Gene study allays folate-prostate cancer fears

Folate levels are not linked with an increased risk of prostate cancer, according to results of a gene study and meta-analysis from the UK.

Analysis of the results of tens of thousands of people, with and without prostate cancer, appears to redress concerns about the nutrient and prostate cancer-risk, first reported earlier this year by Californian scientists.

Speaking to NutraIngredients, lead researcher Dr Simon Collin from the Department of Social Medicine at the University of Bristol said: "If folate had an important role in the initiation or progression of prostate cancer, we would expect genetic variation in enzymes which regulate folate levels to be associated with prostate cancer risk.

“Our study did not find any such association for the most commonly studied 'folate gene' (MTHFR),” he said. “This gene has been associated with other cancers, including leukemia, gastric, and colorectal.”

Folate’s benefits

Folate is found in foods such as green leafy vegetables, chick peas and lentils, and an overwhelming body of evidence links has linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.

This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.

While preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence, parallel measures in Europe and New Zealand. Australia has just announced that mandatory fortification will be introduced.

However, some concerns over consumption of high levels of folic acid have surfaced, linking the nutrient to increased risks of colorectal cancer. Earlier this year, California-based scientists reported that daily folic acid supplements of one milligram were associated with a doubling had more than twice the risk of prostate cancer compared with men who took a placebo (Journal of the National Cancer Institute, doi: 10.1093/jnci/djp019).

However, men with high folate levels at the start of the study were associated with a protective effect against prostate cancer.

Genes and meta-analyses

Writing in the journal Cancer Epidemiology, Biomarkers & Prevention, Dr Collin and his co-workers conducted a systematic review including eight studies, and data from the UK population-based Prostate Testing for Cancer and Treatment study.

Dr Collin explained that by using genes as indicators of exposure to folate levels removes any concerns about confounding by lifestyle factors, “because genes are randomly distributed”, he said.

The researchers found no link between the common folate-pathway and a person’s susceptibility to prostate cancer.

Explaining ‘unfounded’ early concerns

Responding to the Californian study’s findings, Dr Collin said: “It has been suggested that micronutrients such as folate could have a U-shaped relationship with cancer risk - so a higher folate level equals a lower risk of cancer initiation, but a higher rate of cancer progression.

“However, we did not find any difference in the lifetime effects of folate levels on localized versus advanced cancer, so this remains an unfounded hypothesis.”

Source: Cancer Epidemiology, Biomarkers & Prevention

Published online ahead of print, doi: 10.1158/1055-9965.EPI-09-0223

"Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis"

Authors: S.M. Collin, C. Metcalfe, L. Zuccolo, S.J. Lewis, et al.