Analysis of CHEK2 gene for ovarian cancer susceptibility.
OBJECTIVE
A deletion variant in the CHEK2 gene (del1100C) has been implicated as a low-penetrance risk factor for breast cancer. We sought to determine contribution of CHEK2 mutations to the etiology of ovarian cancer (OvCa).


METHODS
We used cases ascertained from the United States through Gynecologic Oncology Group (GOG) protocols 172, 182, and 144, the University of Hawaii Cancer Research Center, and Creighton University. Control women were recruited from Pittsburgh and Hawaii. Denaturing high-performance liquid chromatography, sequence analysis, and single nucleotide polymorphism genotyping by Pyrosequencing were employed to analyze the CHEK2 gene.


RESULTS
Mutation screening of the CHEK2 gene in 48 cases who had a first-degree relative with OvCa uncovered only del1100C and A252G variants. Altogether, the del1100C variant was detected in none of 751 unselected cases, in 1 of 52 (1.9%) cases who had a first-degree relative with OvCa, and in 3 of 521 (0.6%) unselected controls. The frequencies of del1100C and A252G variants did not show statistically significant differences between the cases and the controls.


CONCLUSIONS
These results suggest that variations in CHEK2 do not make a significant contribution to the pathogenesis of OvCa in the U.S. population.
Baysal
Bora E
BE
Department of Obstetrics, Gynecology and Reproductive Sciences, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA. baysalb@mwri.magee.edu
DeLoia
Julie A
JA
Willett-Brozick
Joan E
JE
Goodman
Marc T
MT
Brady
Mark F
MF
Modugno
Francesmary
F
Lynch
Henry T
HT
Conley
Yvette P
YP
Watson
Patrice
P
Gallion
Holly H
HH
D000328:Adult; D000368:Aged; D064447:Checkpoint Kinase 2; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic
D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases