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2. The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium

Author

Hashim, D., Sartori, S., Brennan, P., Curado, M.P., Wünsch-Filho, V., Divaris, K., Olshan, A.F., Zevallos, J.P., Winn, D.M., Franceschi, S., Castellsagué, X., Lissowska, J., Rudnai, P., Matsuo, K., Morgenstern, H., Chen, C., Vaughan, T.L., Hofmann, J.N., D'Souza, G., Haddad, R.I., Wu, H., Lee, Y.-C., Hashibe, M., Vecchia, C.La, and Boffetta, P.

Published
2016
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8. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women

Author

Paavonen, J, Naud, P, Salmerón, J, Wheeler, CM, Chow, S-N, Apter, D, Kitchener, H, Castellsague, X, Teixeira, JC, Skinner, SR, Hedrick, J, Jaisamrarn, U, Limson, G, Garland, S, Szarewski, A, Romanowski, B, Aoki, FY, Schwarz, TF, Poppe, WAJ, Bosch, FX, Jenkins, D, Hardt, K, Zahaf, T, Descamps, D, Struyf, F, Lehtinen, M, and Dubin, G

Published
2009
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10. Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15–25 years with and without serological evidence of previous exposure to HPV-16/18

Author

Szarewski, A., Poppe, W. A.J., Skinner, S. R., Wheeler, C. M., Paavonen, J., Naud, P., Salmeron, J., Chow, S.-N., Apter, D., Kitchener, H., Castellsagué, X., Teixeira, J. C., Hedrick, J., Jaisamrarn, U., Limson, G., Garland, S., Romanowski, B., Aoki, F. Y., Schwarz, T. F., Bosch, F. X., Harper, D. M., Hardt, K., Zahaf, T., Descamps, D., Struyf, F., Lehtinen, M., and Dubin, G.

Published
2012
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17. Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

Author

Castellsagué, X, Pawlita, M, Roura, E, Margall, N, Waterboer, T, Bosch, F, de Sanjosé, S, Gonzalez, C, Dillner, J, Gram, I, Tjønneland, A, Munk, C, Pala, V, Palli, D, Khaw, K, Barnabas, R, Overvad, K, Clavel-Chapelon, F, Boutron-Ruault, M, Fagherazzi, G, Kaaks, R, Lukanova, A, Steffen, A, Trichopoulou, A, and Trichopoulos, D

Abstract

To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2-2.0) and 1.8 (1.1-2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4-2.4) and 7.4 (2.8-19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9-1.9) and 2.3 (1.3-4.1) for CT seropositivity, and 1.4 (1.0-2.0) and 1.5 (0.9-2.6) for HHV-2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR-=-10.2 (3.3-31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non-STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV-2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development. What's New? Limited data are available from prospective studies concerning the role of past exposure to human papillomavirus (HPV) and other infections in cervical carcinogenesis. This study assessed associations between cervical cancer and pre-cancer and serological markers of exposure to mucosal and cutaneous HPVs, Chlamydia trachomatis (CT), Chlamydia pneumonia, human herpes virus-2 (HHV-2), and polyomaviruses using a nested case-control design within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations were found for mucosal HPVs, CT, and HHV-2. A greater number of sexually transmitted diseases further raised the risk of cervical cancer. © 2013 UICC.

Published
2016

18. Smoking as a major risk factor for cervical cancer and pre-cancer: Results from the EPIC cohort

Author

Roura, E, Castellsagué, X, Pawlita, M, Travier, N, Waterboer, T, Margall, N, Bosch, F, de Sanjosé, S, Dillner, J, Gram, I, Tjønneland, A, Munk, C, Pala, V, Palli, D, Khaw, K, Barnabas, R, Overvad, K, Clavel-Chapelon, F, Boutron-Ruault, M, Fagherazzi, G, Kaaks, R, Lukanova, A, Steffen, A, Trichopoulou, A, and Trichopoulos, D

Abstract

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation. What's new? Tobacco smoking is a cited cause of cervical cancer, but whether it causes cervical malignancy independent of human papillomavirus (HPV) infection is unclear. Here, strong associations were found between most measures of tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3/carcinoma in situ and invasive cervical cancer, after taking into account past exposure to HPV infection. Quitting smoking was associated with a 2-fold risk reduction. The findings confirm the role of tobacco smoking in cervical carcinogenesis and show that quitting the habit has important benefits for cancer protection. © 2013 UICC.

Published
2016
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19. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

Author

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. Brennan, P.

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 â'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. © 2016 Nature America, Inc. part of Springer Nature, All Rights reserved.

Published
2016

20. Human papillomavirus 16 E6 antibodies in individuals without diagnosed cancer: A pooled analysis

Author

Lang Kuhs, K.A. Anantharaman, D. Waterboer, T. Johansson, M. Brennan, P. Michel, A. Willhauck-Fleckenstein, M. Purdue, M.P. Holcátová, I. Ahrens, W. Lagiou, P. Polesel, J. Simonato, L. Merletti, F. Healy, C.M. Kjaerheim, K. Conway, D.I. Macfarlane, T.V. Thomson, P. Castellsagué, X. Znaor, A. Black, A. Huang, W.-Y. Krogh, V. Trichopoulou, A. Bueno-De-Mesquita, H.B.A.S. Clavel-Chapelon, F. Weiderpass, E. Ekström, J. Riboli, E. Tjønneland, A. Sánchez, M.-J. Travis, R.C. Hildesheim, A. Pawlita, M. Kreimer, A.R.

Subjects
viruses, virus diseases, female genital diseases and pregnancy complications
Abstract

Background: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted. Methods: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and

Published
2015

21. 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

22. Endogenoussex steroids and risk of cervical carcinoma: results from the EPIC study

Author

Rinaldi S, Plummer M, Biessy C, Castellsagué X, Overvad K, Krüger Kjær S, Tjønneland A, Clavel Chapelon F, Chabbert Buffet N, Mesrine S, Lukanova A, Kaaks R, Weikert C, Boeing H, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Agnoli C, Tumino R, Vineis P, Bueno de Mesquita B, van Kranen HJ, Peeters PH, Bakken K, Lund E, Gram IT, Rodríguez L, Bosch FX, Sánchez MJ, Dorronsoro M, Navarro C, Gurrea AB, Kjellberg L, Dillner J, Manjer J, Butt S, Khaw KT, Wareham N, Allen NE, Travis R, Romieu I, Ferrari P, Riboli E, Franceschi S., PANICO, SALVATORE, Rinaldi, S, Plummer, M, Biessy, C, Castellsagué, X, Overvad, K, Krüger Kjær, S, Tjønneland, A, Clavel Chapelon, F, Chabbert Buffet, N, Mesrine, S, Lukanova, A, Kaaks, R, Weikert, C, Boeing, H, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Palli, D, Agnoli, C, Tumino, R, Vineis, P, Panico, Salvatore, Bueno de Mesquita, B, van Kranen, Hj, Peeters, Ph, Bakken, K, Lund, E, Gram, It, Rodríguez, L, Bosch, Fx, Sánchez, Mj, Dorronsoro, M, Navarro, C, Gurrea, Ab, Kjellberg, L, Dillner, J, Manjer, J, Butt, S, Khaw, Kt, Wareham, N, Allen, Ne, Travis, R, Romieu, I, Ferrari, P, Riboli, E, and Franceschi, S.

