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FACTEURS DE RISQUES EPIDEMIOLOGIE 1- Integrating Epidermal Growth Factor Receptor Assay with Clinical Parameters Improves Risk Classification for Relapse and Survival in Head-and-Neck Squamous Cell Carcinoma Original Research Article International Journal of Radiation Oncology*Biology*Physics, In Press, Corrected Proof, Available online 21 August 2010 Christine H. Chung, Qiang Zhang, Elizabeth M. Hammond, Andy M. Trotti III, Huijun Wang, Sharon Spencer, Hua-Zhong Zhang, Jay Cooper, Richard Jordan, Marvin H. Rotman, K. Kian Ang Purpose Epidermal growth factor receptor (EGFR) overexpression has been consistently found to be an independent predictor of local-regional relapse (LRR) after radiotherapy. We assessed the extent by which it can refine risk classification for overall survival (OS) and LRR in patients with head-andneck squamous cell carcinoma (HNSCC). Methods and Materials EGFR expression in locally advanced HNSCC was measured by immunohistochemistry in a series of patients randomized to receive accelerated or conventional radiation regimens in a Phase III trial. Subsequently, data of the two series were pooled (N = 533) for conducting a recursive partitioning analysis that incorporated clinical parameters (e.g., performance status, primary site, T and N categories) and four molecular markers (EGFR, p53, Ki-67, and microvessel density). Results This study confirmed that patients with higher than median levels of tumor EGFR expression had a lower OS (relative risk [RR]: 1.90, p = 0.0010) and a higher LRR (RR: 1.91, p = 0.0163). Of the four markers analyzed, only EGFR was found to contribute to refining classification of patients into three risk classes with distinct OS and LRR outcomes. The addition of EGFR to three clinical parameters could identify patients having up to a fivefold difference in the risk of LRR. Conclusions Adding pretreatment EGFR expression data to known robust clinical prognostic variables improved the estimation of the probability for OS and LRR after radiotherapy. Its use for stratifying or selecting patients with defined tumor feature and pattern of relapse for enrollment into clinical trials testing specific therapeutic strategy warrants further investigation. 2- Role of NQO1 polymorphisms as risk factors for squamous cell carcinoma of the head and neck Original Research Article 1 FACTEURS DE RISQUES EPIDEMIOLOGIE Oral Oncology, Volume 41, Issue 9, October 2005, Pages 927-933 Asher Begleiter, Alia Norman, Darren Leitao, Teresa Cabral, Donna Hewitt, Sushu Pan, Jennifer R. Grandis, Jill M. Siegfried, Samy El-Sayed, Donna Sutherland, David A. Ross, Paul D. Kerr Summary A case:control study was carried out to determine if inactivating polymorphisms of the NQO1 gene at bases 609 and 465 are associated with altered risk of developing squamous cell carcinoma of the head and neck (SCCHN). Genotyping was carried out by PCR RFLP analysis on whole blood samples. The frequency of the inactive 609T and active 609C forms, and the inactive 465T and active 465C forms, of NQO1 were compared in patient and control groups by a logistic regression analysis and odds ratios (ORs) were calculated. Participants were stratified by tobacco and alcohol use, and genotype distributions in these sub-groups were compared. There were no significant differences in genotype distribution between SCCHN patients and the control population for the base 609 or 465 polymorphisms. There were also no significant differences in genotype distributions between patient and control groups for tobacco and/or alcohol users and non-users. Genotype distributions were similar for SCCHN patients at all disease sites with the exception of the nasopharynx where there was a higher incidence of the 609C:609T and 609T:609T genotypes. These results suggest that individuals having either 609T or 465T alleles generally do not have an altered risk of developing SCCHN. 3- Clinicopathologic risk factors for distant metastases from head and neck squamous cell carcinomas Original Research Article European Journal of Surgical Oncology (EJSO), Volume 35, Issue 12, December 2009, Pages 1348-1353 X. Li, B. Di, Y. Shang, Y. Zhou, J. Cheng, Z. He Abstract Aims The aim of this study is to investigate the clinicopathologic risk factors associated with distant metastases (DMs) from head and neck squamous cell carcinomas (HNSCCs). Methods Between February 1990 and February 2000, a retrospective analysis of 391 HNSCC patients was performed. The frequency and the clinicopathologic risk factors for DM were evaluated by using univariate χ2 tests and multiple stepwise logistic regression models. Statistical analysis of overall survival was performed by using Kaplan–Meier method. 2 FACTEURS DE RISQUES EPIDEMIOLOGIE Results 44 patients (11.3%) developed DM in clinic. In a univariate analysis, clinical N stage, primary tumor site, level of tumor invasion, pathologic N stage and number of levels with pathologic lymph node were found to be significantly associated with the risk of DM. In a multivariate analysis, the most significant risk factors were number of levels with pathologic lymph node, level of tumor invasion, and primary tumor site. Kaplan–Meier analysis showed that overall survival rates of 44 patients with DMs in clinic were 56.8% at 1 year, 9.1% at 3 years, and 6.8% at 5 years, respectively. Conclusions The number of levels with pathologic lymph node, the site of primary tumor and the level of tumor invasion are decisive risk factors in determining the development of DM in head and neck SCC patients. Patients with multilevel nodal involvement in neck, with laryngeal and hypopharyngeal carcinomas, and patients with primary tumor invasion into muscular, bone or cartilage have the highest risk of developing DM. 4- Squamous cell carcinoma of the head and neck in young Irish adults Original Research Article British Journal of Oral and Maxillofacial Surgery, Volume 44, Issue 3, June 2006, Pages 203206 E.M. O’Regan, C. Timon, O. Sheils, Margaret Codd, J.J. O’Leary, M. Toner Abstract Abstract Classically, squamous cell carcinoma (SCC) of the head and neck is a disease of older adults, but recently there have been reports of an increasing incidence in young people. This study of patients in the Republic of Ireland compares sex distribution, sites, risk factors, stage and grade of tumour, and nodal status of 130 patients with SCC of the head and neck, 30 of whom were less than 40 years old. There was a highly significant association between age, smoking status, and site of tumour. For the first time to our knowledge in a study such as this, the preoperative haematological status of the patients was assessed, and although 15% were anaemic there was no significant difference in the occurrence of anaemia between the younger and the older patients. We think that it is possible that the biology of SCC of the head and neck in young people differs from that in older people. 5- The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines Original Research Article 3 FACTEURS DE RISQUES EPIDEMIOLOGIE Oral Oncology, Volume 43, Issue 7, August 2007, Pages 701-712 Jason S. White, Joel L. Weissfeld, Camille C.R. Ragin, Karen M. Rossie, Christa Lese Martin, Michele Shuster, Chandramohan S. Ishwad, John C. Law, Eugene N. Myers, Jonas T. Johnson, Susanne M. Gollin Summary The purpose of this study was to generate stable cell cultures from head and neck squamous cell carcinomas (HNSCC), and retrospectively analyze the factors associated with successful cell line establishment. Fifty-two HNSCC cell lines were isolated from a series of 199 tumors collected between 1992 and 1997 at the University of Pittsburgh Medical Center. Cell lines were characterized at the molecular and cellular level to determine the features associated with cell line formation. Successful cell line formation was dependent on multiple factors, including gene amplification involving chromosomal band 11q13, local and/or regional involvement of lymph nodes, and alcohol usage. The establishment of HNSCC cell lines enriches the resources available for cancer research. Our findings indicate that generation of stable cell lines from HNSCC is biased towards tumors with a poor prognosis. Our 52 stable lines comprise one of the largest series of HNSCC cell lines in the literature, with complete demographic, histopathologic, clinical, and survival data. 6- CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients Original Research Article Oral Oncology, Volume 45, Issue 9, September 2009, Pages e73-e79 Eloisa Helena Ribeiro Olivieri, Sabrina Daniela da Silva, Fernando Fernandes Mendonça, Yuri Nagamine Urata, Daniel Onofre Vidal, Marcilia de Araujo Medrado Faria, Inês Nobuko Nishimoto, Claudia Aparecida Rainho, Luiz Paulo Kowalski, Silvia Regina Rogatto Summary Head and neck squamous cell carcinoma (HNSCC) is associated with environmental factors, especially tobacco and alcohol consumption. Most of the carcinogens present in tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYPs) enzymes and detoxification of these substances is performed by glutathione S-transferases (GSTs). It has been suggested that genetic alterations, such as polymorphisms, play an important role in tumorigenesis and HNSCC progression. The aim of this study was to investigate CYP1A1, CYP1A2, CYP2E1, GSTM1, and GSTT1 polymorphisms as risk factors in HNSCC and their association with clinicopathologic data. The patients comprised 153 individuals with HNSCC (cases) and 145 with no current or previous diagnosis of cancer (controls). Genotyping of the single nucleotide polymorphisms (SNPs) of the CYP1A1, CYP1A2, and CYP2E1 genes was performed by PCR-RFLP and the GSTM1 and GSTT1 copy number polymorphisms (CNPs) were analyzed by PCR-multiplex. As expected, a significant difference was detected for tobacco and alcohol consumption between cases and controls (P < 0.001). It was observed that the CYP1A2*1D (OR = 16.24) variant and GSTM1 null alleles (OR = 0.02) confer increased risk of HNSCC development 4 FACTEURS DE RISQUES EPIDEMIOLOGIE (P < 0.001). In addition, head and neck cancer alcohol consumers were more frequently associated with the CYP2E1*5B variant allele than control alcohol users (P < 0.0001, OR = 190.6). The CYP1A2*1C polymorphism was associated with tumor recurrence (log-rank test, P = 0.0161). The CYP2E1*5B and GSTM1 null alleles were significantly associated with advanced clinical stages (T3 + T4; P = 0.022 and P = 0.028, respectively). Overall, the findings suggested that the genetic polymorphisms studied are predictors of risk and are also associated with tumor recurrence, since they are important for determining the parameters associated with tumor progression and poor outcomes in HNSCC. 