Eleonora Fabianova

Publications of Eleonora Fabianova

• Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium.

  Authors: Michele L Coté, Mei Liu, Stefano Bonassi, Monica Neri, Ann G Schwartz, David C Christiani, Margaret R Spitz, Joshua E Muscat, Gad Rennert, Katja K Aben [......] Donatella Ugolini, Henricus F M van der Heijden, Erich Wichmann, John K Wiencke, Penella J Woll, Ping Yang, David Zaridze, Zuo-Feng Zhang, Carol J Etzel, Rayjean J Hung

  European journal of cancer (Oxford, England : 1990). 03/2012;

  BACKGROUND AND METHODS: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology,BACKGROUND AND METHODS: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals. RESULTS: Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR)=1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR=1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR=1.44, 95% CI: 1.07, 1.93), after adjustment. CONCLUSIONS: The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group.

• A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23.

  Authors: Xifeng Wu, Ghislaine Scelo, Mark P Purdue, Nathaniel Rothman, Mattias Johansson, Yuanqing Ye, Zhaoming Wang, Diana Zelenika, Lee E Moore, Christopher G Wood [......] Doris Lechner, Amy Hutchinson, Meredith Yeager, Joseph F Fraumeni, Mark Lathrop, Konstantin G Skryabin, James D McKay, Jian Gu, Paul Brennan, Stephen J Chanock

  Human molecular genetics. 01/2012; 21(2):456-62.

  Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, weRenal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.

• Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium.

  Authors: Shu-Chun Chuang, Mazda Jenab, Julia E Heck, Cristina Bosetti, Renato Talamini, Keitaro Matsuo, Xavier Castellsague, Silvia Franceschi, Rolando Herrero, Deborah M Winn [......] David I Conway, Peter Thomson, Eleonora Fabianova, Ariana Znaor, Peter Rudnai, Claire M Healy, Gilles Ferro, Paul Brennan, Paolo Boffetta, Mia Hashibe

  Cancer causes & control : CCC. 01/2012; 23(1):69-88.

  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 dataWe 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).

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• Asthma and lung cancer risk: a systematic investigation by the International Lung Cancer Consortium.

  Authors: Albert Rosenberger, Heike Bickeböller, Valerie McCormack, Darren R Brenner, Eric J Duell, Anne Tjønneland, Soren Friis, Joshua E Muscat, Ping Yang, H-Erich Wichmann [......] Loic Lemarchand, Monica Neri, Stefano Bonassi, Angeline S Andrew, Qing Lan, Wei Hu, Irene Orlow, Bernard J Park, Paolo Boffetta, Rayjean J Hung

  Carcinogenesis. 12/2011; 33(3):587-97.

  Asthma has been hypothesized to be associated with lung cancer (LC) risk. We conducted a pooled analysis of 16 studies in the International Lung Cancer Consortium (ILCCO) to quantitatively assessAsthma has been hypothesized to be associated with lung cancer (LC) risk. We conducted a pooled analysis of 16 studies in the International Lung Cancer Consortium (ILCCO) to quantitatively assess this association and compared the results with 36 previously published studies. In total, information from 585 444 individuals was used. Study-specific measures were combined using random effects models. A meta-regression and subgroup meta-analyses were performed to identify sources of heterogeneity. The overall LC relative risk (RR) associated with asthma was 1.28 [95% confidence intervals (CIs) = 1.16-1.41] but with large heterogeneity (I(2) = 73%, P < 0.001) between studies. Among ILCCO studies, an increased risk was found for squamous cell (RR = 1.69, 95%, CI = 1.26-2.26) and for small-cell carcinoma (RR = 1.71, 95% CI = 0.99-2.95) but was weaker for adenocarcinoma (RR = 1.09, 95% CI = 0.88-1.36). The increased LC risk was strongest in the 2 years after asthma diagnosis (RR = 2.13, 95% CI = 1.09-4.17) but subjects diagnosed with asthma over 10 years prior had no or little increased LC risk (RR = 1.10, 95% CI = 0.94-1.30). Because the increased incidence of LC was chiefly observed in small cell and squamous cell lung carcinomas, primarily within 2 years of asthma diagnosis and because the association was weak among never smokers, we conclude that the association may not reflect a causal effect of asthma on the risk of LC.

• Cigarette smoking and lung cancer-relative risk estimates for the major histological types from a pooled analysis of case-control studies.

