DNA repair gene polymorphisms and risk of pancreatic cancer.
OBJECTIVE
The current research was undertaken to examine the association between genetic variations in DNA repair and pancreatic cancer risk.


METHODS
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.
Li
Donghui
D
Department of Gastrointestinal Medical Oncology, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 426, Houston, TX 77030, USA. dli@mdanderson.org
Suzuki
Hideo
H
Liu
Bingrong
B
Morris
Jeffrey
J
Liu
Jun
J
Okazaki
Taro
T
Li
Yanan
Y
Chang
Ping
P
Abbruzzese
James L
JL
D000368:Aged; D004260:DNA Repair; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D016896:Treatment Outcome