Study on the association of p53 codon 72 polymorphisms with risk of gastric cancer in high incidence Hexi area of Gansu Province in China

To investigate the possible association of P53 codon 72 Arg/Pro polymorphisms with risk of gastric cancer in the high incidence Hexi area of Gansu province in China. Blood samples from 140 patients with gastric carcinoma and 125 healthy controls were collected in Hexi area of Gansu province. Polymorphism of P53Arg72Pro was genotyped by PCR-TaqMan. For detection Helicobacter pylori infection, Warhin–Starry staining was used. Three kinds of polymorphisms of P53Arg72Pro were Arg/Arg, Arg/Pro, Pro/Pro. The frequencies in gastric cancer group were 15.7, 60.0, 24.3%, and the frequencies in healthy controls were 25.6, 54.4, 20.0%, respectively. P53 codon 72 Pro carrier genotype (Arg/Pro + Pro/Pro) increased risk of gastric carcinoma with an odds ratio 1.840 (95% CI: 1.006–3.387). Helicobacter pylori infection rate was 68.6% in patients group and 50.4% in healthy controls. Helicobacter pylori infection rate in gastric cancer patients was remarkably higher than that in the controls (OR: 2.147, 95% CI: 1.302–3.541, P = 0.003). Stratification analysis showed that P53 codon 72 Pro carrier genotype with Helicobacter pylori infection was significantly higher in cases than that in the controls (OR: 4.182, 95% CI: 1.850–9.454). P53Arg72Pro polymorphisms could be a risk factor for gastric cancer in high incidence Hexi area of Gansu Province in China. P53 codon 72 Pro carrier genotype and Helicobacter pylori positive infection may have a synergistic effect on gastric cancer in high incidence Hexi area of Gansu Province in China.     

<Emphasis Type="Italic">PARP-1 Val762Ala</Emphasis> polymorphism,CagA<Superscript>+</Superscript><Emphasis Type="Italic">H. pylori</Emphasis> infection and risk for gastric cancer in Han Chinese population

Introduction PARP-1 plays important role in the BER (base excision repair) and maintenance of genomic integrity. Previous study found the Val762Ala genetic variant in the PARP-1 gene contributed to susceptibility of some cancers and decreased PARP-1 enzyme activity in response to oxidative damage. Helicobacter pylori (H. pylori) infection was thought to be one of the major causes of gastric cancer. In this study, we investigated the association between the PARP-1 Val762Ala polymorphism, CagA⁺ H. pylori infection, and the risk for gastric cancer. Methods This hospital-based, case–control study was performed involving 556 individuals (236 cases with gastric cancer and 320 controls without evidence of neoplasm and gastrointestinal disease) using a PCR-RFLP method. Chi-square test and logistic regression analysis were used to count OR and 95% CI. Results 762Ala/Ala genotype was overrepresented in the cases (16.9%) compared with controls (10.3%), (OR, 1.942; 95% CI, 1.157–3.257, P = 0.011). Multivariate analysis showed that two factors were significantly associated with risk of gastric cancer, including CagA⁺ H. pylori infection (OR, 2.562; 95% CI, 1.174–5.240, P = 0.037), PARP-1 762AA genotype (OR, 1.772; 95% CI, 1.065–3.867; P = 0.042). Stratification analysis indicated that among Cag⁺ H. pylori positive subjects, 762Ala/Ala carriers had higher risk for developing gastric cancer compared with 762Val/Val carrier (OR, 2.337; 95% CI, 1.148–4.758; P = 0.017). Conclusion PARP-1 762Ala/Ala could be a risk factor for gastric cancer in Han Chinese population; PARP-1 762Val/Ala polymorphism and Cag⁺ H. pylori infection jointly contribute to higher risk for gastric cancer.     

