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7. Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers

Author

Kachuri, L. Saarela, O. Bojesen, S.E. Davey Smith, G. Liu, G. Landi, M.T. Caporaso, N.E. Christiani, D.C. Johansson, M. Panico, S. Overvad, K. Trichopoulou, A. Vineis, P. Scelo, G. Zaridze, D. Wu, X. Albanes, D. Diergaarde, B. Lagiou, P. Macfarlane, G.J. Aldrich, M.C. Tardón, A. Rennert, G. Olshan, A.F. Weissler, M.C. Chen, C. Goodman, G.E. Doherty, J.A. Ness, A.R. Bickeböller, H. Wichmann, H.-E. Risch, A. Field, J.K. Teare, M.D. Kiemeney, L.A. Van Der Heijden, E.H.F.M. Carroll, J.C. Haugen, A. Zienolddiny, S. Skaug, V. Wünsch-Filho, V. Tajara, E.H. Ayoub Moysés, R. Daumas Nunes, F. Lam, S. Eluf-Neto, J. Lacko, M. Peters, W.H.M. Le Marchand, L. Duell, E.J. Andrew, A.S. Franceschi, S. Schabath, M.B. Manjer, J. Arnold, S. Lazarus, P. Mukeriya, A. Swiatkowska, B. Janout, V. Holcatova, I. Stojsic, J. Mates, D. Lissowska, J. Boccia, S. Lesseur, C. Zong, X. McKay, J.D. Brennan, P. Amos, C.I. Hung, R.J.

Abstract

Background: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. Methods: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. Results: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 × 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. Conclusions: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci. © 2018 The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Published
2019

8. Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers

Author

Kachuri, L., Saarela, O., Bojesen, S.E., Smith, G., Liu, G., Landi, M.T., Caporaso, N.E., Christiani, D.C., Johansson, M., Panico, S., Overvad, K., Trichopoulou, A., Vineis, P., Scelo, G., Zaridze, D., Wu, X., Albanes, D., Diergaarde, B., Lagiou, P., Macfarlane, G.J., Aldrich, M.C., Tardon, A., Rennert, G., Olshan, A.F., Weissler, M.C., Chen, C, Goodman, G.E., Doherty, J.A., Ness, A.R., Bickeboller, H., Wichmann, H.E., Risch, A., Field, J.K., Teare, M.D., Kiemeney, L.A.L.M., Heijden, E. van der, Carroll, J.C., Haugen, A., Zienolddiny, S., Skaug, V., Wunsch-Filho, V., Tajara, E.H., Moyses, R. Ayoub, Nunes, F. Daumas, Lam, S., Eluf-Neto, J., Lacko, M., Peters, W.H.M., Marchand, L. Le, Duell, E.J., Andrew, A.S., Franceschi, S., Schabath, M.B., Manjer, J., Arnold, S, Lazarus, P., Mukeriya, A., Swiatkowska, B., Janout, V., Holcatova, I., Stojsic, J., Mates, D., Lissowska, J., Boccia, S., Lesseur, C., Zong, X., McKay, J.D., Brennan, P., Amos, C.I., Hung, R.J., Kachuri, L., Saarela, O., Bojesen, S.E., Smith, G., Liu, G., Landi, M.T., Caporaso, N.E., Christiani, D.C., Johansson, M., Panico, S., Overvad, K., Trichopoulou, A., Vineis, P., Scelo, G., Zaridze, D., Wu, X., Albanes, D., Diergaarde, B., Lagiou, P., Macfarlane, G.J., Aldrich, M.C., Tardon, A., Rennert, G., Olshan, A.F., Weissler, M.C., Chen, C, Goodman, G.E., Doherty, J.A., Ness, A.R., Bickeboller, H., Wichmann, H.E., Risch, A., Field, J.K., Teare, M.D., Kiemeney, L.A.L.M., Heijden, E. van der, Carroll, J.C., Haugen, A., Zienolddiny, S., Skaug, V., Wunsch-Filho, V., Tajara, E.H., Moyses, R. Ayoub, Nunes, F. Daumas, Lam, S., Eluf-Neto, J., Lacko, M., Peters, W.H.M., Marchand, L. Le, Duell, E.J., Andrew, A.S., Franceschi, S., Schabath, M.B., Manjer, J., Arnold, S, Lazarus, P., Mukeriya, A., Swiatkowska, B., Janout, V., Holcatova, I., Stojsic, J., Mates, D., Lissowska, J., Boccia, S., Lesseur, C., Zong, X., McKay, J.D., Brennan, P., Amos, C.I., and Hung, R.J.

Abstract

Contains fulltext : 208363.pdf (publisher's version ) (Closed access), BACKGROUND: Evidence from observational studies of telomere length (TL) has been conflicting regarding its direction of association with cancer risk. We investigated the causal relevance of TL for lung and head and neck cancers using Mendelian Randomization (MR) and mediation analyses. METHODS: We developed a novel genetic instrument for TL in chromosome 5p15.33, using variants identified through deep-sequencing, that were genotyped in 2051 cancer-free subjects. Next, we conducted an MR analysis of lung (16 396 cases, 13 013 controls) and head and neck cancer (4415 cases, 5013 controls) using eight genetic instruments for TL. Lastly, the 5p15.33 instrument and distinct 5p15.33 lung cancer risk loci were evaluated using two-sample mediation analysis, to quantify their direct and indirect, telomere-mediated, effects. RESULTS: The multi-allelic 5p15.33 instrument explained 1.49-2.00% of TL variation in our data (p = 2.6 x 10-9). The MR analysis estimated that a 1000 base-pair increase in TL increases risk of lung cancer [odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.20-1.65] and lung adenocarcinoma (OR = 1.92, 95% CI: 1.51-2.22), but not squamous lung carcinoma (OR = 1.04, 95% CI: 0.83-1.29) or head and neck cancers (OR = 0.90, 95% CI: 0.70-1.05). Mediation analysis of the 5p15.33 instrument indicated an absence of direct effects on lung cancer risk (OR = 1.00, 95% CI: 0.95-1.04). Analysis of distinct 5p15.33 susceptibility variants estimated that TL mediates up to 40% of the observed associations with lung cancer risk. CONCLUSIONS: Our findings support a causal role for long telomeres in lung cancer aetiology, particularly for adenocarcinoma, and demonstrate that telomere maintenance partially mediates the lung cancer susceptibility conferred by 5p15.33 loci.

