Paolo Boffetta

Publications of Paolo Boffetta

• Recommendations and proposed guidelines for assessing the cumulative evidence on joint effects of genes and environments on cancer occurrence in humans.

  Authors: Paolo Boffetta, Deborah M Winn, John P Ioannidis, Duncan C Thomas, Julian Little, George Davey Smith, Vincent J Cogliano, Stephen S Hecht, Daniela Seminara, Paolo Vineis, Muin J Khoury

  International journal of epidemiology. 05/2012;

  We propose guidelines to evaluate the cumulative evidence of gene-environment (G × E) interactions in the causation of human cancer. Our approach has its roots in the HuGENet and IARC MonographsWe propose guidelines to evaluate the cumulative evidence of gene-environment (G × E) interactions in the causation of human cancer. Our approach has its roots in the HuGENet and IARC Monographs evaluation processes for genetic and environmental risk factors, respectively, and can be applied to common chronic diseases other than cancer. We first review issues of definitions of G × E interactions, discovery and modelling methods for G × E interactions, and issues in systematic reviews of evidence for G × E interactions, since these form the foundation for appraising the credibility of evidence in this contentious field. We then propose guidelines that include four steps: (i) score the strength of the evidence for main effects of the (a) environmental exposure and (b) genetic variant; (ii) establish a prior score category and decide on the pattern of interaction to be expected; (iii) score the strength of the evidence for interaction between the environmental exposure and the genetic variant; and (iv) examine the overall plausibility of interaction by combining the prior score and the strength of the evidence and interpret results. We finally apply the scheme to the interaction between NAT2 polymorphism and tobacco smoking in determining bladder cancer risk.

• A meta-analysis on alcohol drinking and the risk of Hodgkin lymphoma.

  Authors: Irene Tramacere, Claudio Pelucchi, Martina Bonifazi, Vincenzo Bagnardi, Matteo Rota, Rino Bellocco, Lorenza Scotti, Farhad Islami, Giovanni Corrao, Paolo Boffetta, Carlo La Vecchia, Eva Negri

  European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 05/2012; 21(3):268-273.

  The role of alcohol intake in the risk of Hodgkin lymphoma (HL) is still largely unclear. To summarize the evidence on the issue, we carried out a meta-analysis of the available studies. WeThe role of alcohol intake in the risk of Hodgkin lymphoma (HL) is still largely unclear. To summarize the evidence on the issue, we carried out a meta-analysis of the available studies. We identified eight case-control and two cohort studies, including a total of 1488 cases of HL. We derived meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and carried out a dose-risk analysis using nonlinear random-effects metaregression models. Compared with nondrinkers, the relative risk for alcohol consumers was 0.70 [95% confidence interval (CI), 0.60-0.81] overall, 0.66 (95% CI, 0.56-0.78) among case-control, and 0.92 (95% CI, 0.63-1.33) among cohort studies. Compared with nondrinkers, the pooled relative risks were 0.71 (95% CI, 0.57-0.89) for light (i.e. ≤1 drink/day) and 0.73 (95% CI, 0.60-0.87) for moderate-to-heavy (i.e. >1 drink/day) alcohol drinking. This meta-analysis suggests a favourable effect of alcohol on HL, in the absence, however, of a dose-risk relationship. The inverse association was restricted to - or greater in - case-control as compared with cohort studies. This indicates caution in the interpretation of results.

• Food groups and risk of prostate cancer: a case-control study in Uruguay.