7- Analysis of 724 cases of primary head and neck squamous cell carcinoma (HNSCC) with a focus on young patients and p53 immunolocalization Original Research Article Oral Oncology, Volume 45, Issue 9, September 2009, Pages 777-782 A.M.B. De Paula, L.R. Souza, L.C. Farias, G.T.B. Corrêa, C.A.C. Fraga, N.B. Eleutério, A.C.O. Silveira, F.B.G. Santos, D.S. Haikal, A.L.S. Guimarães, R.S. Gomez Summary This study evaluated 724 primary head and neck squamous cell carcinoma (HNSCC) in young and old patients, with regard to clinical profile and immunohistochemical expression of p53 protein. Associations among age, epidemiological and clinicopathological parameters, and survival analysis were evaluated. HNSCC in young people occurred in 14.5% (median age 40.7 years; male-to-female ratio 5.9:1). A statistical association was demonstrated between age and family history of cancer, and between age and anatomical site. Among older patients, a higher presence of disease was noted in posterior sites. Expression of p53 was found in 71.7% of the samples and a higher expression was noted in lesions of young patients. Survival analysis showed that the age parameter is not a reliable prognostic factor for HNSCC. Among young patients, cervical metastasis was associated with worse survival. The presence of a family history of cancer in young patients could indicate genetic susceptibility and molecular disturbances in the p53 pathway in HNSCC of young and older patients seem to be distinct. 8- Promoter polymorphisms of DNMT3B and the risk of head and neck squamous cell carcinoma in Taiwan: A case–control study Original Research Article Oral Oncology, Volume 43, Issue 4, April 2007, Pages 345-351 Kai-Ping Chang, Sheng-Po Hao, Chun-Ting Liu, Ming-Huei Cheng, Yu-Liang Chang, Yun-Shien Lee, Tzu-Hao Wang, Chi-Neu Tsai Close preview | PDF (413 K) | Related articles | Related reference work articles Abstract 5 FACTEURS DE RISQUES EPIDEMIOLOGIE Summary Three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region, C46359T (−149C > T), −283T > C, and −579G > T might be a cancer susceptible factor for several cancers. In this study, we genotyped 226 head-and-neck squamous-cell carcinoma (HNSCC) patients and 249 controls to examine the association between three SNPs of the DNMT3B promoter and the associated risk of the development and/or metastasizing tendency of HNSCC for the population of Taiwan. We observed that only the T/T genotype (C46359T) was found to be present in both patient and control groups (100% frequency). The alleles frequency of −283CC, −283CT and −283TT among patients and controls was, respectively, 88.1% versus 84.3%, 11.9% versus 15.3%, and 0% versus 0.4%. The allele −597GG was not found in both groups, whereas the allele frequency of −597TT and −597GT for patients and controls was, respectively, 88.1% versus 85.5%, and 11.9% versus 14.5%. For both DNMT3B SNPs, inter-group comparison of the allele frequency between patients and controls and distribution of SNPs among cancer patients either featuring or not featuring cervical metastasis did not reveal any significant difference. In conclusion, the relative distribution of three DNMT3B SNPs among a Taiwanese population can not be used as a stratification marker to predict either an individual’s susceptibility to HNSCC and/or the likelihood of cervical metastasis of HNSCC. 9- Patient and tumour factors associated with advanced carcinomas of the head and neck Original Research Article Oral Oncology, Volume 41, Issue 3, March 2005, Pages 313-319 Debbie M. Tromp, Xavier D.R. Brouha, Gert-Jan Hordijk, Jacques A.M. Winnubst, Rob J. de Leeuw Summary This study identifies patient and tumour related factors associated with advanced carcinoma of the head and neck. Special attention was paid to the role of patient and professional diagnostic delays. Three-hundred and six patients newly diagnosed with carcinoma of the pharynx, larynx and oral cavity were included in the study. Logistic regression analyses were used to identify the risk factors for presenting with an advanced tumour. Multivariate analysis found that having a pharyngeal carcinoma (OR 22.68; p = .000), an oral carcinoma (OR 6.51; p = .000), or a supraglottic carcinoma (OR 8.12; p = .000), patient delay >3 months (OR 3.47; p = .001) and having a doctors’ contact for another reason than the head and neck symptom (OR 0.20; p = .022) were predictive of presenting with an advanced tumour. These results suggest that beyond tumour-related factors, the patients’ care seeking behaviour contributes to an increased risk of being diagnosed with an advanced tumour of the head and neck. 10- Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell carcinoma Original Research Article 6 FACTEURS DE RISQUES EPIDEMIOLOGIE Cancer Letters, Volume 248, Issue 2, 18 April 2007, Pages 269-279 Mark G. Slomiany, Leigh Ann Black, Megan M. Kibbey, Melissa A. Tingler, Terry A. Day, Steven A. Rosenzweig Abstract Abstract IGF-1 receptor (IGF-1R) signaling is associated with increased tumorigenesis of epithelial cancers. In light of recent epidemiological studies correlating high circulating levels of IGF-1 with increased risk of second primary tumors (SPTs) of the head and neck, we examined IGF system and epidermal growth factor receptor (EGFR) expression in human head and neck squamous cell carcinoma (HNSCC) matched pairs and a cross-section of HNSCC cell lines. Employing the latter, we demonstrated that IGF-1 stimulated S-phase transition in a PI 3-K/Akt and Erk-dependent manner in 5 of 8 cell lines, with Erk activation being dependent upon EGFR kinase activity. IGF-1 stimulated thymidine incorporation was inhibited by treatment with IGFBP-3, the IGF-1R tyrosine kinase inhibitor NVP-AEW541, or the EGFR tyrosine kinase inhibitor AG1478. Combining IGFBP-3 with NVP-AEW541 or AG1478 abrogated IGF-1 responses at 10-fold lower doses than either compound alone. These results demonstrate the potential for co-targeting the IGF system and EGFR in HNSCC. 