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 Anton-Culver; Natalia Antonenkova; Antonis C. Antoniou; David Goldgar; Mary S. Beattie; Matthias W. Beckmann; Michael J. Birrer; Natalia Bogdanova; Kelly L. Bolton; Wendy Brewster; Angela Brooks-Wilson; Robert Brown; Ralf Butzow; Trinidad Caldes; Maria Adelaide Caligo; Ian Campbell; Jenny Chang-Claude; Y. Ann Chen; Linda S. Cook; Fergus J. Couch; Daniel W. Cramer; Julie M. Cunningham; Evelyn Despierre; Jennifer A. Doherty; Thilo Dörk; Matthias Dürst; Diana M. Eccles; Arif B. Ekici; Douglas Easton; Peter A. Fasching; Anna De Fazio; David A. Fenstermacher; James M. Flanagan; Brooke L. Fridley; Eitan Friedman; Bo Gao; Olga Sinilnikova; Aleksandra Gentry-Maharaj; Andrew K. Godwin; Ellen L. Goode; Marc T. Goodman; Jenny Gross; Thomas V.O. Hansen; Paul Harnett; Matti Rookus; Tuomas Heikkinen; Rebecca Hein; Claus Høgdall; Estrid Høgdall; Edwin S. Iversen; Anna Jakubowska; Sharon E. Johnatty; Beth Y. Karlan; Noah D. Kauff; Stanley B. Kaye; Georgia Chenevix-Trench; Linda E. Kelemen; Lambertus A. Kiemeney; Susanne Krüger Kjaer; Diether Lambrechts; James P. LaPolla; Conxi Lázaro; Nhu D. Le; Arto Leminen; Karin Leunen; Douglas A. Levine; Yi Lu; Lene Lundvall; Stuart Macgregor; Tamara Marees; Leon F. Massuger; John R. McLaughlin; Usha Menon; Marco Montagna; Kirsten B. Moysich; Steven A. Narod; Katherine L. Nathanson; Lotte Nedergaard; Roberta B. Ness; Heli Nevanlinna; Stefan Nickels; Ana Osorio; Jim Paul; Celeste Leigh Pearce; Catherine M. Phelan; Malcolm C. Pike; Paolo Radice; Mary Anne Rossing; Joellen M. Schildkraut; Thomas A. Sellers; Christian F. Singer; Honglin Song; Daniel O. Stram; Rebecca Sutphen; Annika Lindblom; 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 A. 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 Anton-Culver, Natalia Antonenkova, Antonis C. Antoniou, David Goldgar, Mary S. Beattie, Matthias W. Beckmann, Michael J. Birrer, Natalia Bogdanova, Kelly L. Bolton, Wendy Brewster, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Trinidad Caldes, Maria Adelaide CaligoIan Campbell, Jenny Chang-Claude, Y. Ann Chen, Linda S. Cook, Fergus J. Couch, Daniel W. Cramer, Julie M. Cunningham, Evelyn Despierre, Jennifer A. Doherty, Thilo Dörk, Matthias Dürst, Diana M. Eccles, Arif B. Ekici, Douglas Easton, Peter A. Fasching, Anna De Fazio, David A. Fenstermacher, James M. Flanagan, Brooke L. Fridley, Eitan Friedman, Bo Gao, Olga Sinilnikova, Aleksandra Gentry-Maharaj, Andrew K. Godwin, Ellen L. Goode, Marc T. Goodman, Jenny Gross, Thomas V.O. Hansen, Paul Harnett, Matti Rookus, Tuomas Heikkinen, Rebecca Hein, Claus Høgdall, Estrid Høgdall, Edwin S. Iversen, Anna Jakubowska, Sharon E. Johnatty, Beth Y. Karlan, Noah D. Kauff, Stanley B. Kaye, Georgia Chenevix-Trench, Linda E. Kelemen, Lambertus A. Kiemeney, Susanne Krüger Kjaer, Diether Lambrechts, James P. LaPolla, Conxi Lázaro, Nhu D. Le, Arto Leminen, Karin Leunen, Douglas A. Levine, Yi Lu, Lene Lundvall, Stuart Macgregor, Tamara Marees, Leon F. Massuger, John R. McLaughlin, Usha Menon, Marco Montagna, Kirsten B. Moysich, Steven A. Narod, Katherine L. Nathanson, Lotte Nedergaard, Roberta B. Ness, Heli Nevanlinna, Stefan Nickels, Ana Osorio, Jim Paul, Celeste Leigh Pearce, Catherine M. Phelan, Malcolm C. Pike, Paolo Radice, Mary Anne Rossing, Joellen M. Schildkraut, Thomas A. Sellers, Christian F. Singer, Honglin Song, Daniel O. Stram, Rebecca Sutphen, Annika Lindblom, 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 A. Risch

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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 article, 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 19 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 (PFS) data and 18 studies with all-cause mortality data. Results: No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% 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 (HR = 1.10, 95% CI: 0.99-1.22), among serous cases (HR = 1.12, 95% CI = 0.99-1.28), or with PFS 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, seems unwarranted.