Published
2019

11. Moving from theory to practice: A participatory social network mapping approach to address unmet need for family planning in Benin

Author

Baker Ml, Bednarczyk Ra, Kaul P, Eluf-Neto J, Juma M, Ohkubo S, Villa L, Crowley T, Diakite M, Igras S, Williams Jt, Stellenberg El, Figueroa-Downing D, Hofmeyr Gj, Chiang Ed, Nelly Muiruri, Linton A, Moses Mwangi Gitonga, Peters M, Sheeder J, Evans Dp, Lundgren R, Ernest Muthami Mutua, Citeya A, Joyce Jebet Cheptum, Hammond C, Tshitenge S, Harlan S, Mentrop L, Limaye R, Ganiyu A, and Baggio Ml

Subjects
Male, medicine.medical_specialty, Civil society, Population, Social Theory, Interviews as Topic, 03 medical and health sciences, 0302 clinical medicine, medicine, Information system, Benin, Humans, 030212 general & internal medicine, education, Health policy, Qualitative Research, Strategic planning, education.field_of_study, Health Services Needs and Demand, 030505 public health, business.industry, Public health, Public Health, Environmental and Occupational Health, Social Support, Public relations, Information and Communications Technology, Family Planning Services, Health education, Female, 0305 other medical science, business
Abstract

In West Africa, social factors influence whether couples with unmet need for family planning act on birth-spacing desires. Tékponon Jikuagou is testing a social network-based intervention to reduce social barriers by diffusing new ideas. Individuals and groups judged socially influential by their communities provide entrée to networks. A participatory social network mapping methodology was designed to identify these diffusion actors. Analysis of monitoring data, in-depth interviews, and evaluation reports assessed the methodology's acceptability to communities and staff and whether it produced valid, reliable data to identify influential individuals and groups who diffuse new ideas through their networks. Results indicated the methodology's acceptability. Communities were actively and equitably engaged. Staff appreciated its ability to yield timely, actionable information. The mapping methodology also provided valid and reliable information by enabling communities to identify highly connected and influential network actors. Consistent with social network theory, this methodology resulted in the selection of informal groups and individuals in both informal and formal positions. In-depth interview data suggest these actors were diffusing new ideas, further confirming their influence/connectivity. The participatory methodology generated insider knowledge of who has social influence, challenging commonly held assumptions. Collecting and displaying information fostered staff and community learning, laying groundwork for social change.

Published
2016

12. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.

Author

Lesseur, C, Diergaarde, B, Olshan, Af, Wünsch Filho, V, Ness, Ar, Liu, Guopeng, Lacko, M, Eluf Neto, J, Franceschi, S, Lagiou, P, Macfarlane, Gj, Richiardi, L, Boccia, Stefania, Polesel, J, Kjaerheim, K, Zaridze, D, Johansson, M, Menezes, Am, Curado, Mp, Robinson, M, Ahrens, W, Canova, C, Znaor, A, Castellsagué, X, Conway, Di, Holcátová, I, Mates, D, Vilensky, M, Healy, Cm, Szeszenia Dąbrowska, N, Fabiánová, E, Lissowska, J, Grandis, Jr, Weissler, Mc, Tajara, Eh, Nunes, Fd, de Carvalho, Mb, Thomas, S, Hung, Rj, Peters, Wh, Herrero, R, Cadoni, Gabriella, Bueno de Mesquita, Hb, Steffen, A, Agudo, A, Shangina, O, Xiao, X, Gaborieau, V, Chabrier, A, Anantharaman, D, Boffetta, Paolo, Amos, Ci, Mckay, Jd, Brennan, P. 1., Boccia, Stefania (ORCID:0000-0002-1864-749X), Cadoni, Gabriella (ORCID:0000-0001-8244-784X), Lesseur, C, Diergaarde, B, Olshan, Af, Wünsch Filho, V, Ness, Ar, Liu, Guopeng, Lacko, M, Eluf Neto, J, Franceschi, S, Lagiou, P, Macfarlane, Gj, Richiardi, L, Boccia, Stefania, Polesel, J, Kjaerheim, K, Zaridze, D, Johansson, M, Menezes, Am, Curado, Mp, Robinson, M, Ahrens, W, Canova, C, Znaor, A, Castellsagué, X, Conway, Di, Holcátová, I, Mates, D, Vilensky, M, Healy, Cm, Szeszenia Dąbrowska, N, Fabiánová, E, Lissowska, J, Grandis, Jr, Weissler, Mc, Tajara, Eh, Nunes, Fd, de Carvalho, Mb, Thomas, S, Hung, Rj, Peters, Wh, Herrero, R, Cadoni, Gabriella, Bueno de Mesquita, Hb, Steffen, A, Agudo, A, Shangina, O, Xiao, X, Gaborieau, V, Chabrier, A, Anantharaman, D, Boffetta, Paolo, Amos, Ci, Mckay, Jd, Brennan, P. 1., Boccia, Stefania (ORCID:0000-0002-1864-749X), and Cadoni, Gabriella (ORCID:0000-0001-8244-784X)

Abstract

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10−8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2–TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci—9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301–HLA-DQA1*0103–HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10−9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10−6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

Published
2016

13. A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer

Author

Delahaye-Sourdeix, M, Anantharaman, D, Timofeeva, MN, Gaborieau, V, Chabrier, A, Vallee, MP, Lagiou, P, Holcatova, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsague, X, Macfarlane, TV, Barzan, L, Canova, C, Thakker, NS, Conway, DI, Znaor, A, Healy, CM, Ahrens, W, Zaridze, D, Szeszenia-Dabrowska, N, Lissowska, J, Fabianova, E, Mates, IN, Bencko, V, Foretova, L, Janout, V, Curado, MP, Koifman, S, Menezes, A, Wunsch-Filho, V, Eluf-Neto, J, Boffetta, P, Fernandez Garrote, L, Polesel, J, Lener, M, Jaworowska, E, Lubiński, J, BOCCIA, STEFANIA, Rajkumar, T, Samant, TA, Mahimkar, MB, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P, McKay, JD, Delahaye-Sourdeix, M, Anantharaman, D, Timofeeva, MN, Gaborieau, V, Chabrier, A, Vallee, MP, Lagiou, P, Holcatova, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsague, X, Macfarlane, TV, Barzan, L, Canova, C, Thakker, NS, Conway, DI, Znaor, A, Healy, CM, Ahrens, W, Zaridze, D, Szeszenia-Dabrowska, N, Lissowska, J, Fabianova, E, Mates, IN, Bencko, V, Foretova, L, Janout, V, Curado, MP, Koifman, S, Menezes, A, Wunsch-Filho, V, Eluf-Neto, J, Boffetta, P, Fernandez Garrote, L, Polesel, J, Lener, M, Jaworowska, E, Lubiński, J, BOCCIA, STEFANIA, Rajkumar, T, Samant, TA, Mahimkar, MB, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P, and McKay, JD

Published
2015

14. A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer

Author

Delahaye Sourdeix, M, Anantharaman, D, Timofeeva, Mn, Gaborieau, V, Chabrier, A, Vallee, Mp, Lagiou, P, Holcatova, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsague, X, Macfarlane, Tv, Barzan, L, Canova, C, Thakker, N, Conway, Di, Znaor, A, Healy, Cm, Ahrens, W, Zaridze, D, Szeszenia Dabrowska, N, Lissowska, J, Fabianova, E, Mates, In, Bencko, V, Foretova, L, Janout, V, Curado, Mp, Koifman, S, Menezes, A, Wunsch Filho, V, Eluf Neto, J, Boffetta, P, Fernandez Garrote, L, Polesel, J, Lener, M, Jaworowska, E, Lubiński, J, Boccia, Stefania, Rajkumar, T, Samant, Ta, Mahimkar, Mb, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P, Mckay, Jd, Boccia, Stefania (ORCID:0000-0002-1864-749X), Delahaye Sourdeix, M, Anantharaman, D, Timofeeva, Mn, Gaborieau, V, Chabrier, A, Vallee, Mp, Lagiou, P, Holcatova, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsague, X, Macfarlane, Tv, Barzan, L, Canova, C, Thakker, N, Conway, Di, Znaor, A, Healy, Cm, Ahrens, W, Zaridze, D, Szeszenia Dabrowska, N, Lissowska, J, Fabianova, E, Mates, In, Bencko, V, Foretova, L, Janout, V, Curado, Mp, Koifman, S, Menezes, A, Wunsch Filho, V, Eluf Neto, J, Boffetta, P, Fernandez Garrote, L, Polesel, J, Lener, M, Jaworowska, E, Lubiński, J, Boccia, Stefania, Rajkumar, T, Samant, Ta, Mahimkar, Mb, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P, Mckay, Jd, and Boccia, Stefania (ORCID:0000-0002-1864-749X)

