Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

被引：7

作者：

Winham, Stacey J. ^{[1
]}

Pirie, Ailith ^{[2
]}

Chen, Yian Ann ^{[3
]}

Larson, Melissa C. ^{[1
]}

Fogarty, Zachary C. ^{[1
]}

Earp, Madalene A. ^{[4
]}

Anton-Culver, Hoda ^{[5
]}

Bandera, Elisa V. ^{[6
,7
]}

Cramer, Daniel ^{[8
,9
,10
]}

Doherty, Jennifer A. ^{[11
]}

Goodman, Marc T. ^{[12
]}

Gronwald, Jacek ^{[13
]}

Karlan, Beth Y. ^{[14
]}

Kjaer, Susanne K. ^{[15
,16
]}

Levine, Douglas A. ^{[17
]}

Menon, Usha ^{[18
]}

Ness, Roberta B. ^{[19
]}

Pearce, Celeste L. ^{[20
]}

Pejovic, Tanja ^{[21
,22
]}

Rossing, Mary Anne ^{[23
,24
]}

Wentzensen, Nicolas ^{[25
]}

Bean, Yukie T. ^{[21
,22
]}

Bisogna, Maria ^{[17
]}

Brinton, Louise A. ^{[25
]}

Carney, Michael E. ^{[26
]}

Cunningham, Julie M. ^{[27
]}

Cybulski, Cezary ^{[28
]}

Defazio, Anna ^{[29
,30
]}

Dicks, Ed M. ^{[31
]}

Edwards, Robert P. ^{[32
]}

Gayther, Simon A. ^{[20
]}

Gentry-Maharaj, Aleksandra ^{[18
]}

Gore, Martin ^{[33
]}

Iversen, Edwin S. ^{[34
]}

Jensen, Allan ^{[15
]}

Johnatty, Sharon E. ^{[35
]}

Lester, Jenny ^{[14
]}

Lin, Hui-Yi ^{[3
]}

Lissowska, Jolanta ^{[36
]}

Lubinski, Jan ^{[13
]}

Menkiszak, Janusz ^{[37
]}

Modugno, Francesmary ^{[32
,38
,39
,40
]}

Moysich, Kirsten B. ^{[41
]}

Orlow, Irene ^{[42
]}

Pike, Malcolm C. ^{[20
,42
]}

Ramus, Susan J. ^{[20
]}

Song, Honglin ^{[31
]}

Terry, Kathryn L. ^{[8
,9
,10
]}

Thompson, Pamela J. ^{[12
]}

Tyrer, Jonathan P. ^{[31
]}

机构：

[1] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA

[2] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England

[3] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA

[4] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN 55905 USA

[5] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA

[6] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA

[7] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA

[8] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA

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

[10] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[11] Geisel Sch Med Dartmouth, Epidemiol & Biostat Sect, Lebanon, NH USA

[12] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA

[13] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland

[14] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA

[15] Danish Canc Soc, Res Ctr, Virus Lifestyle & Genes, Copenhagen, Denmark

[16] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark

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

[18] UCL, Inst Womens Hlth, Dept Womens Canc, Gynaecol Canc Res Ctr, London, England

[19] Univ Texas Sch Publ Hlth, Houston, TX USA

[20] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

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

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

[23] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[24] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA

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

[26] Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol, Honolulu, HI 96822 USA

[27] Mayo Clin, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN 55905 USA

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

[29] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia

[30] Univ Sydney, Westmead Millennium Inst, Ctr Canc Res, Sydney, NSW 2006, Australia

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

[32] Univ Pittsburgh, Sch Med, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA

[33] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England

[34] Duke Univ, Dept Stat Sci, Durham, NC USA

[35] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia

[36] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland

[37] Pomeranian Med Univ, Dept Surg Gynecol & Gynecol Oncol Adults & Adoles, Szczecin, Poland

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

[39] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA USA

[40] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA

[41] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA

[42] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA

[43] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA

[44] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Dept Epidemiol, Irvine, CA 92717 USA

[45] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA

[46] QIMR Berghofer Med Res Inst, Canc Div, Herston, Qld, Australia

[47] Peter MacCallum Canc Inst, 481 Little Lonsdale St, Melbourne, Vic 3000, Australia

[48] Univ Virginia, Publ Hlth Serv, Charlottesville, VA USA

[49] Univ Kansas, Ctr Canc, Kansas IDeA Network Biomed Res Excellence Bioinfo, Kansas City, KS USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2016年 / 25卷 / 03期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; BREAST-CANCER; MUTATION CARRIERS; COMMON VARIANTS; RARE VARIANTS; BRCA1; WOMEN; AUTOPHAGY; DISEASES;

D O I：

10.1158/1055-9965.EPI-15-0240

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC). Methods: The primary patient set (Set 1) included 14 independent-EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped). Results: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (P-meta = 1.1E-6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (P-meta = 1.1E-6; P-corrected = 0.01). Conclusions: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed.

引用

页码：446 / 454

页数：9

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