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Genes and environment interact to promote cancer

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Washington.– In the granite-rich region of Western North Carolina, taking a daily shower could pose a risk of developing lung cancer. So could working from home every day.

That's because granite emits a carcinogenic gas, radon. Houses that sit atop granite terrain are often contaminated with radon that has seeped into wells and indoor air.

"After smoking, radon is considered to be the second leading cause of lung cancer in the United States, said Avner Vengosh, Ph.D., associate professor at Duke's Nicholas School of the Environment and Earth Sciences. "Western North Carolina is highly affected, and many homes exceed the EPA's recommended levels of radon."

Radon's risk is not new or unknown, but it illustrates the real danger posed by indigenous substances as well as those artificially created by humans, say Duke scientists. More than 80,000 synthetic chemicals have been introduced worldwide since World War II, with little or no knowledge as to how they affect humans or animals.

Day by day, environmental scientists identify new culprits in the cancer equation in which genes, environment and lifestyle interact to increase cancer risks in some people but not in others.

Their synergy is by no means a simple interaction, said H. Kim Lyerly, Director of the Duke Comprehensive Cancer Center. For example, vitamin A can promote lung cancer growth in some women while it maintains healthy breast cell growth and division in others, said Victoria Seewaldt, M.D., director of the Duke Breast Health Clinic.

Chemicals that promote cancer in one fish species do not cause cancer in a closely related species, while populations of another species have adapted to a polluted environment, found Richard Di Giulio, Ph.D., of Duke's Nicholas School. Common nutritional supplements like folic acid, given to pregnant mice, altered their offspri! ngs' coat colors and their adult risk of cancer, found Randy Jirtle, Ph.D. professor of radiation oncology at Duke University Medical Center.

Why these differences exist, and how and when the changes are imposed, are major questions being studied in a partnership between the Duke Comprehensive Cancer Center and Duke's Nicholas School of the Environment and Earth Sciences.

The two groups are hosting their joint conference March 30 to 31 to present their latest findings on how the environment impacts cancer. Collectively, their data show that the timing and dose of exposure, combined with an individual's genetic makeup, play critical roles in cancer susceptibility.

"The nature-versus-nurture argument is rapidly proving to be irrelevant, because we're finding that the two forces interact in highly specific ways that alter gene behavior," said Jirtle.

Select chemicals may damage or "mutate" genes at any given time in the lifespan, contributing to a host of human diseases, he said. But another, more subtle, change is emerging as the trigger for many cancers, diseases and even personality traits.

Called "epigenetic" alterations, they occur when chemicals, nutrients or even behaviors elicit a chemical change in the brain or body that activates or silences a gene - without changing its fundamental genetic code. The chemical or event mobilizes groups of molecules, called methyl or acetyl groups, to attach to the control region of a gene and alter its usual activity.

Such stealth changes often occur during embryonic or fetal development, but emerging data suggests they set the stage for an adult's susceptibility to a host of diseases and behavioral responses.

Moreover, epigenetic changes - so named because they sit on top of the gene and leave its sequence unchanged - can also be passed down from one generation to the next, said Jirtle, who has extensively studied the phenomenon. They can also be reversible. Methyl groups can be added or knocked off following exposure to various substances.

Finding methylated or acetylated genes is no small task, however. Certain genes are more susceptible to epigenetic alterations than others, but no one knows for certain which genes and when the changes occur.

Second, multiple compounds may interact to halt or promote genetic or epigenetic changes. Finally, epigenetic changes may occur so early in prenatal development that gauging its effects in adulthood prove difficult.

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