11- ADH1B and ALDH2 polymorphisms and their associations with increased risk of squamous cell carcinoma of the head and neck in the Korean population Original Research Article Oral Oncology, In Press, Corrected Proof, Available online 14 May 2011 Yong Bae Ji, Kyung Tae, Tae Hwan Ahn, Seung Hwan Lee, Kyung Rae Kim, Chul Won Park, Byung Lae Park, Hyoung Doo Shin Close preview | PDF (218 K) | Related articles | Related reference work articles Abstract Summary Alcohol consumption is a major risk factor for squamous cell carcinoma of the head and neck (SCCHN). Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are key enzymes in ethanol metabolism. The objective of this study was to investigate the relationships of ADH and ALDH single nucleotide polymorphisms (SNPs) with the risk of developing SCCHN in a Korean sample. We genotyped ADH1B +3170A>G (rs1229984) and ALDH2 +1951G>A (rs671) SNPs in 225 Korean SCCHN patients and 301 healthy controls by single base extension and TaqMan assay. The frequencies of the ADH1B +3170A>G (*2*2/*2*1/*1*1) genotypes were 48.0%/38.7%/13.3% in SCCHN patients, and 57.8%/37.2%/5.0% in controls, respectively. The odds ratio (OR) and 95% confidence interval of the ADH1B *1*1 genotype was 1.89 (1.23–2.92) relative to the *2*2 genotype. The 7 FACTEURS DE RISQUES EPIDEMIOLOGIE frequencies of the ALDH2 +1951G>A (*1*1/*1*2/*2*2) genotypes were 67.6%/31.6%/0.9% in SCCHN patients, and 67.8%/29.6%/2.7% in controls, respectively. In subgroup analyses according to smoking and alcohol drinking status, the OR of the ADH1B *1*1 genotype was increased in the heavy drinker group [8.85 (1.095–40.0)] and in the heavy smoker group [4.7 (1.54–14.29)]. We conclude that the ADH1B *1*1 genotype is associated with an increased risk of SCCHN, especially in heavy drinkers and heavy smokers. This genotype could be a useful biomarker for identifying Koreans with a greater risk of SCCHN. 12- Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12):3353-61. Active and involuntary tobacco smoking and upper aerodigestive tract cancer risks in a multicenter case-control study. Lee YC, Marron M, Benhamou S, Bouchardy C, Ahrens W, Pohlabeln H, Lagiou P, Trichopoulos D, Agudo A, Castellsague X, Bencko V, Holcatova I, Kjaerheim K, Merletti F, Richiardi L, Macfarlane GJ, Macfarlane TV, Talamini R, Barzan L, Canova C, Simonato L, Conway DI, McKinney PA, Lowry RJ, Sneddon L, Znaor A, Healy CM, McCartan BE, Brennan P, Hashibe M. Source IARC, Lyon, France. Abstract INTRODUCTION: Several important issues for the established association between tobacco smoking and upper aerodigestive tract (UADT) cancer risks include the associations with smoking by cancer subsite, by type of tobacco, and among never alcohol drinkers and the associations with involuntary smoking among nonsmokers. Our aim was to examine these specific issues in a large-scale case-control study in Europe. METHODS: Analysis was done on 2,103 UADT squamous cell carcinoma cases and 2,221 controls in the AlcoholRelated Cancers and Genetic Susceptibility in Europe project, a multicenter case-control study in 10 European countries. Unconditional logistic regression was done to obtain odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Compared with never tobacco smoking, current smoking was associated with UADT cancer risks (OR, 6.72; 95% CI, 5.45-8.30 for overall; OR, 5.83; 95% CI, 4.50-7.54 for oral cavity and oropharynx; OR, 12.19; 95% CI, 8.29-17.92 for hypopharynx and larynx; and OR, 4.17; 95% CI, 2.45-7.10 for esophagus). Among never drinkers, dose-response relationships with tobacco smoking pack-years were observed for hypopharyngeal and laryngeal cancers (P(trend) = 0.010) but not for oral cavity and 8 FACTEURS DE RISQUES EPIDEMIOLOGIE oropharyngeal cancers (P(trend) = 0.282). Among never smokers, ever exposure to involuntary smoking was associated with an increased risk of UADT cancers (OR, 1.60; 95% CI, 1.04-2.46). CONCLUSION: Our results corroborate that tobacco smoking may play a stronger role in the development of hypopharyngeal and laryngeal cancers than that of oral cavity and oropharyngeal cancers among never drinkers and that involuntary smoking is an important risk factor for UADT cancers. Public health interventions to reduce involuntary smoking exposure could help reduce UADT cancer incidence. 13- J Cancer Res Clin Oncol. 2007 Sep;133(9):673-8. Epub 2007 May 8. Alcohol, smoking and human papillomavirus in laryngeal carcinoma: a Nordic prospective multicenter study. Koskinen WJ, Brøndbo K, Mellin Dahlstrand H, Luostarinen T, Hakulinen T, Leivo I, Molijn A, Quint WG, Røysland T, Munck-Wikland E, Mäkitie AA, Pyykkö I, Dillner J, Vaheri A, Aaltonen LM. Source Department of Virology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, 00014 Helsinki, Finland. [email protected] Abstract PURPOSE: Human papillomavirus (HPV) has been linked to oropharyngeal carcinomas, but its role in laryngeal squamous cell carcinoma (LSCC) is not clear. A prospective multicenter study based on known tumorcell percentage of fresh frozen carcinoma biopsies was established to determine the HPV prevalence. Moreover risk factors such as smoking, alcohol abuse, chronic laryngitis and gastroesophageal reflux disease (GERD) were evaluated METHODS: Fresh-frozen laryngeal cancer biopsies