Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

被引：27

作者：

Lawrenson, Kate ^{[121
]}

Iversen, Edwin S. ^{[1
]}

Tyrer, Jonathan ^{[2
]}

Weber, Rachel Palmieri ^{[3
]}

Concannon, Patrick ^{[4
,5
]}

Hazelett, Dennis J. ^{[6
,7
]}

Li, Qiyuan ^{[8
]}

Marks, Jeffrey R. ^{[9
]}

Berchuck, Andrew ^{[10
]}

Lee, Janet M.

Aben, Katja K. H. ^{[11
,12
]}

Anton-Culver, Hoda ^{[13
]}

Antonenkova, Natalia ^{[14
]}

Bandera, Elisa V. ^{[17
]}

Bean, Yukie ^{[18
,19
]}

Beckmann, Matthias W. ^{[20
]}

Bisogna, Maria ^{[21
]}

Bjorge, Line ^{[22
,23
]}

Bogdanova, Natalia ^{[24
]}

Brinton, Louise A. ^{[25
]}

Brooks-Wilson, Angela ^{[26
,27
]}

Bruinsma, Fiona ^{[28
]}

Butzow, Ralf ^{[29
,30
,31
]}

Campbell, Ian G. ^{[32
,33
,34
]}

Carty, Karen ^{[35
]}

Chang-Claude, Jenny ^{[36
]}

Chenevix-Trench, Georgia ^{[37
]}

Chen, Ann ^{[38
]}

Chen, Zhihua ^{[38
]}

Cook, Linda S. ^{[39
]}

Cramer, Daniel W. ^{[40
,41
,42
]}

Cunningham, Julie M. ^{[43
]}

Cybulski, Cezary

Plisiecka-Halasa, Joanna ^{[45
,46
]}

Dennis, Joe ^{[47
]}

Dicks, Ed ^{[47
]}

Doherty, Jennifer A. ^{[48
]}

Doerk, Thilo ^{[24
]}

du Bois, Andreas ^{[4
,5
,50
]}

Eccles, Diana ^{[51
]}

Easton, Douglas T. ^{[47
]}

Edwards, Robert P. ^{[51
,52
]}

Eilber, Ursula ^{[36
]}

Ekici, Arif B. ^{[53
]}

Fasching, Peter A. ^{[20
,54
]}

Fridley, Brooke L. ^{[55
]}

Gao, Yu-Tang ^{[56
]}

Gentry-Maharaj, Aleksandra ^{[57
]}

Giles, Graham G. ^{[28
,58
]}

Glasspool, Rosalind

机构：

[1] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA

[2] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Dept Oncol, Cambridge CB2 1TN, England

[3] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA

[4] Univ Florida, Genet Inst, Gainesville, FL 32611 USA

[5] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32611 USA

[6] Univ Southern Calif, Keck Sch Med, Norris Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA

[7] Univ Southern Calif, Keck Sch Med, Norris Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA

[8] Xiamen Univ, Sch Med, Xiamen 361000, Peoples R China

[9] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[10] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA

[11] Dept Hlth Evidence, NL-6500 HB Nijmegen, Netherlands

[12] Comprehens Canc Ctr, NL-3542 EG Utrecht, Netherlands

[13] Univ Calif Irvine, Sch Med, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA 92697 USA

[14] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk 223052, BELARUS

[15] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4006, Australia

[16] Peter MacCallum Canc Inst, East Melbourne, Vic 3002, Australia

[17] Rutgers Canc Inst New Jersey, Canc Prevent & Control, New Brunswick, NJ 08903 USA

[18] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA

[19] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA

[20] Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, D-91054 Erlangen, Germany

[21] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA

[22] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway

[23] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, N-5020 Bergen, Norway

[24] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany

[25] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA

[26] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada

[27] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada

[28] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia

[29] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, Finland

[30] Univ Helsinki, Cent Hosp, Helsinki 00029, Finland

[31] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki 00029, Finland

[32] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, Melbourne, Vic 8006, Australia

[33] Univ Melbourne, Dept Pathol, Parkville, Vic 3002, Australia

[34] Univ Melbourne, Dept Oncol, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3002, Australia

[35] Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow G12 0YN, Scotland

[36] German Canc Res Ctr, Div Canc Epidemiol, D-69009 Heidelberg, Germany

[37] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4029, Australia

[38] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL 33612 USA

[39] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA

[40] Harvard Sch Publ Hlth, Boston, MA 02115 USA

[41] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA

[42] Harvard Med Sch, Boston, MA 02115 USA

[43] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

[44] Pomeranian Med Univ, Dept Genet & Pathol, PL-70115 Szczecin, Poland

[45] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland

[46] Inst Oncol, PL-02781 Warsaw, Poland

[47] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England

[48] Geisel Sch Med Dartmouth, Sect Biostat & Epidemiol, Dept Community & Family Med, Lebanon, NH 03756 USA

[49] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, D-45136 Essen, Germany

[50] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, D-65199 Wiesbaden, Germany

来源：

CARCINOGENESIS | 2015年 / 36卷 / 11期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; GERMLINE MUTATIONS; FALLOPIAN-TUBE; REPAIR GENES; DNA-DAMAGE; BREAST; BRCA1; IDENTIFICATION; PROTEIN;

D O I：

10.1093/carcin/bgv138

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P = 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r(2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1 x 10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1: 100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72 x 10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r(2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70 x 10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.

