Citations 5
A targeted genetic association study of epithelial ovarian cancer susceptibility
Earp, Madalene A. , Winham, Stacey J. , Sicotte, Hugues , Chien, Jeremy , Goodman, Marc T. , Levine, Douglas A. , Monteiro, Álvaro N.A. , Ness, Roberta B., Pearce, Celeste Leigh, Rossing, Mary Anne, Tworoger, Shelley S. , Wentzensen, Nicolas , Bisogna, Maria, Brinton, Louise A. , Brooks‐Wilson, Angela , Carney, Michael E. , Cunningham, Julie M. , Edwards, Robert P., Fogarty, Zachary C. , Iversen, Edwin S., Kraft, Peter , Le, Nhu D. , Lin, Hui‐Yi , Lissowska, Jolanta , Moysich, Kirsten B. , Olson, Sara H. , Pike, Malcolm C. , Rider, David N., Terry, Kathryn L. , Thompson, Pamela J., Vierkant, Robert A. , Vitonis, Allison F., Wu, Anna H. , Phelan, Catherine M., Schildkraut, Joellen M. , Chen, Y. Ann , Sellers, Thomas A. , Goode, Ellen L. , Earp, Madalene, Larson, Nicholas, Larson, Nicholas B. , Permuth, Jennifer B. , Anton‐Culver, Hoda , Bandera, Elisa V. , Berchuck, Andrew , Cook, Linda S. , Cramer, Daniel W. , Doherty, Jennifer A. , Larson, Melissa C. , Modugno, Francesmary , Poole, Elizabeth M. , Berg, David Van Den , Wilkens, Lynne R. , Yang, Hannah , Ziogas, Argyrios , Fridley, Brooke L. , Winham, Stacey J , Tworoger, Shelley S , Vierkant, Robert A , Chien, Jeremey , Monteiro, Alvaro N , Moysich, Kirsten , Lissowska, Jolanta , Brooks-Wilson, Angela R , Lin, Hui-Yi , Fogarty, Zachary C , Kraft, Peter , Goodman, Marc T
Oncotarget | February 2, 2016 | Volume: 7 | Issue: 7 | Pages: 7381-7389
Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer
Winham, Stacey J. , Pirie, Ailith, Chen, Y. Ann , Fogarty, Zachary C. , Earp, Madalene A. , Goodman, Marc T. , Levine, Douglas A. , Menon, Usha , Ness, Roberta B., Pearce, Celeste Leigh, Rossing, Mary Anne, Wentzensen, Nicolas , Bean, Yukie T., Bisogna, Maria, Brinton, Louise A. , Carney, Michael E. , Cunningham, Julie M. , DeFazio, Anna , Dicks, Ed , Edwards, Robert P., Gayther, Simon A. , Gore, Martin, Iversen, Edwin S., Jensen, Allan , Johnatty, Sharon E., Lester, Jenny, Lin, Hui‐Yi , Lissowska, Jolanta , Lubiński, Jan , Menkiszak, Janusz , Moysich, Kirsten B. , Pike, Malcolm C. , Ramus, Susan J. , Song, Honglin , Terry, Kathryn L. , Thompson, Pamela J., Berg, David J. van den , Vierkant, Robert A. , Vitonis, Allison F., Walsh, Christine M. , Wu, Anna H. , Group, Georgia Chenevix-Trench on behalf of Australian Ovarian Cancer Study, Schildkraut, Joellen M. , Permuth‐Wey, Jennifer, Phelan, Catherine M., Sellers, Thomas A. , Goode, Ellen L. , Webb, Penelope M. , Whiteman, David C. , Chenevix‐Trench, Georgia , Bowtell, David D.L. , Ewing, Ailith , Fazio, Anna de , Larson, Melissa C. , Anton‐Culver, Hoda , Bandera, Elisa V. , Cramer, Daniel W. , Doherty, Jennifer A. , Gronwald, Jacek , Karlan, Beth Y. , Kjær, Susanne K. , Pejovic, Tanja B. , Cybulski, Cezary , Gentry‐Maharaj, Aleksandra , Modugno, Francesmary , Orlow, Irene , Tyrer, Jonathan P. , Wilkens, Lynne R. , Yang, Hannah , Ziogas, Argyrios , Berchuck, Andrew , Group, Georgia Chenevix-Trench on behalf of Australian Ovarian Cancer Study, Pharoah, Paul D.P. , Fridley, Brooke L. , Winham, Stacey J , Ramus, Susan J , Webb, Penelope M , Jensen, Allan , Vierkant, Robert A , Menon, Usha , Moysich, Kirsten , Lissowska, Jolanta , Menkiszak, Janusz , Lin, Hui-Yi , Fogarty, Zachary C , Ewing, Ailith , Chenevix-Trench, Georgia , Whiteman, David C , Bowtell, David D , Lubinski, Jan , Goodman, Marc T
Cancer Epidemiology, Biomarkers & Prevention | January 8, 2016 | Volume: 25 | Issue: 3 | Pages: 446-454
Abstract 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.