Abstract

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P-het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

Published
2015

15. The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract

Author

Delahaye Sourdeix, M, Oliver, J, Timofeeva, Mn, Gaborieau, V, Johansson, M, Chabrier, A, Wozniak, Mb, Brenner, Dr, Vallée, Mp, Anantharaman, D, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, Tv, Barzan, L, Canova, C, Thakker, N, Conway, Di, Znaor, A, Healy, Cm, Ahrens, W, Zaridze, D, Szeszenia Dabrowska, N, Lissowska, J, Fabianova, E, Mates, In, Bencko, V, Foretova, L, Janout, V, Curado, Mp, Koifman, S, Menezes, A, Wünsch Filho, V, Eluf Neto, J, Boffetta, P, Garrote, Lf, Serraino, D, Lener, M, Jaworowska, E, Lubiński, J, Boccia, Stefania, Rajkumar, T, Samant, Ta, Mahimkar, Mb, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P, Mckay, Jd, Boccia, Stefania (ORCID:0000-0002-1864-749X), Delahaye Sourdeix, M, Oliver, J, Timofeeva, Mn, Gaborieau, V, Johansson, M, Chabrier, A, Wozniak, Mb, Brenner, Dr, Vallée, Mp, Anantharaman, D, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, Tv, Barzan, L, Canova, C, Thakker, N, Conway, Di, Znaor, A, Healy, Cm, Ahrens, W, Zaridze, D, Szeszenia Dabrowska, N, Lissowska, J, Fabianova, E, Mates, In, Bencko, V, Foretova, L, Janout, V, Curado, Mp, Koifman, S, Menezes, A, Wünsch Filho, V, Eluf Neto, J, Boffetta, P, Garrote, Lf, Serraino, D, Lener, M, Jaworowska, E, Lubiński, J, Boccia, Stefania, Rajkumar, T, Samant, Ta, Mahimkar, Mb, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P, Mckay, Jd, and Boccia, Stefania (ORCID:0000-0002-1864-749X)

Abstract

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

Published
2015

16. Using Prior Information from the Medical Literature in\ud GWAS of Oral Cancer Identifies Novel Susceptibility\ud Variant on Chromosome 4 - the AdAPT Method

Author

Johansson, M., Roberts, A., Chen, D., Li, Y., Delahaye-Sourdeix, M., Aswani, N., Greenwood, M.A., Benhamou, S., Lagiou, P., Holcatova, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsague, X., Macfarlane, T.V., Barzan, L., Canova, C., Thakker, N.S., Conway, D.I., Znaor, A., Healy, C.M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Fabianova, E., Mates, I.N., Bencko, V., Foretova, L., Janout, V., Curado, M.P., Koifman, S., Menezes, A., Wuensch-Filho, V., Eluf-Neto, J., Boffetta, P., Franceschi, S., Herrero, R., Fernandez Garrote, L., Talamini, R., Boccia, S., Galan, P., Vatten, L., Thomson, P., Zelenika, D., Lathrop, M., Byrnes, G., Cunningham, H., Brennan, P., Wakefield, J., and Mckay, J.D.

Abstract

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but\ud it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility\ud of automatically retrieving information from the medical literature and leveraging this information in GWAS.\ud Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts,\ud and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the\ud phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can\ud subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We\ud initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and\ud subsequently applied it in a two-phase GWAS of oral cancer.\ud Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the\ud oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the\ud ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (perrare-allele\ud log additive p-value [ptrend] = 2.561023\ud ). The combined OR for having one additional rare allele was 0.83 (95% CI:\ud 0.76–0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall\ud UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper\ud aerodigestive tract (UADT), but no additional association signal was found.\ud Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical\ud literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/\ud lld/gwas/service/config).

Published
2012

17. Diet and the risk of head and neck cancer: A pooled analysis in the INHANCE consortium

Author

Chuang, S.-C. Jenab, M. Heck, J.E. Bosetti, C. Talamini, R. Matsuo, K. Castellsague, X. Franceschi, S. Herrero, R. Winn, D.M. Vecchia, C.L. Morgenstern, H. Zhang, Z.-F. Levi, F. Maso, L.D. Kelsey, K. McClean, M.D. Vaughan, T. Lazarus, P. Muscat, J. Ramroth, H. Chen, C. Schwartz, S.M. Eluf-Neto, J. Hayes, R.B. Purdue, M. Boccia, S. Cadoni, G. Zaridze, D. Koifman, S. Curado, M.P. Ahrens, W. Benhamou, S. Matos, E. Lagiou, P. Szeszenia-Dabrowska, N. Olshan, A.F. Fernandez, L. Menezes, A. Agudo, A. Daudt, A.W. Merletti, F. MacFarlane, G.J. Kjaerheim, K. Mates, D. Holcatova, I. Schantz, S. Yu, G.-P. Simonato, L. Brenner, H. Mueller, H. Conway, D.I. Thomson, P. Fabianova, E. Znaor, A. Rudnai, P. Healy, C.M. Ferro, G. Brennan, P. Boffetta, P. Hashibe, M.

Abstract

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p trend < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p trend = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p trend = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p trend < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97). © 2011 Springer Science+Business Media B.V.

Published
2012

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

Author

Chen, D. Truong, T. Gaborieau, V. Byrnes, G. Chabrier, A. Chuang, S.-C. Olshan, A.F. Weissler, M.C. Luo, J. Romkes, M. Buch, S. Nukui, T. Franceschi, S. Herrero, R. Talamini, R. Kelsey, K.T. Christensen, B. McClean, M.D. Lacko, M. Manni, J.J. Peters, W.H.M. Lubiński, J. Trubicka, J. Lener, M. Muscat, J.E. Lazarus, P. Wei, Q. Sturgis, E.M. Zhang, Z.-F. Chang, S.-C. Wang, R. Schwartz, S.M. Chen, C. Benhamou, S. Lagiou, P. Holcátová, I. Richiardi, L. Kjaerheim, K. Agudo, A. Castellsagué, X. Macfarlane, T.V. Barzan, L. Canova, C. Thakker, N.S. Conway, D.I. Znaor, A. Healy, C.M. Ahrens, W. Zaridze, D. Szeszenia-Dabrowska, N. Lissowska, J. Fabianova, E. Bucur, A. Bencko, V. Foretova, L. Janout, V. Curado, M.P. Koifman, S. Menezes, A. Wünsch-Filho, V. Eluf-Neto, J. Fernandez, L. Boccia, S. Hashibe, M. Hayes, R.B. Boffetta, P. Brennan, P. McKay, J.D.

Abstract

Background: 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). Methods: 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. Results: 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 (Phet = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations.©2011 AACR.

