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

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

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.

This study are going to measure the oxidative stress (TBARs), antioxidant activities and DNA methylation in colorectal cancer patients

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.