Common genetic variants in the 9p21 region and their associations with multiple tumours

被引:52
作者
Gu, F. [1 ]
Pfeiffer, R. M. [1 ]
Bhattacharjee, S. [1 ]
Han, S. S. [1 ]
Taylor, P. R. [1 ]
Berndt, S. [1 ]
Yang, H. [1 ]
Sigurdson, A. J. [1 ]
Toro, J. [1 ]
Mirabello, L. [1 ]
Greene, M. H. [1 ]
Freedman, N. D. [1 ]
Abnet, C. C. [1 ]
Dawsey, S. M. [1 ]
Hu, N. [1 ]
Qiao, Y-L [2 ]
Ding, T. [3 ]
Brenner, A. V. [1 ]
Garcia-Closas, M. [1 ,4 ]
Hayes, R. [1 ]
Brinton, L. A. [1 ]
Lissowska, J. [5 ]
Wentzensen, N. [1 ]
Kratz, C. [1 ]
Moore, L. E. [1 ]
Ziegler, R. G. [1 ]
Chow, W-H [1 ]
Savage, S. A. [1 ]
Burdette, L. [1 ]
Yeager, M. [1 ]
Chanock, S. J. [1 ]
Chatterjee, N. [1 ]
Tucker, M. A. [1 ]
Goldstein, A. M. [1 ]
Yang, X. R. [1 ]
机构
[1] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA
[2] Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100021, Peoples R China
[3] Shanxi Canc Hosp, Taiyuan 30013, Shanxi, Peoples R China
[4] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England
[5] M Sklodowska Curie Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland
关键词
common genetic variants; CDKN2A; 9p21.3; GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; SQUAMOUS-CELL CARCINOMA; CHROMOSOME; 9P21; NONCODING RNA; HIGH-FREQUENCY; BREAST-CANCER; IDENTIFIES; LUNG-CANCER; NECK-CANCER;
D O I
10.1038/bjc.2013.7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. Methods: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. Results: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P = 7 x 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (P-gene = 0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P < 2.46 x 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P = 0.007). Conclusion: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.
引用
收藏
页码:1378 / 1386
页数:9
相关论文
共 48 条
[1]  
[Anonymous], 1994, Ann Epidemiol, V4, P1, DOI 10.1016/1047-2797(94)90036-1
[2]   Genome-wide association study identifies three new melanoma susceptibility loci [J].
Barrett, Jennifer H. ;
Iles, Mark M. ;
Harland, Mark ;
Taylor, John C. ;
Aitken, Joanne F. ;
Andresen, Per Arne ;
Akslen, Lars A. ;
Armstrong, Bruce K. ;
Avril, Marie-Francoise ;
Azizi, Esther ;
Bakker, Bert ;
Bergman, Wilma ;
Bianchi-Scarra, Giovanna ;
Bressac-de Paillerets, Brigitte ;
Calista, Donato ;
Cannon-Albright, Lisa A. ;
Corda, Eve ;
Cust, Anne E. ;
Debniak, Tadeusz ;
Duffy, David ;
Dunning, Alison M. ;
Easton, Douglas F. ;
Friedman, Eitan ;
Galan, Pilar ;
Ghiorzo, Paola ;
Giles, Graham G. ;
Hansson, Johan ;
Hocevar, Marko ;
Hoeiom, Veronica ;
Hopper, John L. ;
Ingvar, Christian ;
Janssen, Bart ;
Jenkins, Mark A. ;
Joensson, Goeran ;
Kefford, Richard F. ;
Landi, Giorgio ;
Landi, Maria Teresa ;
Lang, Julie ;
Lubinski, Jan ;
Mackie, Rona ;
Malvehy, Josep ;
Martin, Nicholas G. ;
Molven, Anders ;
Montgomery, Grant W. ;
van Nieuwpoort, Frans A. ;
Novakovic, Srdjan ;
Olsson, Hakan ;
Pastorino, Lorenza ;
Puig, Susana ;
Puig-Butille, Joan Anton .
NATURE GENETICS, 2011, 43 (11) :1108-U98
[3]   Loss of p16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer [J].
Bartoletti, Riccardo ;
Cai, Tommaso ;
Nesi, Gabriella ;
Girardi, Lucia Roberta ;
Baroni, Gianna ;
Dal Canto, Maurizio .
JOURNAL OF SURGICAL RESEARCH, 2007, 143 (02) :422-427
[4]   A Subset-Based Approach Improves Power and Interpretation for the Combined Analysis of Genetic Association Studies of Heterogeneous Traits [J].
Bhattacharjee, Samsiddhi ;
Rajaraman, Preetha ;
Jacobs, Kevin B. ;
Wheeler, William A. ;
Melin, Beatrice S. ;
Hartge, Patricia ;
Yeager, Meredith ;
Chung, Charles C. ;
Chanock, Stephen J. ;
Chatterjee, Nilanjan .
AMERICAN JOURNAL OF HUMAN GENETICS, 2012, 90 (05) :821-835
[5]   Genome-wide association study identifies three loci associated with melanoma risk [J].
Bishop, D. Timothy ;
Demenais, Florence ;
Iles, Mark M. ;
Harland, Mark ;
Taylor, John C. ;
Corda, Eve ;
Randerson-Moor, Juliette ;
Aitken, Joanne F. ;
Avril, Marie-Francoise ;
Azizi, Esther ;
Bakker, Bert ;
Bianchi-Scarra, Giovanna ;
Bressac-de Paillerets, Brigitte ;
Calista, Donato ;
Cannon-Albright, Lisa A. ;
Chin-A-Woeng, Thomas ;
Debniak, Tadeusz ;
Galore-Haskel, Gilli ;
Ghiorzo, Paola ;
Gut, Ivo ;
Hansson, Johan ;
Hocevar, Marko ;
Hoiom, Veronica ;
Hopper, John L. ;
Ingvar, Christian ;
Kanetsky, Peter A. ;
Kefford, Richard F. ;
Landi, Maria Teresa ;
Lang, Julie ;
Lubinski, Jan ;
Mackie, Rona ;
Malvehy, Josep ;
Mann, Graham J. ;
Martin, Nicholas G. ;
Montgomery, Grant W. ;
van Nieuwpoort, Frans A. ;
Novakovic, Srdjan ;
Olsson, Hakan ;
Puig, Susana ;
Weiss, Marjan ;
van Workum, Wilbert ;
Zelenika, Diana ;
Brown, Kevin M. ;
Goldstein, Alisa M. ;
Gillanders, Elizabeth M. ;
Boland, Anne ;
Galan, Pilar ;
Elder, David E. ;
Gruis, Nelleke A. ;
Hayward, Nicholas K. .
NATURE GENETICS, 2009, 41 (08) :920-U85
[6]   NUTRITION INTERVENTION TRIALS IN LINXIAN, CHINA - SUPPLEMENTATION WITH SPECIFIC VITAMIN MINERAL COMBINATIONS, CANCER INCIDENCE, AND DISEASE-SPECIFIC MORTALITY IN THE GENERAL-POPULATION [J].
BLOT, WJ ;
LI, JY ;
TAYLOR, PR ;
GUO, WD ;
DAWSEY, S ;
WANG, GQ ;
YANG, CS ;
ZHENG, SF ;
GAIL, M ;
LI, GY ;
YU, Y ;
LIU, BQ ;
TANGREA, J ;
SUN, YH ;
LIU, FS ;
FRAUMENI, JF ;
ZHANG, YH ;
LI, B .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (18) :1483-1492
[7]   Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium [J].
Carlson, CS ;
Eberle, MA ;
Rieder, MJ ;
Yi, Q ;
Kruglyak, L ;
Nickerson, DA .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (01) :106-120
[8]   CVD-associated non-coding RNA, ANRIL, modulates pathways in VSMC [J].
Congrains, Ada ;
Kamide, Kei ;
Katsuya, Tomohiro ;
Yasuda, Osamu ;
Oguro, Ryousuke ;
Yamamoto, Koichi ;
Ohishi, Mitsuru ;
Rakugi, Hiromi .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 419 (04) :612-616
[9]   Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression [J].
Cunnington, Michael S. ;
Koref, Mauro Santibanez ;
Mayosi, Bongani M. ;
Burn, John ;
Keavney, Bernard .
PLOS GENETICS, 2010, 6 (04)
[10]   Association of single-nucleotide polymorphisms in the cell cycle genes with breast cancer in the British population [J].
Driver, Kristy E. ;
Song, Honglin ;
Lesueur, Fabienne ;
Ahmed, Shahana ;
Barbosa-Morais, Nuno L. ;
Tyrer, Jonathan P. ;
Ponder, Bruce A. J. ;
Easton, Douglas F. ;
Pharoah, Paul D. P. ;
Dunning, Alison M. .
CARCINOGENESIS, 2008, 29 (02) :333-341