Published
2011

21. Cigarette, Cigar, and Pipe Smoking and the Risk of Head and Neck Cancers: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Author

Wyss, A, Hashibe, M, Chuang, S, Lee, Ya, Zhang, Z, Yu, G, Winn, Dm, Wei, Q, Talamini, R, Szeszenia Dabrowska, N, Sturgis, Em, Smith, E, Shangina, O, Schwartz, Sm, Schantz, S, Rudnai, P, Purdue, Mp, Eluf Neto, J, Muscat, J, Morgenstern, H, Michaluart, P, Menezes, A, Matos, E, Mates, In, Lissowska, J, Levi, F, Lazarus, P, La Vecchia, C, Koifman, S, Herrero, R, Hayes, Rb, Franceschi, S, Wunsch Filho, V, Fernandez, L, Fabianova, E, Daudt, Aw, Dal Maso, L, Curado, Mp, Chen, C, Castellsague, X, De Carvalho, Mb, Cadoni, Gabriella, Boccia, Stefania, Brennan, P, Boffetta, P, Olshan, Af, Cadoni, Gabriella (ORCID:0000-0001-8244-784X), Boccia, Stefania (ORCID:0000-0002-1864-749X), Wyss, A, Hashibe, M, Chuang, S, Lee, Ya, Zhang, Z, Yu, G, Winn, Dm, Wei, Q, Talamini, R, Szeszenia Dabrowska, N, Sturgis, Em, Smith, E, Shangina, O, Schwartz, Sm, Schantz, S, Rudnai, P, Purdue, Mp, Eluf Neto, J, Muscat, J, Morgenstern, H, Michaluart, P, Menezes, A, Matos, E, Mates, In, Lissowska, J, Levi, F, Lazarus, P, La Vecchia, C, Koifman, S, Herrero, R, Hayes, Rb, Franceschi, S, Wunsch Filho, V, Fernandez, L, Fabianova, E, Daudt, Aw, Dal Maso, L, Curado, Mp, Chen, C, Castellsague, X, De Carvalho, Mb, Cadoni, Gabriella, Boccia, Stefania, Brennan, P, Boffetta, P, Olshan, Af, Cadoni, Gabriella (ORCID:0000-0001-8244-784X), and Boccia, Stefania (ORCID:0000-0002-1864-749X)

Abstract

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers

Published
2013

22. Using prior information from the medical literature in GWAS of oral cancer identifies novel susceptibility variant on chromosome 4--the AdAPT method

Author

Johansson, M, Roberts, A, Chen, D, Li, Yuan, Delahaye Sourdeix, M, Aswani, N, Greenwood, Ma, Benhamou, S, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, Tv, Barzan, L, Canova, C, Thakker, N, Conway, Di, Znaor, A, Healy, Cm, Ahrens, W, Zaridze, D, Szeszenia Dabrowska, N, Lissowska, J, Fabiánová, E, Mates, In, Bencko, V, Foretova, L, Janout, V, Curado, Mp, Koifman, S, Menezes, A, Wünsch Filho, V, Eluf Neto, J, Boffetta, P, Franceschi, S, Herrero, R, Fernandez Garrote, L, Talamini, R, Boccia, Stefania, Galan, P, Vatten, L, Thomson, P, Zelenika, D, Lathrop, M, Byrnes, G, Cunningham, H, Brennan, P, Wakefield, J, Mckay, Jd, Boccia, Stefania (ORCID:0000-0002-1864-749X), Johansson, M, Roberts, A, Chen, D, Li, Yuan, Delahaye Sourdeix, M, Aswani, N, Greenwood, Ma, Benhamou, S, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, Tv, Barzan, L, Canova, C, Thakker, N, Conway, Di, Znaor, A, Healy, Cm, Ahrens, W, Zaridze, D, Szeszenia Dabrowska, N, Lissowska, J, Fabiánová, E, Mates, In, Bencko, V, Foretova, L, Janout, V, Curado, Mp, Koifman, S, Menezes, A, Wünsch Filho, V, Eluf Neto, J, Boffetta, P, Franceschi, S, Herrero, R, Fernandez Garrote, L, Talamini, R, Boccia, Stefania, Galan, P, Vatten, L, Thomson, P, Zelenika, D, Lathrop, M, Byrnes, G, Cunningham, H, Brennan, P, Wakefield, J, Mckay, Jd, and Boccia, Stefania (ORCID:0000-0002-1864-749X)

Abstract

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5 x 10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodolog

Published
2012

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

Author

Chuang, S, Jenab, M, Heck, Je, Bosetti, C, Talamini, R, Matsuo, K, Castellsague, X, Franceschi, S, Herrero, R, Winn, Dm, La Vecchia, C, Morgenstern, H, Zhang, Z, Levi, F, Dal Maso, L, Kelsey, K, Mcclean, Md, Vaughan, T, Lazarus, P, Muscat, J, Ramroth, H, Chen, Chen, Schwartz, Sm, Eluf Neto, J, Hayes, Rb, Purdue, M, Boccia, Stefania, Cadoni, Gabriella, Zaridze, D, Koifman, S, Curado, Mp, Ahrens, W, Benhamou, S, Matos, E, Lagiou, P, Szeszenia Dabrowska, N, Olshan, Af, Fernandez, L, Menezes, A, Agudo, A, Daudt, Aw, Merletti, F, Macfarlane, Gj, Kjaerheim, K, Mates, D, Holcatova, I, Schantz, S, Yu, G, Simonato, L, Brenner, H, Mueller, H, Conway, Di, Thomson, P, Fabianova, E, Znaor, A, Rudnai, P, Healy, Cm, Ferro, Giorgia, Brennan, P, Boffetta, P, Hashibe, M., Boccia, Stefania (ORCID:0000-0002-1864-749X), Cadoni, Gabriella (ORCID:0000-0001-8244-784X), Chuang, S, Jenab, M, Heck, Je, Bosetti, C, Talamini, R, Matsuo, K, Castellsague, X, Franceschi, S, Herrero, R, Winn, Dm, La Vecchia, C, Morgenstern, H, Zhang, Z, Levi, F, Dal Maso, L, Kelsey, K, Mcclean, Md, Vaughan, T, Lazarus, P, Muscat, J, Ramroth, H, Chen, Chen, Schwartz, Sm, Eluf Neto, J, Hayes, Rb, Purdue, M, Boccia, Stefania, Cadoni, Gabriella, Zaridze, D, Koifman, S, Curado, Mp, Ahrens, W, Benhamou, S, Matos, E, Lagiou, P, Szeszenia Dabrowska, N, Olshan, Af, Fernandez, L, Menezes, A, Agudo, A, Daudt, Aw, Merletti, F, Macfarlane, Gj, Kjaerheim, K, Mates, D, Holcatova, I, Schantz, S, Yu, G, Simonato, L, Brenner, H, Mueller, H, Conway, Di, Thomson, P, Fabianova, E, Znaor, A, Rudnai, P, Healy, Cm, Ferro, Giorgia, Brennan, P, Boffetta, P, Hashibe, M., Boccia, Stefania (ORCID:0000-0002-1864-749X), and Cadoni, Gabriella (ORCID:0000-0001-8244-784X)

Abstract

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).