from 108 patients in Finland, Norway, and Sweden were investigated. Patients whose biopsy samples contained at least 20% tumor tissue (N = 69) entered the study. HPV DNA was determined with MY09/11 and GP5+ +/6+ + nested PCR and SPF10 PCR hybridization assay. Patients were examined by an ENT specialist and an extensive questionnaire concerning risk factors was filled in. RESULTS: Only three patients (4.4%) harbored HPV DNA in their carcinoma sample. Heavy alcohol drinking was associated with an increased risk of death, advanced-stage disease, and younger age at diagnosis. Chronic laryngitis, GERD, and orogenital sex contacts were rare. Poor oral hygiene was not associated with survival, although it correlated with heavy drinking. CONCLUSION: In our series HPV was not important in LSCC. Heavy drinking led to major mortality in LSCC and promoted early carcinogenesis. 9 FACTEURS DE RISQUES EPIDEMIOLOGIE 14- Eur J Cancer Prev. 2009 Feb;18(1):76-84. Alcoholrelated cancers and genetic susceptibility in Europe: the ARCAGE project: study samples and data collection. Lagiou P, Georgila C, Minaki P, Ahrens W, Pohlabeln H, Benhamou S, Bouchardy C, Slamova A, Schejbalova M, Merletti F, Richiardi L, Kjaerheim K, Agudo A, Castellsague X, Macfarlane TV, Macfarlane GJ, Talamini R, Barzan L, Canova C, Simonato L, Lowry R, Conway DI, McKinney PA, Znaor A, McCartan BE, Healy C, Nelis M, Metspalu A, Marron M, Hashibe M, Brennan PJ. Source Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece. Abstract Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity, pharynx (other than nasopharynx), larynx, and esophagus. Tobacco smoking and consumption of alcoholic beverages are established causes of UADT cancers, whereas reduced intake of vegetables and fruits are likely causes. The role of genetic predisposition and possible interactions of genetic with exogenous factors, however, have not been adequately studied. Moreover, the role of pattern of smoking and drinking, as well as the exact nature of the implicated dietary variables, has not been clarified. To address these issues, the International Agency for Research on Cancer initiated in 2002 the alcohol-related cancers and genetic susceptibility (ARCAGE) in Europe project, with the participation of 15 centers in 11 European countries. Information and biological data from a total of 2304 cases and 2227 controls have been collected and will be used in a series of analyses. A total of 166 single nucleotide polymorphisms of 76 genes are being studied for genetic associations with UADT cancers. We report here the methodology of the ARCAGE project, main demographic and lifestyle characteristics of the cases and controls, as well as the distribution of cases by histology and subsite. About 80% of cases were males and fewer than 20% of all cases occurred before the age of 50 years. Overall, the most common subsite was larynx, followed by oral cavity, oropharynx, esophagus and hypopharynx. Close to 90% of UADT cancers were squamous cell carcinomas. A clear preponderance of smokers and alcohol drinkers among UADT cases compared with controls was observed. 15- Am J Epidemiol. 2007 Apr 1;165(7):814-20. Epub 2007 Jan 22. Contribution of tobacco and alcohol to the high rates of squamous cell carcinoma of the supraglottis and glottis in Central Europe. Hashibe M, Boffetta P, Zaridze D, Shangina O, Szeszenia-Dabrowska N, Mates D, Fabiánová E, Rudnai P, Brennan P. Source International Agency for Research on Cancer, Lyon, France. Abstract Incidence rates for laryngeal cancer in Central Europe are among the highest in the world. The authors recruited cases and controls between 2000 and 2002 for the Central and Eastern Europe Multicenter Study to investigate the role of tobacco and alcohol as causes of laryngeal cancer in this region. A total of 384 incident squamous cell cases were included, comprising 254 glottic and 108 supraglottic cancers. Hospital controls were chosen from within the same catchment area, from diseases unrelated to tobacco or alcohol (n = 918). Significant dose-response trends for frequency and duration of 10 FACTEURS DE RISQUES EPIDEMIOLOGIE tobacco use were observed for both supraglottic and glottic cancers, with potentially a more important effect for supraglottic cancer. Quitting smoking was protective against laryngeal cancers after 5 years. Any increases in risk for alcohol drinking were generally moderate and nonsignificant. A greater than multiplicative interaction was observed between tobacco and alcohol on the risk of laryngeal cancer (p = 0.04). Approximately 87% of laryngeal cancer cases in Central Europe are attributable to tobacco use, of which 75% and 12% are due to current and past smoking, respectively. Approximately 39% are attributable to the interaction between alcohol and tobacco. Preventive efforts to encourage current smokers to quit are likely to be the most effective way to reduce the incidence of laryngeal cancer in this region. 16- Oral Oncol. 