Citations 15
Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk
Kelemen, Linda E. , Terry, Kathryn L. , Goodman, Marc T. , Webb, Penelope M. , McGuire, Valerie , Rossing, Mary Anne, Wang, Qinggang , Dicks, Ed , Song, Honglin , Kupryjańczyk, Jolanta , Dansonka‐Mieszkowska, Agnieszka , Plisiecka-Hałasa, Joanna, Timorek, Agnieszka, Menon, Usha , Gayther, Simon A. , Ramus, Susan J. , Narod, Steven A., McLaughlin, John R., Glasspool, Rosalind , Lubiński, Jan , Jakubowska, Anna , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Altena, Anne M. van , Aben, Katja K.H. , Olson, Sara H. , Orlow, Irene , Levine, Douglas A. , Bisogna, Maria, Southey, Melissa C. , Bruinsma, Fiona , Kjær, Susanne K. , Høgdall, Estrid , Jensen, Allan , Høgdall, Claus , Lundvall, Lene, Engelholm, Svend‐Aage, Harter, Philipp , Schwaab, Ira, Nevanlinna, Heli , Pelttari, Liisa M. , Leminen, Arto, Thompson, Pamela J., Lurie, Galina, Lambrechts, Diether , Nieuwenhuysen, Els Van , Lambrechts, Sandrina, Vergote, Ignace , Beesley, Jonathan, Investigators, AOCS Study Group/ACS, Fasching, Peter A. , Beckmann, Matthias W. , Hein, Alexander , Ekici, Arif B. , Wu, Anna H. , Pearce, Celeste Leigh, Pike, Malcolm C., Chang‐Claude, Jenny , Dörk, Thilo , Hillemanns, Peter , Runnebaum, Ingo B. , Bogdanova, Natalia , Antonenkova, Natalia, Odunsi, Kunle , Edwards, Robert P., Kelley, Joseph L., Ness, Roberta B., Walsh, Christine , Lester, Jenny, Oršulić, Sandra , Vierkant, Robert A. , Cunningham, Julie M. , Wu, Xifeng , Lu, Karen H., Hildebrandt, Michelle A.T., Weber, Rachel Palmieri , Iversen, Edwin S., Tworoger, Shelley S. , Salvesen, Helga B., Tangen, Ingvild L. , Bean, Yukie T., Kellar, Melissa, Wentzensen, Nicolas , Brinton, Louise A. , Lissowska, Jolanta , García‐Closas, Montserrat , Campbell, Ian , Eccles, Diana , Whittemore, Alice S. , Sieh, Weiva , Rothstein, Joseph H. , Phelan, Catherine M., Moysich, Kirsten B., Goode, Ellen L. , Schildkraut, Joellen M. , Sellers, Thomas A. , Le, Nhu D. , Lu, Karen H. , Zheng, Wei , Lambrechts, Diether , Bandera, Elisa V. , Tyrer, Jonathan P. , Gentry‐Maharaj, Aleksandra , Risch, Harvey A. , McLaughlin, John R., Siddiqui, Nadeem , Paul, James , Carty, Karen , Gronwald, Jacek , Cybulski, Cezary , Cramer, Daniel W. , Giles, Graham G. , Heitz, Florian , Bois, Andreas du , Bützow, Ralf C. , Wilkens, Lynne R. , Beesley, Jonathan, Investigators, AOCS Study Group/ACS, Doherty, Jennifer A. , Stram, Daniel O. , Rudolph, Anja , Dürst, Matthias , Modugno, Francesmary , Karlan, Beth Y. , Fridley, Brooke L. , Liang, Dong , Hildebrandt, Michelle A.T. , Poole, Elizabeth M. , Krakstad, Camilla , Bjørge, Line , Pejovic, Tanja B. , Anton‐Culver, Hoda , Ziogas, Argyrios , Berchuck, Andrew , Pharoah, Paul D.P. , Brooks‐Wilson, Angela , Cook, Linda S. , Pelttari, L M , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , Kjaer, Susanne K , Ramus, Susan J , Tworoger, Shelley S , Webb, Penelope M , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Moysich, Kirsten , Orlow, Irene , Lissowska, Jolanta , Campbell, Ian G , Southey, Melissa C , Glasspool, Rosalind , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , García-Closas, Montserrat , Ekici, Arif B , Bogdanova, Natalia V , Zheng, Wei , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T
Molecular Nutrition & Food Research | July 28, 2014 | Volume: 58 | Issue: 10 | Pages: 2023-2035
ScopeWe reevaluated previously reported associations between variants in pathways of one‐carbon (1‐C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.Methods and resultsOdds ratios (OR) for 446 genetic variants were estimated among 13 410 OC cases and 22 635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10−5) and rs828054 (OR = 1.06; p = 1 × 10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1‐C transfer, previously reported with OC, suggested lower risk at higher folate (pinteraction = 0.03–0.006).ConclusionVariation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP‐by‐folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.
