadoni, Gabriella, D'Andrea, G., Almadori, Giovanni, Galli J. (ORCID:0000-0001-6353-6249), Giordano A. (ORCID:0000-0002-6978-0880), Corina L., Cadoni G. (ORCID:0000-0001-8244-784X), and Almadori G. (ORCID:0000-0002-4605-2442)

Abstract

After underlining recent progress in nuclear medicine diagnostics, even in oncology, the authors describe the most important methods used and oncotropic capacity of some radiodrugs currently used in clinical practice: i.e. perfusion tracers. Then they present the results of a personal experience using Tc99m-SestaMIBI SPET in detail. Fifteen patients suffering from various primary head and neck neoplasms underwent systematic clinical evaluation, endoscopy, CT and/or MRI and Tc99m-SestaMIBI SPET. The authors then briefly describe the method and underline the fact that the literature lacks any homogeneous data on the use of Tc99m-SestaMIBI SPET in the study of head and neck neoplasms. The results indicate that the method is reliable in identifying both primary tumors and laterocervical metastases. Then, taking indication from the only case currently available on post-radiotherapy recurrence, the authors suggest an interesting field of application for this technique: the study of post-radio-chemotherapy and/or surgery recurrences. In conclusion, the authors underline the valid contribution this method currently offers both in diagnosis and follow-up as well as its future of ever expanding clinical applications.

Published
1999

110. The contribution of immunoscintigraphy to the diagnosis of head and neck tumours

Author

De Rossi, G. D., Di Giuda, Daniela, Maurizi, Maurizio, Almadori, Giovanni, Paludetti, Gaetano, Cadoni, Gabriella, Ottaviani, F., Galli, Jacopo, Di Giuda D. (ORCID:0000-0002-5758-3986), Maurizi M., Almadori G. (ORCID:0000-0002-4605-2442), Paludetti G. (ORCID:0000-0003-2480-1243), Cadoni G. (ORCID:0000-0001-8244-784X), Galli J. (ORCID:0000-0001-6353-6249), De Rossi, G. D., Di Giuda, Daniela, Maurizi, Maurizio, Almadori, Giovanni, Paludetti, Gaetano, Cadoni, Gabriella, Ottaviani, F., Galli, Jacopo, Di Giuda D. (ORCID:0000-0002-5758-3986), Maurizi M., Almadori G. (ORCID:0000-0002-4605-2442), Paludetti G. (ORCID:0000-0003-2480-1243), Cadoni G. (ORCID:0000-0001-8244-784X), and Galli J. (ORCID:0000-0001-6353-6249)

Abstract

Immunoscintigraphy with 111In-F(ab')2-anti-carcinoembryonic-antigen monoclonal antibody was performed in patients with primary head and neck tumours (n = 14), recurrences (n = 3) and suspected posttherapy lymph node metastases (n = 3). No false-positive but two false-negative results were obtained. Single photon emission tomography was performed 24 h after the intravenous administration of the radiopharmaceutical with a positive predictive value of 100% and a sensitivity of 90%. Only two very small (< 1 mm diameter) and necrotic primary tumours escaped detection, while the recurrences and lymph node metastases were always correctly diagnosed, in contrast to computerized tomography and ultrasound. Even though highly selective patients only were considered in the present research, the results do suggest that immunoscintigraphy may be usefully applied in all routine protocols for the study of head and neck cancer. © 1997 Chapman and Hall ltd.

Published
1997

111. Imaging case study of the month monolateral aplasia of the parotid gland

Author

Almadori, Giovanni, Cadoni, Gabriella, Ottaviani, F., De Rossi, G., Del Ninno, M., Paludetti, Gaetano, Almadori G. (ORCID:0000-0002-4605-2442), Cadoni G. (ORCID:0000-0001-8244-784X), Paludetti G. (ORCID:0000-0003-2480-1243), Almadori, Giovanni, Cadoni, Gabriella, Ottaviani, F., De Rossi, G., Del Ninno, M., Paludetti, Gaetano, Almadori G. (ORCID:0000-0002-4605-2442), Cadoni G. (ORCID:0000-0001-8244-784X), and Paludetti G. (ORCID:0000-0003-2480-1243)

Published
1997

112. Pleomorphic adenoma of the lower turbinates: clinical case and review of literature

Author

Carriero, E., Almadori, Giovanni, Cadoni, Gabriella, Almadori G. (ORCID:0000-0002-4605-2442), Cadoni G. (ORCID:0000-0001-8244-784X), Carriero, E., Almadori, Giovanni, Cadoni, Gabriella, Almadori G. (ORCID:0000-0002-4605-2442), and Cadoni G. (ORCID:0000-0001-8244-784X)

Abstract

A case of pleomorphic adenoma of the lower turbinate salivary glands is presented. A careful review of the literature has revealed that this is a highly unusual site for such neoplasms. The scarcity of symptoms is underlined as the lesion can long go unrecognized. Moreover, it is pointed out that, since only a small number of cases have thus far been presented for this benign lesion the prognostic factors indicating a clinical evolution to malignancy are as yet unknown. For this reason the authors feel it advisable to perform conservative surgery and carry out a careful follow-up.

Published
1997

113. Telomerase activity in human laryngeal squamous cell carcinomas

Author

Hohaus, Stefan, Cavallo, S, Bellacosa, A, Genuardi, Maurizio, Galli, Jacopo, Cadoni, Gabriella, Almadori, Giovanni, Lauriola, Libero, Litwin, S, Maurizi, Maurizio, Neri, G, Hohaus, S (ORCID:0000-0002-5534-7197), Genuardi, M (ORCID:0000-0002-7410-8351), Galli, J (ORCID:0000-0001-6353-6249), Cadoni, G (ORCID:0000-0001-8244-784X), Almadori, G (ORCID:0000-0002-4605-2442), Lauriola, L (ORCID:0000-0003-0481-5138), Maurizi, M, Hohaus, Stefan, Cavallo, S, Bellacosa, A, Genuardi, Maurizio, Galli, Jacopo, Cadoni, Gabriella, Almadori, Giovanni, Lauriola, Libero, Litwin, S, Maurizi, Maurizio, Neri, G, Hohaus, S (ORCID:0000-0002-5534-7197), Genuardi, M (ORCID:0000-0002-7410-8351), Galli, J (ORCID:0000-0001-6353-6249), Cadoni, G (ORCID:0000-0001-8244-784X), Almadori, G (ORCID:0000-0002-4605-2442), Lauriola, L (ORCID:0000-0003-0481-5138), and Maurizi, M

Abstract

The activation of telomerase has been shown to be an important step during tumorigenesis in a variety of malignancies and is associated with characteristics of cellular immortality, such as indefinite proliferative potential, We studied telomerase activity in a series of human laryngeal carcinomas, Thirty-six tumors from 35 patients were studied using a sensitive PCR-based technique, the telomeric repeat amplification protocol assay, Telomerase activity was present in 32 tumors (89%), and the level of activity correlated with the stage of disease. In two of four telomerase-negative tumors, we found evidence of an inhibitor of telomerase activity, In many cases, samples of mucosa surrounding the tumor were also studied, and telomerase could be detected in 16 of 21 patients, For this reason, we proceeded to perform a topographical analysis that demonstrated a pattern of telomerase activity suggestive of a spread of telomerase-positive cells, In conclusion, these data indicate that telomerase activation is important for laryngeal carcinogenesis and that telomerase assay might be a valuable addition to determine the spread of the disease.

Published
1996

114. Facial nerve paralysis in acute otomastoiditis as presenting symptom of FAB M2, T8;21 leukemic relapse. Case report and review of the literature

Author

Almadori, Giovanni, Del Ninno, M., Cadoni, Gabriella, Di Mario, Antonella, Ottaviani, F., Almadori G. (ORCID:0000-0002-4605-2442), Cadoni G. (ORCID:0000-0001-8244-784X), Di Mario A., Almadori, Giovanni, Del Ninno, M., Cadoni, Gabriella, Di Mario, Antonella, Ottaviani, F., Almadori G. (ORCID:0000-0002-4605-2442), Cadoni G. (ORCID:0000-0001-8244-784X), and Di Mario A.

