Age-specific heterogeneity of genetic susceptibility to cardiovascular disease might have opposite outcomes depending on the presence of prediabetes

Examining age-specific heterogeneity of susceptibility to cardiovascular disease is also essential in individuals without prediabetes to determine its relative size and direction compared to those with prediabetes.Of particular interest,age-specific heterogeneity in genetic susceptibility may exhibit opposite directions depending on the presence or absence of prediabetes.

Bladder cancer epidemiology and genetic susceptibility

Bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women （approximately 4：1）. Here, we summarize the bladder cancer-related risk factors, in- cluding environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk fac- tors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study （GWAS） has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction stud- ies need to be conducted to provide more information for the etiology of bladder cancer.

Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management

Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day(diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease(NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual's genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.

Current progress and questions in germline genetics of prostate cancer

Dramatic progress has been made in the area of germline genetics of prostate cancer(PCa)in the past decade.Both common and rare genetic variants with effects on risk ranging from barely detectable to outright practice-changing have been identified.For men with high risk PCa,the application of genetic testing for inherited pathogenic mutations is becoming standard of care.A major question exists about which additional populations of men to test,as men at all risk levels can potentially benefit by knowing their unique genetic profile of germline susceptibility variants.This article will provide a brief overview of some current issues in understanding inherited susceptibility for PCa.

Association of genetic polymorphisms of GSTM1 and smoking status with lung cancer risk

Objective Long-term cigarette smoke exposure damages the airway epithelium.However,the correlation among GSTM1 gene polymorphism,smoking status,and lung cancer susceptibility remains unclear.This study aimed to identify the genetic polymorphism of GSTM1 and examine the association of GSTM1 polymorphism and smoking history with lung cancer susceptibility.Methods The genetic polymorphism of GSTM1 was genotyped by polymerase chain reaction(PCR) in 217 lung cancer patients and 198 controls.The demographic data and smoking history of the patients were collected.The age,sex,and residence of the two groups were also obtained.Results Significant differences in GSTM1 polymorphism were observed between the case and control groups(P=0.024).Smoking time and smoking index were significantly different between the case and control groups.With the increase in smoking time and smoking index,the differences became more obvious.There was a synergistic effect between GSTM1 and smoking(S=3.35).The risk of developing lung cancer increased 4.82 fold in smokers carrying deficient-type GSTM1.Compared with patients carrying wild-type GSTM1,the risk of developing lung cancer was higher in those carrying deficient-type GSTM1 with the increase in smoking time and smoking index.In different pathological types,no significant differences were observed in GSTM1 polymorphism.In different pathological types,the proportions of patients increased with the increase in smoking time and smoking index,especially the proportion of patients with squamous cell carcinoma.Compared with wild-type GSTM1,the proportion of patients with deficient-type GSTM1 increased with the increase in smoking time and smoking index(P=0.003 and 0.017).This trend was mainly observed in those with squamous cell carcinoma.Conclusion GSTM1 mutation is associated with lung cancer susceptibility.Smokers carrying deficienttype GSTM1 are more likely to develop lung cancer.Compared with patients carrying wild-type GSTM1,smokers with deficient-type GSTM1 are more likely develop lung cancer when smoking time is more than 30 years and smoking index is more than 400.In patients carrying deficient-type GSTM1,the risk of developing squamous cell carcinoma increases with an increase in smoking time and smoking dose.

Genetic variants in the Hedgehog signaling pathway genes are associated with gastric cancer risk in a Chinese Han population

The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk.Multi-marker Analysis of GenoMic Annotation(MAGMA)was used to investigate the aggregated genetic effects of single nucleotide polymorphisms(SNPs)assigned to candidate genes.The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses.Gene expression was calculated using databases obtained from The Cancer Genome Atlas(TCGA)and The Gene Expression Omnibus(GEO).Kaplan‐Meier plotter was used to evaluate the association between gene expression with gastric cancer survival.Tumor Immune Estimation Resource 2.0(TIMER 2.0)was applied to determine the correlation between selected gene expression and the immune cell infiltration degree.We identified that the G allele of rs2990912 in KIF27 was associated with higher gastric cancer risk,especially in the young and male subgroups.The expression of KIF27 in gastric cancer tissues was higher than that in normal tissues,leading to poor survival in gastric cancer patients.Besides,KIF27 expression was related to immune cell infiltration and positively correlated with PD-L1 expression.Our findings highlight the key role of genetic variation in the Hedgehog signaling pathway genes in gastric cancer susceptibility,which may provide important insights into the diagnosis,prognosis,and treatment of gastric cancer.

