Search

Your search keyword '"Hautman, C"' showing total 12 results
Start Over Author "Hautman, C" Search Limiters Available in Library Collection
12 results on '"Hautman, C"'

1. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author

Wiencke, John, MacHiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, B, Dagnall, C, Hautman, C, and Jacobs, KB

Abstract

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.2

Published
2016

2. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author

Lu, L. (Lingeng), Lissowska, J. (Jolanta), Liu, J. (Jianjun), Lin, D. (Dongxin), Liao, L. (Linda), Liang, X. (Xiaolin), Li, D. (Donghui), Le-Marchand, L. (Loic), Landi, M.T. (María Teresa), Lan, Q. (Qing), LaCroix, A. (Andrea), Kurtz, R.C. (Robert C.), Krogh, V. (Vittorio), Kraft, P. (Peter), Kooperberg, C. (Charles), Kolonel, L.N. (Laurence N.), Koh, W.P. (Woon-Puay), Klein, R. (Robert), Klein, A.P. (Alison P.), Kim, Y.T. (Young Tae), Kim, Y.H. (Yeul Hong), Kim, H.N. (Hee Nam), Khaw, K.T. (Kay-Tee), Johansen, C. (Christoffer), Jenab, M. (Mazda), Hutchinson, A. (Amy), Hunter, D.J. (David J.), Hu, W. (Wei), Hu, N. (Nan), Hsiung, C.A. (Chao A.), Hoover, R.N. (Robert N.), Hong, Y.C. (Yun-Chul), Holly, E.A. (Elizabeth A.), Henriksson, R. (Roger), Harris, C.C. (Curtis C.), Hankinson, S.E. (Susan E.), Hallmans, G. (Goran), Haiman, C.A. (Christopher A.), Goldstein, A.M. (Alisa M.), Goldin, L. (Lynn), Giovannucci, E.L. (Edward L.), Gillanders, E.M. (Elizabeth M.), Giles, G.G. (Graham G.), Gaziano, J.M. (J. Michael), Gaudet, M.M. (Mia M.), Garcia-Closas, M. (Montserrat), Gapstur, S.M. (Susan M.), Gao, Y.T. (Yu-Tang), Gallinger, S. (Steven), Fuchs, C.S. (Charles S.), Friedenreich, C.M. (Christine M.), Fraumeni, J.F. (Joseph F.), Figueroa, J.D. (Jonine D.), Fan, J.H. (Jin-Hu), Epstein, C.G. (Caroline G.), Duell, E.J. (Eric J.), Doherty, J. (Jennifer), Ding, T. (Ti), De Vivo, I. (Immaculata), Davis, F.G. (Faith G.), Cullen, M. (Michael), Crous Bou, M. (Marta), Cook, L.S. (Linda S.), Chung, C.C. (Charles C.), Chen, K. (Kexin), Chen, C. (Constance), Chen, C. (Chu), Chatterjee, N. (Nilanjan), Chang, I.S. ( I-Shou), Chaffee, K.G. (Kari G.), Carreon, T. (Tania), Canzian, F. (Federico), Butler, M.A. (Mary A.), Buring, J.E. (Julie E.), Burdett, L. (Laurie), Bueno-de-Mesquita, H.B. (H. Bas), Brinton, L.A. (Louise A.), Bracci, P.M. (Paige M.), Bock, C.H. (Cathryn H.), Blot, W.J. (William J.), Black, A. (Amanda), Berndt, S.I. (Sonja I.), Chanock, S.J. (Stephen J.), Yeager, M. (Meredith), Dean, M.C. (Michael C.), Tucker, M. (Margaret), Rothman, N. (Nathaniel), Caporaso, N.E. (Neil E.), Perez-Jurado, L.A. (Luis A.), Beane-Freeman, L.E. (Laura E.), Ziegler, R.G. (Regina G.), Zhou, B. (Baosen), Zheng, W. (Wei), Zeleniuch-Jacquotte, A. (Anne), Zanetti, K.A. (Krista A.), Yu, K. (Kai), Yang, P.C. (Pan-Chyr), Yang, H.P. (Hannah P.), Xia, L. (Lucy), Wunder, J.S. (Jay S.), Arslan, A.A. (Alan A.), Wu, Y.L. (Yi-Long), Wu, Y.Q. (Yan Q.), Wu, T. (Tangchun), Wu, C. (Chen), Wong, M.P. (Maria Pik), Wolpin, B.M. (Brian M.), Wiencke, J.K. (John K.), White, E. (Emily), Wheeler, W. (William), Wentzensen, N. (Nicolas), Amundadottir, L. (Laufey), Wang, Z. (Zhaoming), Wang, J.C. (Jiu-Cun), Wacholder, S. (Sholom), Visvanathan, K. (Kala), Van Den Berg, D. (David), Tobias, G.S. (Geoffrey S.), Teras, L.R. (Lauren R.), Taylor, P.R. (Philip R.), Tang, Z.Z. (Ze-Zhong), Stram, D. (Daniel), Amos, C. (Christopher), Stolzenberg-Solomon, R.Z. (Rachael Z.), Stevens, V.L. (Victoria L.), Spitz, M.R. (Margaret R.), Silverman, D.T. (Debra T.), Shu, X.O. (Xiao-Ou), Shin, M.H. (Min-Ho), Sheng, X. (Xin), Shen, H. (Hongbing), Severi, G. (Gianluca), Setiawan, V.W. (Veronica Wendy), Aldrich, M.C. (Melinda C.), Seow, A. (Adeline), Schwartz, K.L. (Kendra L.), Schwartz, A.G. (Ann G.), Schumacher, F. (Fredrick), Savage, S.A. (Sharon A.), Ruder, A.M. (Avima M.), Rodriguez-Santiago, B. (Benjamin), Risch, H.A. (Harvey A.), Riboli, E. (Elio), Real, F.X. (Francisco X.), Abnet, C.C. (Christian C.), Rajaraman, P. (Preetha), Qiao, Y.L. (You-Lin), Purdue, M. (Mark), Prokunina-Olsson, L. (Ludmila), Prescott, J. (Jennifer), Pooler, L. (Loreall), Petersen, G. (Gloria), Peters, U. (Ulrike), Peplonska, B. (Beata), Park, J.Y. (Jae Yong), Jacobs, K. (Kevin), Orlow, I. (Irene), Olson, S.H. (Sara H.), Moore, L.E. (Lee E.), Mirabello, L. (Lisa), Melin, B.S. (Beatrice S.), McWilliams, R.R. (Robert R.), McNeill, L.H. (Lorna H.), Matsuo, K. (Keitaro), Malats, N. (Nuria), Magliocco, A.M. (Anthony M.), Hautman, C. (Christopher), Dagnall, C. (Casey), Hicks, B. (Belynda), Yang, Q. (Qi), Freedman, N.D. (Neal D.), Sampson, J. (Joshua), Karlins, E. (Eric), Zhou, W. (Weiyin), Mitchell, J.M. (J. Machiela), Machiela, M.J. (Mitchell J.), and Patiño-García, A. (Ana)

Subjects
Chromosome X, Age-related
Abstract

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Published
2016

3. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author

Zhang, M. Wang, Z. Obazee, O. Jia, J. Childs, E.J. Hoskins, J. Figlioli, G. Mocci, E. Collins, I. Chung, C.C. Hautman, C. Arslan, A.A. Beane-Freeman, L. Bracci, P.M. Buring, J. Duell, E.J. Gallinger, S. Giles, G.G. Goodman, G.E. Goodman, P.J. Kamineni, A. Kolonel, L.N. Kulke, M.H. Malats, N. Olson, S.H. Sesso, H.D. Visvanathan, K. White, E. Zheng, W. Abnet, C.C. Albanes, D. Andreotti, G. Brais, L. Bas Bueno-de-Mesquita, H. Basso, D. Berndt, S.I. Boutron-Ruault, M.-C. Bijlsma, M.F. Brenner, H. Burdette, L. Campa, D. Caporaso, N.E. Capurso, G. Cavestro, G.M. Cotterchio, M. Costello, E. Elena, J. Boggi, U. Michael Gaziano, J. Gazouli, M. Giovannucci, E.L. Goggins, M. Gross, M. Haiman, C.A. Hassan, M. Helzlsouer, K.J. Hu, N. Hunter, D.J. Iskierka-Jazdzewska, E. Jenab, M. Kaaks, R. Key, T.J. Khaw, K.-T. Klein, E.A. Kogevinas, M. Krogh, V. Kupcinskas, J. Kurtz, R.C. Landi, M.T. Landi, S. Marchand, L.L. Mambrini, A. Mannisto, S. Milne, R.L. Neale, R.E. Oberg, A.L. Panico, S. Patel, A.V. Peeters, P.H.M. Peters, U. Pezzilli, R. Porta, M. Purdue, M. Ramón Quiros, J. Riboli, E. Rothman, N. Scarpa, A. Scelo, G. Shu, X.-O. Silverman, D.T. Soucek, P. Strobel, O. Sund, M. Malecka-Panas, E. Taylor, P.R. Tavano, F. Travis, R.C. Thornquist, M. Tjønneland, A. Tobias, G.S. Trichopoulos, D. Vashist, Y. Vodicka, P. Wactawski-Wende, J. Wentzensen, N. Yu, H. Yu, K. Zeleniuch-Jacquotte, A. Kooperberg, C. Risch, H.A. Jacobs, E.J. Li, D. Fuchs, C. Hoover, R. Hartge, P. Chanock, S.J. Petersen, G.M. Stolzenberg-Solomon, R.S. Wolpin, B.M. Kraft, P. Klein, A.P. Canzian, F. Amundadottir, L.T.

Abstract

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10-15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10-9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10-8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10-8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10-4-2.0x10-3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Published
2016

4. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author

Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, EJ, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, CC, Hautman, C, Arslan, AA, Beane-Freeman, L, Bracci, PM, Buring, J, Duell, EJ, Gallinger, S, Giles, GG, Goodman, GE, Goodman, PJ, Kamineni, A, Kolonel, LN, Kulke, MH, Malats, N, Olson, SH, Sesso, HD, Visvanathan, K, White, E, Zheng, W, Abnet, CC, Albanes, D, Andreotti, G, Brais, L, Bueno-de-Mesquita, HB, Basso, D, Berndt, SI, Boutron-Ruault, M-C, Bijlsma, MF, Brenner, H, Burdette, L, Campa, D, Caporaso, NE, Capurso, G, Cavestro, GM, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, JM, Gazouli, M, Giovannucci, EL, Goggins, M, Gross, M, Haiman, CA, Hassan, M, Helzlsouer, KJ, Hu, N, Hunter, DJ, Iskierka-Jazdzewska, E, Jenab, M, Kaaks, R, Key, TJ, Khaw, K-T, Klein, EA, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, RC, Landi, MT, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, RL, Neale, RE, Oberg, AL, Panico, S, Patel, AV, Peeters, PHM, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Ramon Quiros, J, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, X-O, Silverman, DT, Soucek, P, Strobel, O, Sund, M, Malecka-Panas, E, Taylor, PR, Tavano, F, Travis, RC, Thornquist, M, Tjonneland, A, Tobias, GS, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski-Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Kooperberg, C, Risch, HA, Jacobs, EJ, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, SJ, Petersen, GM, Stolzenberg-Solomon, RS, Wolpin, BM, Kraft, P, Klein, AP, Canzian, F, Amundadottir, LT, Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, EJ, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, CC, Hautman, C, Arslan, AA, Beane-Freeman, L, Bracci, PM, Buring, J, Duell, EJ, Gallinger, S, Giles, GG, Goodman, GE, Goodman, PJ, Kamineni, A, Kolonel, LN, Kulke, MH, Malats, N, Olson, SH, Sesso, HD, Visvanathan, K, White, E, Zheng, W, Abnet, CC, Albanes, D, Andreotti, G, Brais, L, Bueno-de-Mesquita, HB, Basso, D, Berndt, SI, Boutron-Ruault, M-C, Bijlsma, MF, Brenner, H, Burdette, L, Campa, D, Caporaso, NE, Capurso, G, Cavestro, GM, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, JM, Gazouli, M, Giovannucci, EL, Goggins, M, Gross, M, Haiman, CA, Hassan, M, Helzlsouer, KJ, Hu, N, Hunter, DJ, Iskierka-Jazdzewska, E, Jenab, M, Kaaks, R, Key, TJ, Khaw, K-T, Klein, EA, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, RC, Landi, MT, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, RL, Neale, RE, Oberg, AL, Panico, S, Patel, AV, Peeters, PHM, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Ramon Quiros, J, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, X-O, Silverman, DT, Soucek, P, Strobel, O, Sund, M, Malecka-Panas, E, Taylor, PR, Tavano, F, Travis, RC, Thornquist, M, Tjonneland, A, Tobias, GS, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski-Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Kooperberg, C, Risch, HA, Jacobs, EJ, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, SJ, Petersen, GM, Stolzenberg-Solomon, RS, Wolpin, BM, Kraft, P, Klein, AP, Canzian, F, and Amundadottir, LT

Abstract

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Published
2016

5. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author

Machiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, B, Dagnall, C, Hautman, C, Jacobs, KB, Abnet, CC, Aldrich, MC, Amos, C, Amundadottir, LT, Arslan, AA, Beane-Freeman, LE, Berndt, SI, Black, A, Blot, WJ, Bock, CH, Bracci, PM, Brinton, LA, Bueno-de-Mesquita, HB, Burdett, L, Buring, JE, Butler, MA, Canzian, F, Carreon, T, Chaffee, KG, Chang, I-S, Chatterjee, N, Chen, C, Chen, K, Chung, CC, Cook, LS, Bou, MC, Cullen, M, Davis, FG, De Vivo, I, Ding, T, Doherty, J, Duell, EJ, Epstein, CG, Fan, J-H, Figueroa, JD, Fraumeni, JF, Friedenreich, CM, Fuchs, CS, Gallinger, S, Gao, Y-T, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Gaziano, JM, Giles, GG, Gillanders, EM, Giovannucci, EL, Goldin, L, Goldstein, AM, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Henriksson, R, Holly, EA, Hong, Y-C, Hoover, RN, Hsiung, CA, Hu, N, Hu, W, Hunter, DJ, Hutchinson, A, Jenab, M, Johansen, C, Khaw, K-T, Kim, HN, Kim, YH, Kim, YT, Klein, AP, Klein, R, Koh, W-P, Kolonel, LN, Kooperberg, C, Kraft, P, Krogh, V, Kurtz, RC, LaCroix, A, Lan, Q, Landi, MT, Le Marchand, L, Li, D, Liang, X, Liao, LM, Lin, D, Liu, J, Lissowska, J, Lu, L, Magliocco, AM, Malats, N, Matsuo, K, McNeill, LH, McWilliams, RR, Melin, BS, Mirabello, L, Moore, L, Olson, SH, Orlow, I, Park, JY, Patino-Garcia, A, Peplonska, B, Peters, U, Petersen, GM, Pooler, L, Prescott, J, Prokunina-Olsson, L, Purdue, MP, Qiao, Y-L, Rajaraman, P, Real, FX, Riboli, E, Risch, HA, Rodriguez-Santiago, B, Ruder, AM, Savage, SA, Schumacher, F, Schwartz, AG, Schwartz, KL, Seow, A, Setiawan, VW, Severi, G, Shen, H, Sheng, X, Shin, M-H, Shu, X-O, Silverman, DT, Spitz, MR, Stevens, VL, Stolzenberg-Solomon, R, Stram, D, Tang, Z-Z, Taylor, PR, Teras, LR, Tobias, GS, Van den Berg, D, Visvanathan, K, Wacholder, S, Wang, J-C, Wang, Z, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolpin, BM, Wong, MP, Wu, C, Wu, T, Wu, X, Wu, Y-L, Wunder, JS, Xia, L, Yang, HP, Yang, P-C, Yu, K, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Ziegler, RG, Perez-Jurado, LA, Caporaso, NE, Rothman, N, Tucker, M, Dean, MC, Yeager, M, Chanock, SJ, Machiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, B, Dagnall, C, Hautman, C, Jacobs, KB, Abnet, CC, Aldrich, MC, Amos, C, Amundadottir, LT, Arslan, AA, Beane-Freeman, LE, Berndt, SI, Black, A, Blot, WJ, Bock, CH, Bracci, PM, Brinton, LA, Bueno-de-Mesquita, HB, Burdett, L, Buring, JE, Butler, MA, Canzian, F, Carreon, T, Chaffee, KG, Chang, I-S, Chatterjee, N, Chen, C, Chen, K, Chung, CC, Cook, LS, Bou, MC, Cullen, M, Davis, FG, De Vivo, I, Ding, T, Doherty, J, Duell, EJ, Epstein, CG, Fan, J-H, Figueroa, JD, Fraumeni, JF, Friedenreich, CM, Fuchs, CS, Gallinger, S, Gao, Y-T, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Gaziano, JM, Giles, GG, Gillanders, EM, Giovannucci, EL, Goldin, L, Goldstein, AM, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Henriksson, R, Holly, EA, Hong, Y-C, Hoover, RN, Hsiung, CA, Hu, N, Hu, W, Hunter, DJ, Hutchinson, A, Jenab, M, Johansen, C, Khaw, K-T, Kim, HN, Kim, YH, Kim, YT, Klein, AP, Klein, R, Koh, W-P, Kolonel, LN, Kooperberg, C, Kraft, P, Krogh, V, Kurtz, RC, LaCroix, A, Lan, Q, Landi, MT, Le Marchand, L, Li, D, Liang, X, Liao, LM, Lin, D, Liu, J, Lissowska, J, Lu, L, Magliocco, AM, Malats, N, Matsuo, K, McNeill, LH, McWilliams, RR, Melin, BS, Mirabello, L, Moore, L, Olson, SH, Orlow, I, Park, JY, Patino-Garcia, A, Peplonska, B, Peters, U, Petersen, GM, Pooler, L, Prescott, J, Prokunina-Olsson, L, Purdue, MP, Qiao, Y-L, Rajaraman, P, Real, FX, Riboli, E, Risch, HA, Rodriguez-Santiago, B, Ruder, AM, Savage, SA, Schumacher, F, Schwartz, AG, Schwartz, KL, Seow, A, Setiawan, VW, Severi, G, Shen, H, Sheng, X, Shin, M-H, Shu, X-O, Silverman, DT, Spitz, MR, Stevens, VL, Stolzenberg-Solomon, R, Stram, D, Tang, Z-Z, Taylor, PR, Teras, LR, Tobias, GS, Van den Berg, D, Visvanathan, K, Wacholder, S, Wang, J-C, Wang, Z, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolpin, BM, Wong, MP, Wu, C, Wu, T, Wu, X, Wu, Y-L, Wunder, JS, Xia, L, Yang, HP, Yang, P-C, Yu, K, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Ziegler, RG, Perez-Jurado, LA, Caporaso, NE, Rothman, N, Tucker, M, Dean, MC, Yeager, M, and Chanock, SJ

