Site-specific risk factors for colorectal cancer in a Korean population

We investigated the association of colorectal cancer risk factors with different colorectal cancer subsites to assess etiological differences for cancers of the proximal colon, distal colon, and rectum. Included in this study were 869,725 men and 395,501 women who participated in a health examination provided by the Korean National Health System between 1996 and 1997. During up to 7 years of follow-up, 4,144 incident colorectal cancer cases were detected (3,051 men and 1,093 women). Greater height was associated with elevated risk for distal colon cancer and rectal cancer in both men and women. Family history of cancer was associated with higher risk for cancers of the proximal colon in men and distal colon in both men and women. Frequent alcohol consumption and consuming high amounts of alcohol were associated with elevated risk for distal colon cancer in men and higher risk for rectal cancer in women. Frequent meat consumption was associated with risk for proximal colon cancer in men and for rectal cancer in women. Our findings suggest that risk factors for colorectal cancer are different by subsites of colon and rectum, as well as by sex.     

Proteomic Helicobacter pylori biomarkers discriminating between duodenal ulcer and gastric cancer

Protein patterns of 129 Helicobacter pylori strains isolated from Korean and Colombian patients suffering from duodenal ulcer or gastric cancer were analyzed by the high-throughput methodology SELDI-TOF-MS. Eighteen statistically significant candidate biomarkers discriminating between the two clinical outcomes were selected by using the Mann–Whitney test. Three biomarker proteins were purified and identified as a neutrophil-activating protein NapA (HU HPAG1_0821), a RNA-binding protein (HPAG1_0813), and a DNA-binding histone-like protein HU, respectively (jhp0228). These novel biomarkers can be used for development of diagnostic assays predicting the evolution to gastric cancer in H. pylori-infected patients.     

Risk factors associated with gastric cancer in patients with a duodenal ulcer

Background: Although gastric cancer (GC) and duodenal ulcer (DU) are both strongly associated with Helicobacter pylori infection, a DU is negatively associated with the risk of GC. The aim of the study is to evaluate histologic risk factors for GC among patients with a DU. Materials and Methods: A total of 541 consecutive patients with GC were prospectively evaluated for the presence of a DU. Control patients with only a DU (n = 89) were recruited from health screening population. Histologic grading was assessed using the updated Sydney system for six gastric biopsies from three regions. GC risk among patients with a DU was evaluated using logistic regression analysis. Results: Among patients with GC, 7.6% (41/541) had a concomitant DU or an ulcer scar. Corpus‐predominant/pangastritis were more frequently found in concomitant GC patients with a DU (90%) than in patients with a DU alone (62%) (p = .001). In patients with a DU, moderate–severe chronic inflammation at the lesser and greater curvatures of corpus was associated with GC risk (OR, 3.70; 95% CI, 1.46–9.36, and OR, 7.72; 95% CI, 3.18–18.7, respectively). Additionally, moderate–severe intestinal metaplasia (IM) at the antrum and corpus lesser curvature was associated with GC risk (OR, 7.52; 95% CI, 3.06–18.5, and OR, 9.25, 95% CI, 2.39–35.8, respectively). Conclusions: A DU is not rare in patients with GC in a high‐risk region of GC. Patients with a DU with chronic corpus gastritis and IM have an increased risk of GC, thus those patients should be followed up for GC development.     

Impact of genetic polymorphisms in base excision repair genes on the risk of breast cancer in a Korean population

The contribution of single nucleotide polymorphisms (SNPs) in base excision repair (BER) genes to the risk of breast cancer (BC) was evaluated by focusing on two key genes: apurinic/apyrimidinic endonuclease 1 (APEX1) and 8-oxoguanine DNA glycosylase (OGG1). Genetic variations in the genes encoding these DNA repair enzymes may alter their functions and increase susceptibility to carcinogenesis. The aim of this study was to analyze polymorphisms in two BER genes, exploring their associations and particularly the combined effects of these variants on BC risk in a Korean population. Three SNPs of two BER genes were genotyped using the Illumina GoldenGate™ method. In total, 346 BC patients and 361 cancer-free controls were genotyped for these BER gene polymorphisms and analyzed for their correlation with BC risk in multiple logistic regression models. Multiple logistic regression models adjusted for age, family history of BC, and body mass index were used. The APEX1 Asp148Glu polymorphism was weakly associated with BC risk. The combined analysis among the BER genes, however, showed significant effects on BC risk. The APEX1 Asp148Glu carrier, in combination with OGG1 rs2072668 and OGG1 Ser326Cys, was strongly associated with an increased risk of BC. Moreover, the combination of the C–C haplotype of OGG1 with the APEX1 Asp148Glu genotype was also associated with an additive risk effect of BC [ORs = 2.44, 2.87, and 3.50, respectively]. The combined effect of APEX1 Asp148Glu was found to be associated with an increased risk of BC. These results suggest that the combined effect of different SNPs within BER genes may be useful in predicting BC risk.     

The role of gastric and duodenal pH in the cysteamine-induced duodenal ulcer in the rat

Many secretory studies reported an increase in gastric acid secretion by the duodenal ulcerogen cysteamine. A detailed analysis of these experiments, especially the results from rats with chronic gastric fistula suggest that direct stimulation of gastric acid secretion may not be the primary mechanism of the duodenal ulcerogenic action of cysteamine. We used a different approach and measured the pH at the site of ulceration in the proximal duodenum. A duodenal ulcerogenic dose of cysteamine did not change the pH at the anterior or posterior wall of the duodenum during 4 hr. In the same dose and by the same route of administration, cysteamine nevertheless induced duodenal ulcers in 24 hr. These experiments demonstrate that in addition to the effect on gastric acid secretion, other factors are needed to the effect on gastric acid secretion, other factors are needed to explain the early duodenal ulcerogenic action of cysteamine.     

A functional polymorphism of lymphotoxin-alpha (LTA) gene rs909253 is associated with gastric cancer risk in an Asian population

BackgroundThe potentially functional polymorphism, rs909253 (+252 G>A), in the intron region of the LT-α (TNF-β) gene has been implicated in the risk of gastric cancer (GC) in some individually published studies, but others have shown inconsistent and inconclusive results.MethodsWe conducted a meta-analysis to assess the association between the lymphotoxin-α gene (LTA) + 252 (G>A) polymorphism and gastric cancer susceptibility.ResultsWe demonstrate that there were no significant associations in single-locus analysis between the polymorphism of LTA and gastric cancer risk in all subjects; however, when studies were stratified by ethnicity, these polymorphisms of LTA were found to be associated with a significant cancer risk in different genetic models in an Asian population (heterozygote [GA genotype] comparison: odds ratio [OR] = 1.29, 95% confidence interval [CI]: 1.01–1.65, P = 0.038) in which the risk in the subjects was more than 70% (12 studies with 2074 cases and 3690 controls). Moreover, the susceptibility to gastric carcinogenesis has a substantial influence on the population-attributable risk by modulating the effects of environmental risk factors such as Helicobacter pylori infection (OR = 1.77, 95%CI: 1.05–2.99, P = 0.032).ConclusionsThe present meta-analysis results suggest that the LTA rs909253 GA genotype is a possible risk factor for developing gastric cancer in the Asian population, especially those with H. pylori infection.