A non-synonymous coding SNP Lys45Glu of mmp3 associated with ESCC genetic susceptibility in population of Henan, China

Objective： The aim of the study was to investigate the association of esophageal squamous cell carcinoma （ESCC） genetic susceptibility with the single nucleotide polymorphism （SNP） rs679620 （-Lys45Glu-） in exon 2 of the romp3 gene, and the population in high incidence region of Henan （China） was selected for exploring the mechanism by case-control study, Methods： The romp3 SNP was genotyped by PCR-RFLP analysis in total 605 cases of Henan population, in which there were 227 ESCC cases and 197 controls of An-yang in Henan plus 181 controls of emigrants in Hubei from Xi-chuan of Henan, China. Results： The statistic data showed that GIG and G/A genotype frequencies of SNP rs679620 were significantly different between the controls of emigrants of Xi-chuan in Hubei and controls of An-yang in Henan （P 〈 0.01） also the ESCC cases of An-yang in Henan （P 〈 0.01）, respectively. Conclusion： This study suggests that the SNP rs679620 （-Lys45Glu-） in exon 2 of the mmp3 gene might be associated with ESCC genetic susceptibility.

Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model,cellular platform,and clinical human data

Head and neck squamous cell cancer(HNSCC)is a leading global malignancy.Every year,More than 830000 people are diagnosed with HNSCC globally,with more than 430000 fatalities.HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics.It originates from the squamous epithelium of the oral cavity,oropharynx,nasopharynx,larynx,and hypopharynx.The most frequently impacted regions are the tongue and larynx.Previous investigations have demonstrated the critical role of host genetic susceptibility in the progression of HNSCC.Despite the advances in our knowledge,the improved survival rate of HNSCC patients over the last 40 years has been limited.Failure to identify the molecular origins of development of HNSCC and the genetic basis of the disease and its biological heterogeneity impedes the development of new therapeutic methods.These results indicate a need to identify more genetic factors underlying this complex disease,which can be better used in early detection and prevention strategies.The lack of reliable animal models to investigate the underlying molecular processes is one of the most significant barriers to understanding HNSCC tumors.In this report,we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes(e.g.Smad 4 and P53 genes)to identify genetic factors affecting the development of this complex disease using genome-wide association studies,epigenetics,micro RNA,long noncoding RNA,lnc RNA,histone modifications,methylation,phosphorylation,and proteomics.

GENETIC DELETION OF DETOXIFIC ENZYME GSTM1 AND GSTT1 AS A HOST SUSCEPTIBLE FACTOR FOR NASOPHARYNGEAL CARCINOMA

Objective: To study the gene polymorphisms of GSTT1 and GSTM1 in nasopharyngeal carcinoma (NPC) patients and controls in an incidental area to evaluate the relationship between specific genotype and genotype combinations of these polymorphisms with the risk of NPC. Methods: Cases and controls all came from the Southwestern Guangxi. DNAs were extracted from their WBC. PCR technique was used to calculate the deletion rate of the two detoxific enzyme genes. Results: In this high risk area of NPC, the residents had high level deletion rates of 47.4% (64/135) M1 and T1 40.7% (55/135). The deletion rates were even higher in NPC patients, 61.5% (56/91) for M1 and 59.3% (54/91) for T1 respectively. There were statistical significances compared with control, P<0.05 and P<0.01 for M1 and T1 respectively. The difference was more significant in terms of combined M1 and T1 deletion between patients and controls x2=12.533, P=0.002. Conclusion: The combined deletion of detoxific enzyme genes GSTM1 and GSTT1 may be an important genetic susceptible factor for NPC in Guangxi.

Regional differences in genetic susceptibility to nonalcoholic liver disease in two distinct Indian ethnicities

