Faculty Collaboration Database

Selected polymorphisms of DNA repair genes and risk of pancreatic cancer. Cancer Detect Prev 2006;30(3):284-91

Date

07/18/2006

Pubmed ID

16844323

Pubmed Central ID

PMC1857309

DOI

10.1016/j.cdp.2006.05.002

Scopus ID

2-s2.0-33746747494 (requires institutional sign-in at Scopus site)   70 Citations

Abstract

BACKGROUND: Genetic variants of DNA repair genes may contribute to pancreatic carcinogenesis. O(6)-methylguanine-DNA methyltransferase (MGMT) is the major protein that removes alkylating DNA adducts, and apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing group 1 (XRCC1) play important roles in the base excision repair pathway.

METHODS: We investigated the association between polymorphisms of MGMT (Leu(84)Phe and Ile(143)Val), APE1 (Asp(148)Glu), and XRCC1 (Arg(194)Trp and Arg(399)Gln) and risk of pancreatic cancer in a case-control study. Exposure information from 384 patients with primary pancreatic ductal adenocarcinoma and 357 cancer-free healthy controls were collected and genomic DNAs were genotyped for five markers. Controls were frequency matched to patients by age at enrollment (+/-5 years), gender, and race. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by using unconditional logistic regression models.

RESULTS: There was no significant main effect or interaction with smoking of these genetic variants on the risk of pancreatic cancer. However, the XRCC1(194) polymorphism had a significant interaction with the APE1(148) (p=0.005) or MGMT(84) polymorphism (p=0.02) in modifying the risk of pancreatic cancer.

CONCLUSIONS: This study suggests that polymorphisms of genes involved in the repair of alkylating DNA adduct and DNA base damage may play a role in modulating the risk of pancreatic cancer. Larger studies are required to validate these preliminary findings. The mechanism of the combined genotype effects remains to be elucidated.

Author List

Jiao L, Bondy ML, Hassan MM, Wolff RA, Evans DB, Abbruzzese JL, Li D

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
DNA Repair
Environment
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
O(6)-Methylguanine-DNA Methyltransferase
Pancreatic Neoplasms
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Risk
Smoking