Abstract

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Published
2016

6. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Wang, Z., primary, Zhu, B., additional, Zhang, M., additional, Parikh, H., additional, Jia, J., additional, Chung, C. C., additional, Sampson, J. N., additional, Hoskins, J. W., additional, Hutchinson, A., additional, Burdette, L., additional, Ibrahim, A., additional, Hautman, C., additional, Raj, P. S., additional, Abnet, C. C., additional, Adjei, A. A., additional, Ahlbom, A., additional, Albanes, D., additional, Allen, N. E., additional, Ambrosone, C. B., additional, Aldrich, M., additional, Amiano, P., additional, Amos, C., additional, Andersson, U., additional, Andriole, G., additional, Andrulis, I. L., additional, Arici, C., additional, Arslan, A. A., additional, Austin, M. A., additional, Baris, D., additional, Barkauskas, D. A., additional, Bassig, B. A., additional, Beane Freeman, L. E., additional, Berg, C. D., additional, Berndt, S. I., additional, Bertazzi, P. A., additional, Biritwum, R. B., additional, Black, A., additional, Blot, W., additional, Boeing, H., additional, Boffetta, P., additional, Bolton, K., additional, Boutron-Ruault, M.-C., additional, Bracci, P. M., additional, Brennan, P., additional, Brinton, L. A., additional, Brotzman, M., additional, Bueno-de-Mesquita, H. B., additional, Buring, J. E., additional, Butler, M. A., additional, Cai, Q., additional, Cancel-Tassin, G., additional, Canzian, F., additional, Cao, G., additional, Caporaso, N. E., additional, Carrato, A., additional, Carreon, T., additional, Carta, A., additional, Chang, G.-C., additional, Chang, I.-S., additional, Chang-Claude, J., additional, Che, X., additional, Chen, C.-J., additional, Chen, C.-Y., additional, Chen, C.-H., additional, Chen, C., additional, Chen, K.-Y., additional, Chen, Y.-M., additional, Chokkalingam, A. P., additional, Chu, L. W., additional, Clavel-Chapelon, F., additional, Colditz, G. A., additional, Colt, J. S., additional, Conti, D., additional, Cook, M. B., additional, Cortessis, V. K., additional, Crawford, E. D., additional, Cussenot, O., additional, Davis, F. G., additional, De Vivo, I., additional, Deng, X., additional, Ding, T., additional, Dinney, C. P., additional, Di Stefano, A. L., additional, Diver, W. R., additional, Duell, E. J., additional, Elena, J. W., additional, Fan, J.-H., additional, Feigelson, H. S., additional, Feychting, M., additional, Figueroa, J. D., additional, Flanagan, A. M., additional, Fraumeni, J. F., additional, Freedman, N. D., additional, Fridley, B. L., additional, Fuchs, C. S., additional, Gago-Dominguez, M., additional, Gallinger, S., additional, Gao, Y.-T., additional, Gapstur, S. M., additional, Garcia-Closas, M., additional, Garcia-Closas, R., additional, Gastier-Foster, J. M., additional, Gaziano, J. M., additional, Gerhard, D. S., additional, Giffen, C. A., additional, Giles, G. G., additional, Gillanders, E. M., additional, Giovannucci, E. L., additional, Goggins, M., additional, Gokgoz, N., additional, Goldstein, A. M., additional, Gonzalez, C., additional, Gorlick, R., additional, Greene, M. H., additional, Gross, M., additional, Grossman, H. B., additional, Grubb, R., additional, Gu, J., additional, Guan, P., additional, Haiman, C. A., additional, Hallmans, G., additional, Hankinson, S. E., additional, Harris, C. C., additional, Hartge, P., additional, Hattinger, C., additional, Hayes, R. B., additional, He, Q., additional, Helman, L., additional, Henderson, B. E., additional, Henriksson, R., additional, Hoffman-Bolton, J., additional, Hohensee, C., additional, Holly, E. A., additional, Hong, Y.-C., additional, Hoover, R. N., additional, Hosgood, H. D., additional, Hsiao, C.-F., additional, Hsing, A. W., additional, Hsiung, C. A., additional, Hu, N., additional, Hu, W., additional, Hu, Z., additional, Huang, M.-S., additional, Hunter, D. J., additional, Inskip, P. D., additional, Ito, H., additional, Jacobs, E. J., additional, Jacobs, K. B., additional, Jenab, M., additional, Ji, B.-T., additional, Johansen, C., additional, Johansson, M., additional, Johnson, A., additional, Kaaks, R., additional, Kamat, A. M., additional, Kamineni, A., additional, Karagas, M., additional, Khanna, C., additional, Khaw, K.-T., additional, Kim, C., additional, Kim, I.-S., additional, Kim, J. H., additional, Kim, Y. H., additional, Kim, Y.-C., additional, Kim, Y. T., additional, Kang, C. H., additional, Jung, Y. J., additional, Kitahara, C. M., additional, Klein, A. P., additional, Klein, R., additional, Kogevinas, M., additional, Koh, W.-P., additional, Kohno, T., additional, Kolonel, L. N., additional, Kooperberg, C., additional, Kratz, C. P., additional, Krogh, V., additional, Kunitoh, H., additional, Kurtz, R. C., additional, Kurucu, N., additional, Lan, Q., additional, Lathrop, M., additional, Lau, C. C., additional, Lecanda, F., additional, Lee, K.-M., additional, Lee, M. P., additional, Le Marchand, L., additional, Lerner, S. P., additional, Li, D., additional, Liao, L. M., additional, Lim, W.-Y., additional, Lin, D., additional, Lin, J., additional, Lindstrom, S., additional, Linet, M. S., additional, Lissowska, J., additional, Liu, J., additional, Ljungberg, B., additional, Lloreta, J., additional, Lu, D., additional, Ma, J., additional, Malats, N., additional, Mannisto, S., additional, Marina, N., additional, Mastrangelo, G., additional, Matsuo, K., additional, McGlynn, K. A., additional, McKean-Cowdin, R., additional, McNeill, L. H., additional, McWilliams, R. R., additional, Melin, B. S., additional, Meltzer, P. S., additional, Mensah, J. E., additional, Miao, X., additional, Michaud, D. S., additional, Mondul, A. M., additional, Moore, L. E., additional, Muir, K., additional, Niwa, S., additional, Olson, S. H., additional, Orr, N., additional, Panico, S., additional, Park, J. Y., additional, Patel, A. V., additional, Patino-Garcia, A., additional, Pavanello, S., additional, Peeters, P. H. M., additional, Peplonska, B., additional, Peters, U., additional, Petersen, G. M., additional, Picci, P., additional, Pike, M. C., additional, Porru, S., additional, Prescott, J., additional, Pu, X., additional, Purdue, M. P., additional, Qiao, Y.-L., additional, Rajaraman, P., additional, Riboli, E., additional, Risch, H. A., additional, Rodabough, R. J., additional, Rothman, N., additional, Ruder, A. M., additional, Ryu, J.-S., additional, Sanson, M., additional, Schned, A., additional, Schumacher, F. R., additional, Schwartz, A. G., additional, Schwartz, K. L., additional, Schwenn, M., additional, Scotlandi, K., additional, Seow, A., additional, Serra, C., additional, Serra, M., additional, Sesso, H. D., additional, Severi, G., additional, Shen, H., additional, Shen, M., additional, Shete, S., additional, Shiraishi, K., additional, Shu, X.-O., additional, Siddiq, A., additional, Sierrasesumaga, L., additional, Sierri, S., additional, Loon Sihoe, A. D., additional, Silverman, D. T., additional, Simon, M., additional, Southey, M. C., additional, Spector, L., additional, Spitz, M., additional, Stampfer, M., additional, Stattin, P., additional, Stern, M. C., additional, Stevens, V. L., additional, Stolzenberg-Solomon, R. Z., additional, Stram, D. O., additional, Strom, S. S., additional, Su, W.-C., additional, Sund, M., additional, Sung, S. W., additional, Swerdlow, A., additional, Tan, W., additional, Tanaka, H., additional, Tang, W., additional, Tang, Z.-Z., additional, Tardon, A., additional, Tay, E., additional, Taylor, P. R., additional, Tettey, Y., additional, Thomas, D. M., additional, Tirabosco, R., additional, Tjonneland, A., additional, Tobias, G. S., additional, Toro, J. R., additional, Travis, R. C., additional, Trichopoulos, D., additional, Troisi, R., additional, Truelove, A., additional, Tsai, Y.-H., additional, Tucker, M. A., additional, Tumino, R., additional, Van Den Berg, D., additional, Van Den Eeden, S. K., additional, Vermeulen, R., additional, Vineis, P., additional, Visvanathan, K., additional, Vogel, U., additional, Wang, C., additional, Wang, J., additional, Wang, S. S., additional, Weiderpass, E., additional, Weinstein, S. J., additional, Wentzensen, N., additional, Wheeler, W., additional, White, E., additional, Wiencke, J. K., additional, Wolk, A., additional, Wolpin, B. M., additional, Wong, M. P., additional, Wrensch, M., additional, Wu, C., additional, Wu, T., additional, Wu, X., additional, Wu, Y.-L., additional, Wunder, J. S., additional, Xiang, Y.-B., additional, Xu, J., additional, Yang, H. P., additional, Yang, P.-C., additional, Yatabe, Y., additional, Ye, Y., additional, Yeboah, E. D., additional, Yin, Z., additional, Ying, C., additional, Yu, C.-J., additional, Yu, K., additional, Yuan, J.-M., additional, Zanetti, K. A., additional, Zeleniuch-Jacquotte, A., additional, Zheng, W., additional, Zhou, B., additional, Mirabello, L., additional, Savage, S. A., additional, Kraft, P., additional, Chanock, S. J., additional, Yeager, M., additional, Landi, M. T., additional, Shi, J., additional, Chatterjee, N., additional, and Amundadottir, L. T., additional