Published
2011

23. A genome-wide association study of upperaerodigestive tract cancers conducted within the INHANCE consortium

Author

McKay JD, Truong T, Gaborieau V, Chabrier A, Chuang SC, Byrnes G, Zaridze D, Shangina O, Szeszenia Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Bucur A, Bencko V, Holcatova I, Janout V, Foretova L, Lagiou P, Trichopoulos D, Benhamou S, Bouchardy C, Ahrens W, Merletti F, Richiardi L, Talamini R, Barzan L, Kjaerheim K, Macfarlane GJ, Macfarlane TV, Simonato L, Canova C, Agudo A, Castellsagué X, Lowry R, Conway DI, McKinney PA, Healy CM, Toner ME, Znaor A, Curado MP, Koifman S, Menezes A, Wünsch Filho V, Neto JE, Garrote LF, Boccia S, Cadoni G, Arzani D, Olshan AF, Weissler MC, Funkhouser WK, Luo J, Lubiński J, Trubicka J, Lener M, Oszutowska D, Schwartz SM, Chen C, Fish S, Doody DR, Muscat JE, Lazarus P, Gallagher CJ, Chang SC, Zhang ZF, Wei Q, Sturgis EM, Wang LE, Franceschi S, Herrero R, Kelsey KT, McClean MD, Marsit CJ, Nelson HH, Romkes M, Buch S, Nukui T, Zhong S, Lacko M, Manni JJ, Peters WH, Hung RJ, McLaughlin J, Vatten L, Njølstad I, Goodman GE, Field JK, Liloglou T, Vineis P, Clavel Chapelon F, Palli D, Tumino R, Krogh V, González CA, Quirós JR, Martínez C, Navarro C, Ardanaz E, Larrañaga N, Khaw KT, Key T, Bueno de Mesquita HB, Peeters PH, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjønneland A, Kumle M, Riboli E, Välk K, Vooder T, Metspalu A, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Blanché H, Gut IG, Galan P, Heath S, Hashibe M, Hayes RB, Boffetta P, Lathrop M, Brennan P., PANICO, SALVATORE, Mckay, Jd, Truong, T, Gaborieau, V, Chabrier, A, Chuang, Sc, Byrnes, G, Zaridze, D, Shangina, O, Szeszenia Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Bucur, A, Bencko, V, Holcatova, I, Janout, V, Foretova, L, Lagiou, P, Trichopoulos, D, Benhamou, S, Bouchardy, C, Ahrens, W, Merletti, F, Richiardi, L, Talamini, R, Barzan, L, Kjaerheim, K, Macfarlane, Gj, Macfarlane, Tv, Simonato, L, Canova, C, Agudo, A, Castellsagué, X, Lowry, R, Conway, Di, Mckinney, Pa, Healy, Cm, Toner, Me, Znaor, A, Curado, Mp, Koifman, S, Menezes, A, Wünsch Filho, V, Neto, Je, Garrote, Lf, Boccia, S, Cadoni, G, Arzani, D, Olshan, Af, Weissler, Mc, Funkhouser, Wk, Luo, J, Lubiński, J, Trubicka, J, Lener, M, Oszutowska, D, Schwartz, Sm, Chen, C, Fish, S, Doody, Dr, Muscat, Je, Lazarus, P, Gallagher, Cj, Chang, Sc, Zhang, Zf, Wei, Q, Sturgis, Em, Wang, Le, Franceschi, S, Herrero, R, Kelsey, Kt, Mcclean, Md, Marsit, Cj, Nelson, Hh, Romkes, M, Buch, S, Nukui, T, Zhong, S, Lacko, M, Manni, Jj, Peters, Wh, Hung, Rj, Mclaughlin, J, Vatten, L, Njølstad, I, Goodman, Ge, Field, Jk, Liloglou, T, Vineis, P, Clavel Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, Salvatore, González, Ca, Quirós, Jr, Martínez, C, Navarro, C, Ardanaz, E, Larrañaga, N, Khaw, Kt, Key, T, Bueno de Mesquita, Hb, Peeters, Ph, Trichopoulou, A, Linseisen, J, Boeing, H, Hallmans, G, Overvad, K, Tjønneland, A, Kumle, M, Riboli, E, Välk, K, Vooder, T, Metspalu, A, Zelenika, D, Boland, A, Delepine, M, Foglio, M, Lechner, D, Blanché, H, Gut, Ig, Galan, P, Heath, S, Hashibe, M, Hayes, Rb, Boffetta, P, Lathrop, M, and Brennan, P.

Published
2011

24. Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort

Author

Roura, E, Castellsagué, X, Pawlita, M, Travier, N, Waterboer, T, Margall, N, Bosch, FX, De Sanjosé, S, Dillner, J, Gram, IT, Tjønneland, A, Munk, C, Pala, V, Palli, D, Khaw, K-T, Barnabas, RV, Overvad, K, Clavel-Chapelon, F, Boutron-Ruault, M-C, Fagherazzi, G, Kaaks, R, Lukanova, A, Steffen, A, Trichopoulou, A, Trichopoulos, D, Klinaki, E, Tumino, R, Sacerdote, C, Panico, S, Bueno-De-Mesquita, HB, Peeters, PH, Lund, E, Weiderpass, E, Redondo, ML, Sánchez, M-J, Tormo, M-J, Barricarte, A, Larrañaga, N, Ekström, J, Hortlund, M, Lindquist, D, Wareham, N, Travis, RC, Rinaldi, S, Tommasino, M, Franceschi, S, Riboli, E, Roura, E, Castellsagu?, X, Pawlita, M, Travier, N, Waterboer, T, Margall, N, Bosch, Fx, de Sanjos?, S, Dillner, J, Gram, It, Tj?nneland, A, Munk, C, Pala, V, Palli, D, Khaw, Kt, Barnabas, Rv, Overvad, K, Clavel Chapelon, F, Boutron Ruault, Mc, Fagherazzi, G, Kaaks, R, Lukanova, A, Steffen, A, Trichopoulou, A, Trichopoulos, D, Klinaki, E, Tumino, R, Sacerdote, C, Panico, Salvatore, Bueno de Mesquita, Hb, Peeters, Ph, Lund, E, Weiderpass, E, Redondo, Ml, S?nchez, Mj, Tormo, Mj, Barricarte, A, Larra?aga, N, Ekstr?m, J, Hortlund, M, Lindquist, D, Wareham, N, Travis, Rc, Rinaldi, S, Tommasino, M, Franceschi, S, and Riboli, E.

Subjects
Adult, Cohort Studies, Risk Factors, Case-Control Studies, Surveys and Questionnaires, Smoking, Humans, Uterine Cervical Neoplasms, Female, Middle Aged, Uterine Cervical Dysplasia, female genital diseases and pregnancy complications, Aged
Abstract

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation. What's new? Tobacco smoking is a cited cause of cervical cancer, but whether it causes cervical malignancy independent of human papillomavirus (HPV) infection is unclear. Here, strong associations were found between most measures of tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3/carcinoma in situ and invasive cervical cancer, after taking into account past exposure to HPV infection. Quitting smoking was associated with a 2-fold risk reduction. The findings confirm the role of tobacco smoking in cervical carcinogenesis and show that quitting the habit has important benefits for cancer protection. © 2013 UICC.

Published
2014
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25. 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

26. Natural History of Progression of HPV Infection to Cervical Lesion or Clearance: Analysis of the Control Arm of the Large, Randomised PATRICIA Study

Author

Jaisamrarn U, Castellsagué X, Sm, Garland, Naud P, Palmroth J, Del Rosario-Raymundo MR, Cm, Wheeler, Salmerón J, Chow S, Apter D, Jc, Teixeira, Sr, Skinner, Hedrick J, Szarewski A, Romanowski B, Fy, Aoki, Tf, Schwarz, Waj, Poppe, FRANCESC XAVIER BOSCH JOSÉ, Ns, Carvalho, Mj, Germar, Peters K, Paavonen J, Bozonnat M, Descamps D, Struyf F, Go, Dubin, Rosillon D, and Baril L

Subjects
Multidisciplinary, lcsh:R, Correction, lcsh:Medicine, lcsh:Q, lcsh:Science
Published
2013
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27. All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs

Author

Aj, Schork, Wk, Thompson, Pham P, Torkamani A, Jc, Roddey, Pf, Sullivan, Jr, Kelsoe, Donovan Mc, O., Furberg H, Tobacco and Genetics Consortium, Bipolar Disorder Psychiatric Genomics Consortium, Schizophrenia Psychiatric Genomics Consortium, Nj, Schork, Oa, Andreassen, Am, Dale, Absher D, Agudo A, Almgren P, Ardissino D, Tl, Assimes, Bandinelli S, Barzan L, Bencko V, Benhamou S, Ej, Benjamin, Bernardinelli L, Bis J, Boehnke M, Boerwinkle E, Di, Boomsma, Brennan P, Canova C, Castellsagué X, Chanock S, Chasman D, Di, Conway, Dackor J, Ej, Geus, Duan J, Elosua R, Everett B, Fabianova E, Ferrucci L, Foretova L, Sp, Fortmann, Franceschini N, Frayling T, Furberg C, Pv, Gejman, Groop L, Gu F, Guralnik J, Se, Hankinson, Haritunians T, Healy C, Hofman A, Holcátová I, Dj, Hunter, Sj, Hwang, Jp, Ioannidis, Iribarren C, Au, Jackson, Janout V, Kaprio J, Kim Y, Kjaerheim K, Jw, Knowles, Kraft P, Ladenvall C, Lagiou P, Lanthrop M, Lerman C, Df, Levinson, Levy D, Md, Li, Dy, Lin, Eh, Lips, Lissowska J, Lowry R, Lucas G, Tv, Macfarlane, Maes H, Pm, Mannucci, Mates D, Mauri F, Ja, Mcgovern, Jd, Mckay, McKnight B, Melander O, Pa, Merlini, Milaneschi Y, Kl, Mohlke, Donnell Cj, O., Pare G, Bw, Penninx, Perry J, Posthuma D, Sr, Preis, Psaty B, Quertermous T, Vs, Ramachandran, Richiardi L, Ridker P, Rose J, Rudnai P, Salomaa V, Ar, Sanders, Sm, Schwartz, Shi J, Jh, Smit, Hm, Stringham, Szeszenia-Dabrowska N, Tanaka T, Taylor K, Thacker E, Thornton L, Tiemeier H, Tuomilehto J, Ag, Uitterlinden, Cm, Duijn, Jm, Vink, Vogelzangs N, Bf, Voight, Walter S, Willemsen G, Zaridze D, Znaor A, Akil H, Anjorin A, Backlund L, Ja, Badner, Jd, Barchas, Tb, Barrett, Bass N, Bauer M, Bellivier F, Se, Bergen, Berrettini W, Blackwood D, Cs, Bloss, Breen G, Breuer R, We, Bunner, Burmeister M, Byerley W, Caesar S, Chambert K, Cichon S, St Clair D, Da, Collier, Corvin A, Wh, Coryell, Craddock N, Dw, Craig, Daly M, Day R, Degenhardt F, Djurovic S, Dudbridge F, Hj, Edenberg, Elkin A, Etain B, Ae, Farmer, Ma, Ferreira, Ferrier I, Flickinger M, Foroud T, Frank J, Fraser C, Frisén L, Es, Gershon, Gill M, Gordon-Smith K, Ek, Green, Ta, Greenwood, Grozeva D, Guan W, Gurling H, Ó, Gustafsson, Ml, Hamshere, Hautzinger M, Herms S, Hipolito M, Pa, Holmans, Cm, Hultman, Jamain S, Eg, Jones, Jones I, Jones L, Kandaswamy R, Jl, Kennedy, Gk, Kirov, Dl, Koller, Kwan P, Landén M, Langstrom N, Lathrop M, Lawrence J, Wb, Lawson, Leboyer M, Ph, Lee, Li J, Lichtenstein P, Lin D, Liu C, Fw, Lohoff, Lucae S, Pb, Mahon, Maier W, Ng, Martin, Mattheisen M, Matthews K, Mattingsdal M, Ka, Mcghee, McGuffin P, Mg, Mcinnis, McIntosh A, McKinney R, Aw, Mclean, Fj, Mcmahon, McQuillin A, Meier S, Melle I, Meng F, Pb, Mitchell, Gw, Montgomery, Moran J, Morken G, Dw, Morris, Moskvina V, Muglia P, Tw, Mühleisen, Wj, Muir, Müller-Myhsok B, Rm, Myers, Cm, Nievergelt, Nikolov I, Nimgaonkar V, Mm, Nöthen, Ji, Nurnberger, Ea, Nwulia, O'Dushlaine C, Osby U, Óskarsson H, Mj, Owen, Petursson H, Bs, Pickard, Porgeirsson P, Jb, Potash, Propping P, Sm, Purcell, Quinn E, Raychaudhuri S, Rice J, Rietschel M, Ruderfer D, Schalling M, Af, Schatzberg, Wa, Scheftner, Pr, Schofield, Tg, Schulze, Schumacher J, Mm, Schwarz, Scolnick E, Lj, Scott, Pd, Shilling, Sigurdsson E, Sklar P, En, Smith, Stefansson H, Stefansson K, Steffens M, Steinberg S, Strauss J, Strohmaier J, Szelinger S, Rc, Thompson, Tozzi F, Treutlein J, Jb, Vincent, Sj, Watson, Tf, Wienker, Williamson R, Sh, Witt, Wright A, Xu W, Ah, Young, Pp, Zandi, Zhang P, Zöllner S, Agartz I, Albus M, Alexander M, Rl, Amdur, Amin F, Bitter I, Dw, Black, Ad, Børglum, Ma, Brown, Bruggeman R, Ng, Buccola, Wf, Byerley, Cahn W, Rm, Cantor, Vj, Carr, Sv, Catts, Choudhury K, Cloninger C, Cormican P, Pa, Danoy, Datta S, DeHert M, Demontis D, Dikeos D, Donnelly P, Donohoe G, Duong L, Dwyer S, Fanous A, Fink-Jensen A, Freedman R, Nb, Freimer, Friedl M, Georgieva L, Giegling I, Glenthøj B, Godard S, Golimbet V, de Haan L, Hansen M, Hansen T, Am, Hartmann, Fa, Henskens, Dm, Hougaard, Ingason A, Av, Jablensky, Kd, Jakobsen, Jay M, Eg, Jönsson, Jürgens G, Rs, Kahn, Mc, Keller, Ks, Kendler, Kenis G, Kenny E, Konnerth H, Konte B, Krabbendam L, Krasucki R, Vk, Lasseter, Laurent C, Lencz T, Lerer F, Ky, Liang, Ja, Lieberman, Dh, Linszen, Lönnqvist J, Cm, Loughland, Aw, Maclean, Bs, Maher, Ak, Malhotra, Mallet J, Malloy P, Jj, Mcgrath, McLean DE, Pt, Michie, Milanova V, Mors O, Pb, Mortensen, Bj, Mowry, Myin-Germeys I, Neale B, Da, Nertney, Nestadt G, Nielsen J, Nordentoft M, Norton N, O'Neill F, Olincy A, Olsen L, Ra, Ophoff, Tf, Ørntoft, van Os J, Pantelis C, Papadimitriou G, Cn, Pato, Mt, Pato, Peltonen L, Pickard B, Op, Pietiläinen, Pimm J, Ae, Pulver, Puri V, Digby Quested, Hb, Rasmussen, Jm, Réthelyi, Ribble R, Bp, Riley, Rossin L, Ruggeri M, Rujescu D, Schall U, Sg, Schwab, Rj, Scott, Jm, Silverman, Cc, Spencer, Strange A, Strengman E, Stroup T, Suvisaari J, Terenius L, Thirumalai S, Timm S, Toncheva D, Tosato S, Ej, Den Oord, Veldink J, Pm, Visscher, Walsh D, Ag, Wang, Werge T, Wiersma D, Db, Wildenauer, Hj, Williams, Nm, Williams, van Winkel R, Wormley B., Biological Psychology, Functional Genomics, Educational Neuroscience, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, Biophotonics and Medical Imaging, LEARN! - Brain, learning and development, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, LaserLaB - Biophotonics and Microscopy, ANS - Amsterdam Neuroscience, Adult Psychiatry, Psychiatry, Human genetics, Epidemiology and Data Science, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Gibson, Greg, Germeys, Inez, van Winkel, Ruud, and De Hert, Marc

