Linkage disequilibrium between the 677C>T and 1298A>C polymorphisms in human methylenetetrahydrofolate reductase gene and their contributions to risk of colorectal cancer

被引:100
作者
Chen, J
Ma, J
Stampfer, MJ
Palomeque, C
Selhub, J
Hunter, DJ
机构
[1] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA
[2] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA
[3] Harvard Med Sch, Boston, MA USA
[4] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
[6] Tufts Univ, Jean Mayer USDA Human Nutr Ctr Aging, Boston, MA 02111 USA
来源
PHARMACOGENETICS | 2002年 / 12卷 / 04期
关键词
MTHFR; colorectal cancer; folate; homocysteine;
D O I
10.1097/00008571-200206000-00011
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A common polymorphism in a folate-metabolizing gene, methylenetetrahydrofolate reductase (MTHFR) 677C>T has been associated with reduced risk of colorectal cancer. In this study, we investigated whether a second common polymorphism of the gene, MTHFR 1298A>C, is an independent risk factor for colorectal cancer and if it is associated with plasma folate and total homocysteine (tHcy) levels. We also examined whether the 677C>T and 1298A>C polymorphisms are in linkage disequilibrium and whether combined heterozygosity confers additional (or reduced) risk of colorectal cancer. We conducted a nested case-control study of 211 incident colorectal cancer cases and 343 controls in the prospective Physicians' Health Study. The MTHFR 677C>T and 1298A>C polymorphisms were in linkage disequilibrium in this population. Compared to MTHFR 1298AA genotype, multivariate-adjusted relative risk of colorectal cancer was 0.73 (95% Cl 0.37-1.43) for the MTHFR 1298CC genotype. The slight reduction in risk was not a result of its linkage disequilibrium with the 677C>T polymorphism. This polymorphism was not significantly correlated with the plasma folate and tHcy levels. The combined heterozygosity did not modify the cancer risk; nor did it change the plasma folate and tHcy significantly. We conclude that the MTHFR 1298A>C polymorphism is a less substantial independent risk factor for colorectal cancer compared to the 677C>T polymorphism.
引用
收藏
页码:339 / 342
页数:4
相关论文
共 10 条
[1]   The effect of 677C → T and 1298A → C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects [J].
Chango, A ;
Boisson, F ;
Barbé, F ;
Quilliot, D ;
Droesch, S ;
Pfister, M ;
Fillon-Emery, N ;
Lambert, D ;
Frémont, S ;
Rosenblatt, DS ;
Nicolas, JP .
BRITISH JOURNAL OF NUTRITION, 2000, 83 (06) :593-596
[2]  
Chen J, 1996, CANCER RES, V56, P4862
[3]   A common mutation A1298C in human methylenetetrahydrofolate reductase gene: Association with plasma total homocysteine and folate concentrations [J].
Friedman, G ;
Goldschmidt, N ;
Friedlander, Y ;
Ben-Yehuda, A ;
Selhub, J ;
Babaey, S ;
Mendel, M ;
Kidron, M ;
Bar-On, H .
JOURNAL OF NUTRITION, 1999, 129 (09) :1656-1661
[4]   A CANDIDATE GENETIC RISK FACTOR FOR VASCULAR-DISEASE - A COMMON MUTATION IN METHYLENETETRAHYDROFOLATE REDUCTASE [J].
FROSST, P ;
BLOM, HJ ;
MILOS, R ;
GOYETTE, P ;
SHEPPARD, CA ;
MATTHEWS, RG ;
BOERS, GJH ;
DENHEIJER, M ;
KLUIJTMANS, LAJ ;
VANDENHEUVEL, LP ;
ROZEN, R .
NATURE GENETICS, 1995, 10 (01) :111-113
[5]  
Ma J, 1997, CANCER RES, V57, P1098
[6]  
Rosenblatt DS, 2001, CLIN INVEST MED, V24, P56
[7]  
TERWILLIGER J, 1994, HDB HUMAN GENETIC LI
[8]   A second common mutation in the methylenetetrahydrofolate reductase gene:: An additional risk factor for neural-tube defects? [J].
van der Put, NMJ ;
Gabreëls, F ;
Stevens, EMB ;
Smeitink, JAM ;
Trijbels, FJM ;
Eskes, TKAB ;
van den Heuvel, LP ;
Blom, HJ .
AMERICAN JOURNAL OF HUMAN GENETICS, 1998, 62 (05) :1044-1051
[9]   A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity [J].
Weisberg, I ;
Tran, P ;
Christensen, B ;
Sibani, S ;
Rozen, R .
MOLECULAR GENETICS AND METABOLISM, 1998, 64 (03) :169-172
[10]   The 129XA → C polymorphism in methylenetetrahydrofolate reductase (MTHFR):: in vitro expression and association with homocysteine [J].
Weisberg, IS ;
Jacques, PF ;
Selhub, J ;
Bostom, AG ;
Chen, ZT ;
Ellison, RC ;
Eckfeldt, JH ;
Rozen, R .
ATHEROSCLEROSIS, 2001, 156 (02) :409-415