Published
2014
Full Text
View/download PDF

7. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Hidemi Ito, Stephen K. Van Den Eeden, Abdisamad M. Ibrahim, Ching C. Lau, Preetha Rajaraman, Gloria M. Petersen, Judith Hoffman-Bolton, Colin P.N. Dinney, Chang Hyun Kang, Melinda C. Aldrich, Mark P. Purdue, Xiao-Ou Shu, William J. Blot, Sanjay Shete, Alpa V. Patel, Charles Kooperberg, Paolo Vineis, David Van Den Berg, Chao A. Hsiung, Anthony J. Swerdlow, Qing Lan, Wu Chou Su, Afshan Siddiq, Ulrike Peters, Katia Scotlandi, Sara H. Olson, Kendra Schwartz, Kelly L. Bolton, Chancellor Hohensee, Josep Lloreta, Kevin B. Jacobs, Debra T. Silverman, Rudolf Kaaks, Wei Zheng, Steven Gallinger, Junwen Wang, Angela Carta, Massimo Serra, Petra H.M. Peeters, Victoria L. Stevens, Yasushi Yatabe, Geraldine Cancel-Tassin, Joshua N. Sampson, Young Tae Kim, Graham A. Colditz, Pan-Chyr Yang, Baosen Zhou, Fredrick R. Schumacher, Nicolas Wentzensen, Evelyn Tay, Claudia Maria Hattinger, Chen Wu, Pilar Amiano, Mattias Johansson, Maxwell P. Lee, Christian P. Kratz, Michael B. Cook, Mingfeng Zhang, Kay-Tee Khaw, Jian-Min Yuan, Anne Zeleniuch-Jacquotte, Jinping Jia, Roberto Tirabosco, Jing Ma, Neil E. Caporaso, Christopher A. Haiman, Bu Tian Ji, Adrienne M. Flanagan, Neyssa Marina, Eric J. Jacobs, Sophia S. Wang, Chong-Jen Yu, Edward Giovannucci, Margaret Wrensch, Robert L. Grubb, Bin Zhu, Daniel O. Stram, Manolis Kogevinas, Margaret R. Karagas, Mazda Jenab, Alison M. Mondul, Jun Xu, Preethi S. Raj, Anders Ahlbom, Christine D. Berg, Shelley Niwa, Kala Visvanathan, Loic Le Marchand, Jorge R. Toro, Robert N. Hoover, Heather Spencer Feigelson, Michelle Brotzman, Laurence N. Kolonel, Krista A. Zanetti, Chengfeng Wang, Mary Ann Butler, Ann Truelove, Irene L. Andrulis, Hongbing Shen, H. Dean Hosgood, Ming Shyan Huang, Gee-Chen Chang, Jianjun Liu, John K. Wiencke, Stephanie J. Weinstein, Beatrice Melin, Kouya Shiraishi, Zhihua Yin, Lee E. Moore, Börje Ljungberg, Jolanta Lissowska, Elizabeth M. Gillanders, M. T. Landi, Cari M. Kitahara, Maria Feychting, Kuan-Yu Chen, Matthias Simon, Brian M. Wolpin, Hemang Parikh, Hannah P. Yang, Graham G. Giles, Alison Johnson, Demetrius Albanes, Carlos González, Brian E. Henderson, Xifeng Wu, Harvey A. Risch, Amy Hutchinson, Christopher Hautman, Constance Chen, Zhibin Hu, Donghui Li, Elio Riboli, Julie E. Buring, Curtis C. Harris, Xu Che, Núria Malats, Roger Henriksson, Rosario Tumino, Joanne S. Colt, Alfredo Carrato, Paolo Boffetta, Maria Pik Wong, Hideo Tanaka, Federico Canzian, Alan D. L. Sihoe, Chien-Jen Chen, Kenneth Muir, Chen Ying, Qincheng He, Melissa C. Southey, Marc Sanson, Victoria K. Cortessis, Sharon A. Savage, Wei Hu, Yao Tettey, Daniela S. Gerhard, Sofia Pavanello, Guangwen Cao, H. Barton Grossman, Michael Goggins, Hideo Kunitoh, Peter D. Inskip, Seth P. Lerner, Peter Kraft, David Thomas, Peng Guan, Chung Hsing Chen, I. Shou Chang, Christoffer Johansen, Roberta McKean-Cowdin, Lee J. Helman, Yuh Min Chen, Ana Patiño-García, Pär Stattin, Xiaoping Miao, Tangchun Wu, Jay S. Wunder, Ann W. Hsing, Yu-Tang Gao, Brooke L. Fridley, Tania Carreón, Charles C. Chung, Nan Hu, Yoo Jin Jung, Richard B. Biritwum, Eric J. Duell, Philip R. Taylor, Satu Männistö, Kai Yu, Meredith Yeager, Xia Pu, Vittorio Krogh, Anand P. Chokkalingam, Susan M. Gapstur, W. Ryan Diver, Yuanqing Ye, Keitaro Matsuo, Cecilia Arici, You-Lin Qiao, Alan R. Schned, Dominique S. Michaud, Joanne W. Elena, Christopher Kim, Dongxin Lin, Yun-Chul Hong, Daru Lu, Reina García-Closas, Jonine D. Figueroa, Linda M. Liao, Yi-Long Wu, Heiner Boeing, Mark Lathrop, Göran Hallmans, Elizabeth A. Holly, Carol Giffen, Andrew A. Adjei, Consol Serra, Anne Tjønneland, Joseph F. Fraumeni, Alisa M. Goldstein, Ruth C. Travis, Rebecca Troisi, Dalsu Baris, Nalan Gokgoz, Olivier Cussenot, Xiang Deng, Yeul Hong Kim, Malin Sund, Sonja I. Berndt, E. David Crawford, Edward D. Yeboah, Sook Whan Sung, Françoise Clavel-Chapelon, Woon-Puay Koh, Nilgun Kurucu, Richard B. Hayes, Ashish M. Kamat, Beata Peplonska, Laurie Burdette, Ze Zhang Tang, Alan A. Arslan, Malcolm C. Pike, Sabina Sierri, J. Michael Gaziano, Lorna H. McNeil, Katherine A. McGlynn, Ulla Vogel, Logan G. Spector, H. Bas Bueno-de-Mesquita, Stephen J. Chanock, Jae Yong Park, Jennifer Prescott, Fernando Lecanda, Margaret A. Tucker, Ti Ding, Christian C. Abnet, Jenny Chang-Claude, Dimitrios Trichopoulos, Wei-Yen Lim, Wen Tan, Nick Orr, Jin Hee Kim, Stefano Porru, Chand Khanna, Robert R. McWilliams, Zhaoming Wang, Jeong Seon Ryu, David V. Conti, Alison P. Klein, Adonina Tardón, Robert J. Klein, Rebecca J. Rodabough, Mark H. Greene, Aruna Kamineni, Jie Lin, Rachael Z. Stolzenberg-Solomon, Patricia Hartge, Susan E. Hankinson, Young-Chul Kim, In Sam Kim, Luis Sierrasesúmaga, Roel Vermeulen, Paige M. Bracci, Mariana C. Stern, Louise A. Brinton, Myron D. Gross, Yong-Bing Xiang, Chih Yi Chen, G. A. Gerald Andriole, Paul S. Meltzer, Ying-Huang