The authors investigated 8 functionally significant polymorphisms in 6 genes ( methylenetetrahydrofolate reductase [ MTHFR ] [ C677T , A1298C ] , SLC19A1 [ G80A ] , SHMT1 [ C1420T ] , dihydrofolate reductase [ DHFR ] [ Del19bp ] , TS 1494del , and TSER ) involved in folate metabolism in 745 patients with TNM stage II or III rectal cancer enrolled in a phase 3 adjuvant clinical trial of 3 regimens of 5-FU and radiotherapy ( INT-0144 and SWOG 9304 ) .