Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

被引：24

作者：

Chornokur, Ganna ^{[1
]}

Lin, Hui-Yi ^{[2
]}

Tyrer, Jonathan P. ^{[3
]}

Lawrenson, Kate ^{[4
]}

Dennis, Joe ^{[4
]}

Amankwah, Ernest K. ^{[1
,5
]}

Qu, Xiaotao ^{[2
]}

Tsai, Ya-Yu ^{[1
]}

Jim, Heather S. L. ^{[6
]}

Chen, Zhihua ^{[2
]}

Chen, Ann Y. ^{[2
]}

Permuth-Wey, Jennifer ^{[1
]}

Aben, Katja K. H. ^{[7
,8
]}

Anton-Culver, Hoda ^{[9
]}

Antonenkova, Natalia ^{[10
]}

Bruinsma, Fiona ^{[11
]}

Bandera, Elisa V. ^{[12
]}

Bean, Yukie T. ^{[12
,14
]}

Beckmann, Matthias W. ^{[15
]}

Bisogna, Maria ^{[16
]}

Bjorge, Line ^{[17
,18
]}

Bogdanova, Natalia ^{[19
]}

Brinton, Louise A. ^{[20
]}

Brooks-Wilson, Angela ^{[21
,22
]}

Bunker, Clareann H. ^{[23
]}

Butzow, Ralf ^{[24
,25
,26
]}

Campbell, Ian G. ^{[27
,28
,29
]}

Carty, Karen ^{[30
,31
]}

Chang-Claude, Jenny ^{[32
]}

Cook, Linda S. ^{[33
]}

Cramer, Daniel W. ^{[34
,35
]}

Cunningham, Julie M. ^{[36
]}

Cybulski, Cezary ^{[37
]}

Dansonka-Mieszkowska, Agnieszka ^{[38
,39
]}

du Bois, Andreas ^{[40
,41
]}

Despierre, Evelyn ^{[42
,43
]}

Dicks, Ed ^{[3
]}

Doherty, Jennifer A. ^{[45
,46
]}

Dork, Thilo ^{[47
]}

Durst, Matthias ^{[48
]}

Easton, Douglas F. ^{[4
,49
]}

Eccles, Diana M. ^{[50
]}

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

Ekici, Arif B. ^{[53
]}

Fasching, Peter A. ^{[15
,54
]}

Fridley, Brooke L. ^{[55
]}

Gao, Yu-Tang ^{[56
]}

Gentry-Maharaj, Aleksandra ^{[57
]}

Giles, Graham G. ^{[11
,58
]}

Glasspool, Rosalind ^{[31
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Dept Canc Epidemiol, Tampa, FL 33612 USA

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

[3] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England

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

[5] All Childrens Hosp Johns Hopkins Med, Clin & Translat Res Org, St Petersburg, FL USA

[6] H Lee Moffitt Canc Ctr & Res Inst, Dept Hlth Outcomes & Behav, Tampa, FL USA

[7] Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Med Ctr, Nijmegen, Netherlands

[8] Comprehens Canc Ctr Netherlands, Nijmegen, Netherlands

[9] Univ Calif Irvine, Genet Epidemiol Res Inst, Ctr Canc Genet Res & Prevent, Irvine, CA USA

[10] NN Alexandrov Natl Canc Ctr Belarus, Minsk, BELARUS

[11] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Australia

[12] Rutgers Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ USA

[13] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA

[14] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA

[15] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen Nuremberg Comprehens Canc Ctr,Erlangen E, D-91054 Erlangen, Germany

[16] Mem Sloan Kettering Canc Ctr, Gynecol Serv, Dept Surg, New York, NY 10021 USA

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

[18] Univ Bergen, Dept Clin Med, Ctr Canc Biomarkers, Bergen, Norway

[19] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany

[20] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[21] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

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

[23] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA

[24] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland

[25] Univ Helsinki, Cent Hosp, Helsinki, Finland

[26] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland

[27] Peter MacCallum Canc Ctr, Canc Genet Lab, Div Res, St Andrews, Australia

[28] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia

[29] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia

[30] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland

[31] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland

[32] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

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

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

[35] Harvard Univ, Sch Med, Boston, MA USA

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

[37] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland

[38] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol, Warsaw, Poland

[39] Inst Oncol, Warsaw, Poland

[40] Knappschaft GmbH, Dept Gynaecol & Gynaecol Oncol, Kliniken Essen Mitte Evang Huyssens Stiftung, Essen, Germany

[41] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynaecol & Gynaecol Oncol, Wiesbaden, Germany

[42] Univ Hosp Leuven, Div Gynecol Oncol, Dept Obstet & Gynaecol, Leuven, Belgium

[43] Univ Hosp Leuven, Leuven Canc Inst, Leuven, Belgium

[44] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Ctr Canc Epidemiol, Cambridge, England

[45] Geisel Sch Med, Dept Epidemiol, Hanover, NH USA

[46] Univ Washington, Program Epidemiol, Div Publ Hlth Sci, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA

[47] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany

[48] Univ Jena, Jena Univ Hosp, Dept Gynecol, Jena, Germany

[49] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

[50] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England

来源：

PLOS ONE | 2015年 / 10卷 / 06期

基金：

英国医学研究理事会; 加拿大健康研究院;

关键词：

UDP-GLUCURONOSYLTRANSFERASES; IRON TRANSPORT; FAMILY SLC25; COLON-CANCER; ASSOCIATION; EXPRESSION; POLYMORPHISM; HEPHAESTIN; CARCINOMA; PROTEINS;

D O I：

10.1371/journal.pone.0128106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10(-4)). Conclusion These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.

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