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Review
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Korean J Med. 2006;71(1):181-181.
- Comprehensive analysis of ERCC, XPD, and XRCC polymorphisms: Association with clinical outcomes in patients with advanced gastric cancer
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Bhumsuk Keam, Seock-Ah Im, Hye Seon Ham, Sae-Won Han, Eunkyung Park, Jin-Soo Kim, Eun Young Cho, Jong Eun Lee, Keun-Wook Lee, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, and Yung-Jue Bang
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- Comprehensive analysis of ERCC, XPD, and XRCC polymorphisms: Association with clinical outcomes in patients with advanced gastric cancer
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가천의과대학교길병원
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- Abstract
- Purpose
: Platinum-DNA adducts are repaired by nucleotide excision repair (NER) pathway, in which genes of the excision repair
cross-complementation 1 (ERCC1), xeroderma pigmentosum group D (XPD) and X-ray repair cross-complementing group (XRCC) have
an important role. The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNP)s of these
genes and the clinical outcomes to combination chemotherapy of 5-FU and oxaliplatin in advanced gastric cancer (AGC). Patients and
Methods
: We searched SNPs of NER pathway genes from database of the International Hapmap Project. Tagging SNPs and halpotype
blocks were founded by linakage disequilibrium and haplotype analysis. We conducted genotyping using germ line DNA form peripheral
blood mononuclear cells of the patients. And then germ line DNA from peripheral blood of the AGC patients were analyzed using SNaPshot
methods
. Seventy three metastatic or relapsed AGC patients received 2-hour infusions of OX (100mg/m2) and LV (100mg/m2) followed
by a 46-hour infusion of FU (2400mg/m2) repeated every 2 weeks as a first-line palliative chemotherapy and were analyzed. Results :
By searching the database of the International Hapmap Project, we found 17 SNPs in ERCC, 69 SNPs in XPD, 78 SNPs in XRCC. We
found that some SNPs played a role as a tagging SNP and belonged to haplotype block (5 tapping SNPs and one haplotype block in ERCC,
8 tapping SNPs and two haplotype blocks in XPD, 9 tapping SNPs and two haplotype block in XRCC). Tagging SNPs were analyzed and
matched with clinical significance. Among the 22 tagging SNPs of NER pathway genes, only XPD-C156A SNP (rs238406) showed clinical
correlation. AA genotype of XPD C156A showed higher response rate (CC: CA: AA=29.2%: 43.3%: 63.2% p=0.083) and toxicities
(neutropenia of grade 3 or 4) (CC: CA: AA=4.3%: 3.2%: 21.1%, p=0.060) than CC or CA genotypes. Conclusions : Our results suggest that
some SNPs of ERCC, XPD, XRCC showed linkage disequilibrium and belonged to haplotype blocks. And XPD-C156A SNP showed clinical
correlation in AGC patients treated with modified FOLFOX-6 regimen. These findings require independent prospective confirmation.
Keywords :