2009 Jan;45(1):85-9. Epub 2008 May 19. Diet diversity and the risk of laryngeal cancer: a case-control study from Italy and Switzerland. Garavello W, Lucenteforte E, Bosetti C, Talamini R, Levi F, Tavani A, Franceschi S, Negri E, La Vecchia C. Source Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156 Milan, Italy. Abstract Diet diversity (defined as the number of different foods consumed) has been considered an indicator of a healthy diet, and favorably related to the risk of several digestive tract cancers. We analyzed the relation between diet diversity and the risk of laryngeal cancer using data from a case-control study carried out between 1992 and 2000 in Italy and Switzerland. The subjects of the study were 527 patients with histologically confirmed incident cancers of the larynx and 1297 patients admitted for acute, non-neoplastic diseases, unrelated to tobacco or alcohol consumption. Total diversity was computed as the number of different foods (overall and within four food groups, i.e., vegetables, fruit, meat, and cereals) consumed at least once per week. A significant inverse association was observed for vegetable diversity (OR=0.41, 95% CI: 0.28-0.59, for the highest versus the lowest quartile) and fruit diversity (OR=0.40, 95% CI: 0.27-0.59). Conversely, a direct association was found for meat diversity (OR=1.67, 95% CI: 1.11-2.50), while no meaningful association was found for total diet and cereal diversity. The results were consistent across strata of age, alcohol drinking and tobacco smoking. This study suggests that a diet not only rich but also varied in fruit and vegetables is related to a decreased risk of laryngeal cancer risk. 17- Oral Oncol. 2009 Aug;45(8):e49-53. Epub 2009 Feb 28. Dietary patterns and risk of oral cancer: a factor analysis study of a population in Jakarta, Indonesia. Amtha R, Zain R, Razak IA, Basuki B, Roeslan BO, Gautama W, Purwanto DJ. Source Oral Medicine Department, Trisakti University, Kyai Tapa, Grogol, Jakarta Barat, Indonesia. [email protected] 11 FACTEURS DE RISQUES EPIDEMIOLOGIE Abstract A matched case-control, hospital-based study of oral cancer was conducted in Jakarta population. The sample included 81 cases and 162 controls. The purpose of this study was to determine the association between dietary pattern and oral cancer in a Jakarta population using factor analysis. Dietary data were collected using food frequency questionnaire and factor analysis was performed on 15 food groups resulting in four principle factors/components being retained. The first factor "preferred" was characterized by fast food, fermented food, canned food, snacks high in fat and sugar, cooked and raw vegetables, and seafood. The second factor labeled "combination" was loaded by the intake of dairy product, red meat, white meat and fruits. The third factor labeled "chemical related was loaded by processed food and monosodium glutamate and the fourth principle component consisted of drinks and grain was labeled as "traditional". The conditional logistic regression was done using STATA 8 to obtain the odds ratio (OR) of highest tertile of each component retained from factor analysis and the ORs were then adjusted with risk habits. The consumption the highest tertile of the "preferred" pattern increased the risk of oral cancer by two-times compared to the lowest tertile of consumption [adjusted odds ratio (aOR)=2.17; 95% confidence interval (CI)=1.05-4.50]. The chemical related" pattern showed higher risk of about threefold (aOR=2.56; 95% CI=1.18-5.54), while the "traditional" pattern showed an increased of risk by twofold (aOR=2.04; 95% CI=1.01-4.41). In contrast, the "combination" pattern displayed protective effects in relation to oral cancer (aOR=0.50; 95% CI=0.241.00). This finding suggests that factor analysis may be useful to determine the diet pattern of a big set of food type and establish the correlation with oral cancer. 18- Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in head and neck cancer Original Research Article Cancer Epidemiology, Volume 34, Issue 5, October 2010, Pages 587-592 K. Sabitha, M. Vishnuvardhan Reddy, Kaiser Jamil Abstract Background: CYP1A1 is one of the commonest genes which had been widely investigated to find the risk of various malignancies in different ethnic groups. The polymorphism in these genes with a combination of environmental exposure has been hypothesized to confer a differential risk of cancer for individuals carrying these genetic variants. Based on this model, individuals with higher CYP1A1 activity would be at increased risk of cancer when exposed to high levels of smoke components. The proposed mechanism involves cytochrome P450 1A1 (CYP1A1), a gene that is inducible by xenobiotics to produce genetic susceptibility for malignancies. Patients and procedures: We performed a case–control study in 205 cases with histopathologically confirmed squamous cell carcinoma of head and neck and reported habits of bidi or cigarettes smoking and 245 similar controls to investigate the role of CYP1A1 polymorphisms in the risk of head and neck cancers especially among smokers of Hyderabad Indian population. Venous blood samples (5 ml) were collected from patients and control groups; genomic DNA was extracted and used for polymerase chain reaction (PCR) to determine the genotypes. RFLP assays were designed to detect each of the variant CYP1A1 alleles. Results and discussion: CYP1A1m1/m1 genotype (OR = 8.12, 95% CI: 3.27– 21.30) and CYP1A1w1/m1 showed elevated risk when compared with CYP1A1w1/w1. Similarly CYP1A1w2/m2 (OR = 1.58, 95% CI: 0.94–2.67) and CYP1A1m2/m2 (OR = 6.31, 95% CI: 2.74–18.69) 12 FACTEURS DE RISQUES EPIDEMIOLOGIE genotypes also showed elevated risk when compared with CYP1A1w2/w2 genotype. This data demonstrated that smoking was a risk factor for head and neck cancers. The m2 mutations were in close linkage disequilibrium with the m1 mutations; 53% m1 mutants had the mutation in the m2 site. Conclusion: Those individuals carrying at least one CYP1A1 m1 or m2 variant allele were at a 2fold elevated risk for head and neck cancer. Our data clearly demonstrates that CYP1A1 is an important determinant in susceptibility to tobacco-induced head and neck carcinogens and there is an association between genetic polymorphism in the CYP1A1 locus and elevated risk of the type of smoking among Indians. This appears to be a new and important prognostic and diagnostic marker for determining the risk of head and neck cancers genetically. 