OBJECTIVE: Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case-referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T, to the risk of colorectal cancer, taking into account pre-diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C > T polymorphism, which were analysed in a previous study. MATERIAL AND METHODS: Subjects were 220 cases and 414 matched referents from the population-based Northern Sweden Health and Disease Study. RESULTS: The RFC1 80A-allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T-allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C > T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance. CONCLUSIONS: These findings suggest that although the RFC1 80G > A and FOLH1 1561C > T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.
OBJECTIVE: Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case-referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T, to the risk of colorectal cancer, taking into account pre-diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C > T polymorphism, which were analysed in a previous study. MATERIAL AND METHODS: Subjects were 220 cases and 414 matched referents from the population-based Northern Sweden Health and Disease Study. RESULTS: The RFC1 80A-allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T-allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C > T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance. CONCLUSIONS: These findings suggest that although the RFC1 80G > A and FOLH1 1561C > T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.
Authors: Simone J P M Eussen; Stein Emil Vollset; Jannicke Igland; Klaus Meyer; Ase Fredriksen; Per Magne Ueland; Mazda Jenab; Nadia Slimani; Paolo Boffetta; Kim Overvad; Anne Tjønneland; Anja Olsen; Françoise Clavel-Chapelon; Marie-Christine Boutron-Ruault; Sophie Morois; Cornelia Weikert; Tobias Pischon; Jakob Linseisen; Rudolf Kaaks; Antonia Trichopoulou; Demosthenes Zilis; Michael Katsoulis; Domenico Palli; Franco Berrino; Paolo Vineis; Rosario Tumino; Salvatore Panico; Petra H M Peeters; H Bas Bueno-de-Mesquita; Fränzel J B van Duijnhoven; Inger Torhild Gram; Guri Skeie; Eiliv Lund; Carlos A González; Carmen Martínez; Miren Dorronsoro; Eva Ardanaz; Carmen Navarro; Laudina Rodríguez; Bethany Van Guelpen; Richard Palmqvist; Jonas Manjer; Ulrika Ericson; Sheila Bingham; Kay-Tee Khaw; Teresa Norat; Elio Riboli Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-05 Impact factor: 4.254
Authors: Jong Woo Kim; Young Joo Jeon; Moon Ju Jang; Jung O Kim; So Young Chong; Kwang Hyun Ko; Seong Gyu Hwang; Doyeun Oh; Jisu Oh; Nam Keun Kim Journal: Mol Clin Oncol Date: 2015-02-27
Authors: Dong Yong Kil; Brittany M Vester Boler; Carolyn J Apanavicius; Lawrence B Schook; Kelly S Swanson Journal: PLoS One Date: 2010-09-22 Impact factor: 3.240
Authors: A Joan Levine; Won Lee; Jane C Figueiredo; David V Conti; David J Vandenberg; Brian D Davis; Christopher K Edlund; Susanne M Henning; David Heber; Mariana C Stern; Robert W Haile Journal: Cancer Causes Control Date: 2011-01-28 Impact factor: 2.506