• The aetiology of upper aerodigestive tract cancers among young adults in Europe: the ARCAGE study.

      Macfarlane, Tatiana V; Macfarlane, Gary J; Oliver, Richard J; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Pohlabeln, Hermann; Lagiou, Pagona; Lagiou, Areti; Castellsague, Xavier; Agudo, Antonio; Merletti, Franco; Richiardi, Lorenzo; Kjaerheim, Kristina; Slamova, Alena; Schejbalova, Miriam; Canova, Cristina; Simonato, Lorenzo; Talamini, Renato; Barzan, Luigi; Conway, David I; McKinney, Patricia A; Znaor, Ariana; Lowry, Raymond J; Thomson, Peter; Healy, Claire M; McCartan, Bernard E; Marron, Manuela; Hashibe, Mia; Brennan, Paul; School of Medicine and Dentistry, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK. Tatiana.Macfarlane@abdn.ac.uk. (2010-12)
      Risk factors already identified as being important for UADT cancers in adults are also important influences on risk in younger adults. The implication of these results is that the public health message in preventing UADT cancers remains the same to young and old alike.
    • Alcohol-related cancers and genetic susceptibility in Europe: the ARCAGE project: study samples and data collection.

      Lagiou, Pagona; Georgila, Christina; Minaki, Ploumitsa; Ahrens, Wolfgang; Pohlabeln, Hermann; Benhamou, Simone; Bouchardy, Christine; Slamova, Alena; Schejbalova, Miriam; Merletti, Franco; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsague, Xavier; Macfarlane, Tatiana V; Macfarlane, Gary J; Talamini, Renato; Barzan, Luigi; Canova, Cristina; Simonato, Lorenzo; Lowry, Ray; Conway, David I; McKinney, Patricia A; Znaor, Ariana; McCartan, Bernard E; Healy, Claire; Nelis, Mari; Metspalu, Andres; Marron, Manuela; Hashibe, Mia; Brennan, Paul J; Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece. (2009-02)
      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.
    • The association between change in body mass index and upper aerodigestive tract cancers in the ARCAGE project: multicenter case-control study.

      Park, Sungshim Lani; Lee, Yuan-Chin Amy; Marron, Manuela; Agudo, Antonio; Ahrens, Wolfgang; Barzan, Luigi; Bencko, Vladimir; Benhamou, Simone; Bouchardy, Christine; Canova, Cristina; Castellsague, Xavier; Conway, David I; Healy, Claire M; Holcátová, Ivana; Kjaerheim, Kristina; Lagiou, Pagona; Lowry, Raymond J; Macfarlane, Tatiana V; Macfarlane, Gary J; McCartan, Bernard E; McKinney, Patricia A; Merletti, Franco; Pohlabeln, Hermann; Richiardi, Lorenzo; Simonato, Lorenzo; Sneddon, Linda; Talamini, Renato; Trichopoulos, Dimitrios; Znaor, Ariana; Brennan, Paul; Hashibe, Mia; Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, USA. (2011-03-15)
      Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital- and population-based controls from ten European countries (alcohol-related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <-5%) vs. BMI stability (-5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature.
    • Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium.

