Maternal cured meat intake may increase brain tumor risk in offspring with gene variant
MedWire News: Children with a genetic inability to detoxify nitroso compounds may be at increased risk for brain tumors if their mothers consumed cured meat during pregnancy, a case-control population study has found.
Study co-author Susan Searles Nielsen (Fred Hutchinson Cancer Research Center, Seattle, Washington, USA) and colleagues say the findings provide a solid mechanistic grounding for previous studies that observed this cured meat effect.
Childhood brain tumors (CBTs) are the second most common pediatric cancer after leukemia. Ionizing radiation is the only conclusively established non-genetic risk factor, but several epidemiologic studies suggest that maternal consumption of cured meats during pregnancy increases risk for CBTs in offspring.
Although not all studies have observed this association, the potential relationship remains compelling because cured meat is an important source of nitrite that can combine with other components of meat to form N-nitroso compounds, including nitrosoureas.
These are potent neurocarcinogens in non-human primates and other animals, especially when exposure occurs in utero. Detoxification of nitrosoureas relies on a family of enzymes called glutathione S-transferases (GSTs).
Noting that there are several characterized polymorphisms in the genes encoding GSTs, the researchers sought to establish if they might modify any cured meat-CBT association.
They conducted a population-based study of 202 individuals with CBTs and 286 controls where data on maternal prenatal cured meat consumption was available - defined as ham, bacon, hot dogs, sausage, luncheon meat, or "other" cured meats combined.
DNA was extracted from dried blood spots (DBS) from newborn screening archives and genotyping focused on six polymorphisms across several isoforms of GST, some of which are known to result in complete absence of the respective enzyme activity among homozygous carriers while others simply cause reduced activity.
Nielsen et al report that the risk for CBTs increased with increasing cured meat intake by the mother during pregnancy among children homozygous for a null mutation in GSTT1. The odds ratio (OR) for each increase in the frequency of consumption per week as a continuous variable was 1.29.
Similarly, maternal cured meat intake increased the risk for CBT in individuals with a least one copy of the impaired functioning GSTM3 C allele (OR=1.14 for increasing consumption).
By contrast, there was no increased risk observed among those with intact GSTT1 or GSTM3.
"Together, these results suggest that the possible association between cured meat consumption during pregnancy and CBT risk in offspring may be modified by the fetus' ability to metabolize compounds potentially associated with the consumption of cured meats, such as nitrosoureas," Nielsen et al comment.
They add that future studies will benefit from assessment of maternal cured meat intake by trimester of pregnancy, larger sample sizes, and the inclusion of children conceived in a wider range of birth years in order to examine the effect of decreasing levels of nitrite in cured meats over time.
The research is published in the journal Cancer Epidemiology, Biomarkers and Prevention.
By Andrew Czyzewski