hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population

Abstract

The human oxoguanine glycosylase 1(hOGG1) gene encodes a DNA glycosylase that is involved in excision repair of 8-OH-dG (8-hydroxy-2-deoxyguanine) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in the risk for adenocarcinoma of the gallbladder, we tested the association of this polymorphism with gallbladder cancer in a Chinese population-based, case control study of 204 cases and 209 controls. The subjects were genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) assay. The association between the genetic polymorphism of this gene and risk of the cancer was examined by using a multivariate analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among controls (Ser/Ser, 37.3%; Ser/Cys, 53.6% and Cys/Cys, 9.1%) was significantly different from that among gallbladder cancer cases (Ser/ Ser, 43.1%; Ser/Cys, 36.3% and Cys/Cys, 20.6%). Significantly increased risk for gallbladder cancer was both the hOGG1 326Ser/Cys (Odds ratio [OR] 5 1.9, 95% confidence interval (CI) 5 1.0-3.7) and hOGG1 326Cys/Cys genotypes (OR 5 4.5, 95% CI 5 1.1-22.4). We observed no statistically significant association between hOGG1 genotype and gallbladder cancer association in gallstone absence. In contrast, a near-significant increase in risk for gallbladder cancer was observed for gallstone presence with the hOGG1 326Ser/Cys genotype (OR 5 2.2, CI 5 1.4-3.5) whereas a significant increase in association for gallbladder cancer was observed for gallstone presence with the 326Cys/Cys genotype (OR 5 6.1, CI 5 2.1-27.2). These data corresponded with the fact that a significant trend towards increased association for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallstone presence(p < 0.001, v 2 trend test)but not in gallstone absence(p 5 0.89, v 2 trend test). A significant increase in risk for gallbladder cancer was observed for larger gallstone (those with stone diameters 2 cm or greater) with the hOGG1 326Ser/Cys(OR 5 1.9, 95% CI 5 1.1-2.9) and hOGG1 326Cys/ Cys genotypes(OR 5 5.9, 95% CI 5 1.6-18.0). These data are consistent with the observation that a significant trend towards increased risk for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallbladder cancer patients with larger gallstone (p < 0.001, v 2 trend test). However, we observed no statistically significant association between hOGG1 genotype and gallbladder cancer risk in gallbladder cancer patients with smaller gallstone (those with stone diameters 2 cm smaller) (hOGG1 326Ser/Cys:OR 5 2.2, 95% CI 5 0.8-4.0; hOGG1 326Cys/Cys:OR 5 2.9, 95% CI 5 0.6-29.4; p 5 0.06, v 2 tread test). These results suggest that hOGG1 Ser326Cys polymorphism is associated with gallbladder cancer risk. ' 2007 Wiley-Liss, Inc.Key words: gallbladder cancer; hOGG1; polymorphism; susceptibility; China Carcinoma of the gallbladder has a very unusual geographical distribution with pockets of high incidence seen in Chile, Poland, India, Japan and Israel, 1-4 it occur...

The inflammatory inception of gallbladder cancer

“…The mechanism by which a gain of function in the ABCG5/G8 gene may also enhance the risk for GBC has not been elucidated, although it may be related to a higher risk of developing GSD early in life [53] and/or the capacity to transport other substrates into the biliary tree, such as plant sterols or other chemicals with potentially carcinogenic effects [54–57]. Besides the strong influence of this gallstone-modulating polymorphism in the development of GBC, polymorphisms in genes related to the immune system, inflammation and oxidative stress have been associated with increased risk of GBC, namely PTGS2 [58], TLR2, TLR4 [59], IL1RN, IL1B [60], IL10 [61], IL8 [62], CCR5 [63], LXRβ [64] and OGG1 [65]. Thus, variants in inflammation-related genes may, under the stimulus of gallstones or other insults, accelerate the development of GBC.…”

Lack of Association between the hOGG1 Ser326Cys Polymorphism and Gastric Cancer Risk: a Meta-analysis

“…Studies indicated a role of the HOGG1 Ser326Cys polymorphism in many cancers including oro-laryngeal cancer (Elahi et al, 2002;Yang et al, 2008), esophageal cancer (Xing et al, 2001), lung cancer (Lan et al, 2004), gastric cancer (Hanaoka et al, 2001), renal cell carcinoma (RCC) (Zhao et al, 2011), gallbladder cancer (Jiao et al, 2007), bladder cancer (Arizono et al, 2008), prostate cancer (Zhang et al, 2010) and acute lymphoblastic leukemia (Stanczyk et al, 2011).…”

DNA Damage, Repair and Misrepair in Cancer and in Cancer Therapy

“…Particularly, polymorphisms on hOGG1 and XRCC1 genes are associated with lung, esophagus, stomach and nasopharyngeal (NPC) cancer risk. Similarly to MMR, SNP occurrence in BER genes appears to be dependent on ethnicity: single nucleotide changes at codons 194, 280 and 399 of XRCC1 were associated with risk of several types of gastrointestinal, bladder, breast and lung cancers in the Japanese population (Arizono et al, 2008), while SNPs in hOGG1 codon 326 correlated with increased NPC and gallbladder risk in Southern Chinese populations (Cao et al, 2006;Jiao et al, 2007). The APE1 Asp148Glu polymorphism is highly predictive for lung cancer in Caucasians, and cumulative cigarette smoking modifies the associations between XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms and lung cancer risk in nonsmokers and light smokers (de Ruyck et al, 2007).…”