Cyclooxygenase-2 −765 G/C polymorphisms and susceptibility to hepatitis B-related liver cancer in Han Chinese population

To investigate the relationship of cyclooxygenase-2 (COX-2) polymorphisms [COX-2 −765 G/C (rs 20417)] and susceptibility to hepatitis B-related liver cancer in Han Chinese population. The polymorphisms of COX-2 −765 G/C was detected by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in 300 patients with hepatitis B, 300 patients with cirrhosis, 300 patients with primary liver carcinoma and 300 health controls. The COX-2 −765 G/C genotypes were GG, GC and CC. There frequencies in the hepatitis B patients were 80.33, 17.67 and 2.00%; in the cirrhosis patients were 77.67, 18.00 and 4.33%; in the patients with primary liver carcinoma were 65.67, 28.33 and 6.00% and in the heathy controls were 87.00, 12.33 and 0.67%, respectively, COX-2 −765 C allele carriers had an increased risk of hepatitis B-related liver cancer. COX-2 −765 C allele carriers having drinking history or family history of liver cancer had higher risk for HCC. COX-2 −765 C allele genotype, drinking history and family history of liver cancer may increase the susceptibility to hepatitis B-related liver cancer in Gansu province, China.     

−765G>C and 8473T>C polymorphisms of COX-2 and cancer risk: a meta-analysis based on 33 case–control studies

Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in cancer etiology. The −765G>C and 8473T>C polymorphisms have been implicated in cancer risk. However, the results on the association between the two COX-2 polymorphisms and cancer risk are conflicting. To derive a more precise estimation of the association between them, we performed a meta-analysis of 8,090 cancer cases and 11,010 controls concerning −765G>C polymorphism and 14,283 cancer cases and 15,489 controls concerning 8473T>C polymorphism from 33 case–control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the −765GC or GC/CC genotypes were associated with higher cancer risk than those with the −765GG genotype and in the stratified analysis this effect maintained in colorectal carcinoma or esophageal cancer of Asian descents. Overall, no significant cancer risk of 8473T>C polymorphism was found. Stratified by cancer types, the variant 8473CC was associated with a decreased risk in breast cancer, compared with the TT or TC/TT genotypes and in lung cancer subgroup after sensitive analysis, there was a decreased risk in CC versus TT, TC versus TT and the dominant models. Moreover, a decreased risk of lung cancer was observed among smokers in the dominant model. In summary, this meta-analysis suggesting that −765G>C may cause an increased risk of colorectal carcinoma and esophageal cancer in Asian descents while 8473T>C polymorphism may cause a decreased risk of breast and lung cancer.     

An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration

Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber–Weiss or Fenton reaction. On the other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1 (HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress. In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the −42 + 1444 position in the HMOX2 gene (the −42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the −42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the −42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the −42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the −42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD.     

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.     

Cyclooxygenase-2 gene and epithelial ovarian carcinoma risk

In this study, we aimed to investigate a possible association of the COX-2 polymorphisms (−765G→C and −1195A→G) and with the risk of developing epithelial ovarian carcinoma (EOC). COX-2 gene polymorphisms was investigated in 111 healthy women and 57 patients with EOC. Individuals who had −765 CG, −1195 AA genotype, and −765 C allele had increased risk for ovarian carcinoma (P < 0.01) and individuals with −765 GG, −1195 AG genotypes and −1195 G allele seem to be protected from ovarian carcinoma (P < 0.01). Haplotype analysis confirmed the association of COX-2 gene variants with ovarian carcinoma and revealed that the frequencies of −765C: −1195A haplotype frequencies was significantly higher in patients as compared with those of controls (P = 0.048). We state that there appears to be a modulating role for the COX-2 −1195A→G and −765G→C polymorphisms in the development of EOC. To the best of our knowledge, this is the first study to show such an association.     

Functional polymorphisms in promoter survivin gene and its association with susceptibility to bladder cancer in North Indian cohort

Survivin is a member of novel inhibitor of apoptosis protein family which expressed in human cancers. The molecular detection of bladder cancer by targeting Survivin as a novel marker may be useful in the occurrence and progression of cancer. We genotyped Survivin −31G>C, −1547A>G and −241C>T by PCR-restriction fragment length polymorphism to evaluate the risk of bladder cancer (BC) in 200 BC patients and 200 healthy controls from North Indian cohort. We observed significant increased BC risk associated with variant CC genotype of Survivin −31G>C having 2.6 fold risk. The variant genotype of Survivin −1547A>G was significantly associated with BC risk (P = 0.047). In case of Survivin −241C>T the protective genotype for BC was heterozygous (P = 0.035). Smoking significantly modulated the risk in patients with Survivin −1547A>G polymorphism. Variant as well as hetero genotype of Survivin −31G>C was associated with reduced risk of recurrence (HR = 0.22 and 0.35) in BC patients receiving BCG treatment thus showing least survival. Furthermore, the haplotype analysis revealed C–A–T haplotype to be associated with reduced BC risk. Our findings suggested that the functional polymorphism −31G>C, −1547A>G and −241C>T in the promoter of Survivin gene may play a significant role in mediating the BC risk among North Indian cohort.     