Subjects
False discovery rate, Netherlands Twin Register (NTR), Cancer Research, Linkage disequilibrium, Genome-wide association study, Linkage Disequilibrium, 0302 clinical medicine, 2.1 Biological and endogenous factors, Aetiology, Genetics (clinical), Genetics, 0303 health sciences, Statistics, Genomics, Single Nucleotide, Genome Scans, Tobacco and Genetics Consortium, Functional Genomics, Phenotype, complex trait, Research Article, Bipolar Disorder Psychiatric Genomics Consortium, lcsh:QH426-470, SNP, Single-nucleotide polymorphism, Computational biology, Biostatistics, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, "genome-wide association study", Genome Analysis Tools, Clinical Research, Schizophrenia Psychiatric Genomics Consortium, Genome-Wide Association Studies, Humans, Genetic Predisposition to Disease, Statistical Methods, Polymorphism, Molecular Biology, Genetic Association Studies, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, Linkage (software), Human Genome, Computational Biology, Human Genetics, Heritability, R1, schizophrenia, lcsh:Genetics, Schizophrenia, Mathematics, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology
Abstract

Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1−FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci., Author Summary Modern genome-wide association studies (GWAS) have failed to identify large portions of the genetic basis of common, complex traits. Recent work suggested this could be because many genetic variants, each with individually small effects, compose their genetic architecture, limiting the power of GWAS. Moreover, these variants appear more abundantly in and near genes. Using genome annotations, summary statistics from several of the largest GWAS, and established statistical methods for quantifying distributions of test statistics, we show a consistency across studies. Namely, we show that, across all assessed traits, the test statistics resulting from SNPs that are related to the 5′ UTR of genes show the largest abundance of associations, while SNPs related to exons and the 3′UTR are also enriched. SNPs related to introns are only moderately enriched, and intergenic SNPs show a depletion of associations relative to the average SNP. This enrichment corresponds directly to increased replication across independent samples and can be incorporated a priori into statistical methods to improve discovery and prediction. Our results contribute to on-going debates about the functional nature of the genetic architecture of complex traits and point to avenues for leveraging existing GWAS data for discovery in future GWA and sequencing studies.

Published
2013
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28. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Author

Horwitz, M.S., McKay, J.D., Truong, T., Gaborieau, V., Chabrier, A., Chuang, S.-C., Byrnes, G., Zaridze, D., Shangina, O., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Bucur, A., Bencko, V., Holcatova, I., Janout, V., Foretova, L., Lagiou, P., Trichopoulos, D., Benhamou, S., Bouchardy, C., Ahrens, W., Merletti, F., Richiardi, L., Talamini, R., Barzan, L., Kjaerheim, K., Macfarlane, G.J., Macfarlane, T.V., Simonato, L., Canova, C., Agudo, A., Castellsagué, X., Lowry, R., Conway, D.I., McKinney, P.A., Healy, C.M., Toner, M.E., Znaor, A., Curado, M.P., Koifman, S., Menezes, A., Wünsch-Filho, V., Neto, J.E., Garrote, L.F., Boccia, S., Cadoni, G., Arzani, D., Olshan, A.F., Weissler, M.C., Funkhouser, W.K., Luo, J., Lubiński, J., Trubicka, J., Lener, M., Oszutowska, D., Schwartz, S.M., Chen, C., Fish, S., Doody, D.R., Muscat, J.E., Lazarus, P., Gallagher, C.J., Chang, S.C., Zhang, Z.F., Wei, Q., Sturgis, E.M., Wang, L.E., Franceschi, S., Herrero, R., Kelsey, K.T., McClean, M.D., Marsit, C.J., Nelson, H.H., Romkes, M., Buch, S., Nukui, T., Zhong, S., Lacko, M., Manni, J.J., Peters, W.H.M., Hung, R.J., McLaughlin, J., Vatten, L., Njølstad, I., Goodman, G.E., Field, J.K., Liloglou, T., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., González, C.A., Quirós, J.R., Martínez, C., Navarro, C., Ardanaz, E., Larrañaga, N., Khaw, K.T., Key, T., Bueno-de-Mesquita, H. B., Peeters, P.H.M., Trichopoulou, A., Linseisen, J., Boeing, H., Hallmans, G., Overvad, K., Tjønneland, A., Kumle, M., Riboli, E., Välk, K., Vooder, T., Metspalu, A., Zelenika, D., Boland, A., Delepine, M., Foglio, M., Lechner, D., Blanché, H., Gut, I.G., Galan, P., Heath, S., Hashibe, M., Hayes, R.B., Boffetta, P., Lathrop, M., and Brennan, P.

Abstract

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Published
2011

29. 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

30. P29 The role of HPV in cervical lymph node metastases from squamous cell carcinoma

Author

Schroeder, L., primary, Holzinger, D., additional, Baboci, L., additional, Pawlita, M., additional, Herold-Mende, C., additional, Heß, J., additional, Boscolo-Rizzo, P., additional, Romeo, S., additional, Alemany, L., additional, Castellsagué, X., additional, Quer, M., additional, León, X., additional, Porcel, C.L., additional, Zgorzelski, C., additional, and Dyckhoff, G., additional

Published
2015
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31. SP-0489: HPV-transformation in the cervix and at non-cervical sites

Author

Halec, G., primary, Alemany, L., additional, Castellsagué, X., additional, Lloveras, B., additional, Holzinger, D., additional, Schmitt, M., additional, Tous, S., additional, Alejo, M., additional, Waterboer, T., additional, Bosch, F.X., additional, De Sanjose, S., additional, and Pawlita, M., additional

Published
2015
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33. A common biological basis of obesity and nicotine addiction

Author

Thorgeirsson, T.E. (Thorgeir), Gudbjartsson, D.F. (Daniel), Sulem, P. (Patrick), Besenbacher, S. (Søren), Styrkarsdottir, U. (Unnur), Thorleifsson, G. (Gudmar), Walters, G.B. (Bragi), Furberg, H. (Helena), Sullivan, P. (Patrick), Marchini, J. (Jonathan), McCarthy, M.I. (M.), Steinthorsdottir, V. (Valgerdur), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Surakka, I. (Ida), Vink, J.M. (Jacqueline), Amin, N. (Najaf), Geller, F. (Frank), Rafnar, T. (Thorunn), Esko, T. (Tõnu), Walter, S. (Stefan), Gieger, C. (Christian), Rawal, R. (Rajesh), Mangino, M. (Massimo), Prokopenko, I. (Inga), Mägi, R. (Reedik), Keskitalo, K. (Kaisu), Gudjonsdottir, I.H. (Iris), Gretarsdottir, S. (Solveig), Stefansson, H. (Hreinn), Aulchenko, Y.S. (Yurii), Nelis, M. (Mari), Aben, K.K.H. (Katja), Heijer, M. (Martin) den, Soranzo, N. (Nicole), Valdes, A.M. (Ana Maria), Steves, C.J. (Claire), Uitterlinden, A.G. (André), Hofman, A. (Albert), Tönjes, A. (Anke), Kovacs, P. (Peter), Hottenga, J.J. (Jouke Jan), Willemsen, G.A.H.M. (Gonneke), Vogelzangs, N. (Nicole), Döring, A. (Angela), Dahmen, N. (N.), Nitz, B. (Barbara), Ripatti, S. (Samuli), Perola, M. (Markus), Kettunen, J. (Johannes), Hartikainen, A.L., Pouta, A. (Anneli), Laitinen, J. (Jaana), Isohanni, M.K. (Matti), Huei-Yi, S. (Shen), Allen, M. (Maxine), Krestyaninova, M. (Maria), Hall, A. (Anne), Thompson, J.R. (John), Oskarsson, H. (Hogni), Tyrfingsson, T. (Thorarinn), Kiemeney, L.A.L.M. (Bart), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Stumvoll, M. (Michael), Spector, T.D. (Timothy), Wichmann, H.E. (Heinz Erich), Metspalu, A. (Andres), Samani, N.J. (Nilesh), Penninx, B.W.J.H. (Brenda), Oostra, B.A. (Ben), Boomsma, D.I. (Dorret), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, Kaprio, J. (Jaakko), Gulcher, J.R. (Jeffrey), Kim, Y. (Yunjung), Dackor, J. (Jennifer), Boerwinkle, E.A. (Eric), Franceschini, N. (Nora), Ardissino, D. (Diego), Bernardinelli, L. (Luisa), Mannucci, P.M. (Pier), Mauri, F. (Francesco), Merlini, P.A. (Piera), Absher, D. (Devin), Assimes, T.L. (Themistocles), Fortmann, S.P. (Stephen), Iribarren, C. (Carlos), Knowles, J.W. (Joshua), Quertermous, T. (Thomas), Ferrucci, L. (Luigi), Tanaka, T. (Toshiko), Bis, J.C. (Joshua), Haritunians, T. (Talin), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Taylor, K.D. (Kent), Thacker, E.L. (Evan), Almgren, P. (Peter), Groop, L. (Leif), Ladenvall, C. (Claes), Boehnke, M. (Michael), Jackson, A.U. (Anne), Mohlke, K.L. (Karen), Stringham, H.M. (Heather), Tuomilehto, J. (Jaakko), Benjamin, E.J. (Emelia), Hwang, S.J., Levy, D. (Daniel), Preis, S.R., Vasan, R.S. (Ramachandran Srini), Duan, J. (Jubao), Gejman, P.V. (Pablo), Levinson, D.F. (Douglas), Sanders, A.R. (Alan), Shi, J. (Jianxin), Lips, E.H. (Esther), McKay, J.D. (James), Agudo, A. (Antonio), Barzan, L. (Luigi), Bencko, V. (Vladimir), Benhamou, S. (Simone), Castellsagué, X. (Xavier), Canova, C. (Cristina), Conway, D.I. (David), Fabianova, E. (Eleonora), Foretova, L. (Lenka), Janout, V. (Vladimir), Healy, C.M. (Claire), Holcátová, I. (Ivana), Kjaerheim, K. (Kristina), Lagiou, P., Lissowska, J. (Jolanta), Lowry, R. (Ray), MacFarlane, T.V. (Tatiana), Mates, D. (Dana), Richiardi, L. (Lorenzo), Rudnai, P. (Peter), Szeszenia-Dabrowska, N. (Neonilia), Zaridze, D., Znaor, A. (Ariana), Lathrop, M. (Mark), Brennan, P. (Paul), Bandinelli, S. (Stefania), Frayling, T.M. (Timothy), Guralnik, J.M. (Jack), Milaneschi, Y. (Yuri), Perry, J.R.B. (John), Altshuler, D. (David), Elosua, R. (Roberto), Kathiresan, S. (Sekar), Lucas, G. (Gavin), Melander, O. (Olle), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Voight, B.F. (Benjamin), Smith, A.V. (Davey), Geus, E.J.C. (Eco) de, Chanock, S.J. (Stephen), Gu, F. (Fangyi), Hankinson, S.E. (Susan), Hunter, D. (David), Chasman, D.I. (Daniel), Everett, B.M. (Brendan), Paré, G. (Guillaume), Ridker, P.M. (Paul), Li, M.D. (Ming), Maes, H.H. (Hermine), Audrain-Mcgovern, J. (Janet), Posthuma, D. (Danielle), Thornton, L.M. (Laura), Lerman, C. (Caryn), Rose, J.E. (Jed), Ioannidis, J.P.A. (John), Kraft, P. (Peter), Lin, D.Y. (Dan), Liu, J. (Jason), Muglia, P. (Pierandrea), Waterworth, D. (Dawn), Pillai, A.D. (Ajay), Middleton, L. (Lefkos), Berrettini, W. (Wade), Knouff, C.W. (Christopher), Yuan, X. (Xin), Waeber, G. (Gérard), Vollenweider, P. (Peter), Preisig, M. (Martin), Wareham, N.J. (Nick), Zhao, J.H. (Jing Hua), Loos, R.J.F. (Ruth), Barroso, I.E. (Inês), Khaw, K-T. (Kay-Tee), Grundy, S.M. (Scott), Barter, P. (Phil), Mahley, R. (Robert), Kesaniemi, Y.A. (Antero), McPherson, R. (Ruth), Vincent, J. (John), Strauss, J.S. (John S), Kennedy, J. (James), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Day, R.N. (Richard), Matthews, K. (Keith), Bakke, A.B. (Arnold B.), Gulsvik, A. (Amund), Lucae, S. (Susanne), Ising, M. (Marcus), Brueckl, T. (Tanja), Horstmann, S. (Sonja), Heinrich, J. (Joachim), Lamina, C. (Claudia), Polasek, O. (Ozren), Zgaga, L. (Lina), Huffman, J.E. (Jennifer), Campbell, S. (Susan), Kooner, J.S. (Jaspal), Chambers, J.C. (John), Burnett, M.S., Devaney, J. (Joseph), Pichard, A.D., Kent, K.M. (Kenneth), Satler, L.F., Lindsay, J.M. (Joseph), Waksman, R. (Ron), Epstein, S.E. (Stephen), Wilson, J.F. (James), Wild, S.H. (Sarah), Campbell, H. (Harry), Vitart, V. (Veronique), Reilly, M.P. (Muredach), Li, M. (Mingyao), Qu, L. (Liming), Wilensky, A. (Asaf), Matthai, W. (William), Hakonarson, H. (Hakon), Rader, D.J. (Daniel), Franke, A. (Andre), Wittig, M. (Michael), Schäfer, A. (Arne), Uda, M. (Manuela), Terracciano, A., Xiao, X. (Xiangjun), Busonero, F., Scheet, P. (Paul), Schlessinger, D., Clair, D.S., Rujescu, D. (Dan), Abecasis, G.R. (Gonçalo), Grabe, H.J. (Hans Jörgen), Teumer, A. (Alexander), Völzke, H. (Henry), Petersmann, A. (Astrid), John, U. (Ulrich), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Kolcic, I. (Ivana), Wright, B.J. (Benjamin), Balmforth, A.J. (Anthony), Anderson, C. (Carl), Ahmed, T. (Tariq), Mathew, J. (Joseph), Parkes, M. (Miles), Satsangi, J. (Jack), Caulfield, M. (Mark), Munroe, P. (Patricia), Farrall, M. (Martin), Dominiczak, A. (Anna), Worthington, H. (Helen), Thomson, W. (Wendy), Eyre, D.S. (Dylan