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1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

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