First paper published by Global Alliance for Pharmacogenomics
AnnouncementSeptember 28, 2010
By studying the genomes of breast cancer survivors, scientists supported by the National Institutes of Health and the RIKEN Institute in Japan have identified gene variants associated with the severe joint pain experienced by some users of aromatase inhibitor drugs.
Aromatase inhibitors are prescribed to prevent disease recurrence in tens of thousands of postmenopausal American women with early-stage, estrogen-sensitive breast cancer. About one quarter of these women experience joint pain. For some, it is so severe that they stop taking the potentially life-saving drugs.
The work appears in the September 27 online issue of the Journal of Clinical Oncology.
The paper is the first research article published by the Global Alliance for Pharmacogenomics (http://www.nigms.nih.gov/Research/SpecificAreas/PGRN/GAP/), a joint U.S.-Japan scientific venture established in 2008. The alliance utilizes the research expertise of the NIH Pharmacogenomics Research Network (PGRN, http://www.nigms.nih.gov/Research/SpecificAreas/PGRN) and the high-throughput, genome research technologies of the Center for Genomic Medicine (http://www.src.riken.jp/english/ ) at the RIKEN Institute in Japan.
The research team studied the genes of 878 postmenopausal women who had surgery to remove breast cancer and were taking aromatase inhibitors. Of this group, 293 experienced severe pain in joints, muscles or bones. The other 585 didn’t.
The genome-wide association study analyzed more than 550,000 gene variants (called single nucleotide polymorphisms or SNPs). Four SNPs stood out because they occurred more than twice as often in women who experienced severe musculoskeletal side effects.
The researchers wondered whether the apparent association between these SNPs and musculoskeletal pain was coincidental or whether the SNPs were somehow related to the side effect. To answer that question, the team conducted laboratory tests to determine the function of the gene variants.
They found that the SNPs were all located on chromosome 14, close to a gene involved in the production of an immune system protein called interleukin 17, which plays a role in inflammation.
In people with rheumatoid arthritis, such inflammation causes joint pain. The scientists suggest that the same molecular process might be responsible for similar pain in women taking aromatase inhibitors.
This research could lead to ways of predicting which women are at greatest risk for musculoskeletal side effects from aromatase inhibitors. It could also point to approaches for preventing or reducing this serious side effect of these widely used drugs.
This page last reviewed on
8/9/2018 5:29 PM
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