TY - JOUR
T1 - DNA repair gene polymorphisms and risk of pancreatic cancer
AU - Li, Donghui
AU - Suzuki, Hideo
AU - Liu, Bingrong
AU - Morris, Jeffrey
AU - Liu, Jun
AU - Okazaki, Taro
AU - Li, Yanan
AU - Chang, Ping
AU - Abbruzzese, James L.
PY - 2009/1/15
Y1 - 2009/1/15
N2 - 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 theTaqman 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/TTgenotype, 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.
AB - 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 theTaqman 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/TTgenotype, 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.
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U2 - 10.1158/1078-0432.CCR-08-1607
DO - 10.1158/1078-0432.CCR-08-1607
M3 - Article
C2 - 19147782
AN - SCOPUS:59449090610
SN - 1078-0432
VL - 15
SP - 740
EP - 746
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -