High homocysteine is a risk factor for colorectal cancer

Colorectal cancer can be added to the list of conditions for which high levels of homocysteine are a risk factor according to a study recently published in The American Journal of Clinical Nutrition. Perhaps more important than the association of high homocysteine with low levels of vitamins B12, B6 or folate is the fact that homocysteine is a biomarker for inflammation. The authors state:

"Inflammation underlies the etiology of colorectal cancer (CRC). Hyperhomocysteinemia is associated with inflammation and may be a risk marker for CRC. Cysteine is a metabolic product of homocysteine and a precursor of the antioxidant glutathione. It is unknown whether cysteine is associated with CRC."

The authors went about investigating the link between homocysteine and colorectal cancer in postmenopausal women examining data from the Women's Health Initiative. They compared homocysteine and cysteine levels between 988 women with colorectal cancer and the same number matched for age, ethnicity and hysterectomy status. Their data showed a clear association:

"Multivariate-adjusted ORs for CRC [colorectal cancer] were 1.46 for the highest quartile of homocysteine (>9.85 μmol/L) compared with the lowest quartile (≤6.74 μmol/L) and 0.57 for the highest quartile of cysteine (>309 μmol/L) compared with the lowest quartile (≤260 μmol/L). The association with homocysteine was significant for proximal colon tumors but not for distal or rectal tumors, whereas the association with cysteine was significant for rectal tumors, borderline for proximal tumors, and not significant for distal tumors. The associations with both homocysteine and cysteine were significant for localized tumors but not for metastases."

In other words, proximal colon tumors were significantly less with the lowest homocysteine level. Practitioners take note: higher levels of cysteine, a precursor for both the noxious irritant homocysteine and the profoundly important glutathione, was associated with less rectal and proximal tumors. We should be attentive to functional levels of homocysteine (I always screen homocysteine and note when it is above 6 μmol/L) and support the conversion of cysteine to glutathione as opposed to allowing it to be hijacked down the homocysteine pathway. The authors conclude:

"High plasma homocysteine is associated with increased risk of CRC [colorectal cancer], whereas high cysteine is associated with decreased risk."