Published
2012

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

Author

Chen, D., Truong, T., Gaborieau, V., Byrnes, G., Chabrier, A., Chuang, S.C., Olshan, A.F., Weissler, M.C., Luo, J., Romkes, M., Buch, S., Nukui, T., Franceschi, S., Herrero, R., Talamini, R., Kelsey, K.T., Christensen, B., McClean, M.D., Lacko, M., Manni, J.J., Peters, W.H.M., Lubinski, J., Trubicka, J., Lener, M., Muscat, J.E., Lazarus, P., Wei, Q., Sturgis, E.M., Zhang, Z.F., Chang, S.C., Wang, R., Schwartz, S.M., Chen, C., Benhamou, S., Lagiou, P., Holcatova, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsague, X., Macfarlane, T.V., Barzan, L., Canova, C., Thakker, N.S., Conway, D.I., Znaor, A., Healy, C.M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Fabianova, E., Bucur, A., Bencko, V., Foretova, L., Janout, V., Curado, M.P., Koifman, S., Menezes, A., Wunsch-Filho, V., Eluf-Neto, J., Fernandez, L., Boccia, S., Hashibe, M., Hayes, R.B., Boffetta, P., Brennan, P., McKay, J.D., Chen, D., Truong, T., Gaborieau, V., Byrnes, G., Chabrier, A., Chuang, S.C., Olshan, A.F., Weissler, M.C., Luo, J., Romkes, M., Buch, S., Nukui, T., Franceschi, S., Herrero, R., Talamini, R., Kelsey, K.T., Christensen, B., McClean, M.D., Lacko, M., Manni, J.J., Peters, W.H.M., Lubinski, J., Trubicka, J., Lener, M., Muscat, J.E., Lazarus, P., Wei, Q., Sturgis, E.M., Zhang, Z.F., Chang, S.C., Wang, R., Schwartz, S.M., Chen, C., Benhamou, S., Lagiou, P., Holcatova, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsague, X., Macfarlane, T.V., Barzan, L., Canova, C., Thakker, N.S., Conway, D.I., Znaor, A., Healy, C.M., Ahrens, W., Zaridze, D., Szeszenia-Dabrowska, N., Lissowska, J., Fabianova, E., Bucur, A., Bencko, V., Foretova, L., Janout, V., Curado, M.P., Koifman, S., Menezes, A., Wunsch-Filho, V., Eluf-Neto, J., Fernandez, L., Boccia, S., Hashibe, M., Hayes, R.B., Boffetta, P., Brennan, P., and McKay, J.D.

Abstract

Contains fulltext : 96598.pdf (publisher's version ) (Closed access), BACKGROUND: 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). METHODS: 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. RESULTS: 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 x 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 x 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). CONCLUSIONS: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. IMPACT: Further research is warranted to elucidate the mechanisms underlying these observations.

Published
2011

25. Serum antibodies to human papillomavirus 16 proteins in women from Brazil with invasive cervical carcinoma

Author

Sun Y, Eluf-Neto J, FRANCESC XAVIER BOSCH JOSÉ, Muñoz N, Jm, Walboomers, Cj, Meijer, Kv, Shah, Clayman B, and Rp, Viscidi

Subjects
Adult, Papillomavirus E7 Proteins, Papillomavirus Infections, Uterine Cervical Neoplasms, Enzyme-Linked Immunosorbent Assay, Oncogene Proteins, Viral, Middle Aged, Antibodies, Viral, Uterine Cervical Dysplasia, Repressor Proteins, Tumor Virus Infections, Case-Control Studies, Humans, Female, Papillomaviridae, Brazil, Aged
Abstract

Serum samples from 194 cases and 217 controls participating in a case-control study of invasive cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 virus-like particles (VLPs) by ELISA. The prevalence of antibody in cases and controls was 47.4 versus 24.4% (P0.001). The prevalence was higher in women who had HPV-16 DNA in the genital tract (54.2%) than in those with other HPVs (36.8%) or no HPVs (44.8%), but the differences were not statistically significant. Among cases and controls, HPV-16 VLP antibodies were associated with a greater number of lifetime sexual partners (chi2 for trend, P0.001). Among controls, age was inversely associated with HPV-16 VLP seroreactivity (chi2 for trend, P = 0.019). The sera were previously tested for antibodies to HPV-16 E6 and E7 oncoproteins; there was no correlation between antibody titers to HPV-16 E6 or E7 and VLPs. The HPV-16 serological assays were compared as screening tests for invasive cervical cancer. The sensitivity and specificity estimates were 47.4 and 75.6% for HPV-16 VLP serology, 63.4 and 89.9% for either HPV-16 E6 or E7 serology, and 53.6 and 93.6% for high titers of either HPV-16 E6 or E7 or VLP antibodies. The utility of HPV-16 VLP ELISA as a screening test for invasive cervical cancer is limited by a high seroprevalence in women with probable prior exposure to HVP 16 but without disease.

Published
1999

26. Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer

Author

López, R.V.M., primary, Zago, M.A., additional, Eluf-Neto, J., additional, Curado, M.P., additional, Daudt, A.W., additional, da Silva-Junior, W.A., additional, Zanette, D.L., additional, Levi, J.E., additional, de Carvalho, M.B., additional, Kowalski, L.P., additional, Abrahão, M., additional, de Góis-Filho, J.F., additional, Boffetta, P., additional, and Wünsch-Filho, V., additional

Published
2011
Full Text
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28. Human papillomavirus-related serological markers of invasive cervical carcinoma in Brazil

Author

Sun Y, Eluf-Neto J, FRANCESC XAVIER BOSCH JOSÉ, Muñoz N, Booth M, Jm, Walboomers, Kv, Shah, and Rp, Viscidi

Subjects
Adult, Radioimmunoprecipitation Assay, Papillomavirus E7 Proteins, Carcinoma, Uterine Cervical Neoplasms, Oncogene Proteins, Viral, Middle Aged, Antibodies, Viral, Sensitivity and Specificity, Repressor Proteins, Risk Factors, Case-Control Studies, DNA, Viral, Prevalence, Humans, Female, Neoplasm Invasiveness, Papillomaviridae, Biomarkers, Brazil, Aged, Neoplasm Staging
Abstract

Masked sera from 194 cases and 217 controls participating in a case-control study of cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 E6 and E7 by radioimmunoprecipitation assay. Radiolabeled full-length E6 and E7 proteins expressed by in vitro transcription and translation in rabbit reticulocyte lysate were used as antigens. The antibody prevalences in cases and controls were: 54.1% versus 6% for E6; 30.4% versus 4.6% for E7; 63.4% versus 10.1% for either E6 or E7; and 21.1% versus 0.5% for both E6 and E7. The corresponding odds ratios were 35 ([95% confidence interval (CI)], 15-83), 10 (95% CI, 4-25), 28 (95% CI, 13-61) and 87 (95% CI, 10-736). The most marked contrast between cases and controls was observed for sera with high antibody titers (cpm6000) with an odds ratio of 239 (95% CI, 29-1946) for E6 or E7. Seroreactivity in cases was partially type specific; women who had HPV-16 DNA in the genital tract had higher antibody prevalence rates than those who were negative for HPV DNA. Reactivity to the E6 protein was associated with the stage of disease; the antibody prevalence was 62.7% in cases with stages II-IV and 31.0% in cases with stage I (P0.005). HPV-16 serology and HPV polymerase chain reaction were compared as markers for invasive cervical cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1994

29. TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America

Author

Szymańska, K., primary, Levi, J.E., additional, Menezes, A., additional, Wünsch-Filho, V., additional, Eluf-Neto, J., additional, Koifman, S., additional, Matos, E., additional, Daudt, A.W., additional, Curado, M.P., additional, Villar, S., additional, Pawlita, M., additional, Waterboer, T., additional, Boffetta, P., additional, Hainaut, P., additional, and Brennan, P., additional

Published
2009
Full Text
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30. Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk

Author

Marron, M., primary, Boffetta, P., additional, Zhang, Z.-F., additional, Zaridze, D., additional, Wunsch-Filho, V., additional, Winn, D. M, additional, Wei, Q., additional, Talamini, R., additional, Szeszenia-Dabrowska, N., additional, Sturgis, E. M, additional, Smith, E., additional, Schwartz, S. M, additional, Rudnai, P., additional, Purdue, M. P, additional, Olshan, A. F, additional, Eluf-Neto, J., additional, Muscat, J., additional, Morgenstern, H., additional, Menezes, A., additional, McClean, M., additional, Matos, E., additional, Mates, I. N., additional, Lissowska, J., additional, Levi, F., additional, Lazarus, P., additional, Vecchia, C. L., additional, Koifman, S., additional, Kelsey, K., additional, Herrero, R., additional, Hayes, R. B, additional, Franceschi, S., additional, Fernandez, L., additional, Fabianova, E., additional, Daudt, A. W, additional, Maso, L. D., additional, Curado, M. P., additional, Cadoni, G., additional, Chen, C., additional, Castellsague, X., additional, Boccia, S., additional, Benhamou, S., additional, Ferro, G., additional, Berthiller, J., additional, Brennan, P., additional, Moller, H., additional, and Hashibe, M., additional

Published
2009
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32. Incidence and risk factors of aplastic anemia in Latin American countries: the LATIN case-control study

Author

Maluf, E., primary, Hamerschlak, N., additional, Cavalcanti, A. B., additional, Junior, A. A., additional, Eluf-Neto, J., additional, Falcao, R. P., additional, Lorand-Metze, I. G., additional, Goldenberg, D., additional, Santana, C. L., additional, de Oliveira Werneck Rodrigues, D., additional, Passos, L. N. d. M., additional, Rosenfeld, L. G. M., additional, Pitta, M., additional, Loggetto, S., additional, Feitosa Ribeiro, A. A., additional, Velloso, E. D., additional, Kondo, A. T., additional, de Miranda Coelho, E. O., additional, Pintao, M. C. T., additional, de Souza, H. M., additional, Borbolla, J. R., additional, and Pasquini, R., additional

Published
2009
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34. Oral Health and Risk of Squamous Cell Carcinoma of the Head and Neck and Esophagus: Results of Two Multicentric Case-Control Studies

Author

Guha, N., primary, Boffetta, P., additional, Wunsch Filho, V., additional, Eluf Neto, J., additional, Shangina, O., additional, Zaridze, D., additional, Curado, M. P., additional, Koifman, S., additional, Matos, E., additional, Menezes, A., additional, Szeszenia-Dabrowska, N., additional, Fernandez, L., additional, Mates, D., additional, Daudt, A. W., additional, Lissowska, J., additional, Dikshit, R., additional, and Brennan, P., additional

Published
2007
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35. Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Author

Hashibe, M., primary, Brennan, P., additional, Benhamou, S., additional, Castellsague, X., additional, Chen, C., additional, Curado, M. P., additional, Maso, L. D., additional, Daudt, A. W., additional, Fabianova, E., additional, Wunsch-Filho, V., additional, Franceschi, S., additional, Hayes, R. B., additional, Herrero, R., additional, Koifman, S., additional, La Vecchia, C., additional, Lazarus, P., additional, Levi, F., additional, Mates, D., additional, Matos, E., additional, Menezes, A., additional, Muscat, J., additional, Eluf-Neto, J., additional, Olshan, A. F., additional, Rudnai, P., additional, Schwartz, S. M., additional, Smith, E., additional, Sturgis, E. M., additional, Szeszenia-Dabrowska, N., additional, Talamini, R., additional, Wei, Q., additional, Winn, D. M., additional, Zaridze, D., additional, Zatonski, W., additional, Zhang, Z.-F., additional, Berthiller, J., additional, and Boffetta, P., additional

Published
2007
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39. HUMAN EXPOSURE TO ORGANOCHLORINE COMPOUNDS AT CIDADE DOS MENINOS, DUQUE DE CAXIAS, RIO DE JANEIRO, BRAZIL

Author

Soares Da Silva, A, primary, Carvalho, Tess BH, additional, Cassanha, Galvco LA, additional, Mendes, R, additional, Froes, Asmus Cl, additional, Franco, Netto G, additional, Finkelman, J, additional, Abreu, E, additional, Azevedoe Silva, Mendonca G, additional, Eluf, Neto J, additional, Fernandes, A S, additional, Escamilla, J A, additional, Palácios Da Cunha, E Melo De Ao M, additional, Da Cruz, Gouveia N, additional, Koifman, S F, additional, Wünsch, Filho V F, additional, De Magalhães, Câmara V F, additional, and Andrade, Carvalho W F, additional

Published
2003
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40. Prevalence and determinants of human papillomavirus genital infection in men

Author

Franceschi, S, primary, Castellsagué, X, additional, Dal Maso, L, additional, Smith, J S, additional, Plummer, M, additional, Ngelangel, C, additional, Chichareon, S, additional, Eluf-Neto, J, additional, Shah, K V, additional, Snijders, P J F, additional, Meijer, C J L M, additional, Bosch, F X, additional, and Muñoz, N, additional

Published
2002
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44. Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer.

Author

Smith JS, Herrero R, Bosetti C, Muñoz N, Bosch FX, Eluf-Neto J, Castellsagué X, Meijer CJL, Van den Brule AJC, Franceschi S, Ashley R, International Agency for Research on Cancer (IARC). Multicentric Cervical Cancer Study Group, Smith, Jennifer S, Herrero, Rolando, Bosetti, Cristina, Muñoz, Nubia, Bosch, F Xavier, Eluf-Neto, José, Castellsagué, Xavier, and Meijer, Chris J L M

Abstract

Background: Human papillomavirus (HPV) infection is the main cause of invasive cervical cancer, but cofactors may act in conjunction with HPV. We performed a pooled analysis of seven case-control studies to examine the effect of one possible HPV cofactor, herpes simplex virus-2 (HSV-2) infection, in the etiology of invasive cervical cancer.Methods: Blood and exfoliated cervical specimens were obtained from 1263 case patients with invasive cervical cancer (1158 with squamous-cell carcinomas and 105 with adeno- or adenosquamous-cell carcinomas) and 1117 age-matched control subjects. Western blot analysis and/or an enzyme-linked immunosorbent assay were used to detect type-specific serum antibodies to HSV-2 and HSV-1, and Chlamydia trachomatis serum antibodies were detected using a micro-immunofluorescence assay. HPV DNA was detected using a polymerase chain reaction assay. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models.Results: Overall, HSV-2 seropositivity was higher among case patients with squamous-cell carcinoma (44.4%, 95% CI = 41.5% to 47.3%) or adeno- or adenosquamous-cell carcinoma (43.8%, 95% CI = 34.2% to 53.5%) than among control subjects (25.6%, 95% CI = 23.0% to 28.2%). Cervical specimens from 1098 (94.8%) squamous-cell carcinoma case patients, 95 (90.5%) adeno- or adenosquamous carcinoma case patients, and 164 (14.7%) control subjects were positive for HPV DNA. Among the HPV DNA-positive women, HSV-2 seropositivity was associated with increased risks of squamous-cell carcinoma (OR = 2.19, 95% CI = 1.41 to 3.40) and adeno- or adenosquamous-cell carcinoma (OR = 3.37, 95% CI = 1.47 to 7.74) after adjustment for potential confounders. A similar association between HSV-2 seropositivity and squamous-cell carcinoma risk was observed after further controlling for markers of sexual behavior (OR = 1.96, 95% CI = 1.24 to 3.09). Among control subjects, HSV-2 seropositivity was associated with markers of sexual behavior, but not with cervical HPV DNA positivity.Conclusion: HSV-2 infection may act in conjunction with HPV infection to increase the risk of invasive cervical carcinoma. [ABSTRACT FROM AUTHOR]