The association of garlic with Helicobacter pylori infection and gastric cancer risk: A systematic review and meta‐analysis

Background

Garlic may be protective against Helicobacter pylori infection and gastric cancer development. We conducted this study to quantitatively update evidence on garlic intake and gastric cancer with the inclusion of most recent cohort studies and qualitatively summarize epidemiological studies of garlic consumption and Helicobacter pylori infection.

Materials and Methods

PubMed, Embase, MEDLINE, and Cochrane Library were searched on April 2018. We conducted a meta‐analysis to determine whether garlic intake reduced gastric cancer risk using random‐effect models and a systematic review to summarize evidence on the association between garlic consumption and Helicobacter pylori infection. Risk of bias was assessed using tools of Cochrane risk of bias and Robins‐I for randomized and nonrandomized studies, respectively.

Results

Meta‐analysis of 18 studies (142 921 subjects) demonstrated high garlic consumption (as comparing the highest category to the lowest) was associated with a reduced gastric cancer risk (OR = 0.51, 95% CI = 0.44‐0.57). This association became nonsignificant if only derived from the prospective studies (OR = 0.95, 95% CI = 0.66‐1.24). Thirteen studies (4889 participants) were included in the systematic review for garlic consumption and Helicobacter pylori infection; ten of which found no significant results. The majority of these studies were poor in quality given the small sample size and high risk of bias.

Conclusions

Pooled evidence, mainly from case‐control studies, suggested a significant inverse association of garlic intake with gastric cancer risk. Given the limitations of included studies, current epidemiological evidence is not sufficient to reach any definite conclusion regarding the association of garlic with Helicobacter pylori infection.     

DNMT3B polymorphisms and cancer risk: a meta analysis of 24 case–control studies

The association between polymorphism of DNA methyltransferases 3B and cancer risk has been widely studied recently, and no consensus conclusion is available up to now. We perform a comprehensive search using the databases of Medline, ISI Web of Knowledge and Embase. The odds ratio (OR) and its 95% confidence interval (95% CI) are used to investigate the strength of the association. A total of 24 case–control studies with 15,647 individuals are included in this meta-analysis. For −149C > T (17 studies, 5229 cases and 6910 controls), no evidence indicate that individuals carrying the variant genotypes (CC + CT), relative to those carrying the wild homozygote TT genotype, have an increased risk of cancer (OR = 1.03; 95% CI = 0.84–1.26; P = 0.76). Similarly, no cancer risk is found in the subgroup analyses. For −579G > T (11 studies, 3513 cases and 3714 controls), significantly decreased risks of cancer are observed, and the ORs (95% CI) are 0.70 (0.56–0.87) for GT versus TT, 0.70 (0.57–0.85) for GG + GT versus TT and 0.76 (0.63–0.93) for G-allele versus T-allele, respectively. Subgroup analyses stratified by ethnicity and types of cancer are also performed, and results indicated that −579G > C polymorphism is associated with risk of cancer in Asians [0.68 (0.53–0.87) for GT vs. TT] but not in Europeans [0.82 (0.63–1.07) for GT vs. TT]. We also observe that the −579G is associated with decreased risk of colorectal cancer [0.49(0.38–0.62) for GT vs. TT]. More studies with larger sample size were needed to provide more precise evidence.     

Catalase −262C>T polymorphisms in Hungarian vitiligo patients and in controls: further acatalasemia mutations in Hungary