  Authors: Hugo Deneo-Pellegrini, Alvaro L Ronco, Eduardo De Stefani, Paolo Boffetta, Pelayo Correa, María Mendilaharsu, Gisele Acosta

  Cancer causes & control : CCC. 04/2012;

  OBJECTIVE: The role of foods and beverages has been studied in detail in order to establish probable risk factors for prostate cancer. METHODS: Data were derived from 326 cases with incident andOBJECTIVE: The role of foods and beverages has been studied in detail in order to establish probable risk factors for prostate cancer. METHODS: Data were derived from 326 cases with incident and microscopically confirmed adenocarcinomas of the prostate and 652 controls. Odds ratios and 95 % confidence intervals of prostate cancer were estimated by unconditional multiple logistic regression. RESULTS: We identified the following food items as risk factors: lamb meat, salted meat, whole milk, total eggs, and maté consumption. The highest OR was associated with total eggs (OR, 2.43; 95 % CI, 1.70-3.48), followed by salted meat (OR, 2.65; 95 % CI, 1.36-3.76), maté consumption (OR, 1.96; 95 % CI, 1.17-3.31), and whole milk (OR, 2.01; 95 % CI, 1.26-2.51). CONCLUSIONS: The final model, fitted by stepwise forward method, included total eggs, salted meat, whole milk, and maté consumption, whereas fruits were protective.

• Alcohol drinking and epithelial ovarian cancer risk. A systematic review and meta-analysis.

  Authors: Matteo Rota, Elena Pasquali, Lorenza Scotti, Claudio Pelucchi, Irene Tramacere, Farhad Islami, Eva Negri, Paolo Boffetta, Rino Bellocco, Giovanni Corrao, Carlo La Vecchia, Vincenzo Bagnardi

  Gynecologic oncology. 03/2012;

  OBJECTIVE: In order to provide an updated quantification of the association between alcohol drinking and epithelial ovarian cancer risk, we conducted a meta-analysis of published observationalOBJECTIVE: In order to provide an updated quantification of the association between alcohol drinking and epithelial ovarian cancer risk, we conducted a meta-analysis of published observational studies. METHODS: Using PubMed, we performed a literature search of all case-control and cohort studies published as original articles in English up to September 2011. We included 27 observational studies, of which 23 were case-control studies, 3 cohort studies and one pooled analysis of prospective cohort studies, including a total of 16,554 epithelial ovarian cancer cases. We derived pooled meta-analytic estimates using random-effects models. RESULTS: The pooled relative risk (RR) for any alcohol drinking compared with non/occasional drinking was 1.00 [95% confidence interval (CI), 0.95-1.05]. The RRs were 0.97 (95% CI, 0.92-1.02), 1.03 (95% CI, 0.96-1.11) and 1.09 (95% CI, 0.80-1.50) for light (≤1drink/day), moderate (>1 to <3 drinks) and heavy drinking (≥3drinks/day), respectively. In particular, pooled RR for invasive epithelial ovarian cancers was 1.00 (95% CI, 0.95-1.06), while for borderline cancers was 0.96 (95% CI, 0.74-1.26). Stratified analyses across cancer histotypes revealed a modest protective effect of alcohol on endometrioid epithelial ovarian tumors (RR=0.82, 95% CI, 0.70-0.96), while no association was found for serous (RR=1.00, 95% CI, 0.84-1.19), mucinous (RR=0.91, 95% CI, 0.78-1.08) and clear cell (RR=0.93, 95% CI, 0.76-1.14) cancers. There was no evidence of publication bias. CONCLUSIONS: This comprehensive meta-analysis provided no evidence of a material association between alcohol drinking and epithelial ovarian cancer risk.

• 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.

• DNA methylation changes associated with risk factors in tumors of the upper aerodigestive tract.

  Authors: Samson Mani, Katarzyna Szymańska, Cyrille Cuenin, David Zaridze, Karen Balassiano, Sheila C S Lima, Elena Matos, Alexander Daudt, Sergio Koifman, Victor Wunsch Filho [......] Maria Paula Curado, Gilles Ferro, Thomas Vaissière, Bakary S Sylla, Massimo Tommasino, Luis Felipe Ribeiro Pinto, Paolo Boffetta, Pierre Hainaut, Paul Brennan, Zdenko Herceg

  Epigenetics : official journal of the DNA Methylation Society. 03/2012; 7(3):270-7.

  Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are alsoCancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.

• 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.

• What proportion of lung cancer in never-smokers can be attributed to known risk factors?

  Authors: Julia Sisti, Paolo Boffetta

  International journal of cancer. Journal international du cancer. 02/2012;

  Though tobacco smoking is the primary risk factor for lung cancer, a significant fraction of lung cancer deaths occur in lifetime nonsmokers. In this article, we calculate the burden of lung cancerThough tobacco smoking is the primary risk factor for lung cancer, a significant fraction of lung cancer deaths occur in lifetime nonsmokers. In this article, we calculate the burden of lung cancer in never-smokers attributable to previously identified risk factors in North America, Europe and China, using population-based estimates of exposure prevalence and estimates of relative risk derived from recently published meta-analyses. Population attributable fractions (PAFs) for individual risk factors ranged from 0.40 to 19.93%. Because of differences in the prevalence of exposures, the PAFs associated with several of the risk factors varied greatly by geographical region. Exposure to the selected risk factors appeared to explain a much larger proportion of lung cancer cases in never-smokers in China than in Europe and North America. Our results demonstrate the geographic variability of the epidemiology of lung cancer in never-smokers and highlight the need for further research in this area, particularly in Europe and North America.

• Genome-wide association study of classical hodgkin lymphoma and epstein-barr virus status-defined subgroups.

  Authors: Kevin Y Urayama, Ruth F Jarrett, Henrik Hjalgrim, Arjan Diepstra, Yoichiro Kamatani, Amelie Chabrier, Valerie Gaborieau, Anne Boland, Alexandra Nieters, Nikolaus Becker [......] Elio Riboli, Eve Roman, Paolo Boffetta, Silvia de Sanjosé, Diana Zelenika, Mads Melbye, Anke van den Berg, Mark Lathrop, Paul Brennan, James D McKay

  Journal of the National Cancer Institute. 02/2012; 104(3):240-53.

  Background Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is notBackground 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. Methods We conducted a genome-wide association study of 1200 cHL patients and 6417 control subjects, with validation in an independent replication series, to identify common genetic variants associated with total cHL and subtypes defined by tumor EBV status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) assuming a log-additive genetic model for the variants. All statistical tests were two-sided. Results Two novel loci associated with total cHL irrespective of EBV status were identified in the major histocompatibility complex region; one resides adjacent to MICB (rs2248462: OR = 0.61, 95% CI = 0.53 to 0.69, P = 1.3 × 10(-13)) and the other at HLA-DRA (rs2395185: OR = 0.56, 95% CI = 0.50 to 0.62, P = 8.3 × 10(-25)) with both results confirmed in an independent replication series. Consistent with previous reports, associations were found between EBV-positive cHL and genetic variants within the class I region (rs2734986, HLA-A: OR = 2.45, 95% CI = 2.00 to 3.00, P = 1.2 × 10(-15); rs6904029, HCG9: OR = 0.46, 95% CI = 0.36 to 0.59, P = 5.5 × 10(-10)) and between EBV-negative cHL and rs6903608 within the class II region (rs6903608, HLA-DRA: OR = 2.08, 95% CI = 1.84 to 2.35, P = 6.1 × 10(-31)). The association between rs6903608 and EBV-negative cHL was confined to the nodular sclerosis histological subtype. Evidence for an association between EBV-negative cHL and rs20541 (5q31, IL13: OR = 1.53, 95% CI = 1.32 to 1.76, P = 5.4 x 10(-9)), a variant previously linked to psoriasis and asthma, was observed; however, the evidence for replication was less clear. Notably, one additional psoriasis-associated variant, rs27524 (5q15, ERAP1), showed evidence of an association with cHL in the genome-wide association study (OR = 1.21, 95% CI = 1.10 to 1.33, P = 1.5 × 10(-4)) and replication series (P = .03). Conclusion Overall, these results provide strong evidence that EBV status is an etiologically important classification of cHL and also suggest that some components of the pathological process are common to both EBV-positive and EBV-negative patients.

• Role of stopping exposure and recent exposure to asbestos in the risk of mesothelioma.