Published
2002

46. 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

Author

Maria Paula Curado, Zuo-Feng Zhang, Hal Morgenstern, Philip Lazarus, Jolanta Lissowska, Paul Brennan, Leticia Fernandez, Peter Rudnai, Chu Chen, Julien Berthiller, Paolo Boffetta, Eleonora Fabianova, Andrew F. Olshan, Sergio Koifman, Mia Hashibe, Rolando Herrero, Luigino Dal Maso, Erich M. Sturgis, Fabio Levi, José Eluf-Neto, Deborah M. Winn, Xavier Castellsagué, Alexander W. Daudt, Neolilia Szeszenia-Dabrowska, Stephen M. Schwartz, Karl T. Kelsey, Silva Franceschi, Joshua E. Muscat, Simone Benhamou, Ana M. B. Menezes, Elena Matos, Richard B. Hayes, Carlo La Vecchia, Mia M. Gaudet, Shu Chun Chuang, David Zaridze, V. Wünsch-Filho, Renato Talamini, Alexandru Bucur, Qingyi Wei, Gaudet, M.M., Olshan, A.F., Chuang, S.-C., Berthiller, J., Zhang, Z.-F., Lissowska, J., Zaridze, D., Winn, D.M., Wei, Q., Talamini, R., Szeszenia-Dabrowska, N., Sturgis, E.M., Schwartz, S.M., Rudnai, P., Eluf-Neto, J., Muscat, J., Morgenstern, H., Menezes, A., Matos, E., Bucur, A., Levi, F., Lazarus, P., La Vecchia, C., Koifman, S., Kelsey, K., Herrero, R., Hayes, R.B., Franceschi, S., Wunsch-Filho, V., Fernandez, L., Fabianova, E., Daudt, A.W., Dal Maso, L., Curado, M.P., Chen, C., Castellsague, X., Benhamou, S., Boffetta, P., Brennan, P., and Hashibe, M.

Subjects
Male, Epidemiology, Overweight, 0302 clinical medicine, Risk Factors, Odds Ratio, pooled analysi, 030212 general & internal medicine, Child, 10. No inequality, Prospective cohort study, Body mass index, Cancer, Aged, 80 and over, 2. Zero hunger, Incidence, Smoking, Confounding, General Medicine, Middle Aged, 3. Good health, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Female, medicine.symptom, case-control, Adult, medicine.medical_specialty, INHANCE, Adolescent, Alcohol Drinking, Young Adult, 03 medical and health sciences, Thinness, medicine, Humans, Risk factor, Aged, business.industry, Case-control study, Odds ratio, United States, Surgery, Case-Control Studies, International Head and Neck Cancer Epidemiology, head and neck cancer, business, Consortium, Demography
Abstract

Background: 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 certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. Methods: 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. Results: Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) =18.5 kg/m2 (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m2 (0.52, 0.44-0.60) and BMI =30 kg/m2 (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m2. These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI =18.5 kg/m2 was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m2 was present only in smokers and drinkers. Conclusions: 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. © The Author 2010; Published by Oxford University Press on behalf of the International Epidemiological Association. All rights reserved.

Published
2017

47. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

Author

Stefania Boccia, Wilbert H.M. Peters, Kristina Kjærheim, James McKay, Christopher I. Amos, David I. Conway, Dana Mates, Ana Maria Menezes, Antonio Agudo, Brenda Diergaarde, Rolando Herrero, Valerie Gaborieau, Martin Lacko, Cristina Canova, Neonila Szeszenia-Dąbrowska, Lorenzo Richiardi, Xiangjun Xiao, Victor Wünsch-Filho, Pagona Lagiou, David Zaridze, Maria Paula Curado, H. Bas Bueno-de-Mesquita, Mark C. Weissler, Rayjean J. Hung, Paolo Boffetta, Claire M. Healy, Marcos Brasilino de Carvalho, Fábio Daumas Nunes, Steve Thomas, Devasena Anantharaman, Paul Brennan, Mattias Johansson, Geoffrey Liu, Oxana Shangina, Ariana Znaor, Corina Lesseur, Eleonora Fabianova, Gabriella Cadoni, Andy R Ness, Eloiza H. Tajara, Gary J. Macfarlane, Jennifer R. Grandis, Annika Steffen, Jerry Polesel, Max Robinson, Marta Vilensky, Andrew F. Olshan, Wolfgang Ahrens, Silvia Franceschi, Amelie Chabrier, José Eluf-Neto, Jolanta Lissowska, Ivana Holcatova, Xavier Castellsagué, Nofer Institute of Occupational Medicine, Łódź, Poland, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Keel Neus Oorheelkunde (9), Lesseur, C., Diergaarde, B., Olshan, A.F., Wünsch-Filho, V., Ness, A.R., Liu, G., Lacko, M., Eluf-Neto, J., Franceschi, S., Lagiou, P., Macfarlane, G.J., Richiardi, L., Boccia, S., Polesel, J., Kjaerheim, K., Zaridze, D., Johansson, M., Menezes, A.M., Curado, M.P., Robinson, M., Ahrens, W., Canova, C., Znaor, A., Castellsagué, X., Conway, D.I., Holcátová, I., Mates, D., Vilensky, M., Healy, C.M., Szeszenia-Dabrowska, N., Fabiánová, E., Lissowska, J., Grandis, J.R., Weissler, M.C., Tajara, E.H., Nunes, F.D., De Carvalho, M.B., Thomas, S., Hung, R.J., Peters, W.H.M., Herrero, R., Cadoni, G., Bueno-De-Mesquita, H.B., Steffen, A., Agudo, A., Shangina, O., Xiao, X., Gaborieau, V., Chabrier, A., Anantharaman, D., Boffetta, P., Amos, C.I., McKay, J.D., and Brennan, P.

Subjects
Male, 0301 basic medicine, Epidemiology, Genome-wide association study, Gastroenterology, Genome-wide association studies, INCIDÊNCIA, HLA Antigens, Genetics research, Aged, Case-Control Studies, Female, Genetic Markers, Genetic Variation, Haplotypes, Humans, Middle Aged, Mouth, Mouth Neoplasms, Papillomaviridae, Papillomavirus Infections, Pharyngeal Neoplasms, Genetic Predisposition to Disease, Genome-Wide Association Study, Genetics, Oral cancer, genetic research, 3. Good health, Settore MED/31 - OTORINOLARINGOIATRIA, medicine.medical_specialty, Papillomaviruses, Genome-wide - oral cavity and pharyngeal cancer, Human leukocyte antigen, Biology, Article, 03 medical and health sciences, Internal medicine, medicine, Allele, Papil·lomavirus, Haplotype, Case-control study, Odds ratio, oral cancer, medicine.disease, Càncer de boca, 030104 developmental biology, Nasopharyngeal carcinoma, Immunology, Imputation (genetics)
Abstract