Abstract

Granulocytic sarcoma (chloroma) is a rare solid, extramedullary tumour composed of immature granulocytes, occurring during granulocytic leukemia. Leukemic involvement of the temporal bone is not uncommon and may present in a variety of ways. Symptomatic facial nerve paralysis is one of these. The authors report a case of facial nerve paralysis as the presenting symptom of leukemic relapse in a 16-year-old white male, affected by acute myelogenous leukemia FAB M2, karyotype 46xy, T8;21.

Published
1996

115. Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors

Author

Scambia, G., Catozzi, L., Benedetti Panici, P., Ferrandina, G., Almadori, G., Paludetti, G., Cadoni, G., Distefano, M., Piffanelli, A., Mancuso, S., G. Scambia (ORCID:0000-0003-2758-1063), G. Ferrandina (ORCID:0000-0003-4672-4197), G. Almadori (ORCID:0000-0002-4605-2442), G. Paludetti (ORCID:0000-0003-2480-1243), G. Cadoni (ORCID:0000-0001-8244-784X), S. Mancuso, Scambia, G., Catozzi, L., Benedetti Panici, P., Ferrandina, G., Almadori, G., Paludetti, G., Cadoni, G., Distefano, M., Piffanelli, A., Mancuso, S., G. Scambia (ORCID:0000-0003-2758-1063), G. Ferrandina (ORCID:0000-0003-4672-4197), G. Almadori (ORCID:0000-0002-4605-2442), G. Paludetti (ORCID:0000-0003-2480-1243), G. Cadoni (ORCID:0000-0001-8244-784X), and S. Mancuso

Abstract

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer.

Published
1994

116. Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: Correlation with histopathological features and epidermal growth factor receptors

Author

Scambia, Giovanni, Catozzi, L., Benedetti Panici, P., Ferrandina, Maria Gabriella, Almadori, Giovanni, Paludetti, Gaetano, Cadoni, Gabriella, Distefano, M., Piffanelli, A., Mancuso, Salvatore, Maurizi, Maurizio, Scambia G. (ORCID:0000-0003-2758-1063), Ferrandina G. (ORCID:0000-0003-4672-4197), Almadori G. (ORCID:0000-0002-4605-2442), Paludetti G. (ORCID:0000-0003-2480-1243), Cadoni G. (ORCID:0000-0001-8244-784X), Mancuso S., Maurizi M., Scambia, Giovanni, Catozzi, L., Benedetti Panici, P., Ferrandina, Maria Gabriella, Almadori, Giovanni, Paludetti, Gaetano, Cadoni, Gabriella, Distefano, M., Piffanelli, A., Mancuso, Salvatore, Maurizi, Maurizio, Scambia G. (ORCID:0000-0003-2758-1063), Ferrandina G. (ORCID:0000-0003-4672-4197), Almadori G. (ORCID:0000-0002-4605-2442), Paludetti G. (ORCID:0000-0003-2480-1243), Cadoni G. (ORCID:0000-0001-8244-784X), Mancuso S., and Maurizi M.

Abstract

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer. © 1994 Macmillan Press Ltd.

Published
1994

117. Hemangiopericytoma of parapharyngeal space

Author

Rosignoli, M., Cadoni, Gabriella, Rabitti, Carla, Galli, Jacopo, Cadoni G. (ORCID:0000-0001-8244-784X), Rabitti C., Galli J. (ORCID:0000-0001-6353-6249), Rosignoli, M., Cadoni, Gabriella, Rabitti, Carla, Galli, Jacopo, Cadoni G. (ORCID:0000-0001-8244-784X), Rabitti C., and Galli J. (ORCID:0000-0001-6353-6249)

Abstract

The parapharyngeal space is a rare site of parapharyngeal neoplasms: their diagnosis and therapeutic treatment offer peculiar challenges. Parapharyngeal tumours may be primary, metastatic or diffused with regaed continuity. They are mostly benign (mixed, neurogenic, vascular tumours, etc.) rather than malignant neoplasms (adenocystic carcinoma, adenocarcinoma, lymphoma, etc.). In order to diagnosis parapharyngeal tumours differentially it is important to consider very rare type of neoplasms such as hemangiopericytomas. In this paper the Authors describe a case of hemangiopericytoma of the parapharyngeal space indicating the main diagnosis procedures, especially CT scan, Magnetic resonance and angiography. They discuss pathological aspects with particular regard to the differential diagnosis between benign and malignant tumour of this kind as well as prognoses. The Authors also describe surgical treatment in relation to particular parapharyngeal localization.

Published
1993

118. Consideration on pylomatrixoma in pediatric E.N.T

Author

Ottaviani, F., Rosignoli, M., Scarano, E., Cadoni, Gabriella, Cadoni G. (ORCID:0000-0001-8244-784X), Ottaviani, F., Rosignoli, M., Scarano, E., Cadoni, Gabriella, and Cadoni G. (ORCID:0000-0001-8244-784X)

Abstract

pilomatrixoma

Published
1991

128. Can Chronic Nasal Obstruction Cause Dysfunction of the Paratubal Muscles and Otitis Media? An Experimental Study in Developing Wistar Rats.

Author

Sarcano, E., Fetoni, A.R., Picciotti, P., Cadoni, G., Galli, J., and Paludetti, G.

Subjects
EUSTACHIAN tube, OTITIS media
Abstract

Objective-To quantitatively analyze modifications of the paratubal muscles in developing Wistar rats following nasal obstruction. Material and Methods-Twenty-four Wistar rats were used. Twelve were examined at 6, 8 and 12 weeks after birth and were considered normal controls. The nostrils of the remaining 12 rats were bilaterally obstructed by means of a synthetic resin 28 days after birth. The animals were sacrificed at either 2, 4 or 8 weeks after nostril occlusion. Serial sections were made in the dorsoventral plane and stained with hematoxylin-eosin. Four 5×5 μm[SUP2] areas, selected within the paratubal muscles, were histologically analyzed and the number of muscular fibers was counted manually. Results-The number of tensor veli palatini muscle fibers progressively decreased in the obstructed rats compared with age-matched normal controls and in those that had been obstructed for 4 and 8 weeks these reductions were statistically significant. Conclusion-The correct development of the paratubal muscles seems to be linked to physiological nasal breathing and is negatively affected by oral breathing. [ABSTRACT FROM AUTHOR]

Published
2003

132. Association between cyclin D1 (CCND1) gene amplification and human papillomavirus infection in human laryngeal squamous cell carcinoma

Author

Cattani, P., Hohaus, S., Bellacosa, A., Genuardi, M., Cavallo, S., Valentina Rovella, Almadori, G., Cadoni, G., Galli, J., Maurizi, M., Fadda, G., and Neri, G.

Subjects
Adult, Male, EXPRESSION, HPV, FIBROBLASTS, Settore MED/03 - GENETICA MEDICA, Settore MED/06, POLYMERASE CHAIN-REACTION, NECK-CANCER, VIRUS, HEAD, P53, DNA, MUTATIONS, 80 and over, Humans, Cyclin D1, Viral, Laryngeal Neoplasms, Papillomaviridae, Aged, Aged, 80 and over, Papillomavirus Infections, Carcinoma, Gene Amplification, Middle Aged, Tumor Virus Infections, Squamous Cell, DNA, Viral, Carcinoma, Squamous Cell, Female
Abstract

Head and neck squamous cell carcinomas (SCCs) seem to follow a multistep process of carcinogenesis in which chemical and/or viral agents are associated with specific genetic alterations. The prevalence of human papillomavirus (HPV) infection and the amplification of the cyclin D1 (CCND1) gene were evaluated in a series of 75 laryngeal SCCs by PCR with HPV consensus primers and Southern blot analysis with a CCND1-specific probe, respectively. HPV DNA was detected in 22 of 75 (29.3%) tumors, and it belonged almost exclusively to the highly oncogenic HPV-16, HPV-18, and HPV-33. CCND1 gene amplification was found in 15 of 75 (20%) tumors, and it was associated with HPV infection in a statistically significant manner (chi2 = 20.3; P0.001). Because the viral oncoproteins E6 and E7 from high-risk HPV types are known to promote genomic rearrangements, these findings suggest that amplification of the CCND1 gene in laryngeal SCCs may occur as a consequence of the genomic instability associated with HPV infection. In turn, amplified CCND1, either alone or in conjunction with a direct action of the viral oncoproteins E6 and E7, could lead to a perturbation of the cell cycle. This model could explain the involvement of high-risk HPV types in laryngeal carcinogenesis.

137. A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes, cell cycle control and alcohol metabolism,Revisione narrativa sulla epidemiologia genetica dei polimorfismi, dei geni metabolici, dei geni del ciclo cellulare e dei geni del metabolismo dell'alcool, implicati nel rischio del cancro testa-collo

Author

Cadoni, G., Stefania Boccia, Petrelli, L., Di Giannantonio, P., Arzani, D., Giorgio, A., Feo, E., Pandolfini, M., Gallì, P., Paludetti, G., and Ricciardi, G.

139. Telomerase activity in human laryngeal squamous cell carcinomas

Author

Hohaus, S., Cavallo, S., Bellacosa, A., Genuardi, M., Galli, J., Cadoni, G., Giovanni ALMADORI, Lauriola, L., Litwin, S., Maurizi, M., and Neri, G.

Subjects
EXPRESSION, NECK-CANCER, P53 GENE, MUTATIONS, HEAD, OVEREXPRESSION, ASSOCIATION, SMOKING, TUMORS, Settore MED/03 - GENETICA MEDICA

140. A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

Author

Arzani Dario, Giorgio Arianna, Amore Rosarita, De Feo Emma, Volante Mariangela, Cadoni Gabriella, Gallì Paola, Paludetti Gaetano, Ricciardi Gualtiero, and Boccia Stefania

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The purpose of this study is to analyze the combined effects of selected p53 and p73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population. Methods Two hundred and eighty-three cases and 295 hospital controls were genotyped for p53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and p73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the p53 polymorphisms, and a gene-gene interaction analysis for the combined effects of p73 G4C14-to-A4T14 and p53 polymorphisms. Results We found a significant increased risk of SCCHN among individuals with combined p73 exon 2 G4A and p53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the p53 exon 4-p53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying p73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among p53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16). Conclusion Our study provides for the first time evidence that individuals carrying p53 exon 4 and p53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of p73 exon 2 G4C14-to-A4T14 and p53 intron 3 variant allele. Larger studies are required to confirm these findings.

Published
2009
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141. Lessons learned from the INHANCE consortium: An overview of recent results on head and neck cancer

Author

Bravi, Francesca, Lee, Yuan‐Chin Amy, Hashibe, Mia, Boffetta, Paolo, Conway, David I., Ferraroni, Monica, La Vecchia, Carlo, Edefonti, Valeria, Agudo, Antonio, Ahrens, Wolfgang, Benhamou, Simone, Boccia, Stefania, Brennan, Paul, Brenner, Hermann, Cadoni, Gabriella, Canova, Cristina, Chen, Chu, Chuang, Shu‐Chun, Curado, Maria Paula, Dal Maso, Luigino, Daudt, Alexander W., D'Souza, Gypsyamber, Fabianova, Eleonora, Fernandez, Leticia, Franceschi, Silvia, Garavello, Werner, Gillison, Maura, Gross, Neil D., Hayes, Richard B., Healy, Claire, Herrero, Rolando, Holcatova, Ivana, Kelsey, Karl, Kjaerheim, Kristina, Koifman, Rosalina, Lagiou, Pagona, Lazarus, Philip, Levi, Fabio, Li, Guojun, Lissowska, Jolanta, Luce, Daniele, Macfarlane, Gary J., Mates, Dana, Matsuo, Keitaro, McClean, Michael, Menezes, Ana, Menvielle, Gwenn, Morgenstern, Hal, Moyses, Raquel A., Moysich, Kirsten, Muscat, Joshua, Negri, Eva, Olshan, Andrew F., Pandics, Tamas, Polesel, Jerry, Purdue, Mark P., Radoï, Loredana, Ramroth, Heribert, Richiardi, Lorenzo, Schantz, Stimson, Schwartz, Stephen M., Serraino, Diego, Shangina, Oxana, Smith, Elaine, Sturgis, Erich M., Świątkowska, Beata, Thomson, Peter, Toporcov, Tatiana N., Vaughan, Thomas L., Vilensky, Marta, Winn, Deborah M., Wunsch‐Filho, Victor, Yu, Guo‐Pei, Zevallos, Jose P, Zhang, Zuo‐Feng, Zheng, Tongzhang, Znaor, Ariana, Bravi, F, Lee, Y, Hashibe, M, Boffetta, P, Conway, D, Ferraroni, M, La Vecchia, C, Edefonti, V, Agudo, A, Ahrens, W, Benhamou, S, Boccia, S, Brennan, P, Brenner, H, Cadoni, G, Canova, C, Chen, C, Chuang, S, Curado, M, Dal Maso, L, Daudt, A, D'Souza, G, Fabianova, E, Fernandez, L, Franceschi, S, Garavello, W, Gillison, M, Gross, N, Hayes, R, Healy, C, Herrero, R, Holcatova, I, Kelsey, K, Kjaerheim, K, Koifman, R, Lagiou, P, Lazarus, P, Levi, F, Li, G, Lissowska, J, Luce, D, Macfarlane, G, Mates, D, Matsuo, K, Mcclean, M, Menezes, A, Menvielle, G, Morgenstern, H, Moyses, R, Moysich, K, Muscat, J, Negri, E, Olshan, A, Pandics, T, Polesel, J, Purdue, M, Radoi, L, Ramroth, H, Richiardi, L, Schantz, S, Schwartz, S, Serraino, D, Shangina, O, Smith, E, Sturgis, E, Swiatkowska, B, Thomson, P, Toporcov, T, Vaughan, T, Vilensky, M, Winn, D, Wunsch-Filho, V, Yu, G, Zevallos, J, Zhang, Z, Zheng, T, Znaor, A, Bravi F., Lee Y.-C.A., Hashibe M., Boffetta P., Conway D.I., Ferraroni M., La Vecchia C., Edefonti V., Agudo A., Ahrens W., Benhamou S., Boccia S., Brennan P., Brenner H., Cadoni G., Canova C., Chen C., Chuang S.-C., Curado M.P., Dal Maso L., Daudt A.W., D'Souza G., Fabianova E., Fernandez L., Franceschi S., Garavello W., Gillison M., Gross N.D., Hayes R.B., Healy C., Herrero R., Holcatova I., Kelsey K., Kjaerheim K., Koifman R., Lagiou P., Lazarus P., Levi F., Li G., Lissowska J., Luce D., Macfarlane G.J., Mates D., Matsuo K., McClean M., Menezes A., Menvielle G., Morgenstern H., Moyses R.A., Moysich K., Muscat J., Negri E., Olshan A.F., Pandics T., Polesel J., Purdue M.P., Radoi L., Ramroth H., Richiardi L., Schantz S., Schwartz S.M., Serraino D., Shangina O., Smith E., Sturgis E.M., Swiatkowska B., Thomson P., Toporcov T.N., Vaughan T.L., Vilensky M., Winn D.M., Wunsch-Filho V., Yu G.-P., Zevallos J.P., Zhang Z.-F., Zheng T., and Znaor A.

Subjects
INHANCE, medicine.medical_specialty, Oral health, Cancer recurrence, Article, Tobacco Use, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Epidemiology, medicine, Humans, pooled analysi, prognostic factor, General Dentistry, Beneficial effects, Head and Neck Neoplasm, business.industry, Incidence (epidemiology), Head and neck cancer, oral cavity cancer, Case-control study, prognostic factors, 030206 dentistry, medicine.disease, risk factor, Otorhinolaryngology, Head and Neck Neoplasms, Case-Control Studies, 030220 oncology & carcinogenesis, Family medicine, Etiology, laryngeal cancer, head and neck cancer, Settore MED/31 - OTORINOLARINGOIATRIA, pooled analysis, Neoplasm Recurrence, Local, Case-Control Studie, business, Human
Abstract

Objective:\ud \ud To summarize the latest evidence on head and neck cancer epidemiology from the International Head and Neck Cancer Epidemiology (INHANCE) consortium.\ud \ud Subjects and Methods:\ud \ud INHANCE was established in 2004 to elucidate the etiology of head and neck cancer through pooled analyses of individual‐level data on a large scale. We summarize results from recent INHANCE‐based publications updating our 2015 overview.\ud \ud Results:\ud \ud Seventeen papers were published between 2015 and May 2020. These studies further define the nature of risks associated with tobacco and alcohol, and occupational exposures on head and neck cancer. The beneficial effects on incidence of head and neck cancer were identified for good oral health, endogenous and exogenous hormonal factors, and selected aspects of diet related to fruit and vegetables. INHANCE has begun to develop risk prediction models and to pool follow‐up data on their studies, finding that ~30% of cases had cancer recurrence and 9% second primary cancers, with overall‐ and disease‐specific 5‐year‐survival of 51% and 57%, respectively.\ud \ud Conclusions:\ud \ud The number and importance of INHANCE scientific findings provides further evidence of the advantages of large‐scale internationally collaborative projects and will support the development of prevention strategies.

Published
2020
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142. Reply to Letter from the Editor.

Author

Cadoni, G., Fetoni, A.R., Agostino, S., De Santis, A., Manna, R., Ottaviani, F., and Paludetti, G.

Subjects
*SENSORINEURAL hearing loss, *LETTERS to the editor
Abstract

Presents a letter to the editor of the periodical "Acta Oto-Laryngologica," responding to a critique on a paper about autoimmunity in sudden sensorineural hearing loss.

Published
2003
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143. Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Author

Stefania Boccia, Cristina Bosetti, Livia Petrelli, Rossana Verónica Mendoza López, Luca Giraldi, Gabriella Cadoni, Werner Garavello, Cristina Canova, Diego Serraino, Emanuele Leoncini, Mia Hashibe, Lorenzo Simonato, Lorenzo Richiardi, Victor Wünsch-Filho, Keitaro Matsuo, Paolo Boffetta, Dario Arzani, Jerry Polesel, Yuan Chin Amy Lee, M. B. de Carvalho, C. La Vecchia, Roberta Pastorino, Giraldi, L, Leoncini, E, Pastorino, R, Wunsch-Filho, V, de Carvalho, M, Lopez, R, Cadoni, G, Arzani, D, Petrelli, L, Matsuo, K, Bosetti, C, La Vecchia, C, Garavello, W, Polesel, J, Serraino, D, Simonato, L, Canova, C, Richiardi, L, Boffetta, P, Hashibe, M, Lee, Y, Boccia, S, and Giraldi, L. and Leoncini, E. and Pastorino, R. and Wünsch-Filho, V. and de Carvalho, M. and Lopez, R. and Cadoni, G. and Arzani, D. and Petrelli, L. and Matsuo, K. and Bosetti, C. and La Vecchia, C. and Garavello, W. and Polesel, J. and Serraino, D. and Simonato, L. and Canova, C. and Richiardi, L. and Boffetta, P. and Hashibe, M. and Lee, Y. and Boccia, S.

Subjects
Larynx, Oncology, Male, Epidemiology, 0302 clinical medicine, Japan, Risk Factors, cancer mortality, 030212 general & internal medicine, Univariate analysis, Prognostic factor, Head and Neck Neoplasm, adult, international cooperation, Hazard ratio, Smoking, drinking behavior, Hematology, Middle Aged, hypopharynx cancer, Prognosis, educational statu, 3. Good health, Europe, Survival Rate, Head and neck cancer, Pooled analysis, Prognostic factors, Alcohol Drinking, Female, Follow-Up Studies, Head and Neck Neoplasms, Humans, International Agencies, Meta-Analysis as Topic, medicine.anatomical_structure, Italy, priority journal, Pooled analysi, International Agencie, 030220 oncology & carcinogenesis, meta analysis (topic), Settore MED/31 - OTORINOLARINGOIATRIA, pooled analysis, Brazil, Human, medicine.medical_specialty, lifestyle, Prognosi, alcohol consumption, overall survival, cohort analysi, cancer prognosi, Article, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, follow up, Survival rate, head and neck tumor, business.industry, cancer staging, Risk Factor, Cancer, larynx cancer, prognostic factors, Original Articles, medicine.disease, mouth cancer, oropharynx cancer, major clinical study, mortality, cancer localization, survival rate, Alcohol Drinking, head and neck cancer, business
Abstract

Background: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. Patients and methods: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. Results: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR=2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR=1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR=2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity ( > 20 cigarettes/day HR=1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. Conclusions: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Published
2017

144. Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach

Author

Philip Lazarus, Claire M. Healy, Richard B. Hayes, Rolando Herrero, Elaine M. Smith, Stefania Boccia, Leonardo F. Boaventura Rios, Paolo Boffetta, Dana Mates, Jerry Polesel, Marta Vilensky, Jose P. Zevallos, Diego Serraino, Gypsyamber D'Souza, Joshua E. Muscat, Kirsten B. Moysich, Yuan Chin Amy Lee, Mark P. Purdue, Carlo La Vecchia, Heribert Ramroth, Thomas L. Vaughan, Peter Thomson, Karl T. Kelsey, Nicola Torelli, Wolfgang Ahrens, Hermann Brenner, Lorenzo Richiardi, Victor Wünsch-Filho, Kristina Kjærheim, Beata Swiatkowska, Keitaro Matsuo, Fabio Levi, Erich M. Sturgis, Eva Negri, Lorenzo Simonato, Danièle Luce, Guo Pei Yu, Chu Chen, Pagona Lagiou, Silvia Franceschi, Andrew F. Olshan, Alexander W. Daudt, Antonio Agudo, Maria Paula Curado, Peter Rudnai, Tatiana V. Macfarlane, Zuo-Feng Zhang, Mia Hashibe, Paul Brennan, Tatiana Natasha Toporcov, Stimson P. Schantz, Maura L. Gillison, Isabelle Stücker, Tongzhang Zheng, Shu Chun Chuang, Oxana Shangina, Eleonora Fabianova, Hal Morgenstern, David I. Conway, Valeria Edefonti, Cristina Bosetti, Ariana Znaor, Leticia Fernandez, Michael D. McClean, Luigino Dal Maso, Neil D. Gross, Stephen M. Schwartz, Ivana Holcatova, Guojun Li, Ana M. B. Menezes, Francesco Pauli, Gioia Di Credico, Deborah M. Winn, Rosalina Jorge Koifman, Gwenn Menvielle, Gabriella Cadoni, Werner Garavello, Jolanda Lissowska, Università degli Studi di Milano [Milano] (UNIMI), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Glasgow, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), TW001500, National Institutes of Health, P30ES010126, National Institute of Environmental Health Sciences, Italian Ministry of Education, Università degli Studi di Milano, Jonsson Comprehensive Cancer Center, International Union Against Cancer, Fondo para la Investigacion Cientifica y Tecnologica Argentina, Institut Hospital del Mar d’Investigacions Mediquès (IMIM), Fundação de Amparo à Pesquisa no Estado de São Paulo, Spanish Government, European Community, Ministry of Science, Research and Arts Baden-Wurttemberg, German Ministry of Education and Research, Scientific Research grant from the Ministry of Education, Science, Sports, Culture and Technology of Japan, Labor and Welfare of Japan, Italian Foundation for Cancer Research, Di Credico G., Edefonti V., Polesel J., Pauli F., Torelli N., Serraino D., Negri E., Luce D., Stucker I., Matsuo K., Brennan P., Vilensky M., Fernandez L., Curado M.P., Menezes A., Daudt A.W., Koifman R., Wunsch-Filho V., Holcatova I., Ahrens W., Lagiou P., Simonato L., Richiardi L., Healy C., Kjaerheim K., Conway D.I., Macfarlane T.V., Thomson P., Agudo A., Znaor A., Boaventura Rios L.F., Toporcov T.N., Franceschi S., Herrero R., Muscat J., Olshan A.F., Zevallos J.P., La Vecchia C., Winn D.M., Sturgis E.M., Li G., Fabianova E., Lissowska J., Mates D., Rudnai P., Shangina O., Swiatkowska B., Moysich K., Zhang Z.-F., Morgenstern H., Levi F., Smith E., Lazarus P., Bosetti C., Garavello W., Kelsey K., McClean M., Ramroth H., Chen C., Schwartz S.M., Vaughan T.L., Zheng T., Menvielle G., Boccia S., Cadoni G., Hayes R.B., Purdue M., Gillison M., Schantz S., Yu G.-P., Brenner H., D'Souza G., Gross N.D., Chuang S.-C., Boffetta P., Hashibe M., Lee Y.-C.A., Dal Maso L., Di Credico, G, Edefonti, V, Polesel, J, Pauli, F, Torelli, N, Serraino, D, Negri, E, Luce, D, Stucker, I, Matsuo, K, Brennan, P, Vilensky, M, Fernandez, L, Curado, M, Menezes, A, Daudt, A, Koifman, R, Wunsch-Filho, V, Holcatova, I, Ahrens, W, Lagiou, P, Simonato, L, Richiardi, L, Healy, C, Kjaerheim, K, Conway, D, Macfarlane, T, Thomson, P, Agudo, A, Znaor, A, Boaventura Rios, L, Toporcov, T, Franceschi, S, Herrero, R, Muscat, J, Olshan, A, Zevallos, J, La Vecchia, C, Winn, D, Sturgis, E, Li, G, Fabianova, E, Lissowska, J, Mates, D, Rudnai, P, Shangina, O, Swiatkowska, B, Moysich, K, Zhang, Z, Morgenstern, H, Levi, F, Smith, E, Lazarus, P, Bosetti, C, Garavello, W, Kelsey, K, Mcclean, M, Ramroth, H, Chen, C, Schwartz, S, Vaughan, T, Zheng, T, Menvielle, G, Boccia, S, Cadoni, G, Hayes, R, Purdue, M, Gillison, M, Schantz, S, Yu, G, Brenner, H, D'Souza, G, Gross, N, Chuang, S, Boffetta, P, Hashibe, M, Lee, Y, Dal Maso, L, Di Credico, Gioia, Edefonti, Valeria, Polesel, Jerry, Pauli, Francesco, Torelli, Nicola, Serraino, Diego, Negri, Eva, Luce, Daniele, Stucker, Isabelle, Matsuo, Keitaro, Brennan, Paul, Vilensky, Marta, Fernandez, Leticia, Curado, Maria Paula, Menezes, Ana, Daudt, Alexander W., Koifman, Rosalina, Wunsch-Filho, Victor, Holcatova, Ivana, Ahrens, Wolfgang, Lagiou, Pagona, Simonato, Lorenzo, Richiardi, Lorenzo, Healy, Claire, Kjaerheim, Kristina, Conway, David I., Macfarlane, Tatiana V., Thomson, Peter, Agudo, Antonio, Znaor, Ariana, Boaventura Rios, Leonardo F., Toporcov, Tatiana N., Franceschi, Silvia, Herrero, Rolando, Muscat, Joshua, Olshan, Andrew F., Zevallos, Jose P., La Vecchia, Carlo, Winn, Deborah M., Sturgis, Erich M., Li, Guojun, Fabianova, Eleonora, Lissowska, Jolanda, Mates, Dana, Rudnai, Peter, Shangina, Oxana, Swiatkowska, Beata, Moysich, Kirsten, Zhang, Zuo-Feng, Morgenstern, Hal, Levi, Fabio, Smith, Elaine, Lazarus, Philip, Bosetti, Cristina, Garavello, Werner, Kelsey, Karl, Mcclean, Michael, Ramroth, Heribert, Chen, Chu, Schwartz, Stephen M., Vaughan, Thomas L., Zheng, Tongzhang, Menvielle, Gwenn, Boccia, Stefania, Cadoni, Gabriella, Hayes, Richard B., Purdue, Mark, Gillison, Maura, Schantz, Stimson, Yu, Guo-Pei, Brenner, Hermann, D'Souza, Gypsyamber, Gross, Neil D., Chuang, Shu-Chun, Boffetta, Paolo, Hashibe, Mia, Lee, Yuan-Chin Amy, Dal Maso, Luigino, Università degli Studi di Milano = University of Milan (UNIMI), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Male, Oral cavity and pharyngeal cancers, Cancer Research, Bivariate spline model, medicine.medical_treatment, Logistic regression, Substance Misuse, 0302 clinical medicine, Risk Factors, Laryngeal cancer, 80 and over, 2.2 Factors relating to the physical environment, Aetiology, 030223 otorhinolaryngology, Head and neck cancer, Cancer, Aged, 80 and over, Confounding, Middle Aged, 3. Good health, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Bivariate spline models, Cigarette smoking duration, Cigarette smoking intensity, Public Health and Health Services, Female, Oral Surgery, Adult, INHANCE, Oncology and Carcinogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bivariate analysis, Cigarette Smoking, 03 medical and health sciences, Rare Diseases, Clinical Research, Tobacco, medicine, Humans, Oncology & Carcinogenesis, Dental/Oral and Craniofacial Disease, Aged, Settore MED/06 - ONCOLOGIA MEDICA, Tobacco Smoke and Health, business.industry, Prevention, Case-control study, Odds ratio, medicine.disease, Former Smoker, Good Health and Well Being, Case-Control Studies, Dentistry, Smoking cessation, business, Demography
Abstract

Objectives: \ud This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.\ud \ud Materials and Methods: \ud We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.\ud \ud Results: \ud For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30 years. In former smokers who quit ≥10 years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.\ud \ud Conclusion: \ud Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

Published
2019
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145. 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
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146. The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer

Author

Neonila Szeszenia-Dabrowska, Dana Mates, Danièle Luce, Lorenzo Simonato, José Eluf-Neto, Michael Pawlita, Elaine M. Smith, Kim De Ruyck, Gwenn Menvielle, Cristina Bosetti, Deborah M. Winn, David Zaridze, Gabriella Cadoni, Keitaro Matsuo, Diego Serraino, Isabelle Stücker, Richard B. Hayes, Mia Hashibe, Andrew F. Olshan, Robert I. Haddad, David I. Conway, Guo-Pei Yu, Tatiana V. Macfarlane, Simone Benhamou, Chu Chen, Brenda Diergaarde, Maura L. Gillison, Paul Brennan, Michael D. McClean, Kristina Kjærheim, Vladimir Bencko, Peter Rudnai, Guojun Li, Eleonora Fabianova, Pagona Lagiou, Thomas L. Vaughan, Witold Zatonski, Silvia Franceschi, Gypsyamber D'Souza, Rayjean J. Hung, Victor Wünsch-Filho, Antonio Agudo, Yuan Chin Amy Lee, Martin Lacko, Erich M. Sturgis, Xavier Castellsagué, Fabio Levi, Luigino Dal Maso, Jolanta Lissowska, Carlo La Vecchia, Franco Merletti, Steve Schwartz, Oxana Shangina, Ariana Znaor, Gregory T. Wolf, Jonathan N. Hofmann, Ivana Holcatova, Wolfgang Ahrens, Rolando Herrero, Alexander W. Daudt, Kirsten B. Moysich, Heribert Ramroth, Karl T. Kelsey, Maria Paula Curado, Zuo-Feng Zhang, Ana M. B. Menezes, Philip Lazarus, Laura S. Rozek, Tongzhang Zheng, Paolo Boffetta, Jose P. Zevallos, Peter Thomson, Claire M. Healy, Stefania Boccia, Wilbert H.M. Peters, Stimson P. Schantz, Marta Vilensky, Joshua E. Muscat, Hermann Brenner, Sergio Koifman, Geoffrey Liu, Manoj B. Mahimkar, Leticia Fernandez, Winn, D.M., Lee, Y.-C., Hashibe, M., Boffetta, P., Agudo, A., Ahrens, W., Bencko, V., Benhamou, S., Boccia, S., Bosetti, C., Brennan, P., Brenner, H., Cadoni, G., Castellsague, X., Chen, C., Conway, D., Curado, M.P., D'Souza, G., Maso, L.D., Daudt, A.W., Ruyck, K.D., Diergaarde, B., Eluf-Neto, J., Fabianova, E., Fernandez, L., Franceschi, S., Gillison, M., Haddad, R.I., Hayes, R., Healy, C., Herrero, R., Hofmann, J., Holcátová, I., Hung, R., Kelsey, K., Kjaerheim, K., Koifman, S., Vecchia, C.L., Lacko, M., Lagiou, P., Lazarus, P., Levi, F., Li, G., Lissowska, J., Liu, G., Luce, D., Macfarlane, T., Mahimkar, M., Mates, D., Matsuo, K., McClean, M., Menezes, A., Menvielle, G., Merletti, F., Moysich, K., Muscat, J., Olshan, A., Pawlita, M., Peters, W.H.M., Ramroth, H., Rozek, L., Rudnai, P., Schantz, S., Schwartz, S., Serraino, D., Shangina, O., Simonato, L., Smith, E., Stucker, I., Sturgis, E.M., Szeszenia-Dabrowska, Neonila and Thomson, P., Vaughan, T., Vilensky, M., Wolf, G., Wünsch-Filho, V., Yu, G., Zaridze, D., Zatonski, W., Zevallos, J.P., Zhang, Z.-F., Zheng, T.-Z., and Znaor, A.

