Photo of an young man receiving chemotherapy at home. In background his girlfriend talking with nurse. Illustrating cancer epigenetics.
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A study in rats led by Washington State University suggests that some chemotherapy drugs could impact the disease risk of later generations through epigenetic inheritance pathways.

Writing in the journal iScience, the researchers found that male rats who received the chemotherapy drug ifosfamide during adolescence had offspring with increased risk for delayed pubertal onset, kidney disease, and multiple additional health problems. These problems continued in the next generation of direct offspring.

Ifosfamide was selected as it is often used to treat cancers in young men and boys, such as testicular cancer, osteosarcoma and bladder cancer, among others.

“The findings suggest that if a patient receives chemotherapy, and then later has children, that their grandchildren, and even great-grandchildren, may have an increased disease susceptibility due to their ancestors’ chemotherapy exposure,” said Michael Skinner, a researcher at Washington State University, as well as senior author on the study, in a press statement.

The researchers emphasize that they do not suggest patients stop taking the chemotherapy, as it can very effectively treat their cancer, but instead suggest taking measures such as freezing sperm or eggs before undergoing this kind of treatment.

The team found that the first generation male and female offspring of the male rats exposed to ifosfamide had health problems including delayed pubertal onset, kidney disease, abnormal testes and anxiety. The second-generation offspring had less severe, but still noticeable health problems compared with rats whose parents or grandparents had not been exposed to chemotherapy.

The researchers analyzed the genetics of sperm taken from three generations of male rats to assess potential epigenetic differences compared with unexposed males. They found regions where there were different DNA methylation patterns, suggesting epigenetic inheritance.

The researchers now want to see if their findings extend into human populations of former adolescent cancer survivors and their children, and also assess if epigenetics can shed light on what conditions cancer survivors may be susceptible to in the future.

“We could potentially determine if a person’s exposure had these epigenetic shifts that could direct what diseases they’re going to develop, and what they’re going to potentially pass on to their grandchildren,” said Skinner. “We could use epigenetics to help diagnose whether they’re going to have a susceptibility to disease.”

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