  Authors: Beate Pesch, Benjamin Kendzia, Per Gustavsson, Karl-Heinz Jöckel, Georg Johnen, Hermann Pohlabeln, Ann Olsson, Wolfgang Ahrens, Isabelle Mercedes Gross, Irene Brüske [......] Eleonora Fabianova, Rodica Stanescu Dumitru, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Charles M Rudin, Paul Brennan, Paolo Boffetta, Kurt Straif, Thomas Brüning

  International journal of cancer. Journal international du cancer. 11/2011;

  Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasetsLung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8-143.2) for SqCC, 111.3 (95% CI: 69.8-177.5) for SCLC and 21.9 (95% CI: 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5-124.6), 108.6 (95% CI: 50.7-232.8) and 16.8 (95% CI: 9.2-30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.

• Lung cancer risk attributable to occupational exposures in a multicenter case-control study in Central and Eastern Europe.

  Authors: Ann C Olsson, Per Gustavsson, David Zaridze, Anush Mukeriya, Neonila Szeszenia-Dabrowska, Peter Rudnai, Jolanta Lissowska, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Joelle Fevotte, Andrea 't Mannetje, Tony Fletcher, Paul Brennan, Paolo Boffetta

  Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine. 11/2011; 53(11):1262-7.

  To estimate the lung cancer risk attributable to occupational lung carcinogens. Information was collected through interviews from 2624 newly diagnosed lung cancer cases and 2690 frequency-matchedTo estimate the lung cancer risk attributable to occupational lung carcinogens. Information was collected through interviews from 2624 newly diagnosed lung cancer cases and 2690 frequency-matched controls in Central and Eastern Europe. Industrial hygiene experts evaluated exposure to 70 occupational agents. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression and attributable fractions (AF) by Miettinen's formula. Exposure to at least one occupational lung carcinogen resulted in an AF of 7.9% in men and 1.4% in women. Metals and silica contributed the most to the AF. The AF was highest for squamous cell carcinoma among men (11.4%) and for small cell carcinoma among women (7.1%); the effect of occupational lung carcinogens was stronger overall among current smokers. This estimation of the AF of occupational lung carcinogens is comparable to that estimated in other European studies, and cannot alone explain the high lung cancer rates in Central and Eastern Europe.

• Genome-wide association study of HPV seropositivity.

  Authors: Dan Chen, James D McKay, Gary Clifford, Valérie Gaborieau, Amélie Chabrier, Tim Waterboer, David Zaridze, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova [......] Victor Wünsch-Filho, José Eluf-Neto, Leticia Fernández Garrote, Elena Matos, Diana Zelenika, Anne Boland, Paolo Boffetta, Michael Pawlita, Mark Lathrop, Paul Brennan

  Human molecular genetics. 09/2011; 20(23):4714-23.

  High-risk α mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas β cutaneous HPV types (e.g. HPV8) have been implicated in non-melanoma skin cancer.High-risk α mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas β cutaneous HPV types (e.g. HPV8) have been implicated in non-melanoma skin cancer. Although antibodies against the capsid protein L1 of HPV are considered as markers of cumulative exposure, not all infected persons seroconvert. To identify common genetic variants that influence HPV seroconversion, we performed a two-stage genome-wide association study. Genome-wide genotyping of 316 015 single nucleotide polymorphisms was carried out using the Illumina HumanHap300 BeadChip in 4811 subjects from a central European case-control study of lung, head and neck and kidney cancer that had serology data available on 13 HPV types. Only one association met genome-wide significance criteria, namely that between HPV8 seropositivity and rs9357152 [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.24-1.50 for the minor allele G; P=1.2 × 10(-10)], a common genetic variant (minor allele frequency=0.33) located within the major histocompatibility complex (MHC) II region at 6p21.32. This association was subsequently replicated in an independent set of 2344 subjects from a Latin American case-control study of head and neck cancer (OR=1.35, 95% CI=1.18-1.56, P=2.2 × 10(-5)), yielding P=1.3 × 10(-14) in the combined analysis (P-heterogeneity=0.87). No heterogeneity was noted by cancer status (controls/lung cancer cases/head and neck cancer cases/kidney cancer cases). This study provides a proof of principle that genetic variation plays a role in antibody reactivity to HPV infection.

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• An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies.

  Authors: Jay H Lubin, Joshua Muscat, Mia M Gaudet, Andrew F Olshan, Maria Paula Curado, Luigino Dal Maso, Victor Wünsch-Filho, Erich M Sturgis, Neonilia Szeszenia-Dabrowska, Xavier Castellsague [......] Stephen M Schwartz, Paolo Boffetta, Paul Brennan, Ana Menezes, Carlo La Vecchia, Michael McClean, Renato Talamini, Thangarajan Rajkumar, Richard B Hayes, Mia Hashibe

  Cancer causes & control : CCC. 09/2011; 22(9):1217-31.

  Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are noGreater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors. We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models. ORs were increased in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (≥ 25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers. The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified.

• Occupational exposure to organic dust increases lung cancer risk in the general population.

  Authors: Susan Peters, Hans Kromhout, Ann C Olsson, Heinz-Erich Wichmann, Irene Brüske, Dario Consonni, Maria Teresa Landi, Neil Caporaso, Jack Siemiatycki, Lorenzo Richiardi [......] Vladimir Janout, Isabelle Stücker, Rodica Stanescu Dumitru, Simone Benhamou, Bas Bueno-de-Mesquita, Benjamin Kendzia, Beate Pesch, Kurt Straif, Thomas Brüning, Roel Vermeulen

  Thorax. 08/2011; 67(2):111-6.

  Organic dust is a complex mixture of particulate matter from microbial, plant or animal origin. Occupations with exposure to animal products have been associated with an increased lung cancer risk,Organic dust is a complex mixture of particulate matter from microbial, plant or animal origin. Occupations with exposure to animal products have been associated with an increased lung cancer risk, while exposure to microbial components (eg, endotoxin) has been associated with a decreased risk. To date there has not been a comprehensive evaluation of the possible association between occupational organic dust exposure (and its specific constituents) and lung cancer risk in the general population. The SYNERGY project has pooled information on lifetime working and smoking from 13 300 lung cancer cases and 16 273 controls from 11 case-control studies conducted in Europe and Canada. A newly developed general population job-exposure matrix (assigning no, low or high exposure to organic dust, endotoxin, and contact with animals or fresh animal products) was applied to determine level of exposure. ORs for lung cancer were estimated by logistic regression, adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. Occupational organic dust exposure was associated with increased lung cancer risk. The second to the fourth quartile of cumulative exposure showed significant risk estimates ranging from 1.12 to 1.24 in a dose-dependent manner (p<0.001). This association remained in the highest quartile after restricting analyses to subjects without chronic obstructive pulmonary disease or asthma. No association was observed between lung cancer and exposure to endotoxin or contact with animals or animal products. Occupational exposure to organic dust was associated with increased lung cancer risk in this large pooled case-control study.

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

  Authors: James D McKay, Therese Truong, Valerie Gaborieau, Amelie Chabrier, Shu-Chun Chuang, Graham Byrnes, David Zaridze, Oxana Shangina, Neonila Szeszenia-Dabrowska, Jolanta Lissowska [......] Doris Lechner, Hélène Blanché, Ivo G Gut, Pilar Galan, Simon Heath, Mia Hashibe, Richard B Hayes, Paolo Boffetta, Mark Lathrop, Paul Brennan

  PLoS genetics. 04/2011; 7(4).

  [This corrects the article on p. e1001333 in vol. 7.].

• A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

  Authors: James D McKay, Therese Truong, Valerie Gaborieau, Amelie Chabrier, Shu-Chun Chuang, Graham Byrnes, David Zaridze, Oxana Shangina, Neonila Szeszenia-Dabrowska, Jolanta Lissowska [......] Doris Lechner, Hélène Blanché, Ivo G Gut, Pilar Galan, Simon Heath, Mia Hashibe, Richard B Hayes, Paolo Boffetta, Mark Lathrop, Paul Brennan

  PLoS genetics. 03/2011; 7(3):e1001333.

  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 commonGenome-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.

• Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case-control study.

  Authors: Kevin Y Urayama, Ivana Holcatova, Vladimir Janout, Lenka Foretova, Eleonora Fabianova, Zora Adamcakova, Miroslav Ryska, Arnost Martinek, Olga Shonova, Paul Brennan, Ghislaine Scélo

  International journal of cancer. Journal international du cancer. 02/2011; 129(12):2875-84.