Catalase is the main regulator of hydrogen peroxide metabolism. In vitiligo patients there are conflicting data on its activity and no data on the effect of −262C>T polymorphism in the catalase gene. Blood catalase activity, −262C>T polymorphism and acatalasemia mutations were examined in 75 vitiligo patients and in 162 controls, in Hungary. We measured blood catalase activity and conducted analyses with PCR-SSCP, polyacrylamide gel electrophoresis and silver staining in combination with RFLP and nucleotide sequencing. Comparison of the wild (CC) genotype and the mutant (TT) genotype in the vitiligo patients revealed a non significant (P > 0.19) increase in blood catalase. Male controls with the CT genotype had significantly (P < 0.04) lower blood catalase activity than CC genotype controls. Female vitiligo patients with CC genotype had lower (P < 0.04) blood catalase than female controls. The frequency of wild genotype (CC) and C alleles is significantly (P < 0.04) decreased in Hungarian controls when compared to controls in Slovenia, Morocco, UK, Greece, Turkey, USA, China. The detection of a novel acatalasemia mutation (37C>T in exon 9) and the 113G>A (exon 9) mutation in Hungary are further proofs of genetic heterogeneity origin of acatalasemia mutations. In conclusion, the −262 C>T polymorphism has a reverse effect on blood catalase in vitiligo patients and in controls. In controls the mutant genotypes and alleles are more frequent in Hungary than in several other populations. The new acatalasemia mutations are further examples of heterogeneity of acatalasemia.     

CCL2 −2518 A/G single nucleotide polymorphism as a risk factor for breast cancer

The contribution of the CCL2 −2518 A>G (rs 1024611) polymorphism in the occurrence and progression of various cancers has been found to be discordant. We studied the prevalence of the CCL2 −2518 A>G polymorphism in patients with breast cancer (n = 160) and controls (n = 323) in a sample of the Polish population. There were no significant differences in CCL2 −2518 A>G genotypes between patients with breast tumors and controls. Odds ratio (OR) for patients bearing the GG genotype was 1.481 (95% CI = 0.7711–2.845, P = 0.2358), and OR of the GG and AG genotypes was 0.7269 (95% CI = 0.4967–1.064, P = 0.1002). There was also no significant distinction in the prevalence of alleles between patients and healthy individuals. OR for the CCL2 −2518 G allele frequency was 0.8903 (95% CI = 0.6611–1.199, P = 0.4441). Analysis of the association between tumor size, lymph node metastases, histological grade, and distribution of genotypes and alleles for the CCL2 −2518 A>G polymorphism also did not show significant differences. Our results did not show association of the CCL2 −2518 A>G polymorphism with breast cancer occurrence and clinical characteristics in a sample of the Polish cohort.     

A comprehensive evaluation of an animal model for Helicobacter pylori-associated stomach cancer: Fact and controversy

Even though Helicobacter pylori infection was the most causative factor of gastric cancer, numerous in vivo studies failed to induce gastric cancer using H. pylori infection only. The utilization of established animal studies in cancer research is crucial as they aim to investigate the coincidental association between suspected oncogenes and pathogenesis as well as generate models for the development and testing of potential treatments. The methods to establish gastric cancer using infected animal models remain limited, diverse in methods, and showed different results. This study investigates the differences in animal models, which highlight different pathological results in gaster by literature research. Electronic databases searched were performed in PubMed, Science Direct, and Cochrane, without a period filter. A total of 135 articles were used in this study after a full-text assessment was conducted. The most frequent animal models used for gastric cancer were Mice, while Mongolian gerbils and Transgenic mice were the most susceptible model for gastric cancer associated with H. pylori infection. Additionally, transgenic mice showed that the susceptibility to gastric cancer progression was due to genetic and epigenetic factors. These studies showed that in Mongolian gerbil models, H. pylori could function as a single agent to trigger stomach cancer. However, most gastric cancer susceptibilities were not solely relying on H. pylori infection, and numerous factors are involved in cancer progression. Further study using Mongolian gerbils and Transgenic mice is crucial to conduct and establish the best models for gastric cancer associated H. pylori.     

Helicobacter pylori infection and gastric cardia cancer in Chaoshan region

Helicobacter pylori (H. pylori) infection represents the most important risk factor for gastric cancer, while its association with gastric cardia cancer (GCC) has not been recognized yet. In this current study, we aim to investigate the status of H. pylori infection in the gastric cardia tissue samples from high-risk populations in Chaoshan littoral region, and the relationship between H. pylori infection and chronic inflammation as well as the proliferative activity of the gastric cardia epithelial cells. A total of 706 gastric cardia biopsy specimens were obtained from 372 GCC cases and 334 tumor-free controls in Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. Immunohistochemistry and Giemsa staining were employed for the verification of H. pylori infection. H. pylori infection rate was significantly higher in GCC (81.5%, P < 0.01) and gastric carditis (80.1%, P < 0.01) in comparison with that in the healthy group (34.8%). A significant higher prevalence of chronic inflammation was found in H. pylori+ samples (96.9%) than that in H. pylori− specimens (80.5%) (P < 0.01). To explore the possible role of H. pylori infection-related chronic inflammation in the GCC, we found that the expression of Ki-67 was progressively increased in tissues with chronic inflammation degrees from normal to severe inflammation (P < 0.01). Collectively, these results suggest that persistent H. pylori infection and the related chronic inflammation may contribute to the high incidence of GCC in Chaoshan littoral.     