  Authors: Carlo La Vecchia, Paolo Boffetta

  European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 02/2012; 21(3):227-30.

  The model of asbestos-related mesothelioma implies that the time since first exposure (latency) is the key determinant of subsequent risk. The role of recent exposure or stopping asbestos exposure,The model of asbestos-related mesothelioma implies that the time since first exposure (latency) is the key determinant of subsequent risk. The role of recent exposure or stopping asbestos exposure, if any, is, however, open to discussion. A literature review was conducted to the end of 2010. In a cohort of 1966 Italian textile workers, the standardized mortality ratio, on the basis of 68 deaths from mesothelioma, was 6627 for workers employed only under the age of 30 years, 8019 for those employed both under the age of 30 years and at the age of 30-39 years, and 5891 for those employed both under the age of 30 years and at the age of 40 years or more. In a cohort of Italian asbestos cement workers, including 135 deaths from pleural cancer, compared with workers who had stopped exposure for 3-15 years, the relative risk (RR) was similar for those still employed (RR=0.67) and for those who had stopped for 30 years or more (RR=0.65). In a British case-control study, including 622 cases of mesothelioma and 1420 population controls, the RR substantially increased with increasing duration of exposure under the age of 30 years, but not with exposure at the age of more than 30 years. In the Great Britain Asbestos Workers Survey, including 649 deaths from mesothelioma compared with workers who were still employed and or had stopped for less than 10 years, the multivariate RRs were 0.90 10-20 years after stopping exposure and 0.99 both 20-30 and more than 30 years after stopping. There is consistent evidence showing that, for workers exposed in the distant past, the risk of mesothelioma is not appreciably modified by subsequent exposures, and that stopping exposure does not materially modify the subsequent risk of mesothelioma.

• Meat consumption, cooking methods, mutagens, and risk of squamous cell carcinoma of the esophagus: a case-control study in uruguay.

  Authors: Eduardo De Stefani, Hugo Deneo-Pellegrini, Alvaro L Ronco, Paolo Boffetta, Pelayo Correa, Dagfinn Aune, María Mendilaharsu, Gisele Acosta, Cecilia Silva, Gabriel Landó, María E Luaces

  Nutrition and cancer. 02/2012; 64(2):294-9.

  The role of meat in squamous cell carcinoma of the esophagus (ESCC) has been considered conflictive. For this reason, we decided to conduct a case-control study on meat consumption and ESCC. DataThe role of meat in squamous cell carcinoma of the esophagus (ESCC) has been considered conflictive. For this reason, we decided to conduct a case-control study on meat consumption and ESCC. Data included 234 newly diagnosed and microscopically examined ESCC and 2,020 controls with conditions not related to tobacco smoking nor alcohol drinking and without changes in their diets. We studied total meat, red meat, beef, lamb, processed meat, poultry, fish, total white meat, liver, fried meat, barbecued meat, boiled meat, heterocyclic amines, nitrosodimethylamine, and benzo[a]pyrene in relation with the risk of ESCC. Red meat, lamb, and boiled meat were directly associated with the risk of ESCC, whereas total white meat, poultry, fish, and liver were mainly protective against this malignancy.

• Occupational exposure to beryllium and cancer risk: a review of the epidemiologic evidence.

  Authors: Paolo Boffetta, Jon P Fryzek, Jack S Mandel

  Critical reviews in toxicology. 02/2012; 42(2):107-18.