Subjects
Larynx, Data Pooling, Oncology, medicine.medical_specialty, Research groups, Alcohol Drinking, Scientific productivity, Risk Factors, Internal medicine, Epidemiology, Humans, Medicine, Cooperative Behavior, Family history, Settore MED/42 - IGIENE GENERALE E APPLICATA, General Dentistry, business.industry, Smoking, Head and neck cancer, Confounding, medicine.disease, Diet, Surgery, medicine.anatomical_structure, Socioeconomic Factors, Otorhinolaryngology, Head and Neck Neoplasms, epidemiology, head and neck cancer, Settore MED/31 - OTORINOLARINGOIATRIA, business
Abstract

The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25 500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37 100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects. © 2015 John Wiley & Sons A/S.

Published
2015
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147. Hormone factors play a favorable role in female head and neck cancer risk

Author

Diego Serraino, Gabriella Cadoni, Luigino Dal Maso, Fabio Levi, Hung N. Luu, Elaine M. Smith, Dana Hashim, Stefania Boccia, Mia Hashibe, Carlo La Vecchia, Samantha Sartori, Yuan Chin Amy Lee, Paolo Boffetta, Eva Negri, Hashim, D., Sartori, S., la Vecchia, C., Serraino, D., Maso, L.D., Negri, E., Smith, E., Levi, F., Boccia, S., Cadoni, G., Luu, H.N., Lee, Y.-C.A., Hashibe, M., and Boffetta, P.

Subjects
0301 basic medicine, Alcohol Drinking, Case-Control Studies, Female, Head and Neck Neoplasms/epidemiology, Head and Neck Neoplasms/etiology, Hormone Replacement Therapy/adverse effects, Hormones/adverse effects, Hormones/metabolism, Humans, Menopause, Menstrual Cycle, Middle Aged, Odds Ratio, Reproductive History, Risk, Smoking, Head and neck neoplasms, hormone replacement therapy, mouth neoplasms, reproductive history, women, Cancer Research, medicine.medical_specialty, Hormone Replacement Therapy, media_common.quotation_subject, hormone, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Menstrual cycle, media_common, Original Research, Gynecology, Mouth neoplasm, business.industry, Incidence (epidemiology), Case-control study, Head and neck cancers, exogenous and endogenous hormonal factors, Odds ratio, medicine.disease, Hormones, 3. Good health, 030104 developmental biology, Oncology, Transgender hormone therapy, 030220 oncology & carcinogenesis, head and neck cancer, Settore MED/31 - OTORINOLARINGOIATRIA, business, Cancer Prevention
Abstract

Due to lower female incidence, estimates of exogenous and endogenous hormonal factors in head and neck cancers (HNCs, comprising cancers of the oral cavity, oropharynx, hypopharynx, and larynx) among women have been inconsistent and unable to account for key HNC risk factors. We pooled data from 11 studies from Europe, North America, and Japan. Analysis included 1572 HNC female cases and 4343 controls. Pooled odds ratios (ORs) estimates and their 95% confidence intervals (CIs) were calculated using multivariate logistic regression models adjusting for tobacco smoking and alcohol drinking. Lower risk was observed in women who used hormone replacement therapy (HRT) (OR = 0.58; 95% CI: 0.34–0.77). Pregnancy (OR = 0.61; 95% CI: 0.42–0.90) and giving birth (OR = 0.59; 95% CI: 0.38–0.90) at

Published
2017

148. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

Author

Stefania Boccia, Wilbert H.M. Peters, Kristina Kjærheim, James McKay, Christopher I. Amos, David I. Conway, Dana Mates, Ana Maria Menezes, Antonio Agudo, Brenda Diergaarde, Rolando Herrero, Valerie Gaborieau, Martin Lacko, Cristina Canova, Neonila Szeszenia-Dąbrowska, Lorenzo Richiardi, Xiangjun Xiao, Victor Wünsch-Filho, Pagona Lagiou, David Zaridze, Maria Paula Curado, H. Bas Bueno-de-Mesquita, Mark C. Weissler, Rayjean J. Hung, Paolo Boffetta, Claire M. Healy, Marcos Brasilino de Carvalho, Fábio Daumas Nunes, Steve Thomas, Devasena Anantharaman, Paul Brennan, Mattias Johansson, Geoffrey Liu, Oxana Shangina, Ariana Znaor, Corina Lesseur, Eleonora Fabianova, Gabriella Cadoni, Andy R Ness, Eloiza H. Tajara, Gary J. Macfarlane, Jennifer R. Grandis, Annika Steffen, Jerry Polesel, Max Robinson, Marta Vilensky, Andrew F. Olshan, Wolfgang Ahrens, Silvia Franceschi, Amelie Chabrier, José Eluf-Neto, Jolanta Lissowska, Ivana Holcatova, Xavier Castellsagué, Nofer Institute of Occupational Medicine, Łódź, Poland, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Keel Neus Oorheelkunde (9), Lesseur, C., Diergaarde, B., Olshan, A.F., Wünsch-Filho, V., Ness, A.R., Liu, G., Lacko, M., Eluf-Neto, J., Franceschi, S., Lagiou, P., Macfarlane, G.J., Richiardi, L., Boccia, S., Polesel, J., Kjaerheim, K., Zaridze, D., Johansson, M., Menezes, A.M., Curado, M.P., Robinson, M., Ahrens, W., Canova, C., Znaor, A., Castellsagué, X., Conway, D.I., Holcátová, I., Mates, D., Vilensky, M., Healy, C.M., Szeszenia-Dabrowska, N., Fabiánová, E., Lissowska, J., Grandis, J.R., Weissler, M.C., Tajara, E.H., Nunes, F.D., De Carvalho, M.B., Thomas, S., Hung, R.J., Peters, W.H.M., Herrero, R., Cadoni, G., Bueno-De-Mesquita, H.B., Steffen, A., Agudo, A., Shangina, O., Xiao, X., Gaborieau, V., Chabrier, A., Anantharaman, D., Boffetta, P., Amos, C.I., McKay, J.D., and Brennan, P.