The −1123G>C Variant of <Emphasis Type="Italic">PTPN22</Emphasis> Gene Promoter is Associated with Latent Autoimmune Diabetes in Adult Chinese Hans

The protein tyrosine phosphatase non-receptor 22 (PTPN22) gene encodes for lymphoid protein tyrosine phosphatase. Recent studies demonstrated the association between the +1858T, −1123G>C variants of PTPN22 gene and type 1 diabetes mellitus in Caucasian and Japanese populations. This study examined the relationship between the polymorphism of PTPN22 gene and latent autoimmune 1 diabetes in adults (LADA) in Chinese Hans. We studied 229 adult Chinese patients with LADA (LADA group) and 210 healthy volunteers (control group). The −1123G>C and +1858C>T polymorphisms of PTPN22 gene were determined by PCR-restriction fragment length polymorphism method. Further, genotypic/allelic frequencies and clinical characteristics were compared between two groups. There was a significant difference of frequencies of the −1123G>C polymorphism between LADA and control groups (OR = 1.99, 95% CI = 1.24–3.2; P = 0.001). However, no significant differences in the +1858C>T genotypic (CC, CT) and allelic (C, T) frequencies were found. Furthermore, the frequencies of the −1123 GC, CC genotype in male patients with LADA were significantly higher compared with male healthy volunteers (OR = 1.65, 95% CI = 1.21–2.26; P = 0.005). The analysis of covariance demonstrated no difference between glycosylated hemoglobin, body mass index, duration of diabetes, C-peptide, and GAD-Ab titer between the group carrying GC/CC and the group without allele C. In conclusion, the −1123G>C promoter polymorphism of PTPN22 gene, but not the +1858C>T variant, is associated with LADA in adult Chinese Hans.     

Review: Clinical Management of Helicobacter pylori Infection in China

Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China—where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist—is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth‐containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.     

Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis

Studies investigating the association between X-ray repair cross-complementing gene 1 (XRCC1) polymorphisms and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case–control and cohort studies to better compare results between studies. Published literature from PubMed, EMBASE, and China National Knowledge Infrastructure were retrieved. 18 studies with 3,915 GC cases and 6,759 controls were selected. For XRCC1 Arg194Trp polymorphism, we only found the Trp/Trp genotype carriers might be at high risk of GC (TT vs. CC+CT: OR = 1.31, 95%CI = 1.04–1.65). When stratifying for ethnicity, the results showed there was a significant difference in genotype distribution between GC cases and controls among Asians (especially, in Chinese population), but not among Caucasians. When stratifying for control sources, significant association between Arg194Trp polymorphism and GC risk was only observed in the hospital-based controls’ subgroup (TT vs. CC+CT: OR = 1.45, 95%CI = 1.13–1.87). Additionally, no significant association was detected in the gastric cardia cancer’s subgroup. The results of the overall meta-analysis did not suggest any association between Arg280His/Arg399Gln polymorphisms and GC susceptibility for all genetic models. There was no evidence for the association between these two gene polymorphisms and GC risk in subgroup analyses based on study design, ethnicity, country, tumor location, Helicobacter pylori infection and the Lauren’s classification of GC. In conclusion, XRCC1 Arg194Trp homozygous mutant genotype (Trp/Trp) was found to be associated with increased risk of GC.     