Tsai, Faith G. Davis, Ulrika Andersson, Paul Brennan, Sara Lindström, Chaoyu Wang, Giuseppe Mastrangelo, Laufey T. Amundadottir, Immaculata De Vivo, Bryan A. Bassig, Elisabete Weiderpass, Takashi Kohno, Nilanjan Chatterjee, Margaret R. Spitz, Pier Alberto Bertazzi, William Wheeler, David J. Hunter, Wei Tang, Qiuyin Cai, Naomi E. Allen, Molly Schwenn, Emily White, Min Shen, Adeline Seow, Laura E. Beane Freeman, James E. Mensah, Howard D. Sesso, Anna Luisa Di Stefano, Amanda Black, Manuela Gago-Dominguez, Christine B. Ambrosone, Avima M. Ruder, Martha S. Linet, Meir J. Stampfer, Robert C. Kurtz, Donald A. Barkauskas, Lisa W. Chu, Montserrat Garcia-Closas, Jason W. Hoskins, Melissa A. Austin, Kyoung Mu Lee, Jianxin Shi, Charles S. Fuchs, Nathaniel Rothman, Richard Gorlick, Piero Picci, Gianluca Severi, Ann G. Schwartz, Jian Gu, Christopher I. Amos, Marie-Christine Boutron-Ruault, Salvatore Panico, Alicja Wolk, Sara S. Strom, Lisa Mirabello, Jin-Hu Fan, Chin-Fu Hsiao, Neal D. Freedman, Geoffrey S. Tobias, Julie M. Gastier-Foster, Wang, Z, Zhu, B, Zhang, M, Parikh, H, Jia, J, Chung, Cc, Sampson, Jn, Hoskins, Jw, Hutchinson, A, Burdette, L, Ibrahim, A, Hautman, C, Raj, P, Abnet, Cc, Adjei, Aa, Ahlbom, A, Albanes, D, Allen, Ne, Ambrosone, Cb, Aldrich, M, Amiano, P, Amos, C, Andersson, U, Andriole G., Jr, Andrulis, Il, Arici, C, Arslan, Aa, Austin, Ma, Baris, D, Barkauskas, Da, Bassig, Ba, Beane Freeman, Le, Berg, Cd, Berndt, Si, Bertazzi, Pa, Biritwum, Rb, Black, A, Blot, W, Boeing, H, Boffetta, P, Bolton, K, Boutron Ruault, Mc, Bracci, Pm, Brennan, P, Brinton, La, Brotzman, M, Bueno de Mesquita, Hb, Buring, Je, Butler, Ma, Cai, Q, Cancel Tassin, G, Canzian, F, Cao, G, Caporaso, Ne, Carrato, A, Carreon, T, Carta, A, Chang, Gc, Chang, I, Chang Claude, J, Che, X, Chen, Cj, Chen, Cy, Chen, Ch, Chen, C, Chen, Ky, Chen, Ym, Chokkalingam, Ap, Chu, Lw, Clavel Chapelon, F, Colditz, Ga, Colt, J, Conti, D, Cook, Mb, Cortessis, Vk, Crawford, Ed, Cussenot, O, Davis, Fg, De Vivo, I, Deng, X, Ding, T, Dinney, Cp, Di Stefano, Al, Diver, Wr, Duell, Ej, Elena, Jw, Fan, Jh, Feigelson, H, Feychting, M, Figueroa, Jd, Flanagan, Am, Fraumeni JF, Jr, Freedman, Nd, Fridley, Bl, Fuchs, C, Gago Dominguez, M, Gallinger, S, Gao, Yt, Gapstur, Sm, Garcia Closas, M, Garcia Closas, R, Gastier Foster, Jm, Gaziano, Jm, Gerhard, D, Giffen, Ca, Giles, Gg, Gillanders, Em, Giovannucci, El, Goggins, M, Gokgoz, N, Goldstein, Am, Gonzalez, C, Gorlick, R, Greene, Mh, Gross, M, Grossman, Hb, Grubb R., 3rd, Gu, J, Guan, P, Haiman, Ca, Hallmans, G, Hankinson, Se, Harris, Cc, Hartge, P, Hattinger, C, Hayes, Rb, He, Q, Helman, L, Henderson, Be, Henriksson, R, Hoffman Bolton, J, Hohensee, C, Holly, Ea, Hong, Yc, Hoover, Rn, Hosgood HD, 3rd, Hsiao, Cf, Hsing, Aw, Hsiung, Ca, Hu, N, Hu, W, Hu, Z, Huang, M, Hunter, Dj, Inskip, Pd, Ito, H, Jacobs, Ej, Jacobs, Kb, Jenab, M, Ji, Bt, Johansen, C, Johansson, M, Johnson, A, Kaaks, R, Kamat, Am, Kamineni, A, Karagas, M, Khanna, C, Khaw, Kt, Kim, C, Kim, I, Kim, Yh, Kim, Yc, Kim, Yt, Kang, Ch, Jung, Yj, Kitahara, Cm, Klein, Ap, Klein, R, Kogevinas, M, Koh, Wp, Kohno, T, Kolonel, Ln, Kooperberg, C, Kratz, Cp, Krogh, V, Kunitoh, H, Kurtz, Rc, Kurucu, N, Lan, Q, Lathrop, M, Lau, Cc, Lecanda, F, Lee, Km, Lee, Mp, Le Marchand, L, Lerner, Sp, Li, D, Liao, Lm, Lim, Wy, Lin, D, Lin, J, Lindstrom, S, Linet, M, Lissowska, J, Liu, J, Ljungberg, B, Lloreta, J, Lu, D, Ma, J, Malats, N, Mannisto, S, Marina, N, Mastrangelo, G, Matsuo, K, Mcglynn, Ka, McKean Cowdin, R, Mcneill, Lh, Mcwilliams, Rr, Melin, B, Meltzer, P, Mensah, Je, Miao, X, Michaud, D, Mondul, Am, Moore, Le, Muir, K, Niwa, S, Olson, Sh, Orr, N, Panico, Salvatore, Park, Jy, Patel, Av, Patino Garcia, A, Pavanello, S, Peeters, Ph, Peplonska, B, Peters, U, Petersen, Gm, Picci, P, Pike, Mc, Porru, S, Prescott, J, Pu, X, Purdue, Mp, Qiao, Yl, Rajaraman, P, Riboli, E, Risch, Ha, Rodabough, Rj, Rothman, N, Ruder, Am, Ryu, J, Sanson, M, Schned, A, Schumacher, Fr, Schwartz, Ag, Schwartz, Kl, Schwenn, M, Scotlandi, K, Seow, A, Serra, C, Serra, M, Sesso, Hd, Severi, G, Shen, H, Shen, M, Shete, S, Shiraishi, K, Shu, Xo, Siddiq, A, Sierrasesumaga, L, Sierri, S, Loon Sihoe, Ad, Silverman, Dt, Simon, M, Southey, Mc, Spector, L, Spitz, M, Stampfer, M, Stattin, P, Stern, Mc, Stevens, Vl, Stolzenberg Solomon, Rz, Stram, Do, Strom, S, Su, Wc, Sund, M, Sung, Sw, Swerdlow, A, Tan, W, Tanaka, H, Tang, W, Tang, Zz, Tardon, A, Tay, E, Taylor, Pr, Tettey, Y, Thomas, Dm, Tirabosco, R, Tjonneland, A, Tobias, G, Toro, Jr, Travis, Rc, Trichopoulos, D, Troisi, R, Truelove, A, Tsai, Yh, Tucker, Ma, Tumino, R, Van Den Berg, D, Van Den Eeden, Sk, Vermeulen, R, Vineis, P, Visvanathan, K, Vogel, U, Wang, C, Wang, J, Wang, S, Weiderpass, E, Weinstein, Sj, Wentzensen, N, Wheeler, W, White, E, Wiencke, Jk, Wolk, A, Wolpin, Bm, Wong, Mp, Wrensch, M, Wu, C, Wu, T, Wu, X, Wu, Yl, Wunder, J, Xiang, Yb, Xu, J, Yang, Hp, Yang, Pc, Yatabe, Y, Ye, Y, Yeboah, Ed, Yin, Z, Ying, C, Yu, Cj, Yu, K, Yuan, Jm, Zanetti, Ka, Zeleniuch