  The relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596The relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596 frequency-matched controls from the Czech Republic and Slovakia enrolled between 2004 and 2009. Analyses using multivariable logistic regression showed an increased risk of pancreatic cancer associated with elevated quartiles of BMI at ages 20 [fourth quartile: odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.23, 2.61] and 40 (fourth quartile: OR = 1.57, 95% CI: 1.09, 2.27) compared to the lowest quartile. Consistent results were observed for body size score at ages 20 (high versus low: OR = 1.66, 95% CI: 1.08, 2.57) and 40 (medium versus low: OR = 1.36, 95% CI: 1.00, 1.86), but no association was found for BMI and body size score at 2 years before the interview. Stronger risk estimates for BMI were observed in males than females, particularly at age 20, but the analysis of body size yielded similar estimates by sex. When considering excess body weight at both ages 20 and 40 jointly, the highest risk estimates were observed among subjects with elevated levels at both time periods in the analysis of BMI (OR = 1.86, 95% CI: 1.32, 2.62) and body size (OR = 1.53, 95% CI: 1.09, 2.13). These findings, based on two different measures, provide strong support for an increased risk of pancreatic cancer associated with excess body weight, possibly strongest during early adulthood.

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

  Authors: Dan Chen, Therese Truong, Valerie Gaborieau, Graham Byrnes, Amelie Chabrier, Shu-chun Chuang, Andrew F Olshan, Mark C Weissler, Jingchun Luo, Marjorie Romkes [......] Ana Menezes, Victor Wünsch-Filho, José Eluf-Neto, Leticia Fernandez, Stefania Boccia, Mia Hashibe, Richard B Hayes, Paolo Boffetta, Paul Brennan, James D McKay

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 02/2011; 20(4):658-64.

  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)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). In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies. rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P(het)) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 × 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 × 10(-4)). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P(het) = 0.86). This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Further research is warranted to elucidate the mechanisms underlying these observations.

• Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.

  Authors: Mark P Purdue, Mattias Johansson, Diana Zelenika, Jorge R Toro, Ghislaine Scelo, Lee E Moore, Egor Prokhortchouk, Xifeng Wu, Lambertus A Kiemeney, Valerie Gaborieau [......] Gilles Thomas, Zhaoming Wang, Meredith Yeager, Joseph F Fraumeni, Konstantin G Skryabin, James D McKay, Nathaniel Rothman, Stephen J Chanock, Mark Lathrop, Paul Brennan

  Nature genetics. 01/2011; 43(1):60-5.

  We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.

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• Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions.

  Authors: Karina Braga Ribeiro, José Eduardo Levi, Michael Pawlita, Sérgio Koifman, Elena Matos, José Eluf-Neto, Victor Wunsch-Filho, Maria Paula Curado, Oxana Shangina, David Zaridze [......] Ana Menezes, Vladimir Bencko, Dana Mates, Letícia Fernandez, Eleonora Fabianova, Tarik Gheit, Massimo Tommasino, Paolo Boffetta, Paul Brennan, Tim Waterboer

  International journal of epidemiology. 01/2011; 40(2):489-502.

  Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA)Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1). A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.

• Exposure to diesel motor exhaust and lung cancer risk in a pooled analysis from case-control studies in Europe and Canada.

  Authors: Ann C Olsson, Per Gustavsson, Hans Kromhout, Susan Peters, Roel Vermeulen, Irene Brüske, Beate Pesch, Jack Siemiatycki, Javier Pintos, Thomas Brüning [......] Peter Rudnai, Eleonora Fabianova, Rodica Stanescu Dumitru, Isabelle M Gross, Benjamin Kendzia, Francesco Forastiere, Bas Bueno-de-Mesquita, Paul Brennan, Paolo Boffetta, Kurt Straif

  American journal of respiratory and critical care medicine. 10/2010; 183(7):941-8.

  Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lackDiesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack adequate control for potential confounders and only a few studies have reported on exposure-response relationships. Investigate lung cancer risk associated with occupational exposure to diesel motor exhaust, while controlling for potential confounders. The SYNERGY project pooled information on lifetime work histories and tobacco smoking from 13,304 cases and 16,282 controls from 11 case-control studies conducted in Europe and Canada. A general population job exposure matrix based on ISCO-68 occupational codes, assigning no, low, or high exposure to diesel motor exhaust, was applied to determine level of exposure. Odds ratios of lung cancer and 95% confidence intervals were estimated by unconditional logistic regression, adjusted for age, sex, study, ever-employment in an occupation with established lung cancer risk, cigarette pack-years, and time-since-quitting smoking. Cumulative diesel exposure was associated with an increased lung cancer risk highest quartile versus unexposed (odds ratio 1.31; 95% confidence interval, 1.19-1.43), and a significant exposure-response relationship (P value < 0.01). Corresponding effect estimates were similar in workers never employed in occupations with established lung cancer risk, and in women and never-smokers, although not statistically significant. Our results show a consistent association between occupational exposure to diesel motor exhaust and increased risk of lung cancer. This association is unlikely explained by bias or confounding, which we addressed by adjusted models and subgroup analyses.

• Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

  Authors: Mia M Gaudet, Andrew F Olshan, Shu-Chun Chuang, Julien Berthiller, Zuo-Feng Zhang, Jolanta Lissowska, David Zaridze, Deborah M Winn, Qingyi Wei, Renato Talamini [......] Eleonora Fabianova, Alexander W Daudt, Luigino Dal Maso, Maria Paula Curado, Chu Chen, Xavier Castellsague, Simone Benhamou, Paolo Boffetta, Paul Brennan, Mia Hashibe

  International journal of epidemiology. 08/2010; 39(4):1091-102.

  Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certainHead and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < or =18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI > or =30 kg/m(2) (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < or =18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers. In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

• Body mass index, cigarette smoking, and alcohol consumption and cancers of the oral cavity, pharynx, and larynx: modeling odds ratios in pooled case-control data.

  Authors: Jay H Lubin, Mia M Gaudet, Andrew F Olshan, Karl Kelsey, Paolo Boffetta, Paul Brennan, Xavier Castellsague, Chu Chen, Maria Paula Curado, Luigino Dal Maso [......] Stephen M Schwartz, Oxana Shangina, Erich M Sturgis, Neonilia Szeszenia-Dabrowska, Renato Talamini, Qingyi Wei, Deborah Winn, Zuo-Feng Zhang, Mia Hashibe, Richard B Hayes

  American journal of epidemiology. 06/2010; 171(12):1250-61.

  Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and NeckOdds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer.

• International Lung Cancer Consortium: coordinated association study of 10 potential lung cancer susceptibility variants.

  Authors: Therese Truong, Wiebke Sauter, James D McKay, H Dean Hosgood, Carla Gallagher, Christopher I Amos, Margaret Spitz, Joshua Muscat, Philip Lazarus, Thomas Illig [......] Michael Thun, Maria Teresa Landi, Joanna Trubicka, Marcin Lener, Jan Lubinski, Ying Wang, Amélie Chabrier, Paolo Boffetta, Paul Brennan, Rayjean J Hung

  Carcinogenesis. 04/2010; 31(4):625-33.

  Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the InternationalAnalysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Genotype data from 15 ILCCO case-control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 x 10(-4)). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11,722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89-0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85-0.95), P = 1 x 10(-4)]. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations.

• Family history and lung cancer risk: international multicentre case-control study in Eastern and Central Europe and meta-analyses.

  Authors: Jolanta Lissowska, Lenka Foretova, Joanna Dabek, David Zaridze, Neonila Szeszenia-Dabrowska, Peter Rudnai, Eleonora Fabianova, Adrian Cassidy, Dana Mates, Vladimir Bencko, Vladimir Janout, Rayjean J Hung, Paul Brennan, Paolo Boffetta

  Cancer causes & control : CCC. 03/2010; 21(7):1091-104.

  Lung cancer is the most common neoplastic disease in Eastern and Central Europe. The role of hereditary factors in lung carcinogenesis is not fully understood. Family history (FH) of lung cancer andLung cancer is the most common neoplastic disease in Eastern and Central Europe. The role of hereditary factors in lung carcinogenesis is not fully understood. Family history (FH) of lung cancer and other tobacco-related cancers might be a strong predictor of the lung cancer risk. We investigated family history of cancer among first-degree relatives of 2,861 patients with lung cancer and 3,118 controls from the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and United Kingdom within the IARC Multicenter Case-Control Study. Odds ratios (ORs) and 95% CI were calculated using logistic regression, adjusting for age, gender, study center, education, tobacco smoking, and number of first-degree relatives. In addition, we conducted a meta-analysis of 41 studies on FH of cancer and lung cancer risk. Positive FH of lung cancer increased risk of lung cancer with OR of 1.63 (95%CI: 1.31-2.01), and having two or more affected relatives with lung cancer further increased the risk of lung cancer with OR 3.60 (95%CI: 1.56-8.31). Among subjects aged less than 50, the OR for FH of lung cancer was 2.08 (95%CI: 1.18-3.63). The associations were generally stronger for squamous cell carcinoma and large cell carcinoma subtypes. Heterogeneity in results was not found with respect to smoking status and gender. A significant association was not observed for FH of other smoking-related tumors. The results of meta-analysis were consistent with that of our study with regard to young onset, non-smokers and histology. FH of lung cancer is a predictor of an increased risk of lung cancer, especially in subjects aged less than 50.