The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

Paul D P Pharoah; Rachel T Palmieri; Susan J Ramus; Simon A Gayther; Irene L Andrulis; Hoda A Anton-Culver; Natalia Antonenkova; Antonis C Antoniou; Study Group Of Bcfr Investigators; Mary S Beattie; Matthias W Beckmann; Michael J Birrer; Natalia Bogdanova; Kelly L Bolton; Wendy Brewster; Angela Brooks-Wilson; Robert Brown; Ralf Bützow; Trinidad Caldes; Maria A Caligo; Ian G Campbell; Jenny Chang-Claude; Y Ann Chen; Georgia Chenevix-Trench; Linda S Cook; Fergus J Couch; Daniel W Cramer; Julie M Cunningham; Evelyn Despierre; Jennifer A Doherty; Thilo Dork; Matthias Durst; Diana Eccles; Arif B Ekici; Study Group Of Embrace Investigators; Peter A Fasching; Anna de Fazio; David Fenstermacher; James M Flanagan; Brooke L Fridley; Eitan Friedman; Bo Gao; Study Group Of Gemo Study Collaborators; Aleksandra Gentry-Maharaj; Andrew K Godwin; Ellen L Goode; Marc T Goodman; Jenny Gross; Thomas van Overeem Hansen; Paul R Harnett; Study Group Of Hebon Investigators; Tuomas Heikkinen; Rebecca Hein; Claus K Hogdall; Estrid Vilma Solyom Høgdall; Edwin Iversen; Anna Jakubowska; Sharon E Johnatty; Beth Y Karlan; Noah D Kauff; Stanley B Kaye; Study Group Of Kconfab Investigators; Linda E Kelemen; Lambertus A Kiemeney; Susanne K Kjaer; Diether Lambrechts; James P Lapolla; Conxi Lazaro; Nhu D Le; Arto Leminen; Karin Leunen; Douglas A Levine; Yi Lu; Lene Lundvall; Stuart Macgregor; Tamara Marees; Leon Massuger; John McLaughlin; Usha Menon; Marco Montagna; Kirsten B Moysich; Steven A Narod; Katherine L Nathanson; Lotte Nedergaard; Roberta B Ness; Heli A Nevanlinna; Stefan Nickels; Ana Osorio; James Paul; Celeste Leigh Pearce; Catherine M Phelan; Malcolm C Pike; Paolo Radice; Maria Rossing; Joellen M Schildkraut; Thomas A Sellers; Christian F Singer; Honglin Song; Daniel O Stram; Rebecca Sutphen; Study Group Of Swe-Brca Investigators; Kathryn L Terry; Ya-Yu Tsai; Anne M van Altena; Ignace Vergote; Robert A Vierkant; Allison F Vitonis; Christine Walsh; Shan Wang-Gohrke; Barbara Wappenschmidt; Anna H Wu; Argyrios Ziogas; Andrew Berchuck; Harvey Risch

doi:10.1158/1078-0432.CCR-10-3405

The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

Paul D P Pharoah, Rachel T Palmieri, Susan J Ramus, Simon A Gayther, Irene L Andrulis, Hoda A Anton-Culver, Natalia Antonenkova, Antonis C Antoniou, Study Group Of Bcfr Investigators, Mary S Beattie, Matthias W Beckmann, Michael J Birrer, Natalia Bogdanova, Kelly L Bolton, Wendy Brewster, Angela Brooks-Wilson, Robert Brown, Ralf Bützow, Trinidad Caldes, Maria A CaligoIan G Campbell, Jenny Chang-Claude, Y Ann Chen, Georgia Chenevix-Trench, Linda S Cook, Fergus J Couch, Daniel W Cramer, Julie M Cunningham, Evelyn Despierre, Jennifer A Doherty, Thilo Dork, Matthias Durst, Diana Eccles, Arif B Ekici, Study Group Of Embrace Investigators, Peter A Fasching, Anna de Fazio, David Fenstermacher, James M Flanagan, Brooke L Fridley, Eitan Friedman, Bo Gao, Study Group Of Gemo Study Collaborators, Aleksandra Gentry-Maharaj, Andrew K Godwin, Ellen L Goode, Marc T Goodman, Jenny Gross, Thomas van Overeem Hansen, Paul R Harnett, Study Group Of Hebon Investigators, Tuomas Heikkinen, Rebecca Hein, Claus K Hogdall, Estrid Vilma Solyom Høgdall, Edwin Iversen, Anna Jakubowska, Sharon E Johnatty, Beth Y Karlan, Noah D Kauff, Stanley B Kaye, Study Group Of Kconfab Investigators, Linda E Kelemen, Lambertus A Kiemeney, Susanne K Kjaer, Diether Lambrechts, James P Lapolla, Conxi Lazaro, Nhu D Le, Arto Leminen, Karin Leunen, Douglas A Levine, Yi Lu, Lene Lundvall, Stuart Macgregor, Tamara Marees, Leon Massuger, John McLaughlin, Usha Menon, Marco Montagna, Kirsten B Moysich, Steven A Narod, Katherine L Nathanson, Lotte Nedergaard, Roberta B Ness, Heli A Nevanlinna, Stefan Nickels, Ana Osorio, James Paul, Celeste Leigh Pearce, Catherine M Phelan, Malcolm C Pike, Paolo Radice, Maria Rossing, Joellen M Schildkraut, Thomas A Sellers, Christian F Singer, Honglin Song, Daniel O Stram, Rebecca Sutphen, Study Group Of Swe-Brca Investigators, Kathryn L Terry, Ya-Yu Tsai, Anne M van Altena, Ignace Vergote, Robert A Vierkant, Allison F Vitonis, Christine Walsh, Shan Wang-Gohrke, Barbara Wappenschmidt, Anna H Wu, Argyrios Ziogas, Andrew Berchuck, Harvey Risch

45 Citationer (Scopus)

Abstract

PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene, and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published paper, analyzing fewer than 1,000 subjects in total, has examined this association. EXPERIMENTAL DESIGN: Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from nineteen studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival data and eighteen studies with all-cause mortality data.RESULTS: No evidence of association was observed between genotype and risk of unselected EOC (odds ratio (OR)=1.02, 95% confidence interval (CI)=0.95-1.10), serous EOC (OR=1.08, 95%CI=0.98-1.18), familial EOC (OR=1.09, 95%CI=0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR=1.09, 95%CI=0.88-1.36). There was little evidence for association with survival time among unselected cases (hazard ratio (HR)=1.10, 95%CI=0.99-1.22), among serous cases (HR=1.12, 95%CI=0.99-1.28), or with progression-free survival in 540 cases treated with carboplatin and paclitaxel (HR=1.18, 95%CI=0.93-1.52).CONCLUSIONS: These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction therefore appears unwarranted.

Originalsprog	Engelsk
Tidsskrift	Clinical Cancer Research
Vol/bind	17
Udgave nummer	11
Sider (fra-til)	3742-50
Antal sider	9
ISSN	1078-0432
DOI	https://doi.org/10.1158/1078-0432.CCR-10-3405
Status	Udgivet - 13 apr. 2011

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10.1158/1078-0432.CCR-10-3405

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Pharoah, P. D. P., Palmieri, R. T., Ramus, S. J., Gayther, S. A., Andrulis, I. L., Anton-Culver, H. A., Antonenkova, N., Antoniou, A. C., Bcfr Investigators, S. G. O., Beattie, M. S., Beckmann, M. W., Birrer, M. J., Bogdanova, N., Bolton, K. L., Brewster, W., Brooks-Wilson, A., Brown, R., Bützow, R., Caldes, T., ... Risch, H. (2011). The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing. Clinical Cancer Research, 17(11), 3742-50. https://doi.org/10.1158/1078-0432.CCR-10-3405

Pharoah, PDP, Palmieri, RT, Ramus, SJ, Gayther, SA, Andrulis, IL, Anton-Culver, HA, Antonenkova, N, Antoniou, AC, Bcfr Investigators, SGO, Beattie, MS, Beckmann, MW, Birrer, MJ, Bogdanova, N, Bolton, KL, Brewster, W, Brooks-Wilson, A, Brown, R, Bützow, R, Caldes, T, Caligo, MA, Campbell, IG, Chang-Claude, J, Chen, YA, Chenevix-Trench, G, Cook, LS, Couch, FJ, Cramer, DW, Cunningham, JM, Despierre, E, Doherty, JA, Dork, T, Durst, M, Eccles, D, Ekici, AB, Embrace Investigators, SGO, Fasching, PA, de Fazio, A, Fenstermacher, D, Flanagan, JM, Fridley, BL, Friedman, E, Gao, B, Gemo Study Collaborators, SGO, Gentry-Maharaj, A, Godwin, AK, Goode, EL, Goodman, MT, Gross, J, Hansen, TVO, Harnett, PR, Hebon Investigators, SGO, Heikkinen, T, Hein, R, Hogdall, CK , Høgdall, EVS, Iversen, E, Jakubowska, A, Johnatty, SE, Karlan, BY, Kauff, ND, Kaye, SB, Kconfab Investigators, SGO, Kelemen, LE, Kiemeney, LA, Kjaer, SK, Lambrechts, D, Lapolla, JP, Lazaro, C, Le, ND, Leminen, A, Leunen, K, Levine, DA, Lu, Y, Lundvall, L, Macgregor, S, Marees, T, Massuger, L, McLaughlin, J, Menon, U, Montagna, M, Moysich, KB, Narod, SA, Nathanson, KL, Nedergaard, L, Ness, RB, Nevanlinna, HA, Nickels, S, Osorio, A, Paul, J, Pearce, CL, Phelan, CM, Pike, MC, Radice, P, Rossing, M, Schildkraut, JM, Sellers, TA, Singer, CF, Song, H, Stram, DO, Sutphen, R, Swe-Brca Investigators, SGO, Terry, KL, Tsai, Y-Y, van Altena, AM, Vergote, I, Vierkant, RA, Vitonis, AF, Walsh, C, Wang-Gohrke, S, Wappenschmidt, B, Wu, AH, Ziogas, A, Berchuck, A & Risch, H 2011, 'The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing', Clinical Cancer Research, bind 17, nr. 11, s. 3742-50. https://doi.org/10.1158/1078-0432.CCR-10-3405

@article{de2e5c9e88a64e06b8da3532d205527c,

title = "The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing",

abstract = "PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene, and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published paper, analyzing fewer than 1,000 subjects in total, has examined this association. EXPERIMENTAL DESIGN: Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from nineteen studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival data and eighteen studies with all-cause mortality data.RESULTS: No evidence of association was observed between genotype and risk of unselected EOC (odds ratio (OR)=1.02, 95% confidence interval (CI)=0.95-1.10), serous EOC (OR=1.08, 95%CI=0.98-1.18), familial EOC (OR=1.09, 95%CI=0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR=1.09, 95%CI=0.88-1.36). There was little evidence for association with survival time among unselected cases (hazard ratio (HR)=1.10, 95%CI=0.99-1.22), among serous cases (HR=1.12, 95%CI=0.99-1.28), or with progression-free survival in 540 cases treated with carboplatin and paclitaxel (HR=1.18, 95%CI=0.93-1.52).CONCLUSIONS: These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction therefore appears unwarranted.",

author = "Pharoah, {Paul D P} and Palmieri, {Rachel T} and Ramus, {Susan J} and Gayther, {Simon A} and Andrulis, {Irene L} and Anton-Culver, {Hoda A} and Natalia Antonenkova and Antoniou, {Antonis C} and {Bcfr Investigators}, {Study Group Of} and Beattie, {Mary S} and Beckmann, {Matthias W} and Birrer, {Michael J} and Natalia Bogdanova and Bolton, {Kelly L} and Wendy Brewster and Angela Brooks-Wilson and Robert Brown and Ralf B{\"u}tzow and Trinidad Caldes and Caligo, {Maria A} and Campbell, {Ian G} and Jenny Chang-Claude and Chen, {Y Ann} and Georgia Chenevix-Trench and Cook, {Linda S} and Couch, {Fergus J} and Cramer, {Daniel W} and Cunningham, {Julie M} and Evelyn Despierre and Doherty, {Jennifer A} and Thilo Dork and Matthias Durst and Diana Eccles and Ekici, {Arif B} and {Embrace Investigators}, {Study Group Of} and Fasching, {Peter A} and {de Fazio}, Anna and David Fenstermacher and Flanagan, {James M} and Fridley, {Brooke L} and Eitan Friedman and Bo Gao and {Gemo Study Collaborators}, {Study Group Of} and Aleksandra Gentry-Maharaj and Godwin, {Andrew K} and Goode, {Ellen L} and Goodman, {Marc T} and Jenny Gross and Hansen, {Thomas van Overeem} and Harnett, {Paul R} and {Hebon Investigators}, {Study Group Of} and Tuomas Heikkinen and Rebecca Hein and Hogdall, {Claus K} and H{\o}gdall, {Estrid Vilma Solyom} and Edwin Iversen and Anna Jakubowska and Johnatty, {Sharon E} and Karlan, {Beth Y} and Kauff, {Noah D} and Kaye, {Stanley B} and {Kconfab Investigators}, {Study Group Of} and Kelemen, {Linda E} and Kiemeney, {Lambertus A} and Kjaer, {Susanne K} and Diether Lambrechts and Lapolla, {James P} and Conxi Lazaro and Le, {Nhu D} and Arto Leminen and Karin Leunen and Levine, {Douglas A} and Yi Lu and Lene Lundvall and Stuart Macgregor and Tamara Marees and Leon Massuger and John McLaughlin and Usha Menon and Marco Montagna and Moysich, {Kirsten B} and Narod, {Steven A} and Nathanson, {Katherine L} and Lotte Nedergaard and Ness, {Roberta B} and Nevanlinna, {Heli A} and Stefan Nickels and Ana Osorio and James Paul and Pearce, {Celeste Leigh} and Phelan, {Catherine M} and Pike, {Malcolm C} and Paolo Radice and Maria Rossing and Schildkraut, {Joellen M} and Sellers, {Thomas A} and Singer, {Christian F} and Honglin Song and Stram, {Daniel O} and Rebecca Sutphen and {Swe-Brca Investigators}, {Study Group Of} and Terry, {Kathryn L} and Ya-Yu Tsai and {van Altena}, {Anne M} and Ignace Vergote and Vierkant, {Robert A} and Vitonis, {Allison F} and Christine Walsh and Shan Wang-Gohrke and Barbara Wappenschmidt and Wu, {Anna H} and Argyrios Ziogas and Andrew Berchuck and Harvey Risch",

year = "2011",

month = apr,

day = "13",

doi = "10.1158/1078-0432.CCR-10-3405",

language = "English",

volume = "17",

pages = "3742--50",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "11",

}

TY - JOUR

T1 - The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

AU - Pharoah, Paul D P

AU - Palmieri, Rachel T

AU - Ramus, Susan J

AU - Gayther, Simon A

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda A

AU - Antonenkova, Natalia

AU - Antoniou, Antonis C

AU - Bcfr Investigators, Study Group Of

AU - Beattie, Mary S

AU - Beckmann, Matthias W

AU - Birrer, Michael J

AU - Bogdanova, Natalia

AU - Bolton, Kelly L

AU - Brewster, Wendy

AU - Brooks-Wilson, Angela

AU - Brown, Robert

AU - Bützow, Ralf

AU - Caldes, Trinidad

AU - Caligo, Maria A

AU - Campbell, Ian G

AU - Chang-Claude, Jenny

AU - Chen, Y Ann

AU - Chenevix-Trench, Georgia

AU - Cook, Linda S

AU - Couch, Fergus J

AU - Cramer, Daniel W

AU - Cunningham, Julie M

AU - Despierre, Evelyn

AU - Doherty, Jennifer A

AU - Dork, Thilo

AU - Durst, Matthias

AU - Eccles, Diana

AU - Ekici, Arif B

AU - Embrace Investigators, Study Group Of

AU - Fasching, Peter A

AU - de Fazio, Anna

AU - Fenstermacher, David

AU - Flanagan, James M

AU - Fridley, Brooke L

AU - Friedman, Eitan

AU - Gao, Bo

AU - Gemo Study Collaborators, Study Group Of

AU - Gentry-Maharaj, Aleksandra

AU - Godwin, Andrew K

AU - Goode, Ellen L

AU - Goodman, Marc T

AU - Gross, Jenny

AU - Hansen, Thomas van Overeem

AU - Harnett, Paul R

AU - Hebon Investigators, Study Group Of

AU - Heikkinen, Tuomas

AU - Hein, Rebecca

AU - Hogdall, Claus K

AU - Høgdall, Estrid Vilma Solyom

AU - Iversen, Edwin

AU - Jakubowska, Anna

AU - Johnatty, Sharon E

AU - Karlan, Beth Y

AU - Kauff, Noah D

AU - Kaye, Stanley B

AU - Kconfab Investigators, Study Group Of

AU - Kelemen, Linda E

AU - Kiemeney, Lambertus A

AU - Kjaer, Susanne K

AU - Lambrechts, Diether

AU - Lapolla, James P

AU - Lazaro, Conxi

AU - Le, Nhu D

AU - Leminen, Arto

AU - Leunen, Karin

AU - Levine, Douglas A

AU - Lu, Yi

AU - Lundvall, Lene

AU - Macgregor, Stuart

AU - Marees, Tamara

AU - Massuger, Leon

AU - McLaughlin, John

AU - Menon, Usha

AU - Montagna, Marco

AU - Moysich, Kirsten B

AU - Narod, Steven A

AU - Nathanson, Katherine L

AU - Nedergaard, Lotte

AU - Ness, Roberta B

AU - Nevanlinna, Heli A

AU - Nickels, Stefan

AU - Osorio, Ana

AU - Paul, James

AU - Pearce, Celeste Leigh

AU - Phelan, Catherine M

AU - Pike, Malcolm C

AU - Radice, Paolo

AU - Rossing, Maria

AU - Schildkraut, Joellen M

AU - Sellers, Thomas A

AU - Singer, Christian F

AU - Song, Honglin

AU - Stram, Daniel O

AU - Sutphen, Rebecca

AU - Swe-Brca Investigators, Study Group Of

AU - Terry, Kathryn L

AU - Tsai, Ya-Yu

AU - van Altena, Anne M

AU - Vergote, Ignace

AU - Vierkant, Robert A

AU - Vitonis, Allison F

AU - Walsh, Christine

AU - Wang-Gohrke, Shan

AU - Wappenschmidt, Barbara

AU - Wu, Anna H

AU - Ziogas, Argyrios

AU - Berchuck, Andrew

AU - Risch, Harvey

PY - 2011/4/13

Y1 - 2011/4/13

N2 - PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene, and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published paper, analyzing fewer than 1,000 subjects in total, has examined this association. EXPERIMENTAL DESIGN: Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from nineteen studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival data and eighteen studies with all-cause mortality data.RESULTS: No evidence of association was observed between genotype and risk of unselected EOC (odds ratio (OR)=1.02, 95% confidence interval (CI)=0.95-1.10), serous EOC (OR=1.08, 95%CI=0.98-1.18), familial EOC (OR=1.09, 95%CI=0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR=1.09, 95%CI=0.88-1.36). There was little evidence for association with survival time among unselected cases (hazard ratio (HR)=1.10, 95%CI=0.99-1.22), among serous cases (HR=1.12, 95%CI=0.99-1.28), or with progression-free survival in 540 cases treated with carboplatin and paclitaxel (HR=1.18, 95%CI=0.93-1.52).CONCLUSIONS: These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction therefore appears unwarranted.

AB - PURPOSE: An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3'UTR miRNA binding site of the KRAS oncogene, and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published paper, analyzing fewer than 1,000 subjects in total, has examined this association. EXPERIMENTAL DESIGN: Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from nineteen studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival data and eighteen studies with all-cause mortality data.RESULTS: No evidence of association was observed between genotype and risk of unselected EOC (odds ratio (OR)=1.02, 95% confidence interval (CI)=0.95-1.10), serous EOC (OR=1.08, 95%CI=0.98-1.18), familial EOC (OR=1.09, 95%CI=0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR=1.09, 95%CI=0.88-1.36). There was little evidence for association with survival time among unselected cases (hazard ratio (HR)=1.10, 95%CI=0.99-1.22), among serous cases (HR=1.12, 95%CI=0.99-1.28), or with progression-free survival in 540 cases treated with carboplatin and paclitaxel (HR=1.18, 95%CI=0.93-1.52).CONCLUSIONS: These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction therefore appears unwarranted.

U2 - 10.1158/1078-0432.CCR-10-3405

DO - 10.1158/1078-0432.CCR-10-3405

M3 - Journal article

C2 - 21385923

SN - 1078-0432

VL - 17

SP - 3742

EP - 3750

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 11

ER -

The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

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