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Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer.

Publication ,  Journal Article
Winham, SJ; Pirie, A; Chen, YA; Larson, MC; Fogarty, ZC; Earp, MA; Anton-Culver, H; Bandera, EV; Cramer, D; Doherty, JA; Goodman, MT; Menon, U ...
Published in: Cancer Epidemiol Biomarkers Prev
March 2016

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 (Pmeta = 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 (Pmeta = 1.1E-6; Pcorrected = 0.01). CONCLUSIONS: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed. IMPACT: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446-54. ©2016 AACR.

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Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

March 2016

Volume

25

Issue

3

Start / End Page

446 / 454

Location

United States

Related Subject Headings

  • Survival Rate
  • Ovarian Neoplasms
  • Middle Aged
  • Humans
  • Genotype
  • Female
  • Exome
  • Epidemiology
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Winham, S. J., Pirie, A., Chen, Y. A., Larson, M. C., Fogarty, Z. C., Earp, M. A., … Australian Ovarian Cancer Study Group, . (2016). Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer. Cancer Epidemiol Biomarkers Prev, 25(3), 446–454. https://doi.org/10.1158/1055-9965.EPI-15-0240
Winham, Stacey J., Ailith Pirie, Yian Ann Chen, Melissa C. Larson, Zachary C. Fogarty, Madalene A. Earp, Hoda Anton-Culver, et al. “Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer.Cancer Epidemiol Biomarkers Prev 25, no. 3 (March 2016): 446–54. https://doi.org/10.1158/1055-9965.EPI-15-0240.
Winham SJ, Pirie A, Chen YA, Larson MC, Fogarty ZC, Earp MA, et al. Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer. Cancer Epidemiol Biomarkers Prev. 2016 Mar;25(3):446–54.
Winham, Stacey J., et al. “Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer.Cancer Epidemiol Biomarkers Prev, vol. 25, no. 3, Mar. 2016, pp. 446–54. Pubmed, doi:10.1158/1055-9965.EPI-15-0240.
Winham SJ, Pirie A, Chen YA, Larson MC, Fogarty ZC, Earp MA, Anton-Culver H, Bandera EV, Cramer D, Doherty JA, Goodman MT, Gronwald J, Karlan BY, Kjaer SK, Levine DA, Menon U, Ness RB, Pearce CL, Pejovic T, Rossing MA, Wentzensen N, Bean YT, Bisogna M, Brinton LA, Carney ME, Cunningham JM, Cybulski C, deFazio A, Dicks EM, Edwards RP, Gayther SA, Gentry-Maharaj A, Gore M, Iversen ES, Jensen A, Johnatty SE, Lester J, Lin H-Y, Lissowska J, Lubinski J, Menkiszak J, Modugno F, Moysich KB, Orlow I, Pike MC, Ramus SJ, Song H, Terry KL, Thompson PJ, Tyrer JP, van den Berg DJ, Vierkant RA, Vitonis AF, Walsh C, Wilkens LR, Wu AH, Yang H, Ziogas A, Berchuck A, Chenevix-Trench G, Schildkraut JM, Permuth-Wey J, Phelan CM, Pharoah PDP, Fridley BL, Sellers TA, Goode EL, Australian Ovarian Cancer Study Group. Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer. Cancer Epidemiol Biomarkers Prev. 2016 Mar;25(3):446–454.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

March 2016

Volume

25

Issue

3

Start / End Page

446 / 454

Location

United States

Related Subject Headings

  • Survival Rate
  • Ovarian Neoplasms
  • Middle Aged
  • Humans
  • Genotype
  • Female
  • Exome
  • Epidemiology
  • 42 Health sciences
  • 32 Biomedical and clinical sciences