引用

页码：1341 / 1353

页数：13

共 50 条

[1] CHEK2 Founder Variants and Thyroid Cancer Risk
Brock, Pamela
Liynarachchi, Sandya
Nieminen, Taina T.
Chan, Carlos
Kohlmann, Wendy
Stout, Leigh Anne
Yao, Song
La Greca, Amanda
Jensen, Kirk E.
Kolesar, Jill M.
Salhia, Bodour
Gulhati, Pat
Hicks, J. Kevin
Ringel, Matthew D.
[J]. THYROID, 2024, 34 (04) : 477 - 483
[2] Analysis of CHEK2 gene for ovarian cancer susceptibility
Baysal, BE
DeLoia, JA
Willett-Brozick, JE
Goodman, MT
Brady, MF
Modugno, F
Lynch, HT
Conley, YP
Watson, P
Gallion, HH
[J]. GYNECOLOGIC ONCOLOGY, 2004, 95 (01) : 62 - 69
[3] CHEK2 variants: linking functional impact to cancer risk
Boonen, Rick A. C. M.
Vreeswijk, Maaike P. G.
van Attikum, Haico
[J]. TRENDS IN CANCER, 2022, 8 (09): : 759 - 770
[4] Germline CHEK2 variants and risk of lymphoma
Boddicker, Nicholas J.
Mwangi, Raphael
Robinson, Dennis P.
Rosenthal, Allison C.
Habermann, Thomas M.
Feldman, Andrew L.
Rimsza, Lisa M.
King, Rebecca L.
Larson, Melissa C.
Gysbers, Brianna J.
Ansell, Stephen M.
Abeykoon, Jithma P.
Nowakowski, Grzegorz S.
Witzig, Thomas E.
Novak, Anne J.
Slager, Susan L.
Cerhan, James R.
[J]. CANCER RESEARCH, 2023, 83 (07)
[5] Beyond CHEK2 in breast cancer: Search for additional moderately penetrant risk gene variants by analyzing the oligogenic disease course in CHEK2 mutation carriers
Pohl, E.
Borde, J.
Hauke, J.
Schmidt, S.
Weber-Lassalle, K.
Ernst, C.
Niederacher, D.
Arnold, N.
Hellebrand, H.
Meindl, A.
Gehrig, A.
Schmidt, G.
Dutrannoy, V.
Kast, K.
Hahnen, E.
Schmutzler, R.
[J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2018, 26 : 535 - 536
[6] CHEK2 and breast cancer risk
Coupier, I
Stoppa-Lyonnet, D
[J]. BULLETIN DU CANCER, 2002, 89 (11) : 921 - 922
[7] Classifying variants in the CHEK2 gene: the importance of collaboration
Espenschied, C.
Kleiblova, P.
Richardson, M.
Stolarova, L.
Soukupova, J.
Zemankova, P.
Vocka, M.
Smith, L. Panos
Dolinsky, J.
Gau, C. L.
Kleibl, Z.
[J]. EUROPEAN JOURNAL OF CANCER, 2017, 72 : S25 - S25
[8] Beyond CHEK2 in breast cancer: Search for additional moderately penetrant risk gene variants by analyzing the oligogenic disease course in CHEK2 mutation carriers
Pohl, E.
Richters, L.
Hauke, J.
Ernst, C.
Krober, S.
Niederacher, D.
Arnold, N.
Ramser, J.
Gross, E.
Gehrig, A.
Schmidt, G.
Dutrannoy, V.
Kast, K.
Hahnen, E.
Schmutzler, R.
[J]. CANCER RESEARCH, 2017, 77
[9] Irrelevance of CHEK2 variants to diagnosis of breast/ovarian cancer predisposition in Polish cohort
Myszka, Aleksander
Karpinski, Pawel
Slezak, Ryszard
Czemarmazowicz, Halina
Stembalska, Agnieszka
Gil, Justyna
Laczmanska, Izabela
Bednarczyk, Damian
Szmida, Elzbieta
Sasiadek, Maria Malgorzata
[J]. JOURNAL OF APPLIED GENETICS, 2011, 52 (02) : 185 - 191
[10] CHEK2 variants associate with hereditary prostate cancer
Seppälä, EH
Ikonen, T
Mononen, N
Autio, V
Rökman, A
Matikainen, MP
Tammela, TLJ
Schleutker, J
[J]. BRITISH JOURNAL OF CANCER, 2003, 89 (10) : 1966 - 1970

← 1 2 3 4 5 →