RGD Reference Report - DNA repair gene polymorphisms and risk of pancreatic cancer. - Rat Genome Database

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DNA repair gene polymorphisms and risk of pancreatic cancer.

Authors: Li, D  Suzuki, H  Liu, B  Morris, J  Liu, J  Okazaki, T  Li, Y  Chang, P  Abbruzzese, JL 
Citation: Li D, etal., Clin Cancer Res. 2009 Jan 15;15(2):740-6.
RGD ID: 2317363
Pubmed: PMID:19147782   (View Abstract at PubMed)
PMCID: PMC2629144   (View Article at PubMed Central)
DOI: DOI:10.1158/1078-0432.CCR-08-1607   (Journal Full-text)

PURPOSE: The current research was undertaken to examine the association between genetic variations in DNA repair and pancreatic cancer risk. Experimental Design: We analyzed 9 single nucleotide polymorphisms of 7 DNA repair genes (LIG3, LIG4, OGG1, ATM, POLB, RAD54L, and RECQL) in 734 patients with pancreatic adenocarcinoma and 780 healthy controls using the Taqman method. Information on cigarette smoking, alcohol consumption, medical history, and other risk factors was collected by personal interview. RESULTS: The homozygous mutant genotype of LIG3 G-39A [odds ratio (OR), 0.23; 95% confidence interval (CI), 0.06-0.82; P = 0.027] and ATM D1853N (OR, 2.55; 95% CI, 1.08-6.00; P = 0.032) was significantly associated with altered risk for pancreatic cancer. A statistically significant interaction of ATM D1853N and LIG4 C54T genotype with diabetes on the risk of pancreatic cancer was also detected. Compared with nondiabetics with the ATM D1853N GG genotype, nondiabetics with the GA/AA, diabetics with the GG, and diabetics with the GA/AA genotypes, respectively, had ORs (95% CI) of 0.96 (0.74-1.24), 1.32 (0.89-1.95), and 3.23 (1.47-7.12; P(interaction) = 0.032, likelihood ratio test). The OR (95% CI) was 0.91 (0.71-1.17), 1.11 (0.73-1.69), and 2.44 (1.34-4.46) for nondiabetics carrying the LIG4 CT/TT genotype, diabetics with the CC genotype, and diabetics carrying the CT/TT genotype, respectively, compared with nondiabetics carrying the CC genotype (P(interaction) = 0.02). CONCLUSIONS: These observations suggest that genetic variations in DNA repair may act alone or in concert with other risk factors on modifying a patient's risk for pancreatic cancer.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATMHumanpancreatic cancer susceptibilityIAGP DNA:SNP:exon:rs1801516(human)RGD 
AtmMousepancreatic cancer susceptibilityISOATM (Homo sapiens)DNA:SNP:exon:rs1801516(human)RGD 
AtmRatpancreatic cancer susceptibilityISOATM (Homo sapiens)DNA:SNP:exon:rs1801516(human)RGD 
LIG3Humanpancreatic cancer resistanceIAGP DNA:SNP:intron:rs 2074522 (human)RGD 
LIG4Humanpancreatic cancer susceptibilityIAGP associated with Diabetes Mellitus and DNA:polymorphism: :54C>T (human)RGD 
Lig3Ratpancreatic cancer resistanceISOLIG3 (Homo sapiens)DNA:SNP:intron:rs 2074522 (human)RGD 
Lig3Mousepancreatic cancer resistanceISOLIG3 (Homo sapiens)DNA:SNP:intron:rs 2074522 (human)RGD 
Lig4Ratpancreatic cancer susceptibilityISOLIG4 (Homo sapiens)associated with Diabetes Mellitus and DNA:polymorphism: :54C>T (human)RGD 
Lig4Mousepancreatic cancer susceptibilityISOLIG4 (Homo sapiens)associated with Diabetes Mellitus and DNA:polymorphism: :54C>T (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atm  (ATM serine/threonine kinase)
Lig3  (DNA ligase 3)
Lig4  (DNA ligase 4)

Genes (Mus musculus)
Atm  (ataxia telangiectasia mutated)
Lig3  (ligase III, DNA, ATP-dependent)
Lig4  (ligase IV, DNA, ATP-dependent)

Genes (Homo sapiens)
ATM  (ATM serine/threonine kinase)
LIG3  (DNA ligase 3)
LIG4  (DNA ligase 4)


Additional Information