Variation in NF-κB Signaling Pathways and Survival in Invasive Epithelial Ovarian Cancer
Block, Matthew S. , Charbonneau, Bridget, Vierkant, Robert A. , Fogarty, Zachary C. , Bamlet, William R. , Chenevix-Trench, Georgia, AOCS, for, Group, /ACS, Rossing, Mary Anne, Cramer, Daniel, Pearce, Celeste Leigh, Schildkraut, Joellen, Menon, Usha , Kjær, Susanne K. , Levine, Douglas A. , Culver, Hoda Anton, Whittemore, Alice S. , Lambrechts, Diether , Wentzensen, Nicolas , Kupryjańczyk, Jolanta , Chang‐Claude, Jenny , Bandera, Elisa V. , Høgdall, Estrid , Heitz, Florian , Kaye, Stanley B., Fasching, Peter A. , Campbell, Ian , Goodman, Marc T. , Bean, Yukie T., Hays, Laura E., Lurie, Galina, Eccles, Diana , Hein, Alexander , Beckmann, Matthias W. , Ekici, Arif B. , Paul, James, Brown, Robert , Flanagan, James M. , Harter, Philipp , Schwaab, Ira, Høgdall, Claus , Lundvall, Lene, Olson, Sara H. , Orlow, Irene , Paddock, Lisa E. , Eilber, Ursula, Dansonka‐Mieszkowska, Agnieszka , Rzepecka, Iwona K. , Ziółkowska-Seta, Izabela, Brinton, Louise A. , García‐Closas, Montserrat , Despierre, Evelyn, Lambrechts, Sandrina, Vergote, Ignace , Walsh, Christine , Lester, Jenny, Sieh, Weiva , McGuire, Valerie , Rothstein, Joseph H. , Ziogas, Argyrios, Lubiński, Jan , Menkiszak, Janusz , Jensen, Allan , Gayther, Simon A. , Ramus, Susan J. , Wu, Anna H. , Pike, Malcolm C. , Terry, Kathryn L. , Vitonis, Allison F., Ramirez, Starr M., Rider, David N., Knutson, Keith L. , Sellers, Thomas A. , Phelan, Catherine M., Johnatty, Sharon E., DeFazio, Anna , Song, Honglin , Kalli, Kimberly R., Cunningham, Julie M. , Goode, Ellen L. , Chenevix‐Trench, Georgia , Lambrechts, Diether , Pharoah, Paul D.P. , Chenevix-Trench, Georgia, AOCS, for, Group, /ACS, Gronwald, Jacek , Karlan, Beth Y. , Pejovic, Tanja B. , Bois, Andreas du , Rudolph, Anja , Yang, Hannah , Lester, Jenny, Cybulski, Cezary , Gentry‐Maharaj, Aleksandra , Berchuck, Andrew , Berg, David Van Den , Knutson, Keith L. , Doherty, Jennifer A. , Tyrer, Jonathan P. , Fridley, Brooke L. , Fazio, Anna de , Lambrechts, Diether , Kjaer, Susanne K , Ramus, Susan J , Hein, Alexander , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Orlow, Irene , Campbell, Ian G , Bamlet, William R , Menkiszak, Janusz , Brown, Robert , Fogarty, Zachary C , Flanagan, James M , Heitz, Florian , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , García-Closas, Montserrat , Ekici, Arif B , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T , Bandera, Elisa V.
Cancer Epidemiology, Biomarkers & Prevention | April 17, 2014 | Volume: 23 | Issue: 7 | Pages: 1421-1427
Abstract Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-κB (NF-κB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-κB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10−5). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41–2.35; P = 4.13 × 10−6] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56–0.82; P = 2.33 × 10−5). Other associations of note included TNF receptor–associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77–0.92; P = 6.49 × 10−5) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26–0.73; P = 4.56 × 10−4). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies. Cancer Epidemiol Biomarkers Prev; 23(7); 1421–7. ©2014 AACR.
Large-Scale Evaluation of Common Variation in Regulatory T Cell–Related Genes and Ovarian Cancer Outcome
Charbonneau, Bridget, Moysich, Kirsten B., Kalli, Kimberly R., Oberg, Ann L. , Vierkant, Robert A. , Fogarty, Zachary C. , Block, Matthew S. , Goergen, Krista M., Cunningham, Julie M. , Rider, David N., Hartmann, Lynn C. , Lawrenson, Kate , Wang, Chen , Song, Honglin , DeFazio, Anna , Johnatty, Sharon E., Phelan, Catherine M., Sellers, Thomas A. , Ramirez, Starr M., Vitonis, Allison F., Terry, Kathryn L. , Pike, Malcolm C. , Wu, Anna H. , Ramus, Susan J. , Diergaarde, Brenda , Shen, Howard C., Jensen, Allan , Menkiszak, Janusz , Lubiński, Jan , Rothstein, Joseph H. , McGuire, Valerie , Sieh, Weiva , Lester, Jenny, Walsh, Christine , Vergote, Ignace , Lambrechts, Sandrina, Despierre, Evelyn, García‐Closas, Montserrat , Brinton, Louise A. , Śpiewankiewicz, Beata, Rzepecka, Iwona K. , Dansonka‐Mieszkowska, Agnieszka , Paddock, Lisa E. , Orlow, Irene , Lundvall, Lene, Olson, Sara H. , Høgdall, Claus , Schwaab, Ira, Harter, Philipp , Flanagan, James M. , Brown, Robert , Ekici, Arif B. , Beckmann, Matthias W. , Hein, Alexander , Eccles, Diana , Lurie, Galina, Hays, Laura E., Bean, Yukie T., Goodman, Marc T. , Campbell, Ian , Fasching, Peter A. , Konecny, Gottfried E. , Kaye, Stanley B., Heitz, Florian , Høgdall, Estrid , Chang‐Claude, Jenny , Kupryjańczyk, Jolanta , Wentzensen, Nicolas , Lambrechts, Diether , Whittemore, Alice S. , Culver, Hoda Anton, Levine, Douglas A. , Kjær, Susanne K. , Menon, Usha , Schildkraut, Joellen M. , Pearce, Celeste Leigh, Rossing, Mary Anne, Chenevix‐Trench, Georgia , group, for the AOCS, ACS, Gayther, Simon A. , Ness, Roberta B., Odunsi, Kunle , Sucheston, Lara E., Knutson, Keith L. , Goode, Ellen L. , Lambrechts, Diether , Maurer, Matthew J. , Fridley, Brooke L. , Preston, Claudia C. , Tyrer, Jonathan P. , Doherty, Jennifer A. , Berg, David Van Den , Berchuck, Andrew , Gentry‐Maharaj, Aleksandra , Cybulski, Cezary , Ziogas, Argyrios , Yang, Hannah , Seibold, Petra , Rudolph, Anja , Bois, Andreas du , Paul, James , Pejovic, Tanja B. , Bandera, Elisa V. , Karlan, Beth Y. , Gronwald, Jacek , Cramer, Daniel W. , group, for the AOCS, ACS, Pharoah, Paul D.P. , Knutson, Keith L. , Fazio, Anna de , Lambrechts, Diether , Kjaer, Susanne K , Ramus, Susan J , Hein, Alexander , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Lawrenson, Kate , Moysich, Kirsten , Orlow, Irene , Wang, Chen , Campbell, Ian G , Menkiszak, Janusz , Brown, Robert , Fogarty, Zachary C , Flanagan, James M , Heitz, Florian , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , García-Closas, Montserrat , Ekici, Arif B , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Diergaarde, Brenda , Lubinski, Jan , Goodman, Marc T
Cancer Immunology Research | January 27, 2014 | Volume: 2 | Issue: 4 | Pages: 332-340
Abstract The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22–1.64; P = 5.7 × 10−6], rs791587 (HR, 1.36; 95% CI, 1.17–1.57; P = 6.2 × 10−5), rs2476491 (HR, = 1.40; 95% CI, 1.19–1.64; P = 5.6 × 10−5), and rs10795763 (HR, 1.35; 95% CI, 1.17–1.57; P = 7.9 × 10−5), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54–0.82; P = 9.3 × 10−5) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer. Cancer Immunol Res; 2(4); 332–40. ©2014 AACR.
Analysis of Over 10,000 Cases Finds No Association between Previously Reported Candidate Polymorphisms and Ovarian Cancer Outcome
White, Kristin L., Vierkant, Robert A. , Fogarty, Zachary C. , Charbonneau, Bridget, Block, Matthew S. , Chenevix‐Trench, Georgia , group;, for AOCS/ACS, Rossing, Mary Anne, Pearce, Celeste Leigh, Schildkraut, Joellen M. , Menon, Usha , Kjær, Susanne K. , Levine, Douglas A. , Culver, Hoda Anton, Whittemore, Alice S. , Lambrechts, Diether , Wentzensen, Nicolas , Kupryjańczyk, Jolanta , Chang‐Claude, Jenny , Bandera, Elisa V. , Høgdall, Estrid , Heitz, Florian , Kaye, Stanley B., Fasching, Peter A. , Campbell, Ian , Goodman, Marc T. , Bean, Yukie T., Lurie, Galina, Eccles, Diana , Hein, Alexander , Beckmann, Matthias W. , Ekici, Arif B. , Brown, Robert , Flanagan, James M. , Harter, Philipp , Schwaab, Ira, Høgdall, Claus , Lundvall, Lene, Olson, Sara H. , Orlow, Irene , Paddock, Lisa E. , Rudolph, Anja , Eilber, Ursula, Dansonka‐Mieszkowska, Agnieszka , Rzepecka, Iwona K. , Ziółkowska-Seta, Izabela, Brinton, Louise A. , García‐Closas, Montserrat , Despierre, Evelyn, Lambrechts, Sandrina, Vergote, Ignace , Walsh, Christine , Lester, Jenny, Sieh, Weiva , McGuire, Valerie , Rothstein, Joseph H. , Lubiński, Jan , Menkiszak, Janusz , Jensen, Allan , Gayther, Simon A. , Ramus, Susan J. , Wu, Anna H. , Pike, Malcolm C. , DenBerg, David Van, Terry, Kathryn L. , Vitonis, Allison F., Johnatty, Sharon E., DeFazio, Anna , Song, Honglin , Sellers, Thomas A. , Phelan, Catherine M., Kalli, Kimberly R., Cunningham, Julie M. , Goode, Ellen L. , Lambrechts, Diether , Pharoah, Paul D.P. , group;, for AOCS/ACS, Cramer, Daniel W. , Gronwald, Jacek , Karlan, Beth Y. , Pejovic, Tanja B. , Paul, James , Bois, Andreas du , Yang, Hannah , Ziogas, Argyrios , Cybulski, Cezary , Gentry‐Maharaj, Aleksandra , Berchuck, Andrew , Doherty, Jennifer A. , Tyrer, Jonathan P. , Fridley, Brooke L. , Fazio, Anna de , Rudolph, Anja , Lambrechts, Diether , Kjaer, Susanne K , Ramus, Susan J , Hein, Alexander , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Orlow, Irene , Campbell, Ian G , Menkiszak, Janusz , Brown, Robert , Fogarty, Zachary C , Flanagan, James M , Heitz, Florian , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , García-Closas, Montserrat , Ekici, Arif B , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T , Bandera, Elisa V.
Cancer Epidemiology, Biomarkers & Prevention | March 19, 2013 | Volume: 22 | Issue: 5 | Pages: 987-992
Abstract Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987–. ©2013 AACR.