Mother's diet around conception can affect child's lifelong cancer risk, study says

While it’s known that a mother’s diet can affect her unborn child’s development in utero, a new study found that her eating habits around the time of conception can also alter her child’s lifelong risk of cancer.

A new study published in the journal Genome concluded that a gene affecting a person’s risk of cancer can be permanently altered in utero depending on a mother’s diet. While a child’s genes are directly inherited from his parents, how the genes are expressed is controlled through modifications to the DNA, which occur during embryonic and fetal development, according to the report.

Modifications can occur when gene regions are tagged with chemical compounds called methyl groups that silence genes. The compounds require specific nutrients, which means that a mother’s eating habits before and during pregnancy can permanently affect the “setting” of these tags, the report said.

Researchers at the Baylor College of Medicine, the Children’s Nutrition Research Center at Baylor and Texas Children’s Hospital, the London School of Hygiene & Tropical Medicine in London, the MRC Unit and The Gambia, split into two groups and targeted specific regions of the genome called metastable epiallels that are particularly sensitive to these effects.

The research groups both found that the tumor suppressor gene VTRNA2-1— which helps prevent cells from becoming cancerous— was the most sensitive to the environment created by the mother around the time of conception.

“There are around 20,000 genes in the human genome,” study leader Dr. Robert Waterland, an associate professor of pediatrics and nutrition at Baylor said, according to the report. “So for our two groups, taking different approaches, to identify this same gene as the top epiallele was like both of us digging into different sides of a gigantic haystack containing 20,000 needles… and finding the exact same needle.”

Typically, aside from genes on sex chromosomes, mammals inherit two copies of all genes which function equally. Researchers found that VTRNA2-1 belongs to a special class of genes that are expressed from only the maternal or paternal copy. These genes are labeled imprinted genes because they are imprinted with epigenetic marks inherited from either the sperm or egg, the report said. What further sets VTRNA2-1 apart is that it is the first example of an imprinted metastable epiallele.

“Our results show that the methylation marks that regulate VTRNA2-1 imprinting are lost in some people, and that this ‘loss of imprinting’ is determined by maternal nutrition around the time of conception,” Andrew Prentice, professor at the London School of Hygiene & Tropical Medicine and head of the MRC International Nutrition Group said, according to the report. “These are large changes in gene methylation that affect a substantial subset of individuals.”

Three previous studies showed that an increase in these methylation marks is a risk factor for acute myeloid leukemia, lung and esophageal cancer. However, a decrease in these marks— VTRNA2-1 loss of imprinting— led to individuals with a double-dose of the anti-cancer gene, according to the report.

“The potential implications are enormous,” Prentice told The Guardian. “In this particular example, the gene involved is really crucial – it lies at the center of the immune system so it affects our susceptibility to viral infection. At the very beginning of fetal growth, the way it is labeled is going to affect the baby’s health for the rest of its life,” he said.

“If a mother’s diet is poor then it causes a whole lot of damage to the genome which has a shotgun effect, so a baby might have possible adverse outcomes,” Prentice told the news site. “This general phenomenon might explain preterm births, problems in pregnancy, brain defects, or why some babies are born too small.”

“We could potentially clean up a lot of adverse pregnancy outcomes by getting the diet right,” he told The Guardian.

Researchers also showed the loss of VTRNA2-1 affects all cells of the body, and that the loss of imprinting is stable from childhood to adulthood. Researchers say more studies are under way to test whether methylation at VTRNA2-1 can be used as a screening test to predict risk of cancer.