      Chuang, Shu-Chun; Jenab, Mazda; Heck, Julia E; Bosetti, Cristina; Talamini, Renato; Matsuo, Keitaro; Castellsague, Xavier; Franceschi, Silvia; Herrero, Rolando; Winn, Deborah M; La Vecchia, Carlo; Morgenstern, Hal; Zhang, Zuo-Feng; Levi, Fabio; Dal Maso, Luigino; Kelsey, Karl; McClean, Michael D; Vaughan, Thomas; Lazarus, Philip; Muscat, Joshua; Ramroth, Heribert; Chen, Chu; Schwartz, Stephen M; Eluf-Neto, Jose; Hayes, Richard B; Purdue, Mark; Boccia, Stefania; Cadoni, Gabriella; Zaridze, David; Koifman, Sergio; Curado, Maria Paula; Ahrens, Wolfgang; Benhamou, Simone; Matos, Elena; Lagiou, Pagona; Szeszenia-Dabrowska, Neonilla; Olshan, Andrew F; Fernandez, Leticia; Menezes, Ana; Agudo, Antonio; Daudt, Alexander W; Merletti, Franco; Macfarlane, Gary J; Kjaerheim, Kristina; Mates, Dana; Holcatova, Ivana; Schantz, Stimson; Yu, Guo-Pei; Simonato, Lorenzo; Brenner, Hermann; Mueller, Heiko; Conway, David I; Thomson, Peter; Fabianova, Eleonora; Znaor, Ariana; Rudnai, Peter; Healy, Claire M; Ferro, Gilles; Brennan, Paul; Boffetta, Paolo; Hashibe, Mia; Imperial College London, London, UK. (2012-01)
      We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).
    • Diet and upper-aerodigestive tract cancer in Europe: the ARCAGE study.

      Lagiou, Pagona; Talamini, Renato; Samoli, Evangelia; Lagiou, Areti; Ahrens, Wolfgang; Pohlabeln, Hermann; Benhamou, Simone; Bouchardy, Christine; Slamova, Alena; Schejbalova, Miriam; Merletti, Franco; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsague, Xavier; Macfarlane, Tatiana V; Macfarlane, Gary J; Biggs, Anne-Marie; Barzan, Luigi; Canova, Cristina; Simonato, Lorenzo; Lowry, Raymond J; Conway, David I; McKinney, Patricia A; Znaor, Ariana; McCartan, Bernard E; Healy, Claire M; Marron, Manuela; Hashibe, Mia; Brennan, Paul; Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. pdlagiou@med.uoa.gr (2009-06)
      There is suggestive, but inconclusive, evidence that dietary factors may affect risk of cancers of the upper aerodigestive tract (UADT). In the context of the alcohol-related cancers and genetic susceptibility in Europe study, we have examined the association of dietary factors with UADT cancer risk. We have analyzed data from 2,304 patients with UADT cancer and 2,227 control subjects recruited in 14 centers in 10 European countries. Dietary data were collected through a semi-quantitative food frequency questionnaire that also assessed preferred temperature of hot beverages. Statistical analyses were conducted through multiple logistic regression controlling for potential confounding variables, including alcohol intake and smoking habits. Consumption of red meat (OR per increasing tertile = 1.14, 95% CI: 1.05-1.25), but not poultry, was significantly associated with increased UADT cancer risk and the association was somewhat stronger for esophageal cancer. Consumption of fruits (OR per increasing tertile = 0.68, 95% CI: 0.62-0.75) and vegetables (OR per increasing tertile = 0.73, 95% CI: 0.66-0.81) as well as of olive oil (OR for above versus below median = 0.78, 95% CI 0.67-0.90) and tea (OR for above versus below median = 0.83, 95% CI 0.69-0.98) were significantly associated with reduced risk of UADT cancer. There was no indication that an increase in tea or coffee temperature was associated with increased risk of UADT overall or cancer of the esophagus; in fact, the association was, if anything, inverse. In conclusion, the results of this large multicentric study indicate that diet plays an important role in the etiology of UADT cancer.
    • Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.

      Canova, Cristina; Hashibe, Mia; Simonato, Lorenzo; Nelis, Mari; Metspalu, Andres; Lagiou, Pagona; Trichopoulos, Dimitrios; Ahrens, Wolfgang; Pigeot, Iris; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Macfarlane, Gary J; Macfarlane, Tatiana V; Holcátová, Ivana; Bencko, Vladimir; Benhamou, Simone; Bouchardy, Christine; Kjaerheim, Kristina; Lowry, Ray; Agudo, Antonio; Castellsagué, Xavier; Conway, David I; McKinney, Patricia A; Znaor, Ariana; McCartan, Bernard E; Healy, Claire M; Marron, Manuela; Brennan, Paul; Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy. (2009-04-01)
      Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false-positive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend<0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 -47A>C (rs28399433), a phase I metabolism gene, was associated with reduced UADT cancer risk (P trend=0.01). Three SNPs in the MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend=0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk (for both, P trend=0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways.
    • Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.

