Ovarian cancer risk is associated with a common variant in the promoter sequence of the mismatch repair gene MLH1.
OBJECTIVE
Inherited mutations in the MLH1 gene are associated with a proportion of families with the hereditary non-polyposis colon cancer syndrome (HNPCC). The cardinal features of the syndrome are a predisposition to colon, endometrial and ovarian cancers. Recently, it has been shown that a non-coding polymorphic variant in MLH1 (G>A nt-93) predisposes to colon and endometrial cancer, but with much reduced penetrance. We sought to establish whether or not this polymorphic variant also predisposes to ovarian cancer.


METHODS
We genotyped 899 women with invasive ovarian cancer and 931 controls for the G>A nt-93 variant.


RESULTS
The presence of the variant was associated with a modest, but highly significant risk of ovarian cancer (OR=1.5; 95% CI 1.3-1.9; p=0.00005). The association was present in cancers of all histologies except clear cell, and in all ethnic groups.


CONCLUSIONS
The G>A nt-93 variant of the MLH1 gene is associated with an increased risk of invasive ovarian cancer.
Harley
Ian
I
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, ON, Canada.
Rosen
Barry
B
Risch
Harvey A
HA
Siminovitch
Kathy
K
Beiner
Mario E
ME
McLaughlin
John
J
Sun
Ping
P
Narod
Steven A
SA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D009864:Ontario / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1