Analysis of common variations in tumor-suppressor genes on chr1p36 among Caucasian women with endometriosis.
OBJECTIVE
Epidemiological data indicate that endometriosis increases the risk of epithelial ovarian cancer (EOC), but the mechanism of cancer transition is unknown. Results from genome-wide association studies (GWAS) and transcriptome sequencing have demonstrated that genes located in the 1p36 region are important in both endometriosis and endometriosis-associated cancer development. Therefore, we tested the hypothesis that SNPs in two tumor-suppressor genes (CHD5 and ARID1A) in the 1p36 region are associated with endometriosis.


METHODS
Allele frequencies of SNPs were investigated in 1685 Caucasian women consisting of 947 women with endometriosis and 738 controls. Peripheral blood samples were retrieved, DNA extracted and allelic frequencies of SNPs in two tumor-suppressor genes (CHD5 and ARID1A) were analyzed using TaqMan Open Array technique.


RESULTS
Associations were observed for 3 SNPs in the CHD5 gene: rs1883603 (OR 1.31, 95% CI 1.00-1.71), rs9434741 (OR 1.41, 95% CI 1.16-1.71) and rs17436816 (OR 1.24, 95% CI 1.02-1.50). After correction for multiple comparisons, rs9434741 (CHD5) remained significantly associated with endometriosis (p<0.01). No associations were detected for ARID1A.


CONCLUSIONS
In this Caucasian population, endometriosis seems to be associated with the tumor-suppressor gene CHD5. Our findings support recent data, suggesting that the 1p36 region plays an important role in endometrios. To validate these data, replication in an independent population is warranted.
Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, 171 76 Stockholm, Sweden. henrik.falconer@karolinska.se
Henrik
H
Falconer
Johanna
J
Sundqvist
Hong
H
Xu
Alexandra
A
Vodolazkaia
Amelie
A
Fassbender
Cleophas
C
Kyama
Attila
A
Bokor
Thomas M
TM
D'Hooghe
D000328:Adult; D001530:Belgium; D016022:Case-Control Studies; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins; D004715:Endometriosis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D060005:Genotyping Techniques; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D044465:White People
C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D004265:DNA Helicases; C471926:CHD5 protein, human