Samuel), Barton, A. (Anne), Mooser, V. (Vincent), Francks, C. (Clyde), Thorgeirsson, T.E. (Thorgeir), Gudbjartsson, D.F. (Daniel), Sulem, P. (Patrick), Besenbacher, S. (Søren), Styrkarsdottir, U. (Unnur), Thorleifsson, G. (Gudmar), Walters, G.B. (Bragi), Furberg, H. (Helena), Sullivan, P. (Patrick), Marchini, J. (Jonathan), McCarthy, M.I. (M.), Steinthorsdottir, V. (Valgerdur), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Surakka, I. (Ida), Vink, J.M. (Jacqueline), Amin, N. (Najaf), Geller, F. (Frank), Rafnar, T. (Thorunn), Esko, T. (Tõnu), Walter, S. (Stefan), Gieger, C. (Christian), Rawal, R. (Rajesh), Mangino, M. (Massimo), Prokopenko, I. (Inga), Mägi, R. (Reedik), Keskitalo, K. (Kaisu), Gudjonsdottir, I.H. (Iris), Gretarsdottir, S. (Solveig), Stefansson, H. (Hreinn), Aulchenko, Y.S. (Yurii), Nelis, M. (Mari), Aben, K.K.H. (Katja), Heijer, M. (Martin) den, Soranzo, N. (Nicole), Valdes, A.M. (Ana Maria), Steves, C.J. (Claire), Uitterlinden, A.G. (André), Hofman, A. (Albert), Tönjes, A. (Anke), Kovacs, P. (Peter), Hottenga, J.J. (Jouke Jan), Willemsen, G.A.H.M. (Gonneke), Vogelzangs, N. (Nicole), Döring, A. (Angela), Dahmen, N. (N.), Nitz, B. (Barbara), Ripatti, S. (Samuli), Perola, M. (Markus), Kettunen, J. (Johannes), Hartikainen, A.L., Pouta, A. (Anneli), Laitinen, J. (Jaana), Isohanni, M.K. (Matti), Huei-Yi, S. (Shen), Allen, M. (Maxine), Krestyaninova, M. (Maria), Hall, A. (Anne), Thompson, J.R. (John), Oskarsson, H. (Hogni), Tyrfingsson, T. (Thorarinn), Kiemeney, L.A.L.M. (Bart), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Stumvoll, M. (Michael), Spector, T.D. (Timothy), Wichmann, H.E. (Heinz Erich), Metspalu, A. (Andres), Samani, N.J. (Nilesh), Penninx, B.W.J.H. (Brenda), Oostra, B.A. (Ben), Boomsma, D.I. (Dorret), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, Kaprio, J. (Jaakko), Gulcher, J.R. (Jeffrey), Kim, Y. (Yunjung), Dackor, J. (Jennifer), Boerwinkle, E.A. (Eric), Franceschini, N. (Nora), Ardissino, D. (Diego), Bernardinelli, L. (Luisa), Mannucci, P.M. (Pier), Mauri, F. (Francesco), Merlini, P.A. (Piera), Absher, D. (Devin), Assimes, T.L. (Themistocles), Fortmann, S.P. (Stephen), Iribarren, C. (Carlos), Knowles, J.W. (Joshua), Quertermous, T. (Thomas), Ferrucci, L. (Luigi), Tanaka, T. (Toshiko), Bis, J.C. (Joshua), Haritunians, T. (Talin), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Taylor, K.D. (Kent), Thacker, E.L. (Evan), Almgren, P. (Peter), Groop, L. (Leif), Ladenvall, C. (Claes), Boehnke, M. (Michael), Jackson, A.U. (Anne), Mohlke, K.L. (Karen), Stringham, H.M. (Heather), Tuomilehto, J. (Jaakko), Benjamin, E.J. (Emelia), Hwang, S.J., Levy, D. (Daniel), Preis, S.R., Vasan, R.S. (Ramachandran Srini), Duan, J. (Jubao), Gejman, P.V. (Pablo), Levinson, D.F. (Douglas), Sanders, A.R. (Alan), Shi, J. (Jianxin), Lips, E.H. (Esther), McKay, J.D. (James), Agudo, A. (Antonio), Barzan, L. (Luigi), Bencko, V. (Vladimir), Benhamou, S. (Simone), Castellsagué, X. (Xavier), Canova, C. (Cristina), Conway, D.I. (David), Fabianova, E. (Eleonora), Foretova, L. (Lenka), Janout, V. (Vladimir), Healy, C.M. (Claire), Holcátová, I. (Ivana), Kjaerheim, K. (Kristina), Lagiou, P., Lissowska, J. (Jolanta), Lowry, R. (Ray), MacFarlane, T.V. (Tatiana), Mates, D. (Dana), Richiardi, L. (Lorenzo), Rudnai, P. (Peter), Szeszenia-Dabrowska, N. (Neonilia), Zaridze, D., Znaor, A. (Ariana), Lathrop, M. (Mark), Brennan, P. (Paul), Bandinelli, S. (Stefania), Frayling, T.M. (Timothy), Guralnik, J.M. (Jack), Milaneschi, Y. (Yuri), Perry, J.R.B. (John), Altshuler, D. (David), Elosua, R. (Roberto), Kathiresan, S. (Sekar), Lucas, G. (Gavin), Melander, O. (Olle), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Voight, B.F. (Benjamin), Smith, A.V. (Davey), Geus, E.J.C. (Eco) de, Chanock, S.J. (Stephen), Gu, F. (Fangyi), Hankinson, S.E. (Susan), Hunter, D. (David), Chasman, D.I. (Daniel), Everett, B.M. (Brendan), Paré, G. (Guillaume), Ridker, P.M. (Paul), Li, M.D. (Ming), Maes, H.H. (Hermine), Audrain-Mcgovern, J. (Janet), Posthuma, D. (Danielle), Thornton, L.M. (Laura), Lerman, C. (Caryn), Rose, J.E. (Jed), Ioannidis, J.P.A. (John), Kraft, P. (Peter), Lin, D.Y. (Dan), Liu, J. (Jason), Muglia, P. (Pierandrea), Waterworth, D. (Dawn), Pillai, A.D. (Ajay), Middleton, L. (Lefkos), Berrettini, W. (Wade), Knouff, C.W. (Christopher), Yuan, X. (Xin), Waeber, G. (Gérard), Vollenweider, P. (Peter), Preisig, M. (Martin), Wareham, N.J. (Nick), Zhao, J.H. (Jing Hua), Loos, R.J.F. (Ruth), Barroso, I.E. (Inês), Khaw, K-T. (Kay-Tee), Grundy, S.M. (Scott), Barter, P. (Phil), Mahley, R. (Robert), Kesaniemi, Y.A. (Antero), McPherson, R. (Ruth), Vincent, J. (John), Strauss, J.S. (John S), Kennedy, J. (James), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Day, R.N. (Richard), Matthews, K. (Keith), Bakke, A.B. (Arnold B.), Gulsvik, A. (Amund), Lucae, S. (Susanne), Ising, M. (Marcus), Brueckl, T. (Tanja), Horstmann, S. (Sonja), Heinrich, J. (Joachim), Lamina, C. (Claudia), Polasek, O. (Ozren), Zgaga, L. (Lina), Huffman, J.E. (Jennifer), Campbell, S. (Susan), Kooner, J.S. (Jaspal), Chambers, J.C. (John), Burnett, M.S., Devaney, J. (Joseph), Pichard, A.D., Kent, K.M. (Kenneth), Satler, L.F., Lindsay, J.M. (Joseph), Waksman, R. (Ron), Epstein, S.E. (Stephen), Wilson, J.F. (James), Wild, S.H. (Sarah), Campbell, H. (Harry), Vitart, V. (Veronique), Reilly, M.P. (Muredach), Li, M. (Mingyao), Qu, L. (Liming), Wilensky, A. (Asaf), Matthai, W. (William), Hakonarson, H. (Hakon), Rader, D.J. (Daniel), Franke, A. (Andre), Wittig, M. (Michael), Schäfer, A. (Arne), Uda, M. (Manuela), Terracciano, A., Xiao, X. (Xiangjun), Busonero, F., Scheet, P. (Paul), Schlessinger, D., Clair, D.S., Rujescu, D. (Dan), Abecasis, G.R. (Gonçalo), Grabe, H.J. (Hans Jörgen), Teumer, A. (Alexander), Völzke, H. (Henry), Petersmann, A. (Astrid), John, U. (Ulrich), Rudan, I. (Igor), Hayward, C. (Caroline), Wright, A.F. (Alan), Kolcic, I. (Ivana), Wright, B.J. (Benjamin), Balmforth, A.J. (Anthony), Anderson, C. (Carl), Ahmed, T. (Tariq), Mathew, J. (Joseph), Parkes, M. (Miles), Satsangi, J. (Jack), Caulfield, M. (Mark), Munroe, P. (Patricia), Farrall, M. (Martin), Dominiczak, A. (Anna), Worthington, H. (Helen), Thomson, W. (Wendy), Eyre, D.S. (Dylan Samuel), Barton, A. (Anne), Mooser, V. (Vincent), and Francks, C. (Clyde)

Abstract

Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34 216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10-7). These findings replicate in a second large data set (N=127 274, thereof 76 242 smokers) for both SI (P=1.2 × 10-5) and CPD (P=9.3 × 10-5). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Published
2013
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34. 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

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

Author

McKay, JD, Truong, T, Gaborieau, V, Chabrier, A, Chuang, SC, Byrnes, G, Zaridze, D, Shangina, O, Szeszenia-Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Bucur, A, Bencko, V, Holcatova, I, Janout, V, Foretova, L, Lagiou, P, Trichopoulos, D, Benhamou, S, Bouchardy, C, Ahrens, W, Merletti, F, Richiardi, L, Talamini, R, Barzan, L, Kjaerheim, K, Macfarlane, GJ, Macfarlane, TV, Simonato, L, Canova, C, Agudo, A, Castellsagué, X, Lowry, R, Conway, DI, McKinney, PA, Healy, CM, Toner, ME, Znaor, A, Curado, MP, Koifman, S, Menezes, A, Wünsch-Filho, V, Neto, JE, Garrote, LF, Boccia, S, Cadoni, G, Arzani, D, Olshan, AF, Weissler, MC, Funkhouser, WK, Luo, J, Lubiński, J, Trubicka, J, Lener, M, Oszutowska, D, Schwartz, SM, Chen, C, Fish, S, Doody, DR, Muscat, JE, Lazarus, P, Gallagher, CJ, Chang, SC, Zhang, ZF, Wei, Q, Sturgis, EM, Wang, LE, Franceschi, S, Herrero, R, Kelsey, KT, McClean, MD, Marsit, CJ, Nelson, HH, Romkes, M, Buch, S, Nukui, T, Zhong, S, Lacko, M, Manni, JJ, Peters, WHM, Hung, RJ, McLaughlin, J, Vatten, L, Njølstad, I, Goodman, GE, Field, JK, Liloglou, T, Vineis, P, Clavel-Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, S, González, CA, Quirós, JR, Martínez, C, Navarro, C, Ardanaz, E, Larrañaga, N, McKay, JD, Truong, T, Gaborieau, V, Chabrier, A, Chuang, SC, Byrnes, G, Zaridze, D, Shangina, O, Szeszenia-Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Bucur, A, Bencko, V, Holcatova, I, Janout, V, Foretova, L, Lagiou, P, Trichopoulos, D, Benhamou, S, Bouchardy, C, Ahrens, W, Merletti, F, Richiardi, L, Talamini, R, Barzan, L, Kjaerheim, K, Macfarlane, GJ, Macfarlane, TV, Simonato, L, Canova, C, Agudo, A, Castellsagué, X, Lowry, R, Conway, DI, McKinney, PA, Healy, CM, Toner, ME, Znaor, A, Curado, MP, Koifman, S, Menezes, A, Wünsch-Filho, V, Neto, JE, Garrote, LF, Boccia, S, Cadoni, G, Arzani, D, Olshan, AF, Weissler, MC, Funkhouser, WK, Luo, J, Lubiński, J, Trubicka, J, Lener, M, Oszutowska, D, Schwartz, SM, Chen, C, Fish, S, Doody, DR, Muscat, JE, Lazarus, P, Gallagher, CJ, Chang, SC, Zhang, ZF, Wei, Q, Sturgis, EM, Wang, LE, Franceschi, S, Herrero, R, Kelsey, KT, McClean, MD, Marsit, CJ, Nelson, HH, Romkes, M, Buch, S, Nukui, T, Zhong, S, Lacko, M, Manni, JJ, Peters, WHM, Hung, RJ, McLaughlin, J, Vatten, L, Njølstad, I, Goodman, GE, Field, JK, Liloglou, T, Vineis, P, Clavel-Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, S, González, CA, Quirós, JR, Martínez, C, Navarro, C, Ardanaz, E, and Larrañaga, N

Abstract

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10-7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10-8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10-8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10-8; rs1229984-ADH1B, p = 7×10-9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility. © 2011 McKay et al.

Published
2011

36. End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age.

Author

Castellsagué, X., Muñoz, N., Pitisuttithum, P., Ferris, D., Monsonego, J., Ault, K., Luna, J., Myers, E., Mallary, S., Bautista, O. M., Bryan, J., Vuocolo, S., Haupt, R. M., Saah, A., Castellsagué, X, and Muñoz, N

Subjects
*HUMAN papillomavirus vaccines, *VACCINATION, *DISEASES in women, *GENITAL warts, *COMPARATIVE studies, *IMMUNIZATION, *INTERNATIONAL agencies, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *OVARIAN tumors, *PAPILLOMAVIRUS diseases, *PAPILLOMAVIRUSES, *RESEARCH, *EVALUATION research, *RANDOMIZED controlled trials, *TREATMENT effectiveness, *BLIND experiment, *CERVICAL intraepithelial neoplasia, *PREVENTION, *THERAPEUTICS, CERVICAL vertebrae diseases, PAPILLOMAVIRUS disease prevention
Abstract

Background: Previous analyses from a randomised trial in women aged 24-45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years.Methods: We enrolled 3819 24-45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations.Results: Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported.Conclusions: The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24-45 years, regardless of previous exposure to HPV vaccine type. [ABSTRACT FROM AUTHOR]

Published
2011
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37. Early age at first sexual intercourse and early pregnancy are risk factors for cervical cancer in developing countries.

Author

Louie, K. S., de Sanjose, S., Diaz, M., Castellsagué, X., Herrero, R., Meijer, C. J., Shah, K., Franceschi, S., Muñoz, N., Bosch, F. X., Castellsagué, X, Muñoz, N, and International Agency for Research on Cancer Multicenter Cervical Cancer Study Group

Subjects
SEXUAL intercourse, CERVICAL cancer, CHILD sexual abuse, SEXUAL behavior surveys, PREGNANCY, FIRST sexual experiences, DISEASE risk factors, DEVELOPING countries, RESEARCH, HUMAN sexuality, AGE distribution, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, MATERNAL age, CERVIX uteri tumors
Abstract

Early age at first sexual intercourse (AFSI) has long been associated with an increased risk of invasive cervical carcinoma (ICC). Age at first pregnancy (AFP) and ICC have been investigated less, although AFSI and AFP are strongly interrelated in most developing countries. A pooled analysis of case-control studies on ICC from eight developing countries with 1864 cases and 1719 controls investigated the roles of AFSI, AFP, and ICC risk. Age at first sexual intercourse, AFP and age at first marriage (AFM) were highly interrelated and had similar ICC risk estimates. Compared with women with AFSI > or = 21 years, the odds ratio (OR) of ICC was 1.80 (95% CI: 1.50-2.39) among women with AFSI 17-20 years and 2.31 (95% CI: 1.85-2.87) for AFSI < or = 16 years (P-trend <0.001). No statistical interaction was detected between AFSI and any established risk factors for ICC. The ICC risk was 2.4-fold among those who reported AFSI and AFP at < or = 16 years compared with those with AFSI and AFP at > or = 21 years. These data confirm AFSI and AFB as risk factors for ICC in eight developing countries, but any independent effects of these two events could not be distinguished. [ABSTRACT FROM AUTHOR]

Published
2009
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40. Food groups and risk of squamous cell carcinoma of the oesophagus: a case-control study in Uruguay.

