BRCA1 haplotype influences lung cancer chemotherapy

NEW YORK (Reuters Health) - Carriers of certain haplotypes of the BRCA1 gene, which plays a central role in the DNA repair system, do not appear to respond to platinum-based chemotherapy for non-small-cell lung cancer, Korean researchers report in the Journal of Clinical Oncology published online ahead of print.

"Results from this study," senior investigator Dr. Jeong-Seon Ryu told Reuters Health, "show that lung cancer patients with two copies of AACC of BRCA1 do not benefit from platinum doublets -- gemcitabine/platinum, docetaxel/platinum or paclitaxel/platinum -- that are standard regimens worldwide for locally advanced or metastatic non-small-cell lung cancer."

Dr. Ryu of Inha University Hospital, Inchon, and colleagues came to this conclusion after studying the relationship of 4 tagging single-nucleotide BRCA1 polymorphisms and their haplotypes on the outcome of treatment in 300 patients. The five haplotypes studied were AACC, AACA, GCTC, GATC and AATC.

Median survival was 13 months and the researchers did not find any significant associations between any of the tagging polymorphisms and overall survival.

However, patients with two copies of the AACC (wild type) haplotype had significantly shorter survival than those with one or no copy (8.47 versus 14.57 months). This continued to be true after adjustment for factors including weight loss and second-line treatment (hazard ratio, 2.097).

This effect on survival was seen in patient with squamous cell carcinoma but not in those with adenocarcinomas.

"Therefore," concluded Dr. Ryu, "this result suggests that a new strategy is needed for these patients, especially in squamous cell carcinoma."

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