Subjects
Male, 0301 basic medicine, Epidemiology, Genome-wide association study, Gastroenterology, Genome-wide association studies, INCIDÊNCIA, HLA Antigens, Genetics research, Aged, Case-Control Studies, Female, Genetic Markers, Genetic Variation, Haplotypes, Humans, Middle Aged, Mouth, Mouth Neoplasms, Papillomaviridae, Papillomavirus Infections, Pharyngeal Neoplasms, Genetic Predisposition to Disease, Genome-Wide Association Study, Genetics, Oral cancer, genetic research, 3. Good health, Settore MED/31 - OTORINOLARINGOIATRIA, medicine.medical_specialty, Papillomaviruses, Genome-wide - oral cavity and pharyngeal cancer, Human leukocyte antigen, Biology, Article, 03 medical and health sciences, Internal medicine, medicine, Allele, Papil·lomavirus, Haplotype, Case-control study, Odds ratio, oral cancer, medicine.disease, Càncer de boca, 030104 developmental biology, Nasopharyngeal carcinoma, Immunology, Imputation (genetics)
Abstract

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers. Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through the grant X01HG007492-0. Corina Lesseur undertook this work during the tenure of a Postdoctoral Fellowship awarded by the International Agency for Research on Cancer. The funders did not participate in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all of the participants involved in this research and the funders and support. We thank Dr. Leticia Fernandez (Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba) for her contribution to the IARC ORC multicenter study. We are also grateful to Sergio Koifman (Escola Nacional de Saúde Pública, Rio de Janeiro, Brazil) for his contribution to the IARC Latin America multicenter study (Sergio Koifman passed away in May 2014) and to Xavier Castellsagué from the ARCAGE Barcelona Center who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19 CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission’s 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222).The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to SB, and Fondazione Veronesi to SB. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by European Commission’s INCO-COPERNICUS Program (IC15-CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28.The IARC Oral Cancer Multicenter study was funded by: grant S06 96 202489 05F02 from Europe against Cancer; Grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; UICC Yamagiwa-Yoshida Memorial International Cancer Study; National Cancer Institute of Canada; Italian Association for Research on Cancer; and the Pan American Health Organization. The coordination of EPIC study is financially supported

Published
2016
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149. Low frequency of cigarette smoking and the risk of head and neck cancer in the INHANCE consortium pooled analysis

Author

Berthiller, Julien, Straif, Kurt, Agudo, Antonio, Ahrens, Wolfgang, Bezerra Dos Santos, Alexandre, Boccia, Stefania, Cadoni, Gabriella, Canova, Cristina, Castellsague, Xavier, Chen, Chu, Conway, David, Curado, Maria Paula, Dal Maso, Luigino, Daudt, Alexander W, Fabianova, Eleonora, Fernandez, Leticia, Franceschi, Silvia, Fukuyama, Erica E, Hayes, Richard B, Healy, Claire, Herrero, Rolando, Holcatova, Ivana, Kelsey, Karl, Kjaerheim, Kristina, Koifman, Sergio, Lagiou, Pagona, La Vecchia, Carlo, Lazarus, Philip, Levi, Fabio, Lissowska, Jolanta, Macfarlane, Tatiana, Mates, Dana, McClean, Michael, Menezes, Ana, Merletti, Franco, Morgenstern, Hal, Muscat, Joshua, Olshan, Andrew F, Purdue, Mark, Ramroth, Heribert, Rudnai, Peter, Schwartz, Stephen M, Serraino, Diego, Shangina, Oxana, Smith, Elaine, Sturgis, Erich M, Szeszenia-Dabrowska, Neonila, Thomson, Peter, Vaughan, Thomas L, Vilensky, Marta, Wei, Qingyi, Winn, Deborah M, Wünsch-Filho, Victor, Zhang, Zuo-Feng, Znaor, Ariana, Ferro, Gilles, Brennan, Paul, Boffetta, Paolo, Hashibe, Mia, Lee, Yuan-Chin Amy, International Prevention Research Institute (IPRI), The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), and Berthiller, J. and Straif, K. and Agudo, A. and Ahrens, W. and Bezerra Dos Santos, A. and Boccia, S. and Cadoni, G. and Canova, C. and Castellsague, X. and Chen, C. and Conway, D. and Curado, M.P. and Dal Maso, L. and Daudt, A.W. and Fabianova, E. and Fernandez, L. and Franceschi, S. and Fukuyama, E.E. and Hayes, R.B. and Healy, C. and Herrero, R. and Holcatova, I. and Kelsey, K. and Kjaerheim, K. and Koifman, S. and Lagiou, P. and La Vecchia, C. and Lazarus, P. and Levi, F. and Lissowska, J. and Macfarlane, T. and Mates, D. and McClean, M. and Menezes, A. and Merletti, F. and Morgenstern, H. and Muscat, J. and Olshan, A.F. and Purdue, M. and Ramroth, H. and Rudnai, P. and Schwartz, S.M. and Serraino, D. and Shangina, O. and Smith, E. and Sturgis, E.M. and Szeszenia-Dabrowska, N. and Thomson, P. and Vaughan, T.L. and Vilensky, M. and Wei, Q. and Winn, D.M. and Wünsch-Filho, V. and Zhang, Z.-F. and Znaor, A. and Ferro, G. and Brennan, P. and Boffetta, P. and Hashibe, M. and Lee, Y.-C.A.

Subjects
Male, Gerontology, FATORES DE RISCO, Epidemiology, Head and neck cancer, low frequency cigarette smoking, pooled analysis, risk factors, Substance Misuse, 0302 clinical medicine, Risk Factors, Odds Ratio, Medicine, pooled analysi, Pooled data, European commission, 030212 general & internal medicine, Smoking and Cancer, Cancer, Head and Neck Neoplasm, Statistics, drinking behavior, General Medicine, Middle Aged, statistical model, Adult, Head and neck cancer low frequency cigarette smoking pooled analysis risk factors, 3. Good health, Pooled analysis, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Respiratory, Public Health and Health Services, Female, Christian ministry, Public Health, Settore MED/31 - OTORINOLARINGOIATRIA, Case-Control Studie, Adult, Logistic Model, Alcohol Drinking, European community, Library science, smoking, Cigarette Smoking, 03 medical and health sciences, Rare Diseases, Cigarette smoking, Clinical Research, Tobacco, Humans, human, Frame work, Dental/Oral and Craniofacial Disease, Settore MED/42 - IGIENE GENERALE E APPLICATA, Aged, head and neck tumor, Tobacco Smoke and Health, business.industry, Risk Factor, Prevention, case control study, Logistic Models, Good Health and Well Being, Multicenter study, Case-Control Studies, head and neck cancer, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Funding • The pooled data coordination team (PBoffetta, MH, YCAL) were supported by National Cancer Institute grant R03CA113157 and by National Institute of Dental and Craniofacial Research grant R03DE016611 • The Milan study (CLV) was supported by the Italian Association for Research on Cancer (Grant no. 10068). • The Aviano study (LDM) was supported by a grant from the Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research • The Italy Multicenter study (DS) was supported by the Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research. • The Study from Switzerland (FL) was supported by the Swiss League against Cancer and the Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633]. • The central Europe study (PBoffetta, PBrenan, EF, JL, DM, PR, OS, NS-D) was supported by the World Cancer Research Fund and the European Commission INCO-COPERNICUS Program [Contract No. IC15- CT98-0332] • The New York multicentre study (JM) was supported by a grant from National Institute of Health [P01CA068384 K07CA104231]. • The study from the Fred Hutchison Cancer Research Center from Seattle (CC, SMS) was supported by a National Institute of Health grant [R01CA048996, R01DE012609]. • The Iowa study (ES) was supported by National Institute of Health [NIDCR R01DE011979, NIDCR R01DE013110, FIRCA TW001500] and Veterans Affairs Merit Review Funds. • The North Carolina studies (AFO) were supported by National Institute of Health [R01CA061188], and in part by a grant from the National Institute of Environmental Health Sciences [P30ES010126]. • The Tampa study (PLazarus, JM) was supported by National Institute of Health grants [P01CA068384, K07CA104231, R01DE013158] • The Los Angeles study (Z-F Z, HM) was supported by grants from National Institute of Health [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667] and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center. • The Houston study (EMS, GL) was supported by a grant from National Institute of Health [R01ES011740, R01CA100264]. • The Puerto Rico study (RBH, MPP) was supported by a grant from National Institutes of Health (NCI) US and NIDCR intramural programs. • The Latin America study (PBoffetta, PBrenan, MV, LF, MPC, AM, AWD, SK, VW-F) was supported by Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a‘ Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768-2], and European Commission [IC18-CT97-0222] • The IARC multicentre study (SF, RH, XC) was supported by Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/ 0024, FIS 97/0662, BAE 01/5013], International Union Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International Cancer Study Grant. • The Boston study (KKelsey, MMcC) was supported by a grant from National Institute of Health [R01CA078609, R01CA100679]. • The Rome study (SB, GC) was supported by AIRC (Italian Agency for Research on Cancer). • The US multicentre study (BW) was supported by The Intramural Program of the National Cancer Institute, National Institute of Health, United States. • The Sao Paolo study (V W-F) was supported by Fundacao de Ampara a Pesquisa no Estado de Sao Paulo (FAPESP No 10/51168-0) • The MSKCC study (SS, G-P Y) was supported by a grant from National Institute of Health [R01CA051845]. • The Seattle-Leo stud (FV) was supported by a grant from National Institute of Health [R01CA030022] • The western Europe Study (PBoffetta, IH, WA, PLagiou, DS, LS, FM, CH, KKjaerheim, DC, TMc, PT, AA, AZ) was supported by European Community (5th Frame work Programme) grant no QLK1-CT-2001- 00182. • The Germany Heidelberg study (HR) was supported by the grant No. 01GB9702/3 from the German Ministry of Education and Research.