Author

De Stefani, E., Deneo-Pellegrini, H., Ronco, A.L., Boffetta, P., Brennan, P., Muñoz, N., Castellsagué, X., Correa, P., Mendilaharsu, M., Muñoz, N, and Castellsagué, X

Subjects
SQUAMOUS cell carcinoma, ESOPHAGEAL cancer, CANCER risk factors, COMPARATIVE studies, ALCOHOL drinking, ESOPHAGEAL tumors, FOOD, FOOD habits, FRUIT, RESEARCH methodology, MEAT, MEDICAL cooperation, MEDICINAL plants, EDIBLE plants, QUESTIONNAIRES, RESEARCH, SMOKING, TOBACCO, VEGETABLES, EVALUATION research, CASE-control method, ODDS ratio, PREVENTION
Abstract

In the time period January 1998-December 2000, a case-control study on squamous cell cancer of the oesophagus was conducted in Montevideo, Uruguay. The main objective of the study was to estimate the odds ratios (ORs) associated with main food groups. For this purpose, 166 patients afflicted with squamous cell oesophageal cancer and 664 hospitalised controls were frequency matched on age and sex. Both series of patients were administered with a structured questionnaire. Aside from queries related with tobacco smoking, alcohol drinking and maté drinking, patients were interviewed with a food-frequency questionnaire (FFQ) on 64 items, representative of the usual Uruguayan diet. Red meat, salted meat and boiled meat displayed strong direct associations (OR for red meat 2.4, 95% CI 1.4-4.2). On the other hand, fish and total white meat showed moderate protective effect (OR for total white meat 0.5, 95% CI 0.3-0.9). Total fruit intake displayed a strong inverse association (OR 0.2, 95% CI 0.1-0.4), whereas total vegetable consumption presented a weak inverse association (OR for total vegetable intake 0.7, 95% CI 0.4-1.2). These results suggest that vegetables, mainly cooked vegetables, are rich in thermolabile protective substances. On the other hand, boiled (stewed) meat, which is ingested at high temperature could be, like maté, a risk factor for squamous cell cancer of the oesophagus. [ABSTRACT FROM AUTHOR]

Published
2003
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41. Apoptosis loss and bcl-2 expression: key determinants of lymph node metastases in T1 breast cancer

Author

Sierra A, Castellsagué X, Tórtola S, Escobedo A, Lloveras B, Miguel A. Peinado, Moreno A, and Fabra A

Subjects
Adult, Apoptosis, Breast Neoplasms, Middle Aged, Immunohistochemistry, Proto-Oncogene Mas, Proto-Oncogene Proteins c-bcl-2, Lymphatic Metastasis, Mutation, Biomarkers, Tumor, Humans, Female, Neoplasm Invasiveness, Tumor Suppressor Protein p53, Cell Division, Aged
Abstract

The Bcl-2 proto-oncogene extends cell survival but does not confer any proliferative advantage to cells that express it. Thus, the loss of apoptosis may have a role in progression allowing the acquisition of additional mutations. To determine whether apoptosis loss at diagnosis is associated with the metastatic advantage of ductal breast carcinomas and to examine the relationship between Bcl-2 expression, p53, and tumor cell death status, we examined tumor samples from 116 patients diagnosed with T1 (2 cm or less) breast cancer with (n = 49) or without (n = 67) lymph node metastases. Apoptosis loss in histological sections was considered when1% of tumor nuclei were stained with terminal deoxynucleotidyl transferase labeled with biotin. We studied the expression of Bcl-2 and p53 by immunohistochemistry and in 37 p53 mutations by single-strand conformational polymorphism analysis and cycle sequencing. Multivariate logistic regression modeling was used to estimate prevalence odds ratios (pORs) for apoptosis loss and presence of lymph node metastases. Patients with marked apoptosis loss in their tumor cells were about 5 times more likely to present lymph node metastases than those with no apoptosis loss in their tumor cells (adjusted pOR, 4.7; 95% confidence interval, 1.4-15.6; trend test, P = 0.008). Bcl-2 expression was strongly associated with both apoptosis loss (pOR, 6.9; trend test, P0.0001) and presence of lymph node metastases (pOR, 5.7; trend test, P = 0.002). These associations were more evident in histological grade I and II tumors than in poorly differentiated histological grade III tumors and in p53-negative tumors than in p53-positive tumors. This study demonstrates for the first time that the lymphatic progression of T1 human breast cancer is strongly related to apoptosis loss.

Published
1996

45. Sexual behaviors and the risk of head and neck cancers

Author

Heck, J.E., primary, Berthiller, J., additional, Vaccarella, S., additional, Winn, D.M., additional, Smith, E.M., additional, Shangina, O., additional, Schwartz, S.M., additional, Purdue, M., additional, Eluf-Neto, J., additional, Menezes, A., additional, McClean, M.D., additional, Matos, E., additional, Koifman, S., additional, Kelsey, K.T., additional, Herrero, R., additional, Hayes, R.B., additional, Franceschi, S., additional, Wünsch-Filho, V., additional, Fernandez, L., additional, Daudt, A.W., additional, Curado, M.P., additional, Chen, C., additional, Castellsagué, X., additional, Ferro, G., additional, Brennan, P., additional, Boffetta, P., additional, and Hashibe, M., additional

Published
2008
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49. Difficulty in elucidating the male role in cervical cancer in Colombia, a high-risk area for the disease.

Author

Muñoz N, Castellsagué X, Bosch FX, Tafur L, de Sanjosé S, Aristizabal N, Ghaffari AM, Shah KV, Muñoz, N, Castellsagué, X, Bosch, F X, Tafur, L, de Sanjosé, S, Aristizabal, N, Ghaffari, A M, and Shah, K V

Abstract

Background: Epidemiologic evidence has been inconclusive in linking men's sexual behavior and genital human papillomaviruses (HPVs) with cervical cancer risk in their sexual partners in areas with a high incidence of cervical cancer.Purpose: This study assesses the role of men's sexual behavior and the presence of penile HPV DNA on the risk of their wives' developing cervical neoplasia in an area in Colombia with a high incidence of cervical cancer.Methods: A total of 210 husbands of women with cervical intraepithelial neoplasia grade III (n = 118) or invasive squamous cell carcinoma of the cervix (n = 92) and a total of 262 husbands of women recruited as control subjects (173 and 89, respectively) were interviewed. Questionnaires included detailed information on sexual behavior. Exfoliated cells were obtained from the glans penis and from the distal urethra of the penis. The specimens were analyzed for HPV DNA by use of a polymerase chain reaction-based assay that included a generic probe and 25 type-specific probes. Serum specimens were collected and analyzed for antibodies to Chlamydia trachomatis, Treponema pallidum, herpes simplex virus type II, and Neisseria gonorrhoeae.Results: Limited education (adjusted odds ratio [OR] = 4.4; 95% confidence interval [CI] = 1.9-9.8; for no schooling versus secondary or higher education) and presence of antibodies to C. trachomatis (adjusted OR = 2.5; 95% CI = 1.5-4.4) in husbands were the only identified risk factors for cervical neoplasia in their wives. The prevalence of HPV DNA in the penis was 25.7% among husbands of case women and 18.9% among husbands of control women (adjusted OR = 1.2; 95% CI = 0.6-2.3). Neither the lifetime number of female sexual partners (adjusted OR = 1.0; 95% CI = 0.4-2.6; for > 50 partners versus one to five) nor the lifetime number of female prostitutes as sexual partners (adjusted OR = 1.2; 95% CI = 0.7-2.0; for > or = 21 prostitutes versus one to five) was associated with the risk of cervical cancer.Conclusions: Our results are compatible with the hypothesis that in the population of Cali, whose women are at high risk of developing cervical cancer, exposure to HPV among young men is a common occurrence and is mediated by contacts with large numbers of female sexual partners and prostitutes. These widespread sexual practices limit the power of case-control studies to detect significant associations between men's sexual behavior and the cervical cancer risk in their sexual partners. HPV DNA detection in the penis of adult men is a poor reflection of lifetime exposure or of etiologically relevant exposure to HPV. The role of C. trachomatis in cervical carcinogenesis deserves further investigation.Implications: Further research is needed to elucidate the male's role in cervical carcinogenesis in populations at high risk for cervical cancer. HPV DNA prevalence surveys and studies of the natural history of HPV in young men will be of great value. [ABSTRACT FROM AUTHOR]

Published
1996
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