Photo by Tiffany D. Nicholson
Woman smoking
Smoking by either parent helps promote genetic deletions in children that are associated with the development and progression of acute lymphoblastic leukemia (ALL), according to a study published in Cancer Research.
The strongest associations in this study were found in children whose parents smoked while the children were in utero and during their infancy.
However, the genetic deletions were also noted in the offspring of parents who may have quit smoking even before conception.
The link between ALL and parental smoking has already been established, but this is the first study that points to specific genetic changes in children with ALL, according to study author Adam de Smith, PhD, of the University of California San Francisco.
“With more smoking among the parents, we saw more deletions within the child’s ALL cells at diagnosis,” Dr de smith said.
For this study, he and his colleagues looked at pre-treatment tumor samples from 559 ALL patients.
The team wanted to see if any of the 8 genes that are frequently deleted in ALL patients (CDKN2A, ETV6, IKZF1, PAX5, RB1, BTG1, PAR1 region, and EBF1) were missing in the samples.
Questionnaires were given to parents to find out if smoking habits impacted the number of genetic deletions. Data was corroborated by a biomarker in newborns’ blood samples that indicates exposure to maternal smoking during pregnancy.
The researchers found that approximately two-thirds of the tumor samples (n=353) contained at least 1 deletion.
Deletions were considerably more common in children whose mothers had smoked during pregnancy and after birth.
For each 5 cigarettes smoked daily during pregnancy, there was a 22% increase in the number of deletions. For each 5 cigarettes smoked daily during breastfeeding, there was a 74% increase in the number of deletions.
Smoking of 5 cigarettes daily by the mother or father before conception was associated with a 7% to 8% higher number of deletions.
Role of child age and sex
One discovery the researchers found intriguing was the link between the fathers’ pre-conception smoking and their child’s age at diagnosis.
“There was a significant effect on deletion numbers in cases where the patient was age 6 or younger,” Dr de Smith said. “Our results suggest that paternal pre-conception smoking, which is known to cause oxidative damage to sperm DNA, may lead to a higher propensity of deletions in children with earlier-onset ALL.”
“It is also true that some of those fathers who smoked before conception also continue to smoke in the presence of the mother and child, so more research is needed to explain the mechanism of smoking-related damage in all of the time periods of exposure to the child.”
In addition, male children were found to be more sensitive to the effects of maternal smoking, including smoking that occurred pre-conception.
The researchers said this could be explained by the fact that male fetuses grow more rapidly, which leads to increased vulnerability of developing lymphocytes to toxins that cause genetic damage.
“Our study indicates that the more tobacco exposure, the more cumulative DNA damage is evident in the ALL cell,” said study author Joseph Wiemels, PhD, of the University of California San Francisco.
“While causes of ALL are multifactorial—including the inborn genetic makeup of the child, patterns of infection, pesticides, and other environmental exposure—if there was no smoking in the environment, then there would likely be fewer children with the disease. We may add ALL to the long list of diseases impacted by smoking, and, in this case, affecting one of our most vulnerable populations—our children.”