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers. Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through the grant X01HG007492-0. Corina Lesseur undertook this work during the tenure of a Postdoctoral Fellowship awarded by the International Agency for Research on Cancer. The funders did not participate in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all of the participants involved in this research and the funders and support. We thank Dr. Leticia Fernandez (Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba) for her contribution to the IARC ORC multicenter study. We are also grateful to Sergio Koifman (Escola Nacional de Saúde Pública, Rio de Janeiro, Brazil) for his contribution to the IARC Latin America multicenter study (Sergio Koifman passed away in May 2014) and to Xavier Castellsagué from the ARCAGE Barcelona Center who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19 CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission’s 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222).The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to SB, and Fondazione Veronesi to SB. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by European Commission’s INCO-COPERNICUS Program (IC15-CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28.The IARC Oral Cancer Multicenter study was funded by: grant S06 96 202489 05F02 from Europe against Cancer; Grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; UICC Yamagiwa-Yoshida Memorial International Cancer Study; National Cancer Institute of Canada; Italian Association for Research on Cancer; and the Pan American Health Organization. The coordination of EPIC study is financially supported

Published
2016
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48. Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case–control study

Author

José Eluf-Neto, Elena Matos, Paul Brennan, Sergio Koifman, V. Wünsch-Filho, Rayjean Hung, Maria Paula Curado, Paolo Boffetta, Katarzyna Szymańska, Leticia Fernandez, Ana M. B. Menezes, Alexander W. Daudt, Szymanska, K., Hung, R.J., Wünsch-Filho, V., Eluf-Neto, J., Curado, M.P., Koifman, S., Matos, E., Menezes, A., Fernandez, L., Daudt, A.W., Boffetta, P., and Brennan, P.

Subjects
Adult, Male, Larynx, Cancer Research, medicine.medical_specialty, Latin Americans, Alcohol Drinking, Alcohol, chemistry.chemical_compound, Risk Factors, Tobacco, Epidemiology, medicine, cancer, Humans, risk, Aged, Aged, 80 and over, Ethanol, business.industry, Public health, Carcinoma, Smoking, Pharynx, Case-control study, Cancer, upper, Middle Aged, aerodigestive, medicine.disease, tract, Surgery, Latin America, medicine.anatomical_structure, Oncology, chemistry, Head and Neck Neoplasms, Case-Control Studies, Female, business, Demography
Abstract

Background: Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited. Methods: We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba. Results: We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37-30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72-16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use. Conclusions: In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents. © 2011 Springer Science+Business Media B.V.

Published
2011
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49. Drinking of maté and the risk of cancers of the upper aerodigestive tract in Latin America: a case–control study

Author

Rayjean J. Hung, Victor Wünsch-Filho, José Eluf-Neto, Alexander W. Daudt, Elena Matos, Ana M. B. Menezes, Katarzyna Szymańska, Paolo Boffetta, Paul Brennan, Szymanska, K., Matos, E., Hung, R.J., Wünsch-Filho, V., Eluf-Neto, J., Menezes, A., Daudt, A.W., Brennan, P., and Boffetta, P.

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Esophageal Neoplasms, Argentina, Drinking, Gastroenterology, Beverages, Ilex paraguariensis, Internal medicine, upper aerodigestive tract, Epidemiology, medicine, Carcinoma, Humans, Multicenter Studies as Topic, Esophagus, Aged, Aged, 80 and over, business.industry, Head and neck cancer, Pharynx, Case-control study, Cancer, Middle Aged, Esophageal cancer, medicine.disease, Latin America, medicine.anatomical_structure, Oncology, Drinking of maté, Head and Neck Neoplasms, Case-Control Studies, Carcinoma, Squamous Cell, Female, business, Brazil, Demography
Abstract

Cancers of the upper aerodigestive tract (UADT: oral cavity, oropharynx, hypopharynx, larynx, esophagus) have high incidence rates all over the world and they are especially frequent in some parts of Latin America. In this study, we have evaluated the role of the consumption of maté, a hot herb-based beverage, based on 1168 UADT squamous-cell carcinoma cases and 1,026 frequency-matched controls enrolled from four centers in Brazil and Argentina. The effect of maté drinking on the risk of head-and-neck cancers was borderline significant. A significant effect was observed only for cancer of the esophagus (OR 3.81 (95% CI 1.75-8.30)). While duration of maté drinking was associated with the risk of all UADT cancers, the association with cumulative maté consumption was restricted to esophageal cancer (p-value of linear trend 0.006). The analyses of temperature at which maté was drunk were not conclusive. The increased risk associated with maté drinking was more evident in never-smokers and never-alcohol drinkers than in other individuals. Our study strengthens the evidence of an association between maté drinking and esophageal cancer; the hypothesis of an association with other UADT cancers remains to be clarified. © 2010 Springer Science+Business Media B.V.

Published
2010
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50. Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Author

Elena Matos, Renato Talamini, Karl T. Kelsey, Qingyi Wei, Shu Chun Chuang, Leticia Fernandez, Erich M. Sturgis, Joshua E. Muscat, Xavier Castellsagué, Alexander W. Daudt, Chu Chen, Paul Brennan, Andrew F. Olshan, Carlo La Vecchia, Fabio Levi, Rolando Herrero, Stephen M. Schwartz, Sergio Koifman, Eleonora Fabianova, Dana Mates, Stefania Boccia, Philip Lazarus, Neonilia Szeszenia-Dabrowska, Maria Paula Curado, Victor Wünsch-Filho, Luigino Dal Maso, Agnieszka Pilarska, Zuo-Feng Zhang, Deborah M. Winn, Gilles Ferro, Richard B. Hayes, Peter Rudnai, Paolo Boffetta, Oxana Shangina, Elaine M. Smith, Silvia Franceschi, Julien Berthiller, Mark P. Purdue, Ana Maria Menezes, Mia Hashibe, Juan Lence, Michael D. McClean, José Eluf-Neto, Hashibe, M., Brennan, P., Chuang, S.-C., Boccia, S., Castellsague, X., Chen, C., Curado, M.P., Maso, L.D., Daudt, A.W., Fabianova, E., Fernandez, L., Wünsch-Filho, V., Franceschi, S., Hayes, R.B., Herrero, R., Kelsey, K., Koifman, S., Vecchia, C.L., Lazarus, P., Levi, F., Lence, J.J., Mates, D., Matos, E., Menezes, A., McClean, M.D., Muscat, J., Eluf-Neto, J., Olshan, A.F., Purdue, M., Rudnai, P., Schwartz, S.M., Smith, E., Sturgis, E.M., Szeszenia-Dabrowska, N., Talamini, R., Wei, Q., Winn, D.M., Shangina, O., Pilarska, A., Zhang, Z.-F., Ferro, G., Berthiller, J., and Boffetta, P.

Subjects
education.field_of_study, medicine.medical_specialty, Adult, Aged, Alcohol Drinking, Alcohol Drinking/adverse effects, Alcohol Drinking/epidemiology, Case-Control Studies, Europe, Female, Head and Neck Neoplasms, Head and Neck Neoplasms/epidemiology, Head and Neck Neoplasms/etiology, Humans, Logistic Models, Male, Middle Aged, North America, North America/epidemiology, Risk Factors, Tobacco Use Disorder, Tobacco Use Disorder/complications, Tobacco Use Disorder/epidemiology, Epidemiology, business.industry, Population, Head and neck cancer, Case-control study, tobacco and alcohol use, Cancer, medicine.disease, Confidence interval, Surgery, Oncology, Internal medicine, medicine, head and neck cancer, Risk factor, Risk assessment, education, business
Abstract

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (ψ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

Published
2009
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