Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

Medientyp: E-Artikel
Titel: Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk
Beteiligte: Kelemen, Linda E.; Terry, Kathryn L.; Goodman, Marc T.; Webb, Penelope M.; Bandera, Elisa V.; McGuire, Valerie; Rossing, Mary Anne; Wang, Qinggang; Dicks, Ed; Tyrer, Jonathan P.; Song, Honglin; Kupryjanczyk, Jolanta; Dansonka‐Mieszkowska, Agnieszka; Plisiecka‐Halasa, Joanna; Timorek, Agnieszka; Menon, Usha; Gentry‐Maharaj, Aleksandra; Gayther, Simon A.; Ramus, Susan J.; Narod, Steven A.; Risch, Harvey A.; McLaughlin, John R.; Siddiqui, Nadeem; Glasspool, Rosalind; [...]
Erschienen: Wiley, 2014
Erschienen in: Molecular Nutrition & Food Research
Sprache: Englisch
DOI: 10.1002/mnfr.201400068
ISSN: 1613-4125; 1613-4133
Schlagwörter: Food Science ; Biotechnology
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Beschreibung: <jats:sec><jats:title>Scope</jats:title><jats:p>We reevaluated previously reported associations between variants in pathways of one‐carbon (1‐C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>Odds ratios (OR) for 446 genetic variants were estimated among 13 410 OC cases and 22 635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (<jats:italic>DPYD</jats:italic>) variants rs11587873 (OR = 0.92; <jats:italic>p</jats:italic> = 6 × 10<jats:sup>−5</jats:sup>) and rs828054 (OR = 1.06; <jats:italic>p</jats:italic> = 1 × 10<jats:sup>−4</jats:sup>). Thirteen variants in the pyrimidine metabolism genes, <jats:italic>DPYD</jats:italic>, <jats:italic>DPYS</jats:italic>, <jats:italic>PPAT</jats:italic>, and <jats:italic>TYMS</jats:italic>, also interacted significantly with folate in a multivariant analysis (corrected <jats:italic>p</jats:italic> = 9.9 × 10<jats:sup>−6</jats:sup>) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in <jats:italic>SHMT1</jats:italic> in 1‐C transfer, previously reported with OC, suggested lower risk at higher folate (<jats:italic>p</jats:italic><jats:sub>interaction</jats:sub> = 0.03–0.006).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Variation in pyrimidine metabolism genes, particularly <jats:italic>DPYD</jats:italic>, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. <jats:italic>SHMT1</jats:italic> SNP‐by‐folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.</jats:p></jats:sec>

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