  There is controversy on whether occupational exposure to beryllium causes lung cancer. We conducted a systematic review of epidemiologic studies on cancer among workers exposed to beryllium,There is controversy on whether occupational exposure to beryllium causes lung cancer. We conducted a systematic review of epidemiologic studies on cancer among workers exposed to beryllium, including a study of seven U.S. production plants which has been recently updated, a study of patients with beryllium disease (largely overlapping with the former study) and several smaller studies. A small excess mortality from lung cancer was detected in the large cohort, which was partially explained by confounding by tobacco smoking and urban residence. Other potential confounders have not been addressed. The excess mortality was mainly among workers employed (often for a short duration) in the early phase of the manufacturing industry. There was no relation with duration of employment or cumulative exposure, whereas average and maximum exposure were associated with lung cancer risk. The use of lagged exposure variables resulted in associations with lung cancer risk; however, these associations were due to confounding by year of birth and year of hire. The studies of beryllium disease patients do not provide independent evidence and the results from other studies do not support the hypothesis of an increased risk of lung cancer or any other cancer. Overall, the available evidence does not support a conclusion that a causal association has been established between occupational exposure to beryllium and the risk of cancer.

• A review of cancer in U.S. Hispanic populations.

  Authors: Robert W Haile, Esther M John, A Joan Levine, Victoria K Cortessis, Jennifer B Unger, Melissa Gonzales, Elad Ziv, Patricia Thompson, Donna Spruijt-Metz, Katherine L Tucker [......] Lourdes Baezconde-Garbanati, Victoria Blinder, Patricia Miranda, Richard Hayes, George Friedman-Jiménez, Kristine R Monroe, Christopher A Haiman, Brian E Henderson, Duncan C Thomas, Paolo Boffetta

  Cancer prevention research (Philadelphia, Pa.). 02/2012; 5(2):150-63.

  There are compelling reasons to conduct studies of cancer in Hispanics, the fastest growing major demographic group in the United States (from 15% to 30% of the U.S. population by 2050). TheThere are compelling reasons to conduct studies of cancer in Hispanics, the fastest growing major demographic group in the United States (from 15% to 30% of the U.S. population by 2050). The genetically admixed Hispanic population coupled with secular trends in environmental exposures and lifestyle/behavioral practices that are associated with immigration and acculturation offer opportunities for elucidating the effects of genetics, environment, and lifestyle on cancer risk and identifying novel risk factors. For example, traditional breast cancer risk factors explain less of the breast cancer risk in Hispanics than in non-Hispanic whites (NHW), and there is a substantially greater proportion of never-smokers with lung cancer in Hispanics than in NHW. Hispanics have higher incidence rates for cancers of the cervix, stomach, liver, and gall bladder than NHW. With respect to these cancers, there are intriguing patterns that warrant study (e.g., depending on country of origin, the five-fold difference in gastric cancer rates for Hispanic men but not Hispanic women). Also, despite a substantially higher incidence rate and increasing secular trend for liver cancer in Hispanics, there have been no studies of Hispanics reported to date. We review the literature and discuss study design options and features that should be considered in future studies.

• InterSCOPE study: Associations between esophageal squamous cell carcinoma and human papillomavirus serological markers.

  Authors: Freddy Sitas, Sam Egger, Margaret I Urban, Philip R Taylor, Christian C Abnet, Paolo Boffetta, Dianne L O'Connell, David C Whiteman, Paul Brennan, Reza Malekzadeh, Michael Pawlita, Sanford M Dawsey, Tim Waterboer

  Journal of the National Cancer Institute. 01/2012; 104(2):147-58.

