Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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21385923
TITLE
The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing.
ABSTRACT
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.
DATE PUBLISHED
2011 Jun 01
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2011/03/10 06:00
pubmed 2011/03/10 06:00
medline 2011/12/28 06:00
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
Campbell I Campbell Ian I
Chang-Claude J Chang-Claude Jenny J
Chen YA Chen Y Ann YA
Cook LS Cook Linda S LS
Couch FJ Couch Fergus J FJ
Cramer DW Cramer Daniel W DW
Cunningham JM Cunningham Julie M JM
Despierre E Despierre Evelyn E
Doherty JA Doherty Jennifer A JA
Dörk T Dörk Thilo T
Dürst M Dürst Matthias M
Eccles DM Eccles Diana M DM
Ekici AB Ekici Arif B AB
Easton D Easton Douglas D
EMBRACE Investigators
Fasching PA Fasching Peter A PA
de Fazio A de Fazio Anna A
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
Sinilnikova O Sinilnikova Olga O
GEMO Study Collaborators
Gentry-Maharaj A Gentry-Maharaj Aleksandra A
Godwin AK Godwin Andrew K AK
Goode EL Goode Ellen L EL
Goodman MT Goodman Marc T MT
Gross J Gross Jenny J
Hansen TV Hansen Thomas V O TV
Harnett P Harnett Paul P
Rookus M Rookus Matti M
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
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
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
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
KEYWORDS
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