Chromosome Breakage May Predict Cancer Risk

The sensitivity of an individual’s chromosomes to breakage by a cancer drug is largely inherited, say Dutch researchers.

The findings suggest that “a common genetic susceptibility to DNA damage can exist in the general population,” the team write in the Journal of the National Cancer Institute. Finding the genes responsible for this trait may lead to new ways to treat and prevent cancer.

The study is based on knowledge that the cancer drug bleomycin can cause breaks in the chromosomes of blood cells tested outside the body, according to Dr. Boudewijn Braakhuis and a team of researchers from Vrije University in Amsterdam, The Netherlands.

Because some cancer patients have increased susceptibility to these breaks, the authors explored the heritability of the chromosomes’ sensitivity to bleomycin in cancer patients and their families and in unrelated, healthy individuals.

Using a sophisticated tool called pedigree analysis, the authors estimated that genetic differences account for 75% of the susceptibility of chromosomes to breakage by bleomycin.

This study demonstrates for the first time that such “chromosomal instability… has a clear genetic basis,” according to the report.

Developing tests to identify individuals at high risk for chromosomal damage could lead to doctors warning them to avoid exposure to particular carcinogens, thereby reducing their risk of developing cancer, the authors speculate.

Ultimately, scientists would hope to identify the genes responsible for these differences in susceptibility, which in turn would allow doctors to estimate individual risk, writes Dr. Neil Caporaso of the National Cancer Institute in a related editorial.

“This should lead to a more precise understanding of the contributions of exposure, heredity, and chance in these cancers, an advance that should lead to new insights for prevention and treatment,” he concludes.

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