  The role of human papillomavirus (HPV) in the causation of esophageal squamous cell carcinoma is unclear. We examined the associations between esophageal squamous cell carcinoma and 28 centrallyThe role of human papillomavirus (HPV) in the causation of esophageal squamous cell carcinoma is unclear. We examined the associations between esophageal squamous cell carcinoma and 28 centrally measured HPV serological markers in serum from six existing case-control studies conducted in regions with differing background risks of esophageal cancer. We used centralized multiplex serology to test serum samples from 1561 case subjects and 2502 control subjects from six case-control studies for antibodies to the major HPV capsid protein (L1) and/or the early proteins E6 and/or E7 of eight high-risk, two low-risk, and four cutaneous HPV types. Study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression with adjustment for smoking, alcohol consumption, and other potential confounders. Pooled odds ratios and 95% confidence intervals were calculated using either a linear mixed-effects approach or a joint fixed-effects approach. All statistical tests were two-sided. We found statistically significant associations between esophageal squamous cell carcinoma and antibodies to E6 for HPV16 (OR = 1.89, 95% CI = 1.09 to 3.29, P = .023) and HPV6 (OR = 2.53, 95% CI = 1.51 to 4.25, P < .001) but not for other tested HPV types. There were no statistically significant associations between esophageal squamous cell carcinoma and antibodies to E7 for any of the tested HPV types. Simultaneous seropositivity for HPV16 E6 and E7 was rare (four case subjects, two control subjects; OR = 5.57, 95% CI = 0.90 to 34.35; P = .064). We also found statistically significant associations between esophageal squamous cell carcinoma and capsid antibodies for the high-risk mucosal type HPV33 L1 (OR = 1.30, 95% CI = 1.00 to 1.69; P = .047) and the low-risk mucosal types HPV6 (OR = 1.22, 95% CI = 1.05 to 1.42; P = .010) and HPV11 (OR = 1.30, 95% CI = 1.09 to 1.56, P = .0036). We found limited serological evidence of an association between esophageal squamous cell carcinoma and HPV in the populations studied. Although HPV does not appear to be an important risk factor for esophageal squamous cell carcinoma, we cannot exclude the possibility that certain HPV types may be involved in a small subset of cancers.

• 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.

• Similar DNA methylation pattern in lung tumours from smokers and never-smokers with second-hand tobacco smoke exposure.

  Authors: Asta Scesnaite, Sonata Jarmalaite, Pertti Mutanen, Sisko Anttila, Fredrik Nyberg, Simone Benhamou, Paolo Boffetta, Kirsti Husgafvel-Pursiainen

  Mutagenesis. 01/2012;

  Tobacco smoke causes lung cancer in smokers and in never-smokers exposed to second-hand tobacco smoke (SHS). Nonetheless, molecular mechanisms of lung cancer in SHS-exposed never-smokers are stillTobacco smoke causes lung cancer in smokers and in never-smokers exposed to second-hand tobacco smoke (SHS). Nonetheless, molecular mechanisms of lung cancer in SHS-exposed never-smokers are still elusive. We studied lung cancers from current smokers (n = 109), former smokers (n = 56) and never-smokers (n = 47) for promoter hypermethylation of five tumour suppressor genes-p16, RARB, RASSF1, MGMT and DAPK1-using methylation-specific polymerase chain reaction. Lung tumours from ever-smokers suggested an increased risk of p16 hypermethylation as compared to never-smokers (P = 0.073), with former smokers having the highest frequency of p16 hypermethylation (P = 0.044 versus current smokers and P = 0.009 versus never-smokers). In the never-smoking group, p16 hypermethylation was seen in lung tumours from SHS-exposed individuals (4/33; 12%) but in none of the non-exposed individuals (0/9). The overall occurrence of hypermethylation (measured both as methylation index and as number of genes affected) was similar in those ever exposed to tobacco smoke (smokers, SHS-exposed never-smokers) and differed from non-exposed never-smokers. In multivariate analysis, p16 hypermethylation was more prevalent in lung tumours from male than female patients (P = 0.018) and in squamous cell carcinomas than in adenocarcinomas (P = 0.025). Occurrence of TP53 mutation in the tumour was associated with hypermethylation of at least one gene (P = 0.027). In all, our data suggest that promoter hypermethylation pattern in SHS-exposed never-smokers resembles that observed in smokers. Association between TP53 mutation, a hallmark of smokers' lung cancer, and methylation of one or more of the lung cancer-related genes studied, provides further evidence for common tobacco smoke-related origin for both types of molecular alterations.

• Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50 000 adults in Iran.

  Authors: Hooman Khademi, Reza Malekzadeh, Akram Pourshams, Elham Jafari, Rasool Salahi, Shahryar Semnani, Behrooz Abaie, Farhad Islami, Siavosh Nasseri-Moghaddam, Arash Etemadi, Graham Byrnes, Christian C Abnet, Sanford M Dawsey, Nicholas E Day, Paul D Pharoah, Paolo Boffetta, Paul Brennan, Farin Kamangar

  BMJ (Clinical research ed.). 01/2012; 344:e2502.