      Urayama, Kevin Y; Jarrett, Ruth F; Hjalgrim, Henrik; Diepstra, Arjan; Kamatani, Yoichiro; Chabrier, Amelie; Gaborieau, Valerie; Boland, Anne; Nieters, Alexandra; Becker, Nikolaus; Foretova, Lenka; Benavente, Yolanda; Maynadié, Marc; Staines, Anthony; Shield, Lesley; Lake, Annette; Montgomery, Dorothy; Taylor, Malcolm; Smedby, Karin Ekström; Amini, Rose-Marie; Adami, Hans-Olov; Glimelius, Bengt; Feenstra, Bjarke; Nolte, Ilja M; Visser, Lydia; van Imhoff, Gustaaf W; Lightfoot, Tracy; Cocco, Pierluigi; Kiemeney, Lambertus; Vermeulen, Sita H; Holcatova, Ivana; Vatten, Lars; Macfarlane, Gary J; Thomson, Peter; Conway, David I; Benhamou, Simone; Agudo, Antonio; Healy, Claire M; Overvad, Kim; Tjønneland, Anne; Melin, Beatrice; Canzian, Federico; Khaw, Kay-Tee; Travis, Ruth C; Peeters, Petra H M; González, Carlos A; Quirós, José Ramón; Sánchez, María-José; Huerta, José María; Ardanaz, Eva; Dorronsoro, Miren; Clavel-Chapelon, Françoise; Bueno-de-Mesquita, H Bas; Riboli, Elio; Roman, Eve; Boffetta, Paolo; de Sanjosé, Silvia; Zelenika, Diana; Melbye, Mads; van den Berg, Anke; Lathrop, Mark; Brennan, Paul; McKay, James D; Genetics Section, International Agency for Research on Cancer, Lyon, France. (Journal of the National Cancer Institute, 2012-02-08)
      Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification.
    • A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

      McKay, James D; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Holcatova, Ivana; Janout, Vladimir; Foretova, Lenka; Lagiou, Pagona; Trichopoulos, Dimitrios; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Kjaerheim, Kristina; Macfarlane, Gary J; Macfarlane, Tatiana V; Simonato, Lorenzo; Canova, Cristina; Agudo, Antonio; Castellsagué, Xavier; Lowry, Ray; Conway, David I; McKinney, Patricia A; Healy, Claire M; Toner, Mary E; Znaor, Ariana; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wünsch-Filho, Victor; Neto, José Eluf; Garrote, Leticia Fernández; Boccia, Stefania; Cadoni, Gabriella; Arzani, Dario; Olshan, Andrew F; Weissler, Mark C; Funkhouser, William K; Luo, Jingchun; Lubiński, Jan; Trubicka, Joanna; Lener, Marcin; Oszutowska, Dorota; Schwartz, Stephen M; Chen, Chu; Fish, Sherianne; Doody, David R; Muscat, Joshua E; Lazarus, Philip; Gallagher, Carla J; Chang, Shen-Chih; Zhang, Zuo-Feng; Wei, Qingyi; Sturgis, Erich M; Wang, Li-E; Franceschi, Silvia; Herrero, Rolando; Kelsey, Karl T; McClean, Michael D; Marsit, Carmen J; Nelson, Heather H; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Zhong, Shilong; Lacko, Martin; Manni, Johannes J; Peters, Wilbert H M; Hung, Rayjean J; McLaughlin, John; Vatten, Lars; Njølstad, Inger; Goodman, Gary E; Field, John K; Liloglou, Triantafillos; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; González, Carlos A; Quirós, J Ramón; Martínez, Carmen; Navarro, Carmen; Ardanaz, Eva; Larrañaga, Nerea; Khaw, Kay-Tee; Key, Timothy; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Trichopoulou, Antonia; Linseisen, Jakob; Boeing, Heiner; Hallmans, Göran; Overvad, Kim; Tjønneland, Anne; Kumle, Merethe; Riboli, Elio; Välk, Kristjan; Vooder, Tõnu; Metspalu, Andres; Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Blanché, Hélène; Gut, Ivo G; Galan, Pilar; Heath, Simon; Hashibe, Mia; Hayes, Richard B; Boffetta, Paolo; Lathrop, Mark; Brennan, Paul; International Agency for Research on Cancer (IARC), Lyon, France. (2011-03)
      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.
    • Occupation and risk of upper aerodigestive tract cancer: the ARCAGE study.

