DNA methylation—a key factor in breast cancer prognosis and treatment

Landmark research just published in PLoS Genetics (Public Library of Science) brings to light two important points in breast cancer diagnosis and treatment. First, the authors prove that defects in methylation (addition of a methyl group) a critical process for maintaining DNA health, is a powerful prognostic indicator for breast cancer outcome. The authors first observe:

“Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics…We investigated DNA methylation profiles in over 160 well annotated breast tumor samples and found significant relationships with standard and other known predictors of prognosis, as well as established risk factors for disease: alcohol intake and dietary folate.”

They measured the methylation patterns of critical genes primary breast tumors from 162 women. Their findings are compelling:

Tumor grade, size, estrogen and progesterone receptor status, and triple negative status were significantly associated with altered methylation…”

The second valuable point confirms the role of alcohol intake and folate status, both known to impact methylation capability.

“Using multinomial logistic regression to adjust for potential confounders, patient age and tumor size, as well as known disease risk factors of alcohol intake and total dietary folate, were all significantly associated with methylation class membership.”

The authors’ conclusion indicates the profound importance of assessing and protecting methylation capacity:

Breast cancer prognostic characteristics and risk-related exposures [alcohol and folate status] appear to be associated with gene-specific tumor methylation, as well as overall methylation patterns.”

I use measurements of urinary methylmalonate and formiminoglutamate, objective indicators of important methylation cofactors. One or both of these is typically abnormal in patients with breast cancer. In my opinion, measuring this and treating methylation abnormalities with physiological interventions should be part of the standard of care for breast cancer.

Early pregnancy folate associated with child hyperactivity

Journal of Child Psychology and PsychiatryThe authors of this paper recently published in the Journal of Child Psychology and Psychiatry being by noting:

Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring.”

They correlated maternal red blood cell folate (RCF) at 14 weeks of pregnancy and total folate intake (TFI) from food and supplements with their childrens’ behavioral difficulties. What did the data show?

Lower maternal RCF and TFI in early pregnancy were associated with higher childhood hyperactivity and peer problems scores in the offspring….analyses showed significant inverse indirect associations of RCF with hyperactivity/inattention and peer problems via fetal brain growth.”

Their conclusion:

“…our data provide preliminary support for the hypothesis that lower folate status in early pregnancy might impair fetal brain development and affect hyperactivity/inattention and peer problems in childhood.”

Here we have another compelling reason to ascertain good folate status in early pregnancy, or (even better) before becoming pregnant. Although conventional blood tests for serum folate are not dependable, a convenient and reliable way to do determine folate adequacy is by measuring the organic acid formiminoglutamate in the urine.