HOXA methylation in normal endometrium from premenopausal women is associated with the presence of ovarian cancer: a proof of principle study.
DNA methylation of polycomb group target (PCGT) genes is an early step in carcinogenesis and could potentially be assayed to determine cancer risk prediction. To assess whether methylation changes in PCGT genes in normal tissue is able to predict the presence of cancer, we studied HOXA gene methylation in normal endometrium from premenopausal ovarian cancer patients and age-matched healthy controls without ovarian cancer. DNA methylation of HOXA9 and HOXA11 genes in normal endometrium was associated with ovarian cancer in an initial test set and this was subsequently confirmed in independent validation sample sets. The overall risk of ovarian cancer was increased 12.3-fold by high HOXA9 methylation for all stages, and 14.8-fold for early stage ovarian cancers, independent of age, phase of the menstrual cycle and histology of the cancer. The results of this proof of principle study demonstrate the potential to detect ovarian cancer via analysis of normal endometrial cells and provide insight into the possible contribution of this novel approach in ovarian cancer risk prediction and prevention.
Widschwendter
Martin
M
Department of Gynecological Oncology, Institute for Women's Health, University College London, United Kingdom. M.Widschwendter@ucl.ac.uk
Apostolidou
Sophia
S
Jones
Allison A
AA
Fourkala
Evangelia O
EO
Arora
Rupali
R
Pearce
Celeste Leigh
CL
Frasco
Melissa A
MA
Ayhan
Ayse
A
Zikan
Michal
M
Cibula
David
D
Iyibozkurt
Cem A
CA
Yavuz
Ekrem
E
Hauser-Kronberger
Cornelia
C
Dubeau
Louis
L
Menon
Usha
U
Jacobs
Ian J
IJ
D000328:Adult; D019175:DNA Methylation; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000209:etiology / Q000235:genetics*; D017697:Premenopause; D012306:Risk
D018398:Homeodomain Proteins; C097899:homeobox protein HOXA9