Jacquotte, A, Zheng, W, Zhou, B, Mirabello, L, Savage, Sa, Kraft, P, Chanock, Sj, Yeager, M, Landi, Mt, Shi, J, Chatterjee, N, Amundadottir, Lt, Wang, Z., Zhu, B., Zhang, M., Parikh, H., Jia, J., Chung, C.C., Sampson, J.N., Hoskins, J.W., Hutchinson, A., Burdette, L., Ibrahim, A., Hautman, C., Raj, P.S., Abnet, C.C., Adjei, A.A., Ahlbom, A., Albanes, D., Allen, N.E., Ambrosone, C.B., Aldrich, M., Amiano, P., Amos, C., Andersson, U., Gerald Andriole, G.A., Jr., Andrulis, I.L., Arici, C., Arslan, A.A., Austin, M.A., Baris, D., Barkauskas, D.A., Bassig, B.A., Freeman, L.E.B., Berg, C.D., Berndt, S.I., Bertazzi, P.A., Biritwum, R.B., Black, A., Blot, W., Boeing, H., Boffetta, P., Bolton, K., Boutron-Ruault, M.-C., Bracci, P.M., Brennan, P., Brinton, L.A., Brotzman, M., Bueno-de-Mesquita, H.B., Buring, J.E., Butler, M.A., Cai, Q., Cancel-Tassin, G., Canzian, F., Cao, G., Caporaso, N.E., Carrato, A., Carreon, T., Carta, A., Chang, G.-C., Chang, I.-S., Chang-Claude, J., Che, X., Chen, C.-J., Chen, C.-Y., Chen, C.-H., Chen, C., Chen, K.-Y., Chen, Y.-M., Chokkalingam, A.P., Chu, L.W., Clavel-Chapelon, F., Colditz, G.A., Colt, J.S., Conti, D., Cook, M.B., Cortessis, V.K., Crawford, E.D., Cussenot, O., Davis, F.G., De Vivo, I., Deng, X., Ding, T., Dinney, C.P., Di Stefano, A.L., Diver, W.R., Duell, E.J., Elena, J.W., Fan, J.-H., Feigelson, H.S., Feychting, M., Figueroa, J.D., Flanagan, A.M., Fraumeni, J.F., Jr., Freedman, N.D., Fridley, B.L., Fuchs, C.S., Gago-Dominguez, M., Gallinger, S., Gao, Y.-T., Gapstur, S.M., Garcia-Closas, M., Garcia-Closas, R., Gastier-Foster, J.M., Gaziano, J.M., Gerhard, D.S., Giffen, C.A., Giles, G.G., Gillanders, E.M., Giovannucci, E.L., Goggins, M., Gokgoz, N., Goldstein, A.M., Gonzalez, C., Gorlick, R., Greene, M.H., Gross, M., Grossman, H.B., Grubb, R., III and Gu, J., Guan, P., Haiman, C.A., Hallmans, G., Hankinson, S.E., Harris, C.C., Hartge, P., Hattinger, C., Hayes, R.B., He, Q., Helman, L., Henderson, B.E., Henriksson, R., Hoffman-Bolton, J., Hohensee, C., Holly, E.A., Hong, Y.-C., Hoover, R.N., Dean Hosgood, H., Hsiao, C.-F., Hsing, A.W., Hsiung, C.A., Hu, N., Hu, W., Hu, Z., Huang, M.-S., Hunter, D.J., Inskip, P.D., Ito, H., Jacobs, E.J., Jacobs, K.B., Jenab, M., Ji, B.-T., Johansen, C., Johansson, M., Johnson, A., Kaaks, R., Kamat, A.M., Kamineni, A., Karagas, M., Khanna, C., Khaw, K.-T., Kim, C., Kim, I.-S., Kim, J.H., Kim, Y.H., Kim, Y.-C., Kim, Y.T., Kang, C.H., Jung, Y.J., Kitahara, C.M., Klein, A.P., Klein, R., Kogevinas, M., Koh, W.-P., Kohno, T., Kolonel, L.N., Kooperberg, C., Kratz, C.P., Krogh, V., Kunitoh, H., Kurtz, R.C., Kurucu, N., Lan, Q., Lathrop, M., Lau, C.C., Lecanda, F., Lee, K.-M., Lee, M.P., Marchand, L.L., Lerner, S.P., Li, D., Liao, L.M., Lim, W.-Y., Lin, D., Lin, J., Lindstrom, S., Linet, M.S., Lissowska, J., Liu, J., Ljungberg, B., Lloreta, J., Lu, D., Ma, J., Malats, N., Mannisto, S., Marina, N., Mastrangelo, G., Matsuo, K., McGlynn, K.A., McKean-Cowdin, R., McNeil, L.H., McWilliams, R.R., Melin, B.S., Meltzer, P.S., Mensah, J.E., Miao, X., Michaud, D.S., Mondul, A.M., Moore, L.E., Muir, K., Niwa, S., Olson, S.H., Orr, N., Panico, S., Park, J.Y., Patel, A.V., Patino-Garcia, A., Pavanello, S., Peeters, P.H.M., Peplonska, B., Peters, U., Petersen, G.M., Picci, P., Pike, M.C., Porru, S., Prescott, J., Pu, X., Purdue, M.P., Qiao, Y.-L., Rajaraman, P., Riboli, E., Risch, H.A., Rodabough, R.J., Rothman, N., Ruder, A.M., Ryu, J.-S., Sanson, M., Schned, A., Schumacher, F.R., Schwartz, A.G., Schwartz, K.L., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H.D., Severi, G., Shen, H., Shen, M., Shete, S., Shiraishi, K., Shu, X.-O., Siddiq, A., Sierrasesumaga, L., Sierri, S., Sihoe, A.D.L., Silverman, D.T., Simon, M., Southey, M.C., Spector, L., Spitz, M., Stampfer, M., Stattin, P., Stern, M.C., Stevens, V.L., Stolzenberg-Solomon, R.Z., Stram, D.O., Strom, S.S., Su, W.-C., Sund, M., Sung, S.W., Swerdlow, A., Tan, W., Tanaka, H., Tang, W., Tang, Z.-Z., Tardon, A., Tay, E., Taylor, P.R., Tettey, Y., Thomas, D.M., Tirabosco, R., Tjonneland, A., Tobias, G.S., Toro, J.R., Travis, R.C., Trichopoulos, D., Troisi, R., Truelove, A., Tsai, Y.-H., Tucker, M.A., Tumino, R., Van Den Berg, D., Van Den Eeden, S.K., Vermeulen, R., Vineis, P., Visvanathan, K., Vogel, U., Wang, C., Wang, J., Wang, S.S., Weiderpass, E., Weinstein, S.J., Wentzensen, N., Wheeler, W., White, E., Wiencke, J.K., Wolk, A., Wolpin, B.M., Wong, M.P., Wrensch, M., Wu, C., Wu, T., Wu, X., Wu, Y.-L., Wunder, J.S., Xiang, Y.-B., Xu, J., Yang, H.P., Yang, P.-C., Yatabe, Y., Ye, Y., Yeboah, E.D., Yin, Z., Ying, C., Yu, C.-J., Yu, K., Yuan, J.-M., Zanetti, K.A., Zeleniuch-Jacquotte, A., Zheng, W., Zhou, B., Mirabello, L., Savage, S.A., Kraft, P., Chanock, S.J., Yeager, M., Landi, M.T., Shi, J., Chatterjee, N., and Amundadottir, L.T.

Subjects
Male, SINGLE-NUCLEOTIDE POLYMORPHISM, Genome-wide association study, Epigenesis, Genetic, Gene Frequency, Molecular Biology, Genetics, Genetics (clinical), Neoplasms, Odds Ratio, Genome-wide association studies (GWAS), Telomerase, DNA METHYLATION Author Information, Association Studies Articles, General Medicine, PANCREATIC-CANCER, PROSTATE-CANCER, Neoplasm Proteins, POSTMENOPAUSAL BREAST-CANCER, TERT PROMOTER MUTATIONS, Gene Expression Regulation, Neoplastic, 2 SUSCEPTIBILITY LOCI, DNA methylation, Chromosomes, Human, Pair 5, Female, Risk, Locus (genetics), Single-nucleotide polymorphism, TERT and CLPTM1L gene, Biology, Polymorphism, Single Nucleotide, LUNG-CANCER, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Allele, Gene, Allele frequency, Alleles, Genetic association, chromosome 5p15.33, Computational Biology, Membrane Proteins, DNA Methylation, Genetic Loci, TELOMERE LENGTH, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and PConditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and PConditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10(-15) and PConditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 x 10(-18) and PConditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Published
2014
Full Text
View/download PDF

8. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author

Anne Tjønneland, Jason W. Hoskins, Kala Visvanathan, Yogesh K. Vashist, Dimitrios Trichopoulos, Matthew H. Kulke, Ruth C. Travis, Charles S. Fuchs, Herbert Yu, Kai Yu, Phyllis J. Goodman, Michael Goggins, Jean Wactawski-Wende, Laurie Burdette, Joanne W. Elena, Andrea Mambrini, Petra H.M. Peeters, H. Bas Bueno-de-Mesquita, Maria Teresa Landi, Ulrike Peters, Mingfeng Zhang, Laurence N. Kolonel, Hermann Brenner, Elżbieta Iskierka-Jażdżewska, Robert C. Kurtz, Stephen J. Chanock, Marie-Christine Boutron-Ruault, Ann L. Oberg, Elio Riboli, Maarten F. Bijlsma, Eric J. Jacobs, Manolis Kogevinas, Evelina Mocci, Steven Gallinger, Jinping Jia, Mark P. Purdue, Raffaele Pezzilli, Harvey A. Risch, Demetrius Albanes, Irene Collins, Maria Gazouli, Michelle Cotterchio, Oliver Strobel, Erica J. Childs, Charles C. Chung, Geoffrey S. Tobias, J. Ramón Quirós, Núria Malats, Robert N. Hoover, Pavel Vodicka, Brian M. Wolpin, Ugo Boggi, Patricia Hartge, Gloria M. Petersen, Peter Kraft, Christopher Hautman, Gary E. Goodman, Manal Hassan, Donghui Li, Howard D. Sesso, Malin Sund, Julie E. Buring, Loic Le Marchand, Wei Zheng, Xiao-Ou Shu, Ewa Małecka-Panas, Pavel Soucek, Salvatore Panico, Nicolas Wentzensen, Graham G. Giles, Alpa V. Patel, Daniele Campa, Myron D. Gross, Ghislaine Scelo, J. Michael Gaziano, Juozas Kupcinskas, Debra T. Silverman, Laufey T. Amundadottir, Rachael S. Stolzenberg-Solomon, Neil E. Caporaso, Mazda Jenab, Sara H. Olson, Stefano Landi, Giulia Martina Cavestro, Aruna Kamineni, Laura Beane-Freeman, Roger L. Milne, Rachel E. Neale, Aldo Scarpa, Kathy J. Helzlsouer, Miquel Porta, Emily White, Eric J. Duell, Paige M. Bracci, Nan Hu, Federico Canzian, Eric A. Klein, Gabriele Capurso, Anne Zeleniuch-Jacquotte, Eithne Costello, David J. Hunter, Rudolf Kaaks, Sonja I. Berndt, Kay-Tee Khaw, Nathaniel Rothman, Christian C. Abnet, Francesca Tavano, Christopher A. Haiman, Zhaoming Wang, Ofure Obazee, Alan A. Arslan, Edward Giovannucci, Alison P. Klein, Daniela Basso, Charles Kooperberg, Philip R. Taylor, Satu Männistö, Timothy J. Key, Mark D. Thornquist, Gabriella Andreotti, Lauren K. Brais, Gisella Figlioli, Vittorio Krogh, University Medical Center Utrecht, Imperial College Trust, Cancer Research UK, Medical Research Council UK (MRC), National Institute for Health Research (NIHR), Cancer Research UK (Reino Unido), Medical Research Council (Reino Unido), National Institute for Health Research (Reino Unido), Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetriu, Andreotti, Gabriella, Brais, Lauren, Bueno de Mesquita, H. Ba, Basso, Daniela, Berndt, Sonja I, Boutron Ruault, Marie Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Klein, Eric A, Kogevinas, Manoli, Krogh, Vittorio, Kupcinskas, Juoza, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H. M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J. Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrio, Vashist, Yogesh, Vodicka, Pavel, Wactawski Wende, Jean, Wentzensen, Nicola, Yu, Herbert, Yu, Kai, Zeleniuch Jacquotte, Anne, Kooperberg, Charle, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charle, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, Amundadottir, Laufey T., Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Radiotherapy, Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, Ej, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, Cc, Hautman, C, Arslan, Aa, Beane Freeman, L, Bracci, Pm, Buring, J, Duell, Ej, Gallinger, S, Giles, Gg, Goodman, Ge, Goodman, Pj, Kamineni, A, Kolonel, Ln, Kulke, Mh, Malats, N, Olson, Sh, Sesso, Hd, Visvanathan, K, White, E, Zheng, W, Abnet, Cc, Albanes, D, Andreotti, G, Brais, L, Bueno de Mesquita, Hb, Basso, D, Berndt, Si, Boutron Ruault, Mc, Bijlsma, Mf, Brenner, H, Burdette, L, Campa, D, Caporaso, Ne, Capurso, G, Cavestro, GIULIA MARTINA, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, Jm, Gazouli, M, Giovannucci, El, Goggins, M, Gross, M, Haiman, Ca, Hassan, M, Helzlsouer, Kj, Hu, N, Hunter, Dj, Iskierka Jazdzewska, E, Jenab, M, Kaaks, R, Key, Tj, Khaw, Kt, Klein, Ea, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, Rc, Landi, Mt, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, Rl, Neale, Re, Oberg, Al, Panico, S, Patel, Av, Peeters, Ph, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Quiros, Jr, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, Xo, Silverman, Dt, Soucek, P, Strobel, O, Sund, M, Małecka Panas, E, Taylor, Pr, Tavano, F, Travis, Rc, Thornquist, M, Tjønneland, A, Tobias, G, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch Jacquotte, A, Kooperberg, C, Risch, Ha, Jacobs, Ej, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, Sj, Petersen, Gm, Stolzenberg Solomon, R, Wolpin, Bm, Kraft, P, Klein, Ap, Canzian, F, and Amundadottir, L. T.

Subjects
0301 basic medicine, Candidate gene, Pancreatic disease, GENETIC SUSCEPTIBILITY, pancreatic cancer, Datasets as Topic, Genome-wide association study, imputation, TRET, 0302 clinical medicine, Fine-mapping, GWAS, Imputation, NR5A2, Pancreatic cancer, Oncology, Genotype, Genetics, 3. Good health, fine-mapping, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 8, 616.37-006.6 [udc], BLADDER-CANCER, Single-nucleotide polymorphism, GENOTYPE IMPUTATION, BREAST, Polymorphism, Single Nucleotide, 03 medical and health sciences, Journal Article, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Pàncrees -- Càncer, Cancer och onkologi, LONG-RANGE INTERACTION, business.industry, medicine.disease, Pancreatic neoplasms, genetics, Polymorphism, single nucleotide, RISK LOCI, Fold change, COMMON VARIANT, Cromosomes, Pancreatic Neoplasms, 030104 developmental biology, Cancer and Oncology, business, Imputation (genetics), LRH-1, Priority Research Paper, Genome-Wide Association Study
Abstract

Altres ajuts: The authors acknowledge the contribution of the staff of the Cancer Genomics Research Laboratory (CGR) at the National Cancer Institute, NIH, for their help throughout the project. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Additional acknowledgements for individual participating studies are listed in the Supplemental Materials. Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88×10 −15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22×10 −9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70×10 −8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L - TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7×10 −8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5×10 −4 -2.0×10 −3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Published
2016

9. Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors.