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.
Assessment of Hepatocyte Growth Factor in Ovarian Cancer Mortality
Goode, Ellen L. , Chenevix‐Trench, Georgia , Hartmann, Lynn C. , Kalli, Kimberly R., Vierkant, Robert A. , White, Kristin L., Keeney, Gary L., Oberg, Trynda N., Cunningham, Julie M. , Johnatty, Sharon E. , Chen, Xiaoqing, Goodman, Katelyn E., Armasu, Sebastian M. , Rider, David N., Sicotte, Hugues , Schmidt, Michele M. , Elliott, Elaine A., Høgdall, Estrid , Kjær, Susanne K. , Fasching, Peter A. , Ekici, Arif B. , Lambrechts, Diether , Despierre, Evelyn, Høgdall, Claus , Lundvall, Lene, Gross, Jenny , Brown, Robert , Chien, Jeremy , Duggan, David , Phelan, Catherine M., Kelemen, Linda E. , Peethambaram, Prema P. , Schildkraut, Joellen M. , Shridhar, Vijayalakshmi, Sutphen, Rebecca , Sellers, Thomas A. , Lambrechts, Diether , Fridley, Brooke L. , Larson, Melissa C. , Beesley, Jonathan , Chen, Xiaoqing, Karlan, Beth Y. , Tsai, Ya-Yu , Couch, Fergus J. , Lambrechts, Diether , Kjaer, Susanne K , Vierkant, Robert A , Chien, Jeremey , Brown, Robert , Lambrechts, Diether , Ekici, Arif B , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K
Cancer Epidemiology, Biomarkers & Prevention | August 8, 2011 | Volume: 20 | Issue: 8 | Pages: 1638-1648
Abstract Background: Invasive ovarian cancer is a significant cause of gynecologic cancer mortality. Methods: We examined whether this mortality was associated with inherited variation in approximately 170 candidate genes/regions [993 single-nucleotide polymorphisms (SNPs)] in a multistage analysis based initially on 312 Mayo Clinic cases (172 deaths). Additional analyses used The Cancer Genome Atlas (TCGA; 127 cases, 62 deaths). For the most compelling gene, we immunostained Mayo Clinic tissue microarrays (TMA, 326 cases) and conducted consortium-based SNP replication analysis (2,560 cases, 1,046 deaths). Results: The strongest initial mortality association was in HGF (hepatocyte growth factor) at rs1800793 (HR = 1.7, 95% CI = 1.3–2.2, P = 2.0 × 10−5) and with overall variation in HGF (gene-level test, P = 3.7 × 10−4). Analysis of TCGA data revealed consistent associations [e.g., rs5745709 (r2 = 0.96 with rs1800793): TCGA HR = 2.4, CI = 1.4–4.1, P = 2.2 × 10−3; Mayo Clinic + TCGA HR = 1.6, CI = 1.3–1.9, P = 7.0 × 10−5] and suggested genotype correlation with reduced HGF mRNA levels (P = 0.01). In Mayo Clinic TMAs, protein levels of HGF, its receptor MET (C-MET), and phospho-MET were not associated with genotype and did not serve as an intermediate phenotype; however, phospho-MET was associated with reduced mortality (P = 0.01) likely due to higher expression in early-stage disease. In eight additional ovarian cancer case series, HGF rs5745709 was not associated with mortality (HR = 1.0, CI = 0.9–1.1, P = 0.87). Conclusions: We conclude that although HGF signaling is critical to migration, invasion, and apoptosis, it is unlikely that HGF genetic variation plays a major role in ovarian cancer mortality. Furthermore, any minor role is not related to genetically-determined expression. Impact: Our study shows the utility of multiple data types and multiple data sets in observational studies. Cancer Epidemiol Biomarkers Prev; 20(8); 1638–48. ©2011 AACR.