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Gene Linked to Musculoskeletal Toxicity in Breast Cancer

Last Updated: September 29, 2010.

The T-cell leukemia 1A gene appears to be associated with musculoskeletal adverse events in women undergoing treatment with aromatase inhibitors for early-stage breast cancer, according to a study published online Sept. 27 in the Journal of Clinical Oncology.

WEDNESDAY, Sept. 29 (HealthDay News) -- The T-cell leukemia 1A (TCL1A) gene appears to be associated with musculoskeletal adverse events in women undergoing treatment with aromatase inhibitors (AIs) for early-stage breast cancer, according to a study published online Sept. 27 in the Journal of Clinical Oncology.

James N. Ingle, M.D., of the Mayo Clinic in Rochester, Minn., and colleagues selected 293 patients with early-stage, estrogen receptor-positive breast cancer who were treated with AIs and who developed musculoskeletal toxicity, and matched them with 585 control subjects. The investigators performed a genome-wide association study that included assessment of 551,358 single nucleotide polymorphisms (SNPs).

The investigators identified a set of four SNPs near the TCL1A gene associated with the risk for musculoskeletal toxicity. In addition, functional genomic studies showed that one of the SNPs (rs11849538) resulted in an estrogen response element and that TCL1A expression was estrogen dependent. In addition, TCL1A was found to be associated with expression of interleukin 17 receptor A.

"Additional studies are needed to replicate TCL1A locus SNP associations with the musculoskeletal effects of AIs, and to find other genetic variants associated with this toxicity," the author of an accompanying editorial writes. "However, the study by Ingle et al helps to establish a new pharmacogenomic paradigm and to apply it to a problem of relevance in clinical oncology."

Several authors disclosed financial relationships with pharmaceutical companies.

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