AIM To validate the association of variants in PNPLA3(rs2281135) and TM6SF2(rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease(NAFLD).METHODS A total of 503 individuals with and without fatty infiltration were recruited. Fatty infiltration was confirmed based on ultrasound findings. Anthropometric data and blood samples were collected from the study group. DNA was isolated from peripheral blood, quality and quantity was assessed by gel electrophoresis and spectrophotometer respectively. Genotyping of the variants in PNPLA3 and TM6SF2 genes was carried out by employing taqman probes(C_15875080_10 for PNPLA3 and C_8946351_10 for TM6SF2 SNP) on real time PCR(Stepone-Lifetechnologies). Genotype data was tested for deviations from Hardy-Weinbergequilibrium. χ~2 test was used to analyze the statistical significance of the difference in genotype distribution of the studied variants in patients and controls and the strength of association was expressed as odds ratio(95%CI). A two-tailed P value of ≤ 0.05 was considered statistically significant. RESULTS The study group comprised of 503 individuals of which 256 had fatty infiltration and 247 without fatty infiltration and thus formed the patient and control groups respectively. As the patient group could be divided in to two distinct ethnicities(ancestral South Indians-ASI and North-East Indians-NEI), further recruitment of control cohort and association analyses was carried out based on ethnicities. Of the 256 with fatty infiltration 93 were ASI and 163 were NEI and of the 247 controls 138 were ASI and 109 were NEI. As expected, there were significant differences in the anthropometric and other clinical data between the control and the patient groups. However significant differences within the ethnicities were also noted. While rs2281135 in PNPLA3 gene was significantly associated(P = 0.03) with higher risk(odds 1.9, 95%CI: 1.5-3.14, P = 0.03) of NAFLD in NEI ethnicity, rs58542926 in TM6SF2 gene was significantly associated with NAFLD with a 2.7 fold higher risk(odds 2.7, 95%CI: 1.37-5.3, P = 0.0004) of the disease. There were significantly higher proportions of individuals with variants in both the genes in the patient group in both ASI(patients-14/93 and controls-7/138; P = 0.009) and NEI ethnicities(patients-17/163 and controls-7/109; P = 0.01). CONCLUSION Although the study identified distinct genetic susceptibility in the two ethnicities, transheterozygosity of the variants suggests higher risk of NAFLD in individuals with both the variants.

AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

Objectives. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-based case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel-Gart and Falconer methods were used to analyze the segregation ratio and heritability. Polymerase chain reaction(PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significantly, OR is 3905(95%CI=1079～1413), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 999%, which is larger than that in second, third degree and non-blood relatives. Segregation ratio is 0021, heritability among first degree relatives is 356±58%. Frequencies of LOH at BRCA1 and BRCA2 loci in sporadic breast cancer are 612% and 577% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome aberrations were observed. Conclusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

A Genetic Susceptibility Study of Lung Cancer Risk Potentially Associated with Polycyclic Aromatic Hydrocarbon Inhalation Exposure

For lifetime non-smokers, lung cancer risk is mainly associated with inhalation exposure to air pollution. For the Chinese population, indoor air pollution due to solid fuel combustion has been the primary source of inhalation exposure for decades. Polycyclic aromatic hydrocarbons （PAHs） are the by-products of incomplete combustion.

Genetic counseling in post-genomic era: Don't pretend to know the meaning of a gene mutation if you don't know

In this post-genomic era, more and more susceptibility loci of many possible genetic diseases are published. As our knowledge about these susceptibility loci is limited and partial, we should be very careful and responsible when patients seek genetic counseling about these possible genetic diseases. We should apply Confucius' s principle about knowledge and information to genetic conseling, and tell the truth to our patients about what we know and what we do not know. Like many other cancers, breast cancer is a very complicated, multifactorial disease; genetic factors, lifestyles and eating habits, environmental factors, and viral infections might be involved in breast cancer; hence, it is difficult to figure out the real etiology of breast cancer. It is not crystal clear that a person who carries mutations of the breast cancer 1, early onset and/or breast cancer 2, early onset genes would eventually get breast cancer in her/his lifetime. No person should undergo a preventive double mastectomy, unless we know the etiology of breast cancer someday.

Enumeration,Genetic Characterization and Antimicrobial Susceptibility of Lactobacillus and Streptococcus Isolates from Retail Yoghurt in Beijing,China

Lactic acid bacteria （LAB） are widely used in food industries. Correct identification and safety evaluation of these bacteria at the species even strain level should take considerations into account. In this study, the LAB were recovered from yoghurt and characterized phenotypically and genetically. Fifty-two isolates of LAB from 31 yoghurt samples were cultured and grouped into 6 species including Luctobucillus bulguricus （24 isolates）, Streptococcus thermophilus （15 isolates）, L. ucidophilus （7 isolates）, L. porucusei/cusei （3 isolates）, L. delbrueckii （2 isolates）, and L. fermentum （1 isolate）, based on their Gram-staining, colony morphology and biochemical properties.

A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

NOD2/CARD15 , ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn’s disease

AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn’s disease (CD). METHODS: Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 ; rs2241880 A/G of ATG16L1 , and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 genotyping was performed by allele specific polymerase chain reaction (PCR) or by PCR-restriction fragment length polymor-phism analysis. The polymorphisms rs2241880 A/G of the ATG16L1 , and rs11209026 (R381Q) of the IL23R gene in the children’s cohort were genotyped by PCR and melting curve analysis whereas adult group genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 5.0 (500K). RESULTS: The 3020insC allele in NOD2/CARD15 was significantly higher in childhood than in adult-onset CD (P = 0.0067). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease (with or without co- lonic involvement). Even if the frequency of G allele of the rs2241880 ATG16L1 polymorphism was increased in both paediatric and adult CD patients compared to con- trols (P = 0.017 and P = 0.001, respectively), no difference was observed between the childhood and the adult cohort. The rare Q allele of IL23R rs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms did not influence disease phenotype. CONCLUSION: Polymorphism 3020insC in NOD2/ CARD15 occurs statistically significantly more often in patients with childhood-onset CD than in patients with adult-onset CD. The ATG16L1 and IL23R variants are associated with susceptibility to CD, but not earlyonset disease.