19- Spectra of antinuclear antibodies in patients with squamous cell carcinoma of the lung and of the head and neck Original Research Article Cancer Detection and Prevention, Volume 29, Issue 1, 2005, Pages 59-65 Félix Fernández Madrid, Robert L. Karvonen, John Ensley, Michael Kraut, José L. Granda, Huda Alansari, Naimei Tang, John E. Tomkiel Close preview | PDF (352 K) | Related articles | Related reference work articles Abstract Abstract Squamous cell carcinoma of the head and neck (HNSCC) and of the lung (LSCC) share some important risk factors, but differ substantially in terms of prognosis and treatment. A pulmonary nodule developing in patients with surgically cured HNSCC may pose a diagnostic dilemma. Markers able to distinguish these two common malignancies would be of major clinical importance. In this work we compared the spectrum of antinuclear antibodies (ANA) from 22 patients with SCCL to that of 40 patients with HNSCC. Patient sera were used to probe immunoblots of nuclear extracts from all four major lung cancer cell types, normal lung fibroblasts, cells cultured from a HNSCC, and keratinocytes cultured from the field cancerization. The ability to classify retrospectively LSCC from HNSCC based on serum ANA reactivities was determined by recursive partitioning analyses. We found that while both malignancies share reactivities to a small group of nuclear antigens, other reactivities are directed against proteins uniquely or preferentially expressed in either SCCL or in SCCHN cells. Our work shows that autoimmunity is a prominent feature of squamous cell carcinoma and suggests that molecular characterization of nuclear antigens recognized by ANAs may lead to the discovery of markers valuable to distinguish LSCC from HNSCC. 20- Effect of family history of cancers and environmental factors on risk of nasopharyngeal carcinoma in Guangdong, China Original Research Article Cancer Epidemiology, Volume 34, Issue 4, August 2010, Pages 419-424 13 FACTEURS DE RISQUES EPIDEMIOLOGIE Ze-Fang Ren, Wen-Sheng Liu, Hai-De Qin, Ya-Fei Xu, Dan-Dan Yu, Qi-Sheng Feng, Li-Zhen Chen, Xiao-Ou Shu, Yi-Xin Zeng, Wei-Hua Jia Abstract Background: Family history of nasopharyngeal carcinoma (NPC) is an established risk factor for this cancer, but the contributions of family history of other types of cancer and its interaction with environmental factors have not been well characterized. Methods: A total of 1845 incident cases of NPC and 2275 matched controls from Guangdong, China were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models adjusted for smoking, consumption of alcohol, salted fish consumption, and demographic factors. Results: A significant association between the risk of NPC and family history of any cancers in first degree relatives was observed, and higher number of affected family member was related to a higher risk (Ptrend < 0.01). Family history of NPC was the strongest predictor for NPC (OR: 3.35, 95% CI: 2.46–4.55 for all first degree relatives). The risk of NPC was also positively associated with history of head and neck cancer among parents and lung and breast cancers among siblings. The combination of family history of cancer, especially NPC, and the consumption of salt-preserved fish significantly increased the risk for NPC. Conclusions: These results confirm that the risk for NPC increases with family history of NPC and suggest that lung and breast cancer contribute to risk for NPC. A possible interaction between family history of cancer, especially NPC, and consumption of salt-preserved fish in the development of NPC was also identified. 21- Expression of haptoglobin predicts recurrence in head and neck squamous cell carcinoma Original Research Article Clinica Chimica Acta, Volume 411, Issues 15-16, 5 August 2010, Pages 1116-1121 Ching-Chih Lee, Hsu-Chueh Ho, Moon-Sing Lee, Shih-Kai Hung, Chih-Chia Yu, Yu-Chieh Su Close preview | PDF (996 K) | Supplementary content reference work articles | Related articles | Related Abstract Abstract Background We determined whether expression of haptoglobin by head and neck squamous cell carcinoma (HNSCC) cells is associated with prognosis. Methods 14 FACTEURS DE RISQUES EPIDEMIOLOGIE Western blotting was carried out to investigate the expression of haptoglobin in oral cancer cell lines. We study patients with HNSCC without distant metastasis at diagnosis. Correlation between cellular haptoglobin and clinical characteristics of HNSCC was analyzed to assess the prognostic value of cellular haptoglobin level. Kaplan–Meier survival curves and log-rank test were used to evaluate differences in recurrence, distant metastasis, and overall survival rates between patients grouped according to cellular haptoglobin level in cancer tissues. The relationship of haptoglobin expression with survival was assessed using Cox proportional hazard models. Results Western blotting analysis showed that haptoglobin protein was expressed in 4 oral cancer cell lines. The recurrence rate was higher in HNSCC patients with over-expression of haptoglobin (> 50%) (P = 0.045). Over-expression of haptoglobin was also associated with an increased risk for recurrence (hazard ratio [HR] 3.2; 95% confidence interval [CI], 1.127–8.895; P = 0.029) after adjusting for age, gender, disease site, stage, and treatment modality. Conclusions Altogether, the data presented show that cellular expression of haptoglobin is closely related to recurrence rate in HNSCC patients. The elevated risk of relapse was confirmed in a multivariate analysis. The cellular expression of haptoglobin may be a prognostic factor in HNSCC. 