TY - JOUR
T1 - Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium
AU - Kelemen, Linda E.
AU - Goodman, Marc T.
AU - McGuire, Valerie
AU - Rossing, Mary Anne
AU - Webb, Penelope M.
AU - Köbel, Martin
AU - Anton-Culver, Hoda
AU - Beesley, Jonathan
AU - Berchuck, Andrew
AU - Brar, Sony
AU - Carney, Michael E.
AU - Chang-Claude, Jenny
AU - Chenevix-Trench, Georgia
AU - Cramer, Daniel W.
AU - Cunningham, Julie M.
AU - DiCioccio, Richard A.
AU - Doherty, Jennifer A.
AU - Easton, Douglas F.
AU - Fredericksen, Zachary S.
AU - Fridley, Brooke L.
AU - Gates, Margaret A.
AU - Gayther, Simon A.
AU - Gentry-Maharaj, Aleksandra
AU - Høgdall, Estrid
AU - Kjær, Susanne Krüger
AU - Lurie, Galina
AU - Menon, Usha
AU - Moorman, Patricia G.
AU - Moysich, Kirsten
AU - Ness, Roberta B.
AU - Palmieri, Rachel T.
AU - Pearce, Celeste L.
AU - Pharoah, Paul D.P.
AU - Ramus, Susan J.
AU - Song, Honglin
AU - Stram, Daniel O.
AU - Tworoger, Shelley S.
AU - Van Den Berg, David
AU - Vierkant, Robert A.
AU - Wang-Gohrke, Shan
AU - Whittemore, Alice S.
AU - Wilkens, Lynne R.
AU - Wu, Anna H.
AU - Schildkraut, Joellen M.
AU - Sellers, Thomas A.
AU - Goode, Ellen L.
PY - 2010/7
Y1 - 2010/7
N2 - Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type. Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site. Results: The five polymorphisms were not associated with ovarian carcinoma overall (P trend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P heterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05). Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.
AB - Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type. Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site. Results: The five polymorphisms were not associated with ovarian carcinoma overall (P trend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P heterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05). Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.
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U2 - 10.1158/1055-9965.EPI-09-1317
DO - 10.1158/1055-9965.EPI-09-1317
M3 - Article
C2 - 20570913
AN - SCOPUS:77954506113
SN - 1055-9965
VL - 19
SP - 1822
EP - 1830
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -