Assessment of Hepatocyte Growth Factor in Ovarian Cancer Mortality

被引：32

作者：

Goode, Ellen L. ^{[17
]}

Chenevix-Trench, Georgia ^{[3
]}

Hartmann, Lynn C. ^{[1
]}

Fridley, Brooke L. ^{[17
]}

Kalli, Kimberly R.

Vierkant, Robert A. ^{[17
]}

Larson, Melissa C. ^{[17
]}

White, Kristin L. ^{[17
]}

Keeney, Gary L. ^{[2
]}

Oberg, Trynda N. ^{[2
]}

Cunningham, Julie M. ^{[2
]}

Beesley, Jonathan ^{[3
]}

Johnatty, Sharon E. ^{[3
]}

Chen, Xiaoqing ^{[3
]}

Goodman, Katelyn E. ^{[17
]}

Armasu, Sebastian M. ^{[17
]}

Rider, David N. ^{[17
]}

Sicotte, Hugues ^{[17
]}

Schmidt, Michele M. ^{[17
]}

Elliott, Elaine A. ^{[17
]}

Hogdall, Estrid ^{[4
]}

Kjaer, Susanne Krueger ^{[4
]}

Fasching, Peter A. ^{[5
]}

Ekici, Arif B. ^{[8
]}

Lambrechts, Diether ^{[9
,10
]}

Despierre, Evelyn ^{[9
,10
]}

Hogdall, Claus ^{[4
]}

Lundvall, Lene ^{[4
]}

Karlan, Beth Y. ^{[6
]}

Gross, Jenny ^{[7
]}

Brown, Robert ^{[11
]}

Chien, Jeremy ^{[2
]}

Duggan, David J. ^{[12
]}

Tsai, Ya-Yu ^{[13
]}

Phelan, Catherine M. ^{[13
]}

Kelemen, Linda E. ^{[15
]}

Peethambaram, Prema P. ^{[1
]}

Schildkraut, Joellen M. ^{[16
]}

Shridhar, Vijayalakshmi ^{[2
]}

Sutphen, Rebecca ^{[14
]}

Couch, Fergus J. ^{[2
]}

Sellers, Thomas A. ^{[13
]}

机构：

[1] Mayo Clin, Dept Oncol, Coll Med, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Lab Med & Pathol, Coll Med, Rochester, MN 55905 USA

[3] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[4] Danish Canc Soc, Dept Virus Hormones & Canc, Inst Canc Epidemiol, Copenhagen, Denmark

[5] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA

[6] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Los Angeles, CA 90048 USA

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

[8] Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany

[9] VIB, Vesalius Res Ctr, Louvain, Belgium

[10] Katholieke Univ Leuven, Louvain, Belgium

[11] Univ London Imperial Coll Sci Technol & Med, London, England

[12] Translat Genom Res Inst, Phoenix, AZ USA

[13] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Epidemiol & Genet, Tampa, FL 33682 USA

[14] Univ S Florida, Dept Epidemiol, Tampa, FL USA

[15] Alberta Hlth Serv Canc Care, Dept Populat Hlth Res, Calgary, AB, Canada

[16] Duke Univ, Sch Med, Dept Community & Family Med, Durham, NC USA

[17] Mayo Clin, Dept Hlth Sci Res, Coll Med, Rochester, MN 55905 USA

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2011年 / 20卷 / 08期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

RECURRENT OVARIAN; C-MET; EXPRESSION; VARIANTS; SURVIVAL; RISK; 8Q24; SUSCEPTIBILITY; POLYMORPHISMS; PERITONEAL;

D O I：

10.1158/1055-9965.EPI-11-0455

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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 x 10(-5)) and with overall variation in HGF (gene-level test, P = 3.7 x 10(-4)). Analysis of TCGA data revealed consistent associations [e.g., rs5745709 (r(2) = 0.96 with rs1800793): TCGA HR = 2.4, CI = 1.4-4.1, P = 2.2 x 10(-3); Mayo Clinic + TCGA HR = 1.6, CI = 1.3-1.9, P = 7.0 x 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. (C)2011 AACR.

引用

页码：1638 / 1648

页数：11

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