Author

Patro SC, Brandt LD, Bale MJ, Halvas EK, Joseph KW, Shao W, Wu X, Guo S, Murrell B, Wiegand A, Spindler J, Raley C, Hautman C, Sobolewski M, Fennessey CM, Hu WS, Luke B, Hasson JM, Niyongabo A, Capoferri AA, Keele BF, Milush J, Hoh R, Deeks SG, Maldarelli F, Hughes SH, Coffin JM, Rausch JW, Mellors JW, and Kearney MF

Subjects
Anti-Retroviral Agents therapeutic use, Base Sequence, Cell Line, DNA, Viral genetics, Drug Resistance, Viral, HIV Infections virology, Humans, Leukocytes, Mononuclear virology, Lymph Nodes virology, Mutation, Proviruses genetics, Virus Integration physiology, HIV-1 genetics, Virus Integration genetics, Virus Replication genetics
Abstract

Understanding HIV-1 persistence despite antiretroviral therapy (ART) is of paramount importance. Both single-genome sequencing (SGS) and integration site analysis (ISA) provide useful information regarding the structure of persistent HIV DNA populations; however, until recently, there was no way to link integration sites to their cognate proviral sequences. Here, we used multiple-displacement amplification (MDA) of cellular DNA diluted to a proviral endpoint to obtain full-length proviral sequences and their corresponding sites of integration. We applied this method to lymph node and peripheral blood mononuclear cells from 5 ART-treated donors to determine whether groups of identical subgenomic sequences in the 2 compartments are the result of clonal expansion of infected cells or a viral genetic bottleneck. We found that identical proviral sequences can result from both cellular expansion and viral genetic bottlenecks occurring prior to ART initiation and following ART failure. We identified an expanded T cell clone carrying an intact provirus that matched a variant previously detected by viral outgrowth assays and expanded clones with wild-type and drug-resistant defective proviruses. We also found 2 clones from 1 donor that carried identical proviruses except for nonoverlapping deletions, from which we could infer the sequence of the intact parental virus. Thus, MDA-SGS can be used for "viral reconstruction" to better understand intrapatient HIV-1 evolution and to determine the clonality and structure of proviruses within expanded clones, including those with drug-resistant mutations. Importantly, we demonstrate that identical sequences observed by standard SGS are not always sufficient to establish proviral clonality., Competing Interests: Competing interest statement: J.W.M. is a consultant to Gilead Sciences, Merck Research Laboratories, Janssen Pharmaceuticals, and AccelevirDx, and a share option holder of Co-Crystal, Inc. B.F.K. and J.A.H. are co-authors on an October 2015 article. The remaining authors have no potential conflicts.

Published
2019
Full Text
View/download PDF

10. Genome Assembly and Annotation of the Trichoplusia ni Tni-FNL Insect Cell Line Enabled by Long-Read Technologies.

Author

Talsania K, Mehta M, Raley C, Kriga Y, Gowda S, Grose C, Drew M, Roberts V, Cheng KT, Burkett S, Oeser S, Stephens R, Soppet D, Chen X, Kumar P, German O, Smirnova T, Hautman C, Shetty J, Tran B, Zhao Y, and Esposito D

Subjects
Animals, Cell Line, Contig Mapping, High-Throughput Nucleotide Sequencing, Insect Proteins chemistry, Insect Proteins genetics, Lepidoptera cytology, Protein Domains, Sequence Analysis, DNA, Genome, Insect, Lepidoptera genetics, Molecular Sequence Annotation
Abstract

Background: Trichoplusia ni derived cell lines are commonly used to enable recombinant protein expression via baculovirus infection to generate materials approved for clinical use and in clinical trials. In order to develop systems biology and genome engineering tools to improve protein expression in this host, we performed de novo genome assembly of the Trichoplusia ni -derived cell line Tni-FNL., Methods: By integration of PacBio single-molecule sequencing, Bionano optical mapping, and 10X Genomics linked-reads data, we have produced a draft genome assembly of Tni-FNL., Results: Our assembly contains 280 scaffolds, with a N50 scaffold size of 2.3 Mb and a total length of 359 Mb. Annotation of the Tni-FNL genome resulted in 14,101 predicted genes and 93.2% of the predicted proteome contained recognizable protein domains. Ortholog searches within the superorder Holometabola provided further evidence of high accuracy and completeness of the Tni-FNL genome assembly., Conclusions: This first draft Tni-FNL genome assembly was enabled by complementary long-read technologies and represents a high-quality, well-annotated genome that provides novel insight into the complexity of this insect cell line and can serve as a reference for future large-scale genome engineering work in this and other similar recombinant protein production hosts., Competing Interests: The authors declare that they have no competing interests.

Published
2019
Full Text
View/download PDF

11. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

Author

Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, Figlioli G, Mocci E, Collins I, Chung CC, Hautman C, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Kamineni A, Kolonel LN, Kulke MH, Malats N, Olson SH, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Brais L, Bueno-de-Mesquita HB, Basso D, Berndt SI, Boutron-Ruault MC, Bijlsma MF, Brenner H, Burdette L, Campa D, Caporaso NE, Capurso G, Cavestro GM, Cotterchio M, Costello E, Elena J, Boggi U, Gaziano JM, Gazouli M, Giovannucci EL, Goggins M, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Hu N, Hunter DJ, Iskierka-Jazdzewska E, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Neale RE, Oberg AL, Panico S, Patel AV, Peeters PH, Peters U, Pezzilli R, Porta M, Purdue M, Quiros JR, Riboli E, Rothman N, Scarpa A, Scelo G, Shu XO, Silverman DT, Soucek P, Strobel O, Sund M, Małecka-Panas E, Taylor PR, Tavano F, Travis RC, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vashist Y, Vodicka P, Wactawski-Wende J, Wentzensen N, Yu H, Yu K, Zeleniuch-Jacquotte A, Kooperberg C, Risch HA, Jacobs EJ, Li D, Fuchs C, Hoover R, Hartge P, Chanock SJ, Petersen GM, Stolzenberg-Solomon RS, Wolpin BM, Kraft P, Klein AP, Canzian F, and Amundadottir LT

Subjects
Datasets as Topic, Genome-Wide Association Study methods, Genotype, Humans, Polymorphism, Single Nucleotide genetics, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 5 genetics, Chromosomes, Human, Pair 8 genetics, Genetic Predisposition to Disease genetics, Pancreatic Neoplasms genetics
Abstract

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Published
2016
Full Text
View/download PDF

12. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.

Author

Machiela MJ, Zhou W, Karlins E, Sampson JN, Freedman ND, Yang Q, Hicks B, Dagnall C, Hautman C, Jacobs KB, Abnet CC, Aldrich MC, Amos C, Amundadottir LT, Arslan AA, Beane-Freeman LE, Berndt SI, Black A, Blot WJ, Bock CH, Bracci PM, Brinton LA, Bueno-de-Mesquita HB, Burdett L, Buring JE, Butler MA, Canzian F, Carreón T, Chaffee KG, Chang IS, Chatterjee N, Chen C, Chen C, Chen K, Chung CC, Cook LS, Crous Bou M, Cullen M, Davis FG, De Vivo I, Ding T, Doherty J, Duell EJ, Epstein CG, Fan JH, Figueroa JD, Fraumeni JF, Friedenreich CM, Fuchs CS, Gallinger S, Gao YT, Gapstur SM, Garcia-Closas M, Gaudet MM, Gaziano JM, Giles GG, Gillanders EM, Giovannucci EL, Goldin L, Goldstein AM, Haiman CA, Hallmans G, Hankinson SE, Harris CC, Henriksson R, Holly EA, Hong YC, Hoover RN, Hsiung CA, Hu N, Hu W, Hunter DJ, Hutchinson A, Jenab M, Johansen C, Khaw KT, Kim HN, Kim YH, Kim YT, Klein AP, Klein R, Koh WP, Kolonel LN, Kooperberg C, Kraft P, Krogh V, Kurtz RC, LaCroix A, Lan Q, Landi MT, Marchand LL, Li D, Liang X, Liao LM, Lin D, Liu J, Lissowska J, Lu L, Magliocco AM, Malats N, Matsuo K, McNeill LH, McWilliams RR, Melin BS, Mirabello L, Moore L, Olson SH, Orlow I, Park JY, Patiño-Garcia A, Peplonska B, Peters U, Petersen GM, Pooler L, Prescott J, Prokunina-Olsson L, Purdue MP, Qiao YL, Rajaraman P, Real FX, Riboli E, Risch HA, Rodriguez-Santiago B, Ruder AM, Savage SA, Schumacher F, Schwartz AG, Schwartz KL, Seow A, Wendy Setiawan V, Severi G, Shen H, Sheng X, Shin MH, Shu XO, Silverman DT, Spitz MR, Stevens VL, Stolzenberg-Solomon R, Stram D, Tang ZZ, Taylor PR, Teras LR, Tobias GS, Van Den Berg D, Visvanathan K, Wacholder S, Wang JC, Wang Z, Wentzensen N, Wheeler W, White E, Wiencke JK, Wolpin BM, Wong MP, Wu C, Wu T, Wu X, Wu YL, Wunder JS, Xia L, Yang HP, Yang PC, Yu K, Zanetti KA, Zeleniuch-Jacquotte A, Zheng W, Zhou B, Ziegler RG, Perez-Jurado LA, Caporaso NE, Rothman N, Tucker M, Dean MC, Yeager M, and Chanock SJ

Subjects
DNA Methylation genetics, Female, Humans, Male, Polymerase Chain Reaction, Reproducibility of Results, Aging genetics, Chromosomes, Human, X genetics, Mosaicism, X Chromosome Inactivation genetics
Abstract

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results