      Richiardi, Lorenzo; Corbin, Marine; Marron, Manuela; Ahrens, Wolfgang; Pohlabeln, Hermann; Lagiou, Pagona; Minaki, Ploumitsa; Agudo, Antonio; Castellsague, Xavier; Slamova, Alena; Schejbalova, Miriam; Kjaerheim, Kristina; Barzan, Luigi; Talamini, Renato; Macfarlane, Gary J; Macfarlane, Tatiana V; Canova, Cristina; Simonato, Lorenzo; Conway, David I; McKinney, Patricia A; Sneddon, Linda; Thomson, Peter; Znaor, Ariana; Healy, Claire M; McCartan, Bernard E; Benhamou, Simone; Bouchardy, Christine; Hashibe, Mia; Brennan, Paul; Merletti, Franco; University of Turin, Turin, Italy. lorenzo.richiardi@unito.it (2012-05-15)
      We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry.
    • Population attributable risk of tobacco and alcohol for upper aerodigestive tract cancer.

      Anantharaman, Devasena; Marron, Manuela; Lagiou, Pagona; Samoli, Evangelia; Ahrens, Wolfgang; Pohlabeln, Hermann; Slamova, Alena; Schejbalova, Miriam; Merletti, Franco; Richiardi, Lorenzo; Kjaerheim, Kristina; Castellsague, Xavier; Agudo, Antonio; Talamini, Renato; Barzan, Luigi; Macfarlane, Tatiana V; Tickle, Martin; Simonato, Lorenzo; Canova, Cristina; Conway, David I; McKinney, Patricia A; Thomson, Peter; Znaor, Ariana; Healy, Claire M; McCartan, Bernard E; Hashibe, Mia; Brennan, Paul; Macfarlane, Gary J; International Agency for Research on Cancer, Lyon, France. (2011-08)
      Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR=85%) than oropharyngeal (PAR=74%), esophageal (PAR=67%) and oral cancer (PAR=61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR=84%) than southern (PAR=72%) and western Europe (PAR=67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe.
    • Risk of upper aerodigestive tract cancer and type of alcoholic beverage: a European multicenter case-control study.

      Marron, Manuela; Boffetta, Paolo; Møller, Henrik; Ahrens, Wolfgang; Pohlabeln, Hermann; Benhamou, Simone; Bouchardy, Christine; Lagiou, Pagona; Lagiou, Areti; Slámová, Alena; Schejbalová, Miriam; Merletti, Franco; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsague, Xavier; Macfarlane, Tatiana Victorovna; Macfarlane, Gary John; Talamini, Renato; Barzan, Luigi; Canova, Cristina; Simonato, Lorenzo; Biggs, Anne-Marie; Thomson, Peter; Conway, David Ian; McKinney, Patricia Ann; Znaor, Ariana; Healy, Claire Marie; McCartan, Bernard Eugene; Brennan, Paul; Hashibe, Mia; Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany. marron@uni-mainz.de (European journal of epidemiology, 2012-07)
      The general relationship between cancers of the upper aerodigestive tract (UADT) and alcohol drinking is established. Nevertheless, it is uncertain whether different types of alcoholic beverages (wine, beer and liquor) carry different UADT cancer risks. Our study included 2,001 UADT cancer cases and 2,125 controls from 14 centres in 10 European countries. All cases were histologically or cytologically confirmed squamous cell carcinomas. Controls were frequency matched by sex, age and centre. Logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (95 %CI) adjusted for age, sex, centre, education level, vegetable and fruit intake, tobacco smoking and alcohol drinking, where appropriate. Risk of beverage-specific alcohol consumption were calculated among 'pure drinker' who consumed one beverage type exclusively, among 'predominant drinkers' who consumed one beverage type to more than 66 % and among 'mixed drinkers' who consumed more than one beverage type to similar proportions. Compared to never drinkers and adjusted for cumulative alcohol consumption, the OR and 95 %CI for wine, beer and liquor drinking, respectively, were 1.24 (0.86, 1.78), 1.54 (1.05, 2.27) and 0.94 (0.53, 1.64) among 'pure drinkers' (p value for heterogeneity across beverage types = 0.306), 1.05 (0.76,1.47), 1.25 (0.87,1.79) and 1.43 (0.95, 2.16) among 'predominant drinkers' (p value = 0.456), and 1.09 (0.79, 1.50), 1.20 (0.88, 1.63) and 1.12 (0.82, 1.53) among 'mixed drinkers' (p value = 0.889). Risk of UADT cancer increased with increasing consumption of all three alcohol beverage types. Our findings underscore the strong and comparable carcinogenic effect of ethanol in wine, beer and liquor on organs of the UADT.
    • A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers.