Published
2016
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150. Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium

Author

Gabriella Cadoni, Stefania Boccia, Alexander W. Daudt, Maria Paula Curado, Philip Lazarus, Kristina Kjærheim, Renato Talamini, Zuo-Feng Zhang, Wolfgang Ahrens, Thomas L. Vaughan, Marta Vilensky, Joshua E. Muscat, Mark P. Purdue, Qingyi Wei, Otávio Alberto Curioni, Guo Pei Yu, Claire M. Healy, Keitaro Matsuo, Dana Mates, Yuan Chin Amy Lee, Rolando Herrero, Paolo Boffetta, José Leopoldo Ferreira Antunes, Mia Hashibe, Elaine M. Smith, Lorenzo Richiardi, Oxana Shangina, Chu Chen, Antonio Agudo, Victor Wünsch Filho, Sergio Koifman, Pagona Lagiou, Deborah M. Winn, Michael D. McClean, Cristina Canova, Heribert Ramroth, Karl T. Kelsey, Peter Rudnai, Peter Thomson, Leticia Fernandez, P Brennan, Neonila Szeszenia-Dabrowska, Eleonora Fabianova, Hal Morgenstern, Stephen M. Schwartz, Xavier Castellsagué, Jolanta Lissowska, Andrew F. Olshan, Tatiana V. Macfarlane, Carlo La Vecchia, Ivana Holcatova, Ariana Znaor, Raquel Ajub Moyses, José Eluf-Neto, David I. Conway, Tatiana Natasha Toporcov, Stimson P. Schantz, Richard B. Hayes, Fabio Levi, Erich M. Sturgis, Luigino Dal Maso, Ana M. B. Menezes, Silvia Franceschi, International Prevention Research Institute (IPRI), The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Toporcov, T.N., Znaor, A., Zhang, Z.-F., Yu, G.-P., Winn, D.M., Wei, Q., Vilensky, M., Vaughan, T., Thomson, P., Talamini, R., Szeszenia-Dabrowska, N., Sturgis, E.M., Smith, E., Shangina, O., Schwartz, S.M., Schantz, S., Rudnai, P., Richiardi, L., Ramroth, H., Purdue, M.P., Olshan, A.F., Eluf-Neto, J., Muscat, J., Moyses, R.A., Morgenstern, H., Menezes, A., McClean, M., Matsuo, K., Mates, D., Macfarlane, T.V., Lissowska, J., Levi, F., Lazarus, P., Vecchia, C.L., Lagiou, P., Koifman, S., Kjaerheim, K., Kelsey, K., Holcatova, I., Herrero, R., Healy, C., Hayes, R.B., Franceschi, S., Fernandez, L., Fabianova, E., Daudt, A.W., Curioni, O.A., Maso, L.D., Curado, M.P., Conway, D.I., Chen, C., Castellsague, X., Canova, C., Cadoni, G., Brennan, P., Boccia, S., Antunes, J.L.F., Ahrens, W., Agudo, A., Boffetta, P., Hashibe, M., Lee, Y.-C.A., and Filho, V.W.

Subjects
Male, Aging, Epidemiology, head and neck cancer (HNC), Adult Age Factors Alcohol Drinking/*epidemiology Case-Control Studies Female Genetic Predisposition to Disease Head and Neck Neoplasms/*epidemiology/genetics Humans Incidence Male Middle Aged Odds Ratio Registries Risk Factors Sex Factors Smoking/*epidemiology Head and neck neoplasms alcohol drinking diet smoking, Risk Factors, Odds Ratio, Registries, Family history, Young adult, Cancer, Incidence (epidemiology), Incidence, Medicine (all), Statistics, Smoking, Age Factors, General Medicine, Middle Aged, 3. Good health, Public Health and Health Services, Female, Settore MED/31 - OTORINOLARINGOIATRIA, Adult, medicine.medical_specialty, Alcohol Drinking, Head and neck neoplasms, smoking, Rare Diseases, Sex Factors, Clinical Research, Internal medicine, Tobacco, medicine, Humans, Genetic Predisposition to Disease, Dental/Oral and Craniofacial Disease, Tobacco Smoke and Health, business.industry, Prevention, Head and neck cancer, Alcohol drinking, Diet, Case-Control Studies, Head and Neck Neoplasms, Case-control study, prognostic factors, Odds ratio, medicine.disease, Confidence interval, Surgery, Good Health and Well Being, Attributable risk, head and neck cancer, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, diet, Digestive Diseases, business
Abstract

Toporcov, Tatiana Natasha Znaor, Ariana Zhang, Zuo-Feng Yu, Guo-Pei Winn, Deborah M Wei, Qingyi Vilensky, Marta Vaughan, Thomas Thomson, Peter Talamini, Renato Szeszenia-Dabrowska, Neonila Sturgis, Erich M Smith, Elaine Shangina, Oxana Schwartz, Stephen M Schantz, Stimson Rudnai, Peter Richiardi, Lorenzo Ramroth, Heribert Purdue, Mark P Olshan, Andrew F Eluf-Neto, Jose Muscat, Joshua Moyses, Raquel Ajub Morgenstern, Hal Menezes, Ana McClean, Michael Matsuo, Keitaro Mates, Dana Macfarlane, Tatiana V Lissowska, Jolanta Levi, Fabio Lazarus, Philip La Vecchia, Carlo Lagiou, Pagona Koifman, Sergio Kjaerheim, Kristina Kelsey, Karl Holcatova, Ivana Herrero, Rolando Healy, Claire Hayes, Richard B Franceschi, Silvia Fernandez, Leticia Fabianova, Eleonora Daudt, Alexander W Curioni, Otavio Alberto Maso, Luigino Dal Curado, Maria Paula Conway, David I Chen, Chu Castellsague, Xavier Canova, Cristina Cadoni, Gabriella Brennan, Paul Boccia, Stefania Antunes, Jose Leopoldo Ferreira Ahrens, Wolfgang Agudo, Antonio Boffetta, Paolo Hashibe, Mia Lee, Yuan-Chin Amy Filho, Victor Wunsch eng FIRCA TW01500/TW/FIC NIH HHS/ K07CA104231/CA/NCI NIH HHS/ P01CA068384/CA/NCI NIH HHS/ P30ES010126/ES/NIEHS NIH HHS/ P50CA90388/CA/NCI NIH HHS/ R01CA048996/CA/NCI NIH HHS/ R01CA100264/CA/NCI NIH HHS/ R01CA30022/CA/NCI NIH HHS/ R01CA51845/CA/NCI NIH HHS/ R01CA61188/CA/NCI NIH HHS/ R01DA11386/DA/NIDA NIH HHS/ R01DE012609/DE/NIDCR NIH HHS/ R01DE11979/DE/NIDCR NIH HHS/ R01DE13110/DE/NIDCR NIH HHS/ R01DE13158/DE/NIDCR NIH HHS/ R01ES11740/ES/NIEHS NIH HHS/ R03CA113157/CA/NCI NIH HHS/ R03CA77954/CA/NCI NIH HHS/ R03DE016611/DE/NIDCR NIH HHS/ R21ES011667/ES/NIEHS NIH HHS/ T32CA09142/CA/NCI NIH HHS/ U01CA96134/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2015/01/24 06:00 Int J Epidemiol. 2015 Feb;44(1):169-85. doi: 10.1093/ije/dyu255. Epub 2015 Jan 22.; International audience; BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults 45 years old ('older adults', 17700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI=9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking=5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR=2.27 (95% CI=1.26, 4.10)], but not in the older adults [OR=1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.

Published
2015
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