Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study.
BACKGROUND
The sex hormone-binding globulin (SHBG) is a carrier protein that modulates the bio-availability of serum sex steroid hormones, which may be involved in ovarian cancer. We evaluated whether common genetic variation in SHBG and its 3' neighbor ATP1B2, in linkage disequilibrium, is associated with the risk of epithelial ovarian cancer.


METHODS
The study population included 264 women with ovarian carcinoma and 625 controls participating in a population-based case-control study in Poland. Five common single nucleotide polymorphisms (SNPs) in SHGB and five in ATP1B2 were selected to capture most common variation in this region.


RESULTS
None of the SNPs evaluated was significantly associated with ovarian cancer risk, including the putative functional SNPs SHBG D356N (rs6259) and -67G>A 5'UTR (rs1799941). However, our data were consistent with a decreased ovarian cancer risk associated with the variant alleles for these two SNPs, which have been previously associated with increased circulating levels of SHBG.


CONCLUSIONS
These data do not support a substantial association between common genetic variation in SHBG and ovarian cancer risk.
Garcia-Closas
Montserrat
M
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD 20952-7234, USA. montse@nih.gov
Brinton
Louise A
LA
Lissowska
Jolanta
J
Richesson
Douglas
D
Sherman
Mark E
ME
Szeszenia-Dabrowska
Neonila
N
Peplonska
Beata
B
Welch
Robert
R
Yeager
Meredith
M
Zatonski
Witold
W
Chanock
Stephen J
SJ
D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*
C504190:ATP1B2 protein, human; D027682:Cation Transport Proteins; D015816:Cell Adhesion Molecules, Neuronal; D012738:Sex Hormone-Binding Globulin; D000251:Adenosine Triphosphatases