      Chen, Dan; Truong, Therese; Gaborieau, Valerie; Byrnes, Graham; Chabrier, Amelie; Chuang, Shu-chun; Olshan, Andrew F; Weissler, Mark C; Luo, Jingchun; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Franceschi, Silvia; Herrero, Rolando; Talamini, Renato; Kelsey, Karl T; Christensen, Brock; McClean, Michael D; Lacko, Martin; Manni, Johannes J; Peters, Wilbert H M; Lubiński, Jan; Trubicka, Joanna; Lener, Marcin; Muscat, Joshua E; Lazarus, Philip; Wei, Qingyi; Sturgis, Erich M; Zhang, Zuo-Feng; Chang, Shen-Chih; Wang, Renyi; Schwartz, Stephen M; Chen, Chu; Benhamou, Simone; Lagiou, Pagona; Holcátová, Ivana; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsagué, Xavier; Macfarlane, Tatiana V; Barzan, Luigi; Canova, Cristina; Thakker, Nalin S; Conway, David I; Znaor, Ariana; Healy, Claire M; Ahrens, Wolfgang; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wünsch-Filho, Victor; Eluf-Neto, José; Fernandez, Leticia; Boccia, Stefania; Hashibe, Mia; Hayes, Richard B; Boffetta, Paolo; Brennan, Paul; McKay, James D; International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, France. (2011-04)
      Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35).
    • Using prior information from the medical literature in GWAS of oral cancer identifies novel susceptibility variant on chromosome 4--the AdAPT method.

      Johansson, Mattias; Roberts, Angus; Chen, Dan; Li, Yaoyong; Delahaye-Sourdeix, Manon; Aswani, Niraj; Greenwood, Mark A; Benhamou, Simone; Lagiou, Pagona; Holcátová, Ivana; Richiardi, Lorenzo; Kjaerheim, Kristina; Agudo, Antonio; Castellsagué, Xavier; Macfarlane, Tatiana V; Barzan, Luigi; Canova, Cristina; Thakker, Nalin S; Conway, David I; Znaor, Ariana; Healy, Claire M; Ahrens, Wolfgang; Zaridze, David; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Fabiánová, Eleonóra; Mates, Ioan Nicolae; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wünsch-Filho, Victor; Eluf-Neto, Jose; Boffetta, Paolo; Franceschi, Silvia; Herrero, Rolando; Fernandez Garrote, Leticia; Talamini, Renato; Boccia, Stefania; Galan, Pilar; Vatten, Lars; Thomson, Peter; Zelenika, Diana; Lathrop, Mark; Byrnes, Graham; Cunningham, Hamish; Brennan, Paul; Wakefield, Jon; McKay, James D; Section of Genetics, International Agency for Research on Cancer (IARC), Lyon, France. johanssonm@iarc.fr (2012)
      Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS.