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PMID |
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TITLE |
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The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing. |
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ABSTRACT |
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PURPOSE |
NlmCategory: OBJECTIVE |
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 |
NlmCategory: METHODS |
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. 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 |
NlmCategory: RESULTS |
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. 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. 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 |
NlmCategory: CONCLUSIONS |
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. 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. 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). 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. |
©2011 AACR. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
entrez |
2011/03/10 06:00 |
pubmed |
2011/03/10 06:00 |
medline |
2011/12/28 06:00 |
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AUTHORS |
|
NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Pharoah PD |
|
Pharoah |
Paul D P |
PD |
|
Department of Oncology, University of Cambridge, Cambridge, United Kingdom. |
Palmieri RT |
|
Palmieri |
Rachel T |
RT |
|
|
Ramus SJ |
|
Ramus |
Susan J |
SJ |
|
|
Gayther SA |
|
Gayther |
Simon A |
SA |
|
|
Andrulis IL |
|
Andrulis |
Irene L |
IL |
|
|
Anton-Culver H |
|
Anton-Culver |
Hoda |
H |
|
|
Antonenkova N |
|
Antonenkova |
Natalia |
N |
|
|
Antoniou AC |
|
Antoniou |
Antonis C |
AC |
|
|
Goldgar D |
|
Goldgar |
David |
D |
|
|
|
BCFR Investigators |
|
|
|
|
|
Beattie MS |
|
Beattie |
Mary S |
MS |
|
|
Beckmann MW |
|
Beckmann |
Matthias W |
MW |
|
|
Birrer MJ |
|
Birrer |
Michael J |
MJ |
|
|
Bogdanova N |
|
Bogdanova |
Natalia |
N |
|
|
Bolton KL |
|
Bolton |
Kelly L |
KL |
|
|
Brewster W |
|
Brewster |
Wendy |
W |
|
|
Brooks-Wilson A |
|
Brooks-Wilson |
Angela |
A |
|
|
Brown R |
|
Brown |
Robert |
R |
|
|
Butzow R |
|
Butzow |
Ralf |
R |
|
|
Caldes T |
|
Caldes |
Trinidad |
T |
|
|
Caligo MA |
|
Caligo |
Maria Adelaide |
MA |
|
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Campbell I |
|
Campbell |
Ian |
I |
|
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Chang-Claude J |
|
Chang-Claude |
Jenny |
J |
|
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Chen YA |
|
Chen |
Y Ann |
YA |
|
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Cook LS |
|
Cook |
Linda S |
LS |
|
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Couch FJ |
|
Couch |
Fergus J |
FJ |
|
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Cramer DW |
|
Cramer |
Daniel W |
DW |
|
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Cunningham JM |
|
Cunningham |
Julie M |
JM |
|
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Despierre E |
|
Despierre |
Evelyn |
E |
|
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Doherty JA |
|
Doherty |
Jennifer A |
JA |
|
|
Dörk T |
|
Dörk |
Thilo |
T |
|
|
Dürst M |
|
Dürst |
Matthias |
M |
|
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Eccles DM |
|
Eccles |
Diana M |
DM |
|
|
Ekici AB |
|
Ekici |
Arif B |
AB |
|
|
Easton D |
|
Easton |
Douglas |
D |
|
|
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EMBRACE Investigators |
|
|
|
|
|
Fasching PA |
|
Fasching |
Peter A |
PA |
|
|
de Fazio A |
|
de Fazio |
Anna |
A |
|
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Fenstermacher DA |
|
Fenstermacher |
David A |
DA |
|
|
Flanagan JM |
|
Flanagan |
James M |
JM |
|
|
Fridley BL |
|
Fridley |
Brooke L |
BL |
|
|
Friedman E |
|
Friedman |
Eitan |
E |
|
|
Gao B |
|
Gao |
Bo |
B |
|
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Sinilnikova O |
|
Sinilnikova |
Olga |
O |
|
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GEMO Study Collaborators |
|
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|
|
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Gentry-Maharaj A |
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Gentry-Maharaj |
Aleksandra |
A |
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Godwin AK |
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Godwin |
Andrew K |
AK |
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Goode EL |
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Goode |
Ellen L |
EL |
|
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Goodman MT |
|
Goodman |
Marc T |
MT |
|
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Gross J |
|
Gross |
Jenny |
J |
|
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Hansen TV |
|
Hansen |
Thomas V O |
TV |
|
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Harnett P |
|
Harnett |
Paul |
P |
|
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Rookus M |
|
Rookus |
Matti |
M |
|
|
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HEBON Investigators |
|
|
|
|
|
Heikkinen T |
|
Heikkinen |
Tuomas |
T |
|
|
Hein R |
|
Hein |
Rebecca |
R |
|
|
Høgdall C |
|
Høgdall |
Claus |
C |
|
|
Høgdall E |
|
Høgdall |
Estrid |
E |
|
|
Iversen ES |
|
Iversen |
Edwin S |
ES |
|
|
Jakubowska A |
|
Jakubowska |
Anna |
A |
|
|
Johnatty SE |
|
Johnatty |
Sharon E |
SE |
|
|
Karlan BY |
|
Karlan |
Beth Y |
BY |
|
|
Kauff ND |
|
Kauff |
Noah D |
ND |
|
|
Kaye SB |
|
Kaye |
Stanley B |
SB |
|
|
Chenevix-Trench G |
|
Chenevix-Trench |
Georgia |
G |
|
|
|
kConFab Investigators and the Consortium of Investigators of Modifiers of BRCA1/2 |
|
|
|
|
|
Kelemen LE |
|
Kelemen |
Linda E |
LE |
|
|
Kiemeney LA |
|
Kiemeney |
Lambertus A |
LA |
|
|
Kjaer SK |
|
Kjaer |
Susanne Krüger |
SK |
|
|
Lambrechts D |
|
Lambrechts |
Diether |
D |
|
|
Lapolla JP |
|
Lapolla |
James P |
JP |
|
|
Lázaro C |
|
Lázaro |
Conxi |
C |
|
|
Le ND |
|
Le |
Nhu D |
ND |
|
|
Leminen A |
|
Leminen |
Arto |
A |
|
|
Leunen K |
|
Leunen |
Karin |
K |
|
|
Levine DA |
|
Levine |
Douglas A |
DA |
|
|
Lu Y |
|
Lu |
Yi |
Y |
|
|
Lundvall L |
|
Lundvall |
Lene |
L |
|
|
Macgregor S |
|
Macgregor |
Stuart |
S |
|
|
Marees T |
|
Marees |
Tamara |
T |
|
|
Massuger LF |
|
Massuger |
Leon F |
LF |
|
|
McLaughlin JR |
|
McLaughlin |
John R |
JR |
|
|
Menon U |
|
Menon |
Usha |
U |
|
|
Montagna M |
|
Montagna |
Marco |
M |
|
|
Moysich KB |
|
Moysich |
Kirsten B |
KB |
|
|
Narod SA |
|
Narod |
Steven A |
SA |
|
|
Nathanson KL |
|
Nathanson |
Katherine L |
KL |
|
|
Nedergaard L |
|
Nedergaard |
Lotte |
L |
|
|
Ness RB |
|
Ness |
Roberta B |
RB |
|
|
Nevanlinna H |
|
Nevanlinna |
Heli |
H |
|
|
Nickels S |
|
Nickels |
Stefan |
S |
|
|
Osorio A |
|
Osorio |
Ana |
A |
|
|
Paul J |
|
Paul |
Jim |
J |
|
|
Pearce CL |
|
Pearce |
Celeste Leigh |
CL |
|
|
Phelan CM |
|
Phelan |
Catherine M |
CM |
|
|
Pike MC |
|
Pike |
Malcolm C |
MC |
|
|
Radice P |
|
Radice |
Paolo |
P |
|
|
Rossing MA |
|
Rossing |
Mary Anne |
MA |
|
|
Schildkraut JM |
|
Schildkraut |
Joellen M |
JM |
|
|
Sellers TA |
|
Sellers |
Thomas A |
TA |
|
|
Singer CF |
|
Singer |
Christian F |
CF |
|
|
Song H |
|
Song |
Honglin |
H |
|
|
Stram DO |
|
Stram |
Daniel O |
DO |
|
|
Sutphen R |
|
Sutphen |
Rebecca |
R |
|
|
Lindblom A |
|
Lindblom |
Annika |
A |
|
|
|
SWE-BRCA Investigators |
|
|
|
|
|
Terry KL |
|
Terry |
Kathryn L |
KL |
|
|
Tsai YY |
|
Tsai |
Ya-Yu |
YY |
|
|
van Altena AM |
|
van Altena |
Anne M |
AM |
|
|
Vergote I |
|
Vergote |
Ignace |
I |
|
|
Vierkant RA |
|
Vierkant |
Robert A |
RA |
|
|
Vitonis AF |
|
Vitonis |
Allison F |
AF |
|
|
Walsh C |
|
Walsh |
Christine |
C |
|
|
Wang-Gohrke S |
|
Wang-Gohrke |
Shan |
S |
|
|
Wappenschmidt B |
|
Wappenschmidt |
Barbara |
B |
|
|
Wu AH |
|
Wu |
Anna H |
AH |
|
|
Ziogas A |
|
Ziogas |
Argyrios |
A |
|
|
Berchuck A |
|
Berchuck |
Andrew |
A |
|
|
Risch HA |
|
Risch |
Harvey A |
HA |
|
|
|
Ovarian Cancer Association Consortium |
|
|
|
|
|
|
INVESTIGATORS |
|
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JOURNAL |
|
VOLUME: 17 |
ISSUE: 11 |
TITLE: Clinical cancer research : an official journal of the American Association for Cancer Research |
ISOABBREVIATION: Clin Cancer Res |
YEAR: 2011 |
MONTH: Jun |
DAY: 01 |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1557-3265 |
ISSNTYPE: Electronic |
|
MEDLINE JOURNAL |
|
MEDLINETA: Clin Cancer Res |
COUNTRY: United States |
ISSNLINKING: 1078-0432 |
NLMUNIQUEID: 9502500 |
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PUBLICATION TYPE |
|
PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
|
COMMENTS AND CORRECTIONS |
|
REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
CommentIn |
Clin Cancer Res. 2011 Oct 15;17(20):6600; author reply 6601 |
22003074 |
|
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GRANTS |
|
GRANTID |
AGENCY |
COUNTRY |
U01 CA069417 |
NCI NIH HHS |
United States |
U01 CA069638 |
NCI NIH HHS |
United States |
R01 CA114343-05 |
NCI NIH HHS |
United States |
R01 CA063682 |
NCI NIH HHS |
United States |
5R01-CA087538 |
NCI NIH HHS |
United States |
R01 CA140323 |
NCI NIH HHS |
United States |
K07 CA092044-04 |
NCI NIH HHS |
United States |
5P30-CA014089 |
NCI NIH HHS |
United States |
5U01-CA069446 |
NCI NIH HHS |
United States |
5R01-CA063464 |
NCI NIH HHS |
United States |
N01-PC67010 |
NCI NIH HHS |
United States |
N01 PC067010 |
NCI NIH HHS |
United States |
P50 CA159981 |
NCI NIH HHS |
United States |
5R01-CA076016 |
NCI NIH HHS |
United States |
K07 CA092044-01A2 |
NCI NIH HHS |
United States |
R01 CA087538 |
NCI NIH HHS |
United States |
R01 CA126841-03 |
NCI NIH HHS |
United States |
5R01-CA112523 |
NCI NIH HHS |
United States |
R01 CA063678-03 |
NCI NIH HHS |
United States |
5R01-CA122443 |
NCI NIH HHS |
United States |
P50 CA105009-05 |
NCI NIH HHS |
United States |
R01 CA106414 |
NCI NIH HHS |
United States |
11174 |
Cancer Research UK |
United Kingdom |
R01 CA095023 |
NCI NIH HHS |
United States |
5U01-CA069467 |
NCI NIH HHS |
United States |
U01 CA069467 |
NCI NIH HHS |
United States |
U01 CA069467-12 |
NCI NIH HHS |
United States |
R03 CA121881 |
NCI NIH HHS |
United States |
5R01-CA095023 |
NCI NIH HHS |
United States |
R03 CA121881-02 |
NCI NIH HHS |
United States |
R03 CA113148 |
NCI NIH HHS |
United States |
R01 CA095023-02 |
NCI NIH HHS |
United States |
11022 |
Cancer Research UK |
United Kingdom |
A8339 |
Cancer Research UK |
United Kingdom |
R01 CA058860 |
NCI NIH HHS |
United States |
5R01-CA128978 |
NCI NIH HHS |
United States |
U01 CA069398 |
NCI NIH HHS |
United States |
5R01-CA126841 |
NCI NIH HHS |
United States |
R01 CA063678 |
NCI NIH HHS |
United States |
K07 CA092044 |
NCI NIH HHS |
United States |
5U01-CA069631 |
NCI NIH HHS |
United States |
5R01-CA106414 |
NCI NIH HHS |
United States |
N02-PC45022 |
NCI NIH HHS |
United States |
5R01-CA114343 |
NCI NIH HHS |
United States |
P50 CA105009 |
NCI NIH HHS |
United States |
A10119 |
Cancer Research UK |
United Kingdom |
5U01-CA069417 |
NCI NIH HHS |
United States |
5R03-CA121881 |
NCI NIH HHS |
United States |
5R01-CA061132 |
NCI NIH HHS |
United States |
R01 CA128978 |
NCI NIH HHS |
United States |
076113 |
Wellcome Trust |
United Kingdom |
5R01-CA063682 |
NCI NIH HHS |
United States |
R01 CA063682-02 |
NCI NIH HHS |
United States |
P30 CA076292 |
NCI NIH HHS |
United States |
P30 CA014089 |
NCI NIH HHS |
United States |
5R01-CA058860 |
NCI NIH HHS |
United States |
5K07-CA092044 |
NCI NIH HHS |
United States |
R01 CA087538-05 |
NCI NIH HHS |
United States |
G0801875 |
Medical Research Council |
United Kingdom |
R01 CA063464 |
NCI NIH HHS |
United States |
K07 CA092044-02 |
NCI NIH HHS |
United States |
R01 CA140323-02 |
NCI NIH HHS |
United States |
U01 CA069631 |
NCI NIH HHS |
United States |
R01 CA054419 |
NCI NIH HHS |
United States |
5R01-CA054419 |
NCI NIH HHS |
United States |
R01 CA122443 |
NCI NIH HHS |
United States |
R01 CA076016 |
NCI NIH HHS |
United States |
R01 CA063682-05 |
NCI NIH HHS |
United States |
1R01-CA140323 |
NCI NIH HHS |
United States |
R01 CA054419-15 |
NCI NIH HHS |
United States |
R01 CA058860-14 |
NCI NIH HHS |
United States |
P01 CA017054 |
NCI NIH HHS |
United States |
13086 |
Cancer Research UK |
United Kingdom |
5R01-CA063678 |
NCI NIH HHS |
United States |
5P50-CA105009 |
NCI NIH HHS |
United States |
5R01-CA061107 |
NCI NIH HHS |
United States |
U01 CA069446 |
NCI NIH HHS |
United States |
K07 CA092044-03 |
NCI NIH HHS |
United States |
R01 CA112523-05 |
NCI NIH HHS |
United States |
5U01-CA069638 |
NCI NIH HHS |
United States |
10118 |
Cancer Research UK |
United Kingdom |
R01 CA076016-09 |
NCI NIH HHS |
United States |
R01 CA112523 |
NCI NIH HHS |
United States |
5R03-CA113148 |
NCI NIH HHS |
United States |
R01 CA106414-05 |
NCI NIH HHS |
United States |
P50 CA136393 |
NCI NIH HHS |
United States |
R01 CA126841 |
NCI NIH HHS |
United States |
5U01-CA069398 |
NCI NIH HHS |
United States |
R03 CA113148-02 |
NCI NIH HHS |
United States |
A10124 |
Cancer Research UK |
United Kingdom |
R01 CA128978-04 |
NCI NIH HHS |
United States |
R01 CA114343 |
NCI NIH HHS |
United States |
R01 CA122443-05 |
NCI NIH HHS |
United States |
10124 |
Cancer Research UK |
United Kingdom |
5P01-CA017054 |
NCI NIH HHS |
United States |
|
GENERAL NOTE |
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KEYWORDS |
|
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MESH HEADINGS |
|
DESCRIPTORNAME |
QUALIFIERNAME |
3' Untranslated Regions |
|
Carcinoma, Ovarian Epithelial |
|
Disease-Free Survival |
|
Early Detection of Cancer |
|
Female |
|
Genes, BRCA1 |
|
Genetic Predisposition to Disease |
|
Genotype |
|
Humans |
|
MicroRNAs |
genetics |
Neoplasm Invasiveness |
genetics |
Neoplasms, Glandular and Epithelial |
genetics |
Ovarian Neoplasms |
genetics |
Polymorphism, Single Nucleotide |
genetics |
Proto-Oncogene Proteins |
genetics |
Proto-Oncogene Proteins p21(ras) |
genetics |
Risk |
genetics |
ras Proteins |
genetics |
|
SUPPLEMENTARY MESH |
|
SUPPLMESHNAME |
SUPPLMESHTYPE |
Ovarian epithelial cancer |
Disease |
|
GENE SYMBOLS |
|
|
CHEMICALS |
|
REGISTRYNUMBER |
NAMEOFSUBSTANCE |
0 |
3' Untranslated Regions |
0 |
KRAS protein, human |
0 |
MicroRNAs |
0 |
Proto-Oncogene Proteins |
EC 3.6.5.2 |
Proto-Oncogene Proteins p21(ras) |
EC 3.6.5.2 |
ras Proteins |
|
OTHER ID's |
|
|
|