22- Future challenges in head and neck cancer: From the bench to the bedside? Review Article Critical Reviews in Oncology/Hematology, In Press, Corrected Proof, Available online 9 December 2010 Luca Calabrese, Angelo Ostuni, Mohssen Ansarin, Gioacchino Giugliano, Fausto Maffini, Daniela Alterio, Maria Cossu Rocca, Giuseppe Petralia, Roberto Bruschini, Fausto Chiesa and on behalf of AROME Close preview | PDF (176 K) | Related articles | Related reference work articles Abstract Abstract HNC is the 11th most frequent carcinoma with a world-wide yearly incidence exceeding over half a million cases [1], a 10:1 male gender predilection and country specific variability [2]. The principal risk factors are tobacco and alcohol use and, in a growing population without these exposures, HPV infection. While much progress has been made in understanding the molecular basis of cancer, the 5-year mortality of head and neck cancer has remained approximately 50%. To this date we have not been 15 FACTEURS DE RISQUES EPIDEMIOLOGIE able to translate as much of our basic science knowledge into significant disease altering therapeutic strategies in terms of local, loco-regional, functional and overall survival. Challenges remain in all aspects of head and neck cancer management: prevention, diagnosis, surgical and non-surgical treatment. 23- Head Face Med. 2006 Oct 16;2:33. Circulating immune complexes and trace elements (Copper, Iron and Selenium) as markers in oral precancer and cancer : a randomised, controlled clinical trial. Khanna SS, Karjodkar FR. Source Department of Oral Medicine and Radiology, Nair Hospital Dental College, Mumbai, India. [email protected] Abstract AIM: To evaluate the levels of circulating immune complexes, trace elements (copper, iron and selenium) in serum of patients with oral submucous fibrosis (OSMF), oral leukoplakia (L), and oral squamous cell carcinoma (SCC), analyze the alteration and identify the best predictors amongst these parameters for disease occurrence and progression. METHODS: Circulating immune complexes (CIC) were estimated using 37.5% Polyethylene Glycol 6000(PEG) serum precipitation. Serum estimation of copper (Cu), Iron (Fe) and selenium (Se) was done using the Oxalyl Dihydrazide method, Colorimetric Dipyridyl method and the Differential Pulse Cathodic Stripping Voltametry respectively. RESULTS: The data analysis revealed increased circulating immune complex levels in the precancer and cancer patients. Serum copper levels showed gradual increase from precancer to cancer patients. However, serum iron levels were decreased significantly in the cancer group. Selenium levels showed marked decrease in the cancer group. Among CIC, serum, copper, iron and selenium the best predictors for the occurrence of lesions were age, serum iron, CIC, serum selenium in the decreasing order. CONCLUSION: The present study shows that these immunological and biological markers may be associated with the pathogenesis of oral premalignant and malignant lesions and their progressions. Concerted efforts would, therefore, help in early detection, management, and monitoring the efficacy of treatment. 24- Diversité des modèles d’évolution des incidences : implication en cancérogenèse ? Original Research Article 16 FACTEURS DE RISQUES EPIDEMIOLOGIE Revue des Maladies Respiratoires, Volume 28, Issue 1, January 2011, Pages 41-50 G. Buiret, G. Launoy, L. Remontet, N. Bossard, J. Iwaz, A. Belot, R. Ecochard Close preview | PDF (882 K) | Related articles | Related reference work articles Abstract Résumé Objectif Les cancers ORL, bronchiques et œsophagiens sont principalement liés à la consommation d’alcool et/ou de tabac. L’incidence des cancers ayant les mêmes facteurs de risque devrait varier de façon similaire dans le temps et l’espace. Le but de cette étude était d’identifier des groupes de cancers ayant la même évolution spatiotemporelle. Méthodes Cinquante mille neuf cent quatre-vingt cas de dix types de cancers différents ont été recueillis entre 1982 et 2002 dans six départements français. Les niveaux d’incidence et leur tendance évolutive ont été analysés en utilisant un modèle âge–cohorte avec un effet aléatoire qui prenait en compte l’hétérogénéité entre départements. Résultats Trois groupes de cancers ayant une évolution similaire de l’incidence spatiotemporelle ont été identifiés : (1) cavité orale, oropharynx, hypopharynx, larynx, œsophage et carcinomes épidermoïdes bronchiques dont les incidences diminuaient uniformément ; (2) adénocarcinomes bronchiques et autres histologies bronchiques dont les incidences augmentaient uniformément ; (3) carcinomes bronchiques à grandes et à petites cellules dont l’évolution des incidences spatiotemporelles était très hétérogène. Conclusion Par l’utilisation de méthodes d’épidémiologie descriptive, différents groupes de cancers ont été individualisés. Cette diversité pourrait suggérer des latences et des sensibilités différentes vis-à-vis des carcinogènes. 17