title: Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium.
abstract: 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.
  
  
  CONCLUSIONS
  Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.
authors.affiliation: Department of Population Health Research, Alberta Health Services-Cancer Care, 1331 29th Street Northwest, Calgary, Alberta T2N4N2, Canada. lkelemen@post.harvard.edu
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.forename: Valerie
authors.initials: V
authors.lastname: McGuire
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Rossing
authors.forename: Penelope M
authors.initials: PM
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authors.forename: Martin
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authors.lastname: Köbel
authors.forename: Hoda
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authors.lastname: Anton-Culver
authors.forename: Jonathan
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authors.lastname: Beesley
authors.forename: Andrew
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authors.forename: Sony
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authors.forename: Michael E
authors.initials: ME
authors.lastname: Carney
authors.forename: Jenny
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authors.lastname: Chang-Claude
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: Daniel W
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authors.lastname: Cramer
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dicioccio
authors.forename: Jennifer A
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authors.lastname: Doherty
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Zachary S
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authors.lastname: Fredericksen
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Gates
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
authors.forename: Susanne Krüger
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Galina
authors.initials: G
authors.lastname: Lurie
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Moorman
authors.forename: Kirsten
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authors.lastname: Moysich
authors.forename: Roberta B
authors.initials: RB
authors.lastname: Ness
authors.forename: Rachel T
authors.initials: RT
authors.lastname: Palmieri
authors.forename: Celeste L
authors.initials: CL
authors.lastname: Pearce
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Shan
authors.initials: S
authors.lastname: Wang-Gohrke
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases / Q000235:genetics; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D013940:Thymidylate Synthase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C000717967:DNMT3A protein, human; D015778:Minor Histocompatibility Antigens; D005492:Folic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D013940:Thymidylate Synthase; D019731:Carbon-Nitrogen Ligases; C021557:5,10-methenyltetrahydrofolate synthetase