title: Association between folate metabolism-related polymorphisms and colorectal cancer risk.
abstract: Folate has essential roles in DNA synthesis, repair and methylation. Folate metabolism-related gene variants may modulate the levels of this vitamin and affect the cancer risk. Thus, whether these polymorphisms play an important role in carcinogenesis, particularly colorectal cancer (CRC) development, has been a subject interest. The present study investigated the association between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS) and the reduced folate carrier 1 (RFC1) genes and CRC risk. Polymorphisms inMTHFR(677C>T and 1298A>C),TS[1494del6 and theTSenhancer region (TSER)] andRFC1(-43T>C, 80G>A and 696C>T) were characterized using polymerase chain reaction-restriction fragment length polymorphism in 477 CRC cases and 514 controls. Although no polymorphisms were significantly associated with the CRC risk in the overall sample, significant associations between folate metabolism-related polymorphisms and CRC risk were identified in the stratified analyses. TheMTHFR677CT/1298AC andMTHFR1298AC+CC/TSER2R3R genotypes in the presence of plasma folate levels ≤4.12 ng/ml were associated with significantly increased CRC risk. In addition, individuals with theMTHFR677TT/TSER3R3R orMTHFR677/TSER3R3R/TS1494 0bp6bp+6bp6bp genotypes and diabetes mellitus (DM) were at an increased risk for CRC. Therefore, the data suggest that i)MTHFRpolymorphisms combined with low plasma folate levels and ii) polymorphisms in folate metabolism-related genes combined with metabolic syndrome risk factors (hypertension and DM) increase the odds of developing CRC.
authors.affiliation: Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Institute for Clinical Research, School of Medicine, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Moon Ju
authors.initials: MJ
authors.lastname: Jang
authors.affiliation: Institute for Clinical Research, School of Medicine, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Jung O
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Chong
authors.affiliation: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Ko
authors.affiliation: Institute for Clinical Research, School of Medicine, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea ; Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Hwang
authors.affiliation: Institute for Clinical Research, School of Medicine, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea ; Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Doyeun
authors.initials: D
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Jisu
authors.initials: J
authors.lastname: Oh
authors.affiliation: Institute for Clinical Research, School of Medicine, CHA University, Seongnam, Gyeonggi 463-712, Republic of Korea.
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
keywords: colorectal cancer; folate; methylenetetrahydrofolate reductase; reduced folate carrier 1; thymidylate synthase