OBJECTIVE: Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene. METHODS: We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New England Case Control Study (NEC), Nurses' Health Study (NHS), and Mayo Clinic Ovarian Cancer Case Control Study (MAY). RESULTS: Overall, we observed no association between either SNP and ovarian cancer risk (pooled C677T p(trend)=0.59 and A1298C p(trend)=0.58). Significant associations (C677T p(trend)=0.001, A1298C p(trend)=0.02) between these MTHFR SNPs and serous ovarian cancer risk were observed in the NEC study, but were not replicated in the NHS and MAY studies. CONCLUSIONS: MTHFR SNPs C677T and A1298C are not associated with ovarian cancer risk. Our results highlight the need for validation of genetic findings.
OBJECTIVE:Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene. METHODS: We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New England Case Control Study (NEC), Nurses' Health Study (NHS), and Mayo Clinic Ovarian Cancer Case Control Study (MAY). RESULTS: Overall, we observed no association between either SNP and ovarian cancer risk (pooled C677T p(trend)=0.59 and A1298C p(trend)=0.58). Significant associations (C677T p(trend)=0.001, A1298C p(trend)=0.02) between these MTHFR SNPs and serous ovarian cancer risk were observed in the NEC study, but were not replicated in the NHS and MAY studies. CONCLUSIONS:MTHFR SNPs C677T and A1298C are not associated with ovarian cancer risk. Our results highlight the need for validation of genetic findings.
Authors: S E McCann; J L Freudenheim; J R Marshall; J R Brasure; M K Swanson; S Graham Journal: Cancer Causes Control Date: 2000-12 Impact factor: 2.506
Authors: T A Sellers; L H Kushi; J R Cerhan; R A Vierkant; S M Gapstur; C M Vachon; J E Olson; T M Therneau; A R Folsom Journal: Epidemiology Date: 2001-07 Impact factor: 4.822
Authors: K J Lievers; G H Boers; P Verhoef; M den Heijer; L A Kluijtmans; N M van der Put; F J Trijbels; H J Blom Journal: J Mol Med (Berl) Date: 2001-09 Impact factor: 4.599
Authors: A Chango; F Boisson; F Barbé; D Quilliot; S Droesch; M Pfister; N Fillon-Emery; D Lambert; S Frémont; D S Rosenblatt; J P Nicolas Journal: Br J Nutr Date: 2000-06 Impact factor: 3.718
Authors: A Joan Levine; Jane C Figueiredo; Won Lee; Jenny N Poynter; David Conti; David J Duggan; Peter T Campbell; Polly Newcomb; Maria Elena Martinez; John L Hopper; Loic Le Marchand; John A Baron; Paul J Limburg; Cornelia M Ulrich; Robert W Haile Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-01 Impact factor: 4.254
Authors: Honglin Song; Susan J Ramus; Jonathan Tyrer; Kelly L Bolton; Aleksandra Gentry-Maharaj; Eva Wozniak; Hoda Anton-Culver; Jenny Chang-Claude; Daniel W Cramer; Richard DiCioccio; Thilo Dörk; Ellen L Goode; Marc T Goodman; Joellen M Schildkraut; Thomas Sellers; Laura Baglietto; Matthias W Beckmann; Jonathan Beesley; Jan Blaakaer; Michael E Carney; Stephen Chanock; Zhihua Chen; Julie M Cunningham; Ed Dicks; Jennifer A Doherty; Matthias Dürst; Arif B Ekici; David Fenstermacher; Brooke L Fridley; Graham Giles; Martin E Gore; Immaculata De Vivo; Peter Hillemanns; Claus Hogdall; Estrid Hogdall; Edwin S Iversen; Ian J Jacobs; Anna Jakubowska; Dong Li; Jolanta Lissowska; Jan Lubiński; Galina Lurie; Valerie McGuire; John McLaughlin; Krzysztof Medrek; Patricia G Moorman; Kirsten Moysich; Steven Narod; Catherine Phelan; Carole Pye; Harvey Risch; Ingo B Runnebaum; Gianluca Severi; Melissa Southey; Daniel O Stram; Falk C Thiel; Kathryn L Terry; Ya-Yu Tsai; Shelley S Tworoger; David J Van Den Berg; Robert A Vierkant; Shan Wang-Gohrke; Penelope M Webb; Lynne R Wilkens; Anna H Wu; Hannah Yang; Wendy Brewster; Argyrios Ziogas; Richard Houlston; Ian Tomlinson; Alice S Whittemore; Mary Anne Rossing; Bruce A J Ponder; Celeste Leigh Pearce; Roberta B Ness; Usha Menon; Susanne Krüger Kjaer; Jacek Gronwald; Montserrat Garcia-Closas; Peter A Fasching; Douglas F Easton; Georgia Chenevix-Trench; Andrew Berchuck; Paul D P Pharoah; Simon A Gayther Journal: Nat Genet Date: 2009-08-02 Impact factor: 38.330
Authors: Kathryn L Terry; Shelley S Tworoger; Allison F Vitonis; Jason Wong; Linda Titus-Ernstoff; Immaculata De Vivo; Daniel W Cramer Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-01-20 Impact factor: 4.254
Authors: Piotr Pawlik; Adrianna Mostowska; Margarita Lianeri; Stefan Sajdak; Helena Kędzia; Paweł P Jagodzinski Journal: Mol Biol Rep Date: 2011-12-20 Impact factor: 2.316
Authors: Elizabeth M Poole; Margaret A Gates; Brigit A High; Stephen J Chanock; Daniel W Cramer; Julie M Cunningham; Brooke L Fridley; Simon A Gayther; Ellen L Goode; Edwin S Iversen; Jolanta Lissowska; Rachel T Palmieri Weber; Paul D P Pharoah; Catherine M Phelan; Susan J Ramus; Joellen M Schildkraut; Rebecca Sutphen; Ya-Yu Tsai; Jonathan Tyrer; Robert A Vierkant; Nicolas Wentzensen; Hannah P Yang; Kathryn L Terry; Shelley S Tworoger Journal: Cancer Causes Control Date: 2012-09-08 Impact factor: 2.506
Authors: Weiva Sieh; Shannon Salvador; Valerie McGuire; Rachel Palmieri Weber; Kathryn L Terry; Mary Anne Rossing; Harvey Risch; Anna H Wu; Penelope M Webb; Kirsten Moysich; Jennifer A Doherty; Anna Felberg; Dianne Miller; Susan J Jordan; Marc T Goodman; Galina Lurie; Jenny Chang-Claude; Anja Rudolph; Susanne Krüger Kjær; Allan Jensen; Estrid Høgdall; Elisa V Bandera; Sara H Olson; Melony G King; Lorna Rodriguez-Rodriguez; Lambertus A Kiemeney; Tamara Marees; Leon F Massuger; Anne M van Altena; Roberta B Ness; Daniel W Cramer; Malcolm C Pike; Celeste Leigh Pearce; Andrew Berchuck; Joellen M Schildkraut; Alice S Whittemore Journal: Int J Epidemiol Date: 2013-04 Impact factor: 7.196
Authors: Linda E Kelemen; Elisa V Bandera; Kathryn L Terry; Mary Anne Rossing; Louise A Brinton; Jennifer A Doherty; Roberta B Ness; Susanne Krüger Kjaer; Jenny Chang-Claude; Martin Köbel; Galina Lurie; Pamela J Thompson; Michael E Carney; Kirsten Moysich; Robert Edwards; Clare Bunker; Allan Jensen; Estrid Høgdall; Daniel W Cramer; Allison F Vitonis; Sara H Olson; Melony King; Urmila Chandran; Jolanta Lissowska; Montserrat Garcia-Closas; Hannah Yang; Penelope M Webb; Joellen M Schildkraut; Marc T Goodman; Harvey A Risch Journal: BMC Cancer Date: 2013-01-22 Impact factor: 4.430