Original language	English
Pages (from-to)	3742-3750
Number of pages	9
Journal	Clinical Cancer Research
Volume	17
Issue number	11
DOIs	https://doi.org/10.1158/1078-0432.CCR-10-3405
State	Published - 1 Jun 2011

Funding

Funders	Funder number
National Cancer Institute	P50CA105009

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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., Antonenkova, N., Antoniou, A. C., Goldgar, D., Beattie, M. S., Beckmann, M. W., Birrer, M. J., Bogdanova, N., Bolton, K. L., Brewster, W., Brooks-Wilson, A., Brown, R., Butzow, R., Caldes, T., ... Risch, H. A. (2011). The role of KRAS rs61764370 in invasive epithelial ovarian cancer: Implications for clinical testing. Clinical Cancer Research, 17(11), 3742-3750. https://doi.org/10.1158/1078-0432.CCR-10-3405

@article{0b408f79bf594c98bc31e92a82b63b93,

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 article, 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 19 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 (PFS) data and 18 studies with all-cause mortality data. Results: No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% 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 (HR = 1.10, 95% CI: 0.99-1.22), among serous cases (HR = 1.12, 95% CI = 0.99-1.28), or with PFS 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, seems unwarranted.",

author = "Pharoah, {Paul D.P.} and Palmieri, {Rachel T.} and Ramus, {Susan J.} and Gayther, {Simon A.} and Andrulis, {Irene L.} and Hoda Anton-Culver and Natalia Antonenkova and Antoniou, {Antonis C.} and David Goldgar 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 Butzow and Trinidad Caldes and Caligo, {Maria Adelaide} and Ian Campbell and Jenny Chang-Claude and Chen, {Y. Ann} 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 D{\"o}rk and Matthias D{\"u}rst and Eccles, {Diana M.} and Ekici, {Arif B.} and Douglas Easton and Fasching, {Peter A.} and {De Fazio}, Anna and Fenstermacher, {David A.} and Flanagan, {James M.} and Fridley, {Brooke L.} and Eitan Friedman and Bo Gao and Olga Sinilnikova and Aleksandra Gentry-Maharaj and Godwin, {Andrew K.} and Goode, {Ellen L.} and Goodman, {Marc T.} and Jenny Gross and Hansen, {Thomas V.O.} and Paul Harnett and Matti Rookus and Tuomas Heikkinen and Rebecca Hein and Claus H{\o}gdall and Estrid H{\o}gdall and Iversen, {Edwin S.} and Anna Jakubowska and Johnatty, {Sharon E.} and Karlan, {Beth Y.} and Kauff, {Noah D.} and Kaye, {Stanley B.} and Georgia Chenevix-Trench and Kelemen, {Linda E.} and Kiemeney, {Lambertus A.} and Kjaer, {Susanne Kr{\"u}ger} and Diether Lambrechts and LaPolla, {James P.} and Conxi L{\'a}zaro 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 Massuger, {Leon F.} and McLaughlin, {John R.} 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 Heli Nevanlinna and Stefan Nickels and Ana Osorio and Jim Paul and Pearce, {Celeste Leigh} and Phelan, {Catherine M.} and Pike, {Malcolm C.} and Paolo Radice and Rossing, {Mary Anne} and Schildkraut, {Joellen M.} and Sellers, {Thomas A.} and Singer, {Christian F.} and Honglin Song and Stram, {Daniel O.} and Rebecca Sutphen and Annika Lindblom and Terry, {Kathryn L.} and Tsai, {Ya Yu} 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 Risch, {Harvey A.}",

year = "2011",

month = jun,

day = "1",

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

language = "אנגלית",

volume = "17",

pages = "3742--3750",

journal = "Clinical Cancer Research",

issn = "1078-0432",

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

number = "11",

}

Pharoah, PDP, Palmieri, RT, Ramus, SJ, Gayther, SA, Andrulis, IL, Anton-Culver, H, Antonenkova, N, Antoniou, AC, Goldgar, D, Beattie, MS, Beckmann, MW, Birrer, MJ, Bogdanova, N, Bolton, KL, Brewster, W, Brooks-Wilson, A, Brown, R, Butzow, R, Caldes, T, Caligo, MA, Campbell, I, Chang-Claude, J, Chen, YA, Cook, LS, Couch, FJ, Cramer, DW, Cunningham, JM, Despierre, E, Doherty, JA, Dörk, T, Dürst, M, Eccles, DM, Ekici, AB, Easton, D, Fasching, PA, De Fazio, A, Fenstermacher, DA, Flanagan, JM, Fridley, BL, Friedman, E, Gao, B, Sinilnikova, O, Gentry-Maharaj, A, Godwin, AK, Goode, EL, Goodman, MT, Gross, J, Hansen, TVO, Harnett, P, Rookus, M, Heikkinen, T, Hein, R, Høgdall, C, Høgdall, E, Iversen, ES, Jakubowska, A, Johnatty, SE, Karlan, BY, Kauff, ND, Kaye, SB, Chenevix-Trench, G, Kelemen, LE, Kiemeney, LA, Kjaer, SK, Lambrechts, D, LaPolla, JP, Lázaro, C, Le, ND, Leminen, A, Leunen, K, Levine, DA, Lu, Y, Lundvall, L, Macgregor, S, Marees, T, Massuger, LF, McLaughlin, JR, Menon, U, Montagna, M, Moysich, KB, Narod, SA, Nathanson, KL, Nedergaard, L, Ness, RB, Nevanlinna, H, Nickels, S, Osorio, A, Paul, J, Pearce, CL, Phelan, CM, Pike, MC, Radice, P, Rossing, MA, Schildkraut, JM, Sellers, TA, Singer, CF, Song, H, Stram, DO, Sutphen, R, Lindblom, A, Terry, KL, Tsai, YY, Van Altena, AM, Vergote, I, Vierkant, RA, Vitonis, AF, Walsh, C, Wang-Gohrke, S, Wappenschmidt, B, Wu, AH, Ziogas, A, Berchuck, A & Risch, HA 2011, 'The role of KRAS rs61764370 in invasive epithelial ovarian cancer: Implications for clinical testing', Clinical Cancer Research, vol. 17, no. 11, pp. 3742-3750. https://doi.org/10.1158/1078-0432.CCR-10-3405

TY - JOUR

T1 - The role of KRAS rs61764370 in invasive epithelial ovarian cancer

T2 - 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

AU - Antonenkova, Natalia

AU - Antoniou, Antonis C.

AU - Goldgar, David

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 - Butzow, Ralf

AU - Caldes, Trinidad

AU - Caligo, Maria Adelaide

AU - Campbell, Ian

AU - Chang-Claude, Jenny

AU - Chen, Y. Ann

AU - Cook, Linda S.

AU - Couch, Fergus J.

AU - Cramer, Daniel W.

AU - Cunningham, Julie M.

AU - Despierre, Evelyn

AU - Doherty, Jennifer A.

AU - Dörk, Thilo

AU - Dürst, Matthias

AU - Eccles, Diana M.

AU - Ekici, Arif B.

AU - Easton, Douglas

AU - Fasching, Peter A.

AU - De Fazio, Anna

AU - Fenstermacher, David A.

AU - Flanagan, James M.

AU - Fridley, Brooke L.

AU - Friedman, Eitan

AU - Gao, Bo

AU - Sinilnikova, Olga

AU - Gentry-Maharaj, Aleksandra

AU - Godwin, Andrew K.

AU - Goode, Ellen L.

AU - Goodman, Marc T.

AU - Gross, Jenny

AU - Hansen, Thomas V.O.

AU - Harnett, Paul

AU - Rookus, Matti

AU - Heikkinen, Tuomas

AU - Hein, Rebecca

AU - Høgdall, Claus

AU - Høgdall, Estrid

AU - Iversen, Edwin S.

AU - Jakubowska, Anna

AU - Johnatty, Sharon E.

AU - Karlan, Beth Y.

AU - Kauff, Noah D.

AU - Kaye, Stanley B.

AU - Chenevix-Trench, Georgia

AU - Kelemen, Linda E.

AU - Kiemeney, Lambertus A.

AU - Kjaer, Susanne Krüger

AU - Lambrechts, Diether

AU - LaPolla, James P.

AU - Lázaro, 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 F.

AU - McLaughlin, John R.

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

AU - Nickels, Stefan

AU - Osorio, Ana

AU - Paul, Jim

AU - Pearce, Celeste Leigh

AU - Phelan, Catherine M.

AU - Pike, Malcolm C.

AU - Radice, Paolo

AU - Rossing, Mary Anne

AU - Schildkraut, Joellen M.

AU - Sellers, Thomas A.

AU - Singer, Christian F.

AU - Song, Honglin

AU - Stram, Daniel O.

AU - Sutphen, Rebecca

AU - Lindblom, Annika

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 A.

PY - 2011/6/1

Y1 - 2011/6/1

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 article, 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 19 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 (PFS) data and 18 studies with all-cause mortality data. Results: No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% 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 (HR = 1.10, 95% CI: 0.99-1.22), among serous cases (HR = 1.12, 95% CI = 0.99-1.28), or with PFS 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, seems 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 article, 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 19 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 (PFS) data and 18 studies with all-cause mortality data. Results: No evidence of association was observed between genotype and risk of unselected EOC (OR = 1.02, 95% 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 (HR = 1.10, 95% CI: 0.99-1.22), among serous cases (HR = 1.12, 95% CI = 0.99-1.28), or with PFS 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, seems unwarranted.

UR - http://www.scopus.com/inward/record.url?scp=79957925584&partnerID=8YFLogxK

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

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

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C2 - 21385923

AN - SCOPUS:79957925584

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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