  To investigate the association between opium use and subsequent risk of death. Prospective cohort study. The Golestan Cohort Study in north-eastern Iran collected detailed validated data on opium useTo investigate the association between opium use and subsequent risk of death. Prospective cohort study. The Golestan Cohort Study in north-eastern Iran collected detailed validated data on opium use and other exposures at baseline. Participants were enrolled between January 2004 and June 2008 and were followed to May 2011, with a follow-up success rate of over 99%. 50 045 participants aged 40-75 at baseline. Mortality, all cause and major subcategories. 17% (n=8487) of the participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 2145 deaths were reported. The adjusted hazard ratio for all cause mortality associated with ever use of opium was 1.86 (95% confidence interval 1.68 to 2.06). Opium consumption was significantly associated with increased risks of deaths from several causes including circulatory diseases (hazard ratio 1.81) and cancer (1.61). The strongest associations were seen with deaths from asthma, tuberculosis, and chronic obstructive pulmonary disease (11.0, 6.22, and 5.44, respectively). After exclusion of people who self prescribed opium after the onset of major chronic illnesses, the associations remained strong with a dose-response relation. Opium users have an increased risk of death from multiple causes compared with non-users. Increased risks were also seen in people who used low amounts of opium for a long period and those who had no major illness before use.

• Nutrient-derived Dietary Patterns and Risk of Colorectal Cancer: a Factor Analysis in Uruguay.

  Authors: Eduardo De Stefani, Alvaro L Ronco, Paolo Boffetta, Hugo Deneo-Pellegrini, Pelayo Correa, Gisele Acosta, Maria Mendilaharsu

  Asian Pacific journal of cancer prevention : APJCP. 01/2012; 13(1):231-5.

  In order to explore the role of nutrients and bioactive related substances in colorectal cancer, we conducted a case-control in Uruguay, which is the country with the highest production of beef inIn order to explore the role of nutrients and bioactive related substances in colorectal cancer, we conducted a case-control in Uruguay, which is the country with the highest production of beef in the world. Six hundred and eleven (611) cases afflicted with colorectal cancer and 1,362 controls drawn from the same hospitals in the same time period were analyzed through unconditional multiple logistic regression. This base population was submitted to a principal components factor analysis and three factors were retained. They were labeled as the meat-based, plant-based, and carbohydrates patterns. They were rotated using orthogonal varimax method. The highest risk was positively associated with the meat-based pattern (OR for the highest quartile versus the lowest one 1.63, 95 % CI 1.22-2.18, P value for trend = 0.001), whereas the plant-based pattern was strongly protective (OR 0.60, 95 % CI 0.45-0.81, P value for trend <0.0001. The carbohydrates pattern was only positively associated with colon cancer risk (OR 1.46, 95 % CI 1.02-2.09). The meat-based pattern was rich in saturated fat, animal protein, cholesterol, and phosphorus, nutrients originated in red meat. Since herocyclic amines are formed in the well-done red meat through the action of amino acids and creatine, it is suggestive that this pattern could be an important etiologic agent for colorectal cancer.

• Is opium a real risk factor for esophageal cancer or just a methodological artifact? Hospital and neighborhood controls in case-control studies.

  Authors: Ramin Shakeri, Farin Kamangar, Dariush Nasrollahzadeh, Mehdi Nouraie, Hooman Khademi, Arash Etemadi, Farhad Islami, Hajiamin Marjani, Saman Fahimi, Alireza Sepehr, Atieh Rahmati, Christian C Abnet, Sanford M Dawsey, Paul Brennan, Paolo Boffetta, Reza Malekzadeh, Reza Majdzadeh

  PloS one. 01/2012; 7(3):e32711.

  Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors ofControl selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC). We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age- and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age- and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17-2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63-1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure. Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.

• 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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