Vladimir Bencko

Publications of Vladimir Bencko

• 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.

• Welding and Lung Cancer in Central and Eastern Europe and the United Kingdom.

  Authors: Andrea 't Mannetje, Paul Brennan, David Zaridze, Neonila Szeszenia-Dabrowska, Peter Rudnai, Jolanta Lissowska, Eleonóra Fabiánová, Adrian Cassidy, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Joelle Fevotte, Tony Fletcher, Paolo Boffetta

  American journal of epidemiology. 02/2012;

  Occupation as a welder has been associated with a 25%-40% increase in lung cancer risk. This study aims to elucidate to what extent confounding by smoking and asbestos drives this association and toOccupation as a welder has been associated with a 25%-40% increase in lung cancer risk. This study aims to elucidate to what extent confounding by smoking and asbestos drives this association and to evaluate the role of welding-related exposures such as chromium. The study included 2,197 male incident lung cancer cases and 2,295 controls from Romania, Hungary, Poland, Russia, Slovakia, the Czech Republic, and the United Kingdom from 1998 to 2001. Information on risk factors was collected through face-to-face interviews. Experts assessed exposure to 70 agents, and risk estimates were adjusted for smoking and occupational exposures. Occupation as a welder/flame cutter (prevalence controls: 3.7%) was associated with an odds ratio of 1.36 (95% confidence interval (CI): 1.00, 1.86) after adjustment for smoking and occupational exposures including asbestos. An odds ratio of 1.18 (95% CI: 1.01, 1.38) was found for welding fumes (prevalence controls: 22.8%), increasing to 1.38 for more than 25 exposure years (95% CI: 1.09, 1.75). A duration-response association was also observed for mild steel welding without chromium exposure. In this population, occupational exposure to welding fumes accounted for approximately 4% of lung cancer cases, to which both stainless and mild steel welding contributed equally. Given that welding remains a common task for many workers, exposure to welding fumes represents an important risk factor for lung cancer.

• 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.

• 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.

• The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma.

  Authors: Summer S Han, Meredith Yeager, Lee E Moore, Ming-Hui Wei, Ruth Pfeiffer, Ousmane Toure, Mark P Purdue, Mattias Johansson, Ghislaine Scelo, Charles C Chung [......] James D McKay, Joseph F Fraumeni, Nilanjan Chatterjee, Philip S Rosenberg, Nathaniel Rothman, Paul Brennan, Wong-Ho Chow, Margaret A Tucker, Stephen J Chanock, Jorge R Toro

  Human molecular genetics. 11/2011; 21(5):1190-200.

  In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of aIn follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10(-8), per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10(-14)) and rs12617313 (P = 7.48 × 10(-12)), both highly correlated with rs9679290 (r(2) > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10(-9), per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.

• 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.

• Von Hippel-Lindau (VHL) inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.

  Authors: Lee E Moore, Michael L Nickerson, Paul Brennan, Jorge R Toro, Erich Jaeger, Jessica Rinsky, Summer S Han, David Zaridze, Vsevolod Matveev, Vladimir Janout [......] Laura S Schmidt, Petra Lenz, Sara Karami, W Marston Linehan, Maria Merino, Stephen Chanock, Paolo Boffetta, Wong-Ho Chow, Frederic M Waldman, Nathaniel Rothman

  PLoS genetics. 10/2011; 7(10):e1002312.

  Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis.Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC) and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs). VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5). Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors [former: OR = 0.70 (0.20-1.31) and current: OR = 0.56 (0.32-0.99); P-trend = 0.04]. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation) in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases.

• Occupational exposure to metal compounds and lung cancer. Results from a multi-center case-control study in Central/Eastern Europe and UK.

  Authors: Andrea 't Mannetje, Vladimir Bencko, Paul Brennan, David Zaridze, Neonila Szeszenia-Dabrowska, Peter Rudnai, Jolanta Lissowska, Eleonóra Fabiánová, Adrian Cassidy, Dana Mates, Lenka Foretova, Vladimir Janout, Joelle Fevotte, Tony Fletcher, Paolo Boffetta

  Cancer causes & control : CCC. 09/2011; 22(12):1669-80.

  To study the association between occupational exposure to metals including chromium, cadmium, nickel, and arsenic compounds, within a population-based study design, while adjusting for confoundingTo study the association between occupational exposure to metals including chromium, cadmium, nickel, and arsenic compounds, within a population-based study design, while adjusting for confounding factors. A population-based lung cancer case-control study in Central/Eastern Europe and UK was conducted in 1998-2003, including 2,853 cases and 3,104 controls. Exposure to 70 occupational agents was assessed by local expert-teams for all subjects. Odds ratios (OR) for exposure to dust and fumes/mist of chromium, nickel, cadmium, arsenic, as well as inorganic pigment dust and inorganic acid mist, were adjusting for smoking, age, center, sex, and exposure to other occupational agents including the metals under study. Exposure to arsenic (prevalence = 1.4%) was associated with an increased lung cancer risk ((OR) 1.65, 95% confidence interval (95% CI):1.05-2.58). For chromium dust (prevalence = 4.8%, OR: 1.25, 95% CI: 0.95-1.65), a linear upward trend for duration and cumulative exposure was observed. A weak association was observed for exposure to cadmium fumes (prevalence = 1.8%, OR: 1.19, 95% CI: 0.77-1.82), which was strongest for the highest category of cumulative exposure (OR: 2.04, 95% CI: 1.07-3.90). No increased risk was observed for inorganic acid mist, inorganic pigment dust, or nickel, after adjustment for other metals. An independent effect of nickel cannot be excluded, due to its collinearity with chromium exposure. Occupational exposure to metals is an important risk factor for lung cancer. Although the strongest risk was observed for arsenic, exposure to chromium dust was most important in terms of attributable risk due to its high prevalence.

• 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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• 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.].

• The association between change in body mass index and upper aerodigestive tract cancers in the ARCAGE project: multicenter case-control study.

  Authors: Sungshim Lani Park, Yuan-Chin Amy Lee, Manuela Marron, Antonio Agudo, Wolfgang Ahrens, Luigi Barzan, Vladimir Bencko, Simone Benhamou, Christine Bouchardy, Cristina Canova [......] Franco Merletti, Hermann Pohlabeln, Lorenzo Richiardi, Lorenzo Simonato, Linda Sneddon, Renato Talamini, Dimitrios Trichopoulos, Ariana Znaor, Paul Brennan, Mia Hashibe

  International journal of cancer. Journal international du cancer. 03/2011; 128(6):1449-61.

  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 previousPrevious 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.

• 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.

• Renal cancer risk and occupational exposure to polycyclic aromatic hydrocarbons and plastics.

  Authors: Sara Karami, Paolo Boffetta, Paul Brennan, Patricia A Stewart, David Zaridze, Vsevolod Matveev, Vladimir Janout, Helena Kollarova, Vladimir Bencko, Marie Navratilova, Neonila Szeszenia-Dabrowska, Dana Mates, Jan P Gromiec, Roman Sobotka, Wong-Ho Chow, Nathaniel Rothman, Lee E Moore

  Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine. 02/2011; 53(2):218-23.

  To investigate whether occupational exposure to polycyclic aromatic hydrocarbons and certain plastic monomers increased renal cell carcinoma (RCC) risk. Unconditional logistic regression was used toTo investigate whether occupational exposure to polycyclic aromatic hydrocarbons and certain plastic monomers increased renal cell carcinoma (RCC) risk. Unconditional logistic regression was used to calculate RCC risk in relation to exposure. No association between RCC risk and having ever been occupationally exposed to any polycyclic aromatic hydrocarbons or plastics was observed. Duration of exposure and average exposure also showed no association with risk. Suggestive positive associations between RCC risk and cumulative exposure to styrene (P-trend = 0.02) and acrylonitrile (P-trend = 0.06) were found. Cumulative exposure to petroleum/gasoline engine emissions was inversely associated with risk (P-trend = 0.02). Results indicate a possible association between occupational styrene and acrylonitrile exposure and RCC risk. Additional studies are needed to replicate findings, as this is the first time these associations have been reported and they may be due to chance.

• 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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• Occupational exposure to arsenic, cadmium, chromium, lead and nickel, and renal cell carcinoma: a case-control study from Central and Eastern Europe.

  Authors: Paolo Boffetta, Luc Fontana, Patricia Stewart, David Zaridze, Neonilia Szeszenia-Dabrowska, Vladimir Janout, Vladimir Bencko, Lenka Foretova, Viorel Jinga, Vsevolod Matveev, Helena Kollarova, Gilles Ferro, Wong-Ho Chow, Nathaniel Rothman, Dana van Bemmel, Sara Karami, Paul Brennan, Lee E Moore

  Occupational and environmental medicine. 01/2011; 68(10):723-8.

  To investigate the risk of renal cell carcinoma (RCC) in Central and Eastern Europe in relation to exposure to known and suspected carcinogenic metals. During 1999-2003, the authors conducted aTo investigate the risk of renal cell carcinoma (RCC) in Central and Eastern Europe in relation to exposure to known and suspected carcinogenic metals. During 1999-2003, the authors conducted a hospital-based study in Czech Republic, Poland, Romania and Russia, including 1097 cases of RCC and 1476 controls. Occupational exposure to arsenic, cadmium, chromium(III), chromium(VI), lead and nickel was assessed by teams of local industrial hygiene experts, based on detailed occupational questionnaires. The ORs for RCC were 1.55 (95% CI 1.09 to 2.21) for exposure to lead and 1.40 (95% CI 0.69 to 2.85) for exposure to cadmium. No clear monotonic exposure-response relation was apparent for either duration of exposure or cumulative exposure to either metal, although the OR for the highest category of cumulative exposure to lead was 2.25 (95% CI 1.21 to 4.19). Exposure to other metals did not entail an increased risk of RCC. For cadmium, the lack of statistical significance of most results, potential confounding and the absence of clear dose-response relations suggest that an association with RCC is unlikely to be causal. In the case of lead, however, the elevated risk in the category of highest cumulative exposure is noteworthy and justifies further investigation.

• 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.

• Comprehensive evaluation of one-carbon metabolism pathway gene variants and renal cell cancer risk.

  Authors: Todd M Gibson, Paul Brennan, Summer Han, Sara Karami, David Zaridze, Vladimir Janout, Helen Kollarova, Vladimir Bencko, Marie Navratilova, Neonila Szeszenia-Dabrowska [......] Ruth M Pfeiffer, Rachael Z Stolzenberg-Solomon, Susan T Mayne, Meredith Yeager, Stephen Chanock, Nat Rothman, Wong-Ho Chow, Philip S Rosenberg, Paolo Boffetta, Lee E Moore

  PloS one. 01/2011; 6(10):e26165.

  Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has beenFolate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer. Tag single nucleotide polymorphisms (SNPs) selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS) and the closely associated glutathione synthesis pathway (CTH, GGH, GSS) were genotyped for 777 renal cell carcinoma (RCC) cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163) with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P) tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes. The strongest associations with RCC risk were observed for SLC19A1 (P(min-P) = 0.03) and MTHFR (P(min-P) = 0.13). A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785) was associated with a 37% increased risk (p = 0.02), and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake. To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings.