Surprising findings on
genetic disease impact
of cancer treatment
Massive Study Sees Whether Radiation, Chemotherapy Lead to Birth Defects in Children of Cancer Survivors
October 13, 2009
by Brendon Nafziger
, DOTmed News Associate Editor
In the largest study of its kind, researchers from around the world have sought to determine if chemotherapy drugs or radiation treatment cause genetic damage that leads to birth defects in the offspring of cancer patients.
To the surprise of even the researchers, the answer seems to be: no.
Preliminary findings from a study started in the U.S. 15 years ago are to be presented at the American Society of Human Genetics meeting in Hawaii at the end of the month.
The work draws on profiles of 14,357 people from across the U.S. who, from 1970 through 1986, were diagnosed with various cancers before they turned 21, as well as two massive studies in Finland and Denmark, stretching back more than 50 years, that have analyzed 14,519 patients diagnosed while they were under 35.
Altogether, over 30,000 children conceived after their parents' cancer diagnosis were studied.
And all these data point toward one conclusion. "There's no excess of genetic disease or birth defects [in the offspring of cancer patients], however defined," John Mulvihill, M.D., a geneticist at University of Oklahoma, and one of the consultants on the study, tells DOTmed News.
No evidence of higher-than-normal risk for birth defects
Dr. Mulvihill and the other researchers looked to see if these cancer patients were more likely to have children who were still-born, of low birth weight, had conditions like Down syndrome that are the result of chromosomal errors, or were afflicted with one of around 50 rare genetic disorders known to be produced by damage to single genes.
The initial results are, in Dr. Mulvihill's words, "unbelievable." The children of these parents were no more likely to suffer from any of these effects than the children of anybody else.
However, all the studies did show a slight increase in cancer rates among the children of cancer survivors, though the cause of this is probably not an after-effect of the treatment, but rather heredity. Parents pass on the genes that make them susceptible to certain kinds of cancer in the first place.
As an example, Dr. Mulvihill mentions a well-known tumor, the retinoblastoma of the eye. "Sometimes it's familial," he says. "If a parent has it and gets cured, there's a 50-50 chance the offspring will have it, too."
Presumed danger of treatment
Radiation therapy works in part by damaging the DNA in cancer cells. Many chemotherapy drugs target a similar mechanism. "They zap [genetic material] just like radiation does," says Dr. Mulvihill.
The fear is that if this DNA-damage occurs in the sex cells, it could cause mutations that would result in birth defects or miscarriages.
In fact, many cancer treatments can impair fertility. And as a precaution, couples are warned to wait at least six months to one year after their last radiation or chemotherapy dose before trying to conceive, Dr. Mulvihill says, although new sperm is cycled in only 90 days. As for eggs, because they are "quiet and not metabolizing," if they survive the radiation blast or chemo dose, "there's no sort of chemistry going on that would make chemo or radiation do a mutation in the ovary," says Dr. Mulvihill.
Although no effects have been seen so far, the teams of researchers are still teasing apart the data.
For instance, some of the researchers on the project have now built dummies with every inch covered by radiation sensors, so they can measure exactly how much radiation the gonads received from different techniques, different machines, and in different time periods -- radiation doses and the protection offered have changed a lot since the '50s or '60s, Dr. Mulvihill says, when patients getting radiation may not have had their gonads covered by "clamshell" lead casings, currently in wide use.
The researchers are also looking to see if there is any correlation between cancer treatment and the likelihood to have offspring with birth defects among sub-populations -- patients who had, say, especially high-dose therapies, or who were given limited protection.
Ultimately, Dr. Mulvihill wants to see if these treatments cause genetic changes that might be too faint to show up clinically. "Given how unbelievable our hypothesis is," says Dr. Mulvihill, "my swan song is to look at it at the DNA level, when genome sequencing gets cheap enough." He wants to compare a child's DNA against that inherited from his or her parents, to see if an unusually high number of new mutations have cropped up, even among the so-called junk DNA that might not play any role in the child's development.
And those findings could have implications not just for cancer treatment, but for the whole science of genetics. "If our study's sequencing showed changes to junk DNA, and the kids are normal, then maybe it really is junk DNA, because it can be changed without injury to the next generation," Dr. Mulvihill says.
For now, though, Dr. Mulvihill believes the study is a reassuring one for patients and doctors: "Toxicity to gonads [from these treatments] doesn't appear to exist," he says.