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Other highlights in the January 21 issue of JNCI

Journal of the National Cancer Institute

Review Examines Effect of Genetic Counseling on Awareness, Risk Perception
Genetic counseling leads to increased knowledge of cancer genetics and does not have an adverse impact on anxiety or distress of the patients being counseled, according to a systematic review.

The identification of genes that are associated with a high risk of certain types of cancer has led to an increased demand for genetic counseling from individuals at increased risk for the disease. To determine the quality and strength of evidence related to psychological outcomes of genetic counseling for familial cancer, Dejana Braithwaite, of the Institute of Public Health at the University of Cambridge, and colleagues conducted a meta-analysis of 21 controlled trials and prospective studies of the impact of genetic counseling for breast, ovarian, and colorectal cancer on cognitive, affective, and behavioral outcomes.

They found that, in controlled studies, genetic counseling for familial cancer was associated with improved knowledge of cancer genetics but did not alter the level of perceived risk, whereas, in prospective studies, there was an improvement in accuracy of perceived risk. The authors conclude that these findings should be investigated further through well-designed, well-reported, randomized controlled trials with suitable comparison groups and additional outcome measures.

Gene Mutation Affects Sensitivity of Cancer Cells to Chemotherapy Drugs
A research team has found that a specific mutation in a gene critical to folate metabolism alters the sensitivity of colon and breast cancer cells to common chemotherapy drugs, suggesting that the gene might be a useful marker for tailoring chemotherapy or that it is a potential target to improve sensitivity to chemotherapy.

Folate is a form of a B vitamin that is critical for DNA synthesis, DNA repair, and epigenetic regulation. About 35% of the general North American population has a common mutation in an enzyme, MTHFR, that is critical to the metabolism of folate. This mutation is associated with changes in cellular composition of folates. Because the response of cancer cells to two common chemotherapy drugs, 5-fluorouracil (5FU) and methotrexate, is dependent on the interaction with folate metabolism, Kyoung-Jin Sohn and Young-In Kim, M.D., of the University of Toronto, tested whether this common mutation--called the MTHFR C677T polymorphism--affected the sensitivity of cancer cells to 5FU and methotrexate.

The authors found that colon and breast cancer cells that had the mutation had decreased MTHFR activity, altered intracellular folate distribution, accelerated cellular growth rate, and increased chemosensitivity to 5FU. Breast cancer cells had decreased chemosensitivity to methotrexate. In mice, tumors with the mutated gene grew faster but were more sensitive to 5FU than tumors with the normal gene. "Our data suggest that the MTHFR C677T polymorphism may be a useful pharmacogenetic determinant for providing rational and effective tailored chemotherapy," the authors write. "Furthermore, our data suggest that antisense inhibition of MTHFR may be a potential target for increasing chemosensitivity of colon and breast cancer cells to 5FU-based chemotherapy."

Titles of additional articles appearing in the January 21 JNCI:

  • Exposure to carcinogens not proportionally decreased by reduction in smoking:
  • Radiotherapy improves survival after breast-conserving surgery for early-stage breast cancer:
  • Fecundity and twining rates as measures of fertility before diagnosis of germ-cell testicular cancer, Lorenzo Richiardi, Karolinska Institute, Stockholm, Sweden, et al.
  • Retention of enrollees following a cancer diagnosis within health maintenance organizations in the Cancer Research Network, Terry S. Field, Meyers Primary Care Institute, et al.
  • Circulating DNA microsatellites: Molecular determinants of response to biochemotherapy in patients with metastatic melanoma, Bret Taback, Dave S. B. Hoon, John Wayne Cancer Institute, et al.


Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at

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