Helicobacter pylori Infection – A Boon or a Bane: Lessons from Studies in a Low‐Prevalence Population

Helicobacter pylori (H. pylori) infection is etiologically associated with gastric cancer and peptic ulcer diseases which are both important public health burdens which could be largely eliminated by H. pylori eradication. However, some investigators urge caution based on the hypothesis that eradication of H. pylori may result in an increase in the incidence of gastroesophageal reflux disease, esophageal adenocarcinoma, and childhood asthma. The ethnic Malays of northeastern Peninsular Malaysia have long had a low prevalence of H. pylori infection and, as expected, the incidence of gastric cancer and its precursor lesions is exceptionally low. The availability of a population with a low H. pylori prevalence and generally poor sanitation allows separation of H. pylori from the hygiene hypothesis and direct testing of whether absence of H. pylori is associated with untoward consequence. Contrary to predictions, in Malays, erosive esophagitis, Barrett's esophagus, distal esophageal cancers, and childhood asthma are all of low incidence. This suggests that H. pylori is not protective rather the presence of H. pylori infection is likely a surrogate for poor hygiene and not an important source of antigens involved in the hygiene hypothesis. Helicobacter pylori in Malays is related to transmission from H. pylori‐infected non‐Malay immigrants. The factors responsible for low H. pylori acquisition, transmission, and burden of H. pylori infection in Malays remain unclear and likely involves a combination of environmental, host (gene polymorphisms), and strain virulence factors. Based on evidence from this population, absence of H. pylori infection is more likely to be boon than a bane.     

Helicobacter Pylori infection of the gallbladder and the risk of chronic cholecystitis and cholelithiasis: A systematic review and meta‐analysis

Background

Helicobacter pylori is coexisted with various diseases, including chronic gastritis, ulcer, and gastric cancer. Besides, chronic cholecystitis and cholelithiasis are extremely widespread over the world, which are considered as high health‐care cost burdens of digestive diseases. Epidemiologic evidence on Helicobacter pylori infection in gallbladder increasing the risk of biliary diseases has been contradictory.

Aim

Conduct a meta‐analysis of overall studies and investigate an association between Helicobacter pylori infection of the gallbladder with chronic cholecystitis/cholelithiasis.

Methods

We used PubMed, EMBASE, and Cochrane library databases to identify all published studies before August 2017. Pooled odds ratios (OR) and corresponding 95% confidence intervals (CIs) were obtained using the random effects model. Heterogeneity, sensitivity, and stratified analyses were also performed.

Results

Eighteen studies involving 1544 participants and 1061 biliary cases with chronic cholecystitis/cholelithiasis were included. Helicobacter pylori infection of the gallbladder was significantly associated with an increased risk of chronic cholecystitis and cholecystitis (OR = 3.022; 95% CI, 1.897‐4.815; I² = 20.1%). In addition, country‐based subgroup analysis also showed a positive association between Helicobacter pylori positivity and chronic cholecystitis/cholelithiasis risk. The ORs (95% CIs) for Asian and non‐Asian region studies were 3.75 (1.83‐7.71) and 2.25 (1.29‐3.89), respectively.

Conclusion

This meta‐analysis suggests that infection of the gallbladder with Helicobacter pylori is closely related to an increased risk of chronic cholecystitis and cholelithiasis.     

An association between DNA repair gene polymorphisms and survival in patients with resected non-small cell lung cancer

DNA repair genetic polymorphisms have been studied extensively in relation to lung cancer susceptibility, but much less is known about their role in clinical outcome modulation. In this report, we examined effect of the XPA −4G>A, XPD Asp312Asn, Leu751Gln, hHR23B Ala249Val, XPG Asp1104His, XRCC1 Arg399Gln, XRCC2 −4234G>C and XRCC3 Thr241Met polymorphisms on overall survival in 162 patients with resected non-small cell lung cancer (NSCLC). The XRCC3 Met/Met genotype was significantly associated with increased risk of death among all patients and men in uni- and multivariate analyses. The risk was higher for adenocarcinoma patients possessing the XRCC3 Met/Met or XRCC1 Gln/Gln genotypes, although their frequency was small. The XRCC1 399Gln allele was also associated with poor prognosis in stage II–IIIA and among older individuals. Men homozygous for the XPD 312 Asn/Asn had significantly better survival with the risk of death being at borderline significance in uni- and multivariate models. Younger cases and ever smokers smoking less than median pack-years showed significantly increased risk of death associated with the XPA −4A allele. A presence of one or two XRCC2 −4234C alleles had a protective effect in males and ever smokers with lower cumulative smoking dose, although the CC genotype was rarely observed. When number of combined risk alleles was considered, we found that carriers of >4 adverse alleles were at significantly increased risk of death in uni- and multivariate models. Therefore, our results indicate that selected genetic polymorphisms in DNA repair genes may influence overall survival in resected NSCLC.