ERCC2 K751Q - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

ERCC2 K751Q

(ERCC2 Lys751Gln)


Short summary

Increased risk of early relapse in Asian patients with fluoruracil or leucovorin.

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr19:45854919: 31.9% (3432/10758) in EVS
  • G @ chr19:50546758: 24.6% (31/126) in GET-Evidence
  • Frequency shown in summary reports: 31.9% (3432/10758)

Publications
 

Huang MY, Fang WY, Lee SC, Cheng TL, Wang JY, Lin SR. ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: a preliminary study. BMC Cancer. 2008 Feb 12;8:50. PubMed PMID: 18267032; PubMed Central PMCID: PMC2262891.

 

Caronia D, Patiño-García A, Milne RL, Zalacain-Díez M, Pita G, Alonso MR, Moreno LT, Sierrasesumaga-Ariznabarreta L, Benítez J, González-Neira A. Common variations in ERCC2 are associated with response to cisplatin chemotherapy and clinical outcome in osteosarcoma patients. Pharmacogenomics J. 2009 Oct;9(5):347-53. Epub 2009 May 12. PubMed PMID: 19434073.

 

Genomes
 

hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
hom G @ chr19:45854919

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het G @ chr19:45854919

 

 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het G @ chr19:45854919

 

hu2D6140 - CGI sample GS01173-DNA_F06 from PGP sample 64191565
het G @ chr19:45854919

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
hom G @ chr19:45854919

 

 

 

hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
het G @ chr19:45854919

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
hom G @ chr19:45854919

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
hom G @ chr19:45854919

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het G @ chr19:45854919

 

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
hom G @ chr19:45854919

 

hu7A4AD1 - CGI sample GS01669-DNA_C05 from PGP sample 42408046
het G @ chr19:45854919

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het G @ chr19:45854919

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
hom G @ chr19:45854919

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het G @ chr19:45854919

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het G @ chr19:45854919

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
hom G @ chr19:45854919

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het G @ chr19:45854919

 

huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het G @ chr19:45854919

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het G @ chr19:45854919

 

GS06994 - var-GS06994-1100-36-ASM
het G @ chr19:50546759

 

GS07357 - var-GS07357-1100-36-ASM
het G @ chr19:50546759

 

GS12004 - var-GS12004-1100-36-ASM
hom G @ chr19:50546759

 

GS18502 - var-GS18502-1100-36-ASM
hom G @ chr19:50546759

 

GS18504 - var-GS18504-1100-36-ASM
hom G @ chr19:50546759

 

GS18940 - var-GS18940-1100-36-ASM
het G @ chr19:50546759

 

GS18947 - var-GS18947-1100-36-ASM
het G @ chr19:50546759

 

GS19025 - var-GS19025-1100-36-ASM
het G @ chr19:50546759

 

GS19704 - var-GS19704-1100-36-ASM
het G @ chr19:50546759

 

GS20502 - var-GS20502-1100-36-ASM
het G @ chr19:50546759

 

GS21767 - var-GS21767-1100-36-ASM
het G @ chr19:50546759

 

Other external references
 

    dbSNP
  • rs13181
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Colorectal Neoplasms]
    [fluorouracil; leucovorin]
    Asian colorectal cancer patients carrying the ERCC2 2251AC or 2251CC genotypes had significantly increased risk of early relapse following treatments that included 5FU and LV (n=201; OR = 3.294).
    www.ncbi.nlm.nih.gov/pubmed/18267032
  • [Osteosarcoma]
    [cisplatin]
    Risk or phenotype-associated allele: G. Phenotype: The G allele of ERCC2:Lys751Gln was significantly associated with shorter event free survival. Study size: 70. Study population/ethnicity: Patients with osteosarcoma treated with cisplatin; Spain. Significance metric(s): HR = 5.76; 95% CI=1.30-25.55; p = 0.021. Type of association: CO. Phenotype: The G allele of ERCC2:Lys751Gln was significantly associated with decreased response to cisplatin. Study size: 70. Study population/ethnicity: Patients with osteosarcoma treated with cisplatin; Spain. Significance metric(s): OR = 4.9; 95% confidence interval=1.64-14.54; p = 0.047. Type of association: PD.
    www.ncbi.nlm.nih.gov/pubmed/19434073
    PolyPhen-2
  • Score: 0 (benign)
    Web search results (219 hits -- see all)
  • ERCC1 and ERCC2 polymorphisms and adult glioma
    For ERCC2 K751Q, 87 of 416 subjects from the Caggana et al. (2001) ... Haplotype frequencies for ERCC2 K751Q and R156R and case-control ORs for ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC1871723
  • Ethnic disparities in Americans of European descent versus ...
    ERCC1 and ERCC2 are important molecular markers for NER; XRCC1 and PARP1 are important ... these two ethnic groups for ERCC2 K751Q (P = < 0.006675), XRCC1 R399Q ...
    www.ncbi.nlm.nih.gov/pubmed/18483312
  • poster session G
    N118N (500C>T), ERCC1 C8092A, ERCC2 K751Q (2282A>C), XRCC1 R399Q ... groups for ERCC2 K751Q (p=0.006675), XRCC1 R399Q (p=0.000000), PARP1 V762A ...
    annonc.oxfordjournals.org/cgi/reprint/19/suppl_3/iii42.pdf
  • BiomedExperts: Japanese-US common-arm analysis of paclitaxel ...
    Sign-in free and Explore the Exciting World of BiomedExperts: ... associations with patient outcomes were observed for CYP3A4*1B and ERCC2 K751Q. ...
    biomedexperts.com/Abstract.bme/19470925/...
  • DNA repair polymorphisms and the risk of stomach ...
    The K751Q polymorphism in the NER ERCC2 was associated with an increased risk ... The ERCC2 D312N and K751Q alleles and XRCC1 R399Q allele were associated with an ...
    ije.oxfordjournals.org/cgi/content/full/37/6/1316
  • ERCC1 and ERCC2 polymorphisms and adult glioma -- Wrensch et ...
    ERCC2 and ERCC1 are important in DNA nucleotide excision repair and ... However, among whites, for those with ERCC2 K751Q genotype QQ versus QK/KK, the ...
    neuro-oncology.dukejournals.org/cgi/content/abstract/7/4/495
  • Clinical Newswire
    Clinical Newswire, July 20, 2009-Analysis of a paclitaxel plus carboplatin ... related DNA repair enzymes ERCC1 (118C&#61664;T, silent) and ERCC2 (XPD, K751Q) ...
    www.clinicalnewswire.com/news/detail.php?id=401&lng=ENG
  • Japanese-US Common-Arm Analysis of Paclitaxel Plus ...
    JCO Early Release, published online ahead of print May 26 2009 ... associations with patient outcomes were observed for CYP3A4*1B and ERCC2 K751Q. ...
    www.jcojournal.org/cgi/content/abstract/JCO.2008.20.8793v1
  • DNA repair polymorphisms and the risk of stomach ...
    However, ERCC2 K751Q polymorphism was associated with an increased risk for non ... Conclusion Our study supports a role of ERCC2 in non-cardial GC but not in cardial cancer. ...
    ije.oxfordjournals.org/cgi/content/abstract/dyn145v1
  • Pharmacogenomic (PG) analysis of Japan-SWOG common arm study ...
    Genotypic correlations were observed between CYP3A4*1b for PFS (HR 2.75, 1.06-7.08, p=0.04) & ERCC2 k751q for response (HR 0.33, 0.13-0.84, p=0.02) ...
    asco.org/ASCOv2/Meetings/Abstracts?...

Other in silico analyses
 

  • NBLOSUM100 score = –2
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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