the effects of vitamin b-6 status on homocysteine, oxidative stress, one-carbon metabolism and methylation: cross-section, case-control, intervention and follow-up studies in colorectal cancer

Conditions: Colorectal Cancer

Summary: vitamin b-6, folate and homocysteine may play a critical role in the colorectal cancer progression. this is a 4-y study and the specific aims are: 1) to compare vitamin b-6, folate and homocysteine status, oxidative stress, antioxidant activities and dna methylation between subjects with colorectal polyps and colorectal cancer; 2) to study the effects of vitamin b-6, folate and homocysteine status on oxidative stress, antioxidant activities and dna methylation in colorectal cancer patients; 3) to evaluate whether folic acid and/or pyridoxine supplementation had a beneficial effect on oxidative stress, antioxidant activities and dna methylation in patients with colorectal; 4) to compare vitamin b-6, folate and homocysteine status, oxidative stress, antioxidant activities and dna methylation between colorectal cancer patients and age-, sex-matched healthy subjects; 5) to evaluate the effect of vitamin b-6, folate and homocysteine status, oxidative stress, antioxidant activities and dna methylation on the risk of colorectal cancer (odds ratio); 6) to follow the effects of vitamin b-6, folate and homocysteine status, oxidative stress, antioxidant activities and dna methylation on the occurrence of colorectal cancer; 7) to follow the effects of pyridoxine and/or folic acid supplementation on the occurrence of colorectal cancer. this protocol is designed as a hospital-based cross-sectional, case-control, double blinded randomized placebo-controlled intervention and follow-up trial. three hundred colorectal cancer patients and 300 age-, sex-matched controls who meet the inclusion criteria will be recruited from taichung general veterans hospital. if cancer patients' plasma pyridoxal 5'-phosphate (plp) level less than 30 nmol/l will be asked to participate the intervention study and will be blinded and randomly assigned to either the 1) control (vitamin c, 100 mg/d); 2) 50 mg vitamin b-6; 3) 400 microgram/d folic acid; or 4) vitamin b-6 (50 mg/d) plus folic acid (400 microgram/d) for 1 year. data on demography, anthropometry, medical history, food frequency questionnaire and 24-h diet recall will be collected. cancer patients will have fasting blood drawn before surgery or receiving chemotherapy. additionally, fasting blood samples will be obtained at month 0, 3, 6, 9 and 12 during intervention period and at month 6, 12, 18, 24, 30, 36, 42 and 48 during follow-up. hematological, plasma and erythrocyte plp, plasma pyridoxal and 4-pyridoxic acid, serum and erythrocyte folate, serum vitamin b-12, homocysteine, sam, sah, lipid peroxidation indicators (tbars, oxidized ldl), glutathione, antioxidant enzymatic activities and dna methylation and mthfr 677c\>t polymorphism will be measured.


Eligibility criteria:
inclusion criteria: * colorectal cancer participants were identified by colonoscopy to have at least one historically confirmed colorectal cancer. exclusion criteria: * age\<18 years * pregnant women * had a history of colorectal cancer * attenuated adenomatous polyposis coli * inflammatory bowel disease or were taking any medication which could influence homocysteine, folate, vitamin b6 and b12 status, such as h2 blockers, proton pump inhibitors, metformin, phenytoin, methotrexates.