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CHICAGO Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.
Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.
The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.
The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.
No association was found for the other nine SNPs.
"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.
"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.
The researchers reported that they had no conflicts of interest.
CHICAGO Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.
Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.
The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.
The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.
No association was found for the other nine SNPs.
"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.
"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.
The researchers reported that they had no conflicts of interest.
CHICAGO Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.
Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.
The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.
The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.
No association was found for the other nine SNPs.
"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.
"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.
The researchers reported that they had no conflicts of interest.