Adult acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects the myeloid type of white blood cells, called myeloblasts. It’s the most common type of acute leukemia in adults. It affects men and smokers more often than other people. Previous chemotherapy recipients are also at risk.
Rather than maturing as healthy white blood cells, the myeloblasts in people with this condition become abnormal white blood cells, red blood cells, or platelets. The abnormal cells can crowd out healthy ones, leading to infection, anemia, and easy bleeding. They can also spread to other parts of the body.
Medical researchers suspect that AML is caused by the interaction of several factors. MTHFR gene variants are one possibility. By metabolizing folate, the MTHFR gene helps regulate the chemical reactions that synthesize DNA. Certain MTHFR mutations can cause a 30% – 60% drop in enzyme activity, likely leading to imbalances in the chemicals that reduce DNA errors.
Researchers from Guangxi Medical University recently conducted a study to find out more. 98 AML patients and 2016 healthy controls from Southern China participated in the study. The authors extracted their genotypes and examined variants at two locations on the MTHFR gene (C677T and A1298C).
They found that one variant genotype (1298AC) was associated with a decreased risk of AML, as compared to the prevalent genetic profile. The other variant genotype (677TT) had no affect on AML risk.
Since different snippets of DNA often affect each other, the authors also looked at the combined effects of the two MTHFR gene variants. They found that AML risk among participants with a specific combination (677CC/1298AC) was cut in half. The result held when the researchers accounted for age and smoking and drinking history. Non-smokers and non-drinkers with this genetic profile were nearly four times less likely to develop AML.
Since smoking and drinking may affect folate levels, the study also looked at a subset of people who did not smoke or drink (70 AML patients and 160 healthy people). While you might assume this group would fare better, genetics is full of surprises. Researchers did find that a particular variant (1298AC) decreased AML risk among this group. Another variant (677TT), however, was associated with increased AML risk only in non-smokers and non-drinkers.
The differences between participants who drink and smoke and those who don’t point to lifestyle as a significant factor. The results suggest that exposure to very low levels of carcinogens among non-smokers may cause people with certain MTHFR gene variants to eventually develop AML. Smokers who enhale larger amounts of carcinogens may trigger different genetic pathways.
Interestingly, a variant at one location decreases AML risk, while a variant at a different location on the same gene increases risk. The authors think the conflict may be due to chance, the different roles of the variants, or unknown interactions. Folate deficiency may also play a part.
While the results are promising, the study was limited by a small sample size and lack of information on folate levels. Further studies with larger sample sizes that incorporate data on folate availability will help clarify the MTHFR gene’s possible role in ALM risk.
The paper, published in The International Journal of Cancer Epidemiology, is available online.