Analysis of HLA alleles polymorphism in Chinese patients with primary biliary cirrhosis

BACKGROUND: A familial dustering of patients with primary biliary cirrhosis (PBC) and the presence of immunological abnormalities in family members suggest a genetic component involved in the pathogenesis of PBC. The aims of this study are to investigate the frequencies of human leukocyte antigen HLA-A, -B, and -DRB1 alleles in Chinese patients with PBC by polymerase chain reaction (PCR)-based techniques, and to assess the correlation of the above-mentioned HLA with some clinical and laboratory features. METHODS: Genotyping of HLA alleles were performed in 65 well-characterized PBC patients and 431 healthy controls with sequence-specifc primers PCR amplification. RESULTS: HLA-DRB1~*07 allele detected in 19 of the 65 (29.2%) PBC patients was subtyped as DRB1~*0701, as well as in 13.9% of controls (P_C<0.05, OR=2.55, 95% CI: 1.4-4.6). An increased frequency of DRB1~*03 (18.4% vs. 7.2% in healthy controls) and a decreased frequency of DRB1~*12 (16.9% vs. 28.8%) in PBC patients were statistically significant. There was no association with HLADRB1~*08 reported. The frequencies for HLA-A, B and the other DRB1 alleles were similar between patients and healthy controls. CONCLUSIONS: The susceptibility to PBC in Chinese individuals is associated with DRB1~*0701 allele. This association differs from that in North Americans, South Americans, North Europeans and even Japanese, but it is not restricted to any particular subgroup of patients.

Relationship between XRCC1 polymorphisms and susceptibility to prostate cancer in men from Han, Southern China

Aim： To investigate the association among XRCC1 polymorphisms, smoking, drinking and the risk of prostate cancer （PCa） in men from Han, Southern China. Methods： In a case-control study of 207 patients with PCa and 235 cancerfree controls, frequency-matched by age, we genotyped three XRCC1 polymorphisms （codons 194, 280 and 399） using the polymerase chain reaction-restriction fragment length polymorphism （PCR-RELP） method. Results： Among the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk （adjusted odd ratio [OR]： 1.67, 95% confident interval [CI]： 1.11-2.51）, but the XRCC1 Arg 194Trp variant allele had a 38% reduction in risk of PCa （adjusted OR： 0.62, 95% CI： 0.41-0.93）. However, there was no significant risk of PCa associated with Arg280His polymorphism. When we evaluated the three polymorphisms together, we found that the individuals with 194Arg/Arg wild-type genotype, Arg280His and Arg399Gln variant genotypes had a significantly higher risk of PCa （adjusted OR： 4.31; 95% CI： 1.24-14.99） than those with three wild-type genotypes. In addition, we found that Arg399Gln variant genotypes had a significant risk of PCa among heavy smokers （adjusted OR： 2.04; 95% CI： 1.03-4.05）. Conclusion： These results suggest that polymorphisms of XRCC1 appear to influence the risk of PCa and may modify risks attributable to environmental exposure.

Cytochrome p450 2E1 polymorphisms and the risk of gastric cardia cancer

AIM: Genetic polymorphisms of drug-metabolizing enzymes have recently been shown to affect susceptibility to chemical carcinogenesis. Cytochrome P450 2E1 (CYP2E1) enzyme catalyzes the metabolism of many procarcinogens, such as N-nitrosamines and related compounds. The gene coding for this enzyme is polymorphic and thus may play a role in gastric cardia cancer (GCC) etiology. In this hospital-based case-control study, we evaluate the relationship between genetic polymorphisms of CYP2E1 and the risk of GCC. METHODS: The study subjects comprised 159 histologically confirmed GCC cases identified via hospital cancer registry and surgical records at five hospitals in Fuzhou, Fujian Province, China, between April and November 2001. Controls were 192 patients admitted to the same hospitals for nonmalignant conditions. The genotypes of CYP2E1 were detected by a PCR-based RFLP assay. The odds ratios were estimated by logistic regression analyses and were adjusted for potential confounding factors. RESULTS: The distribution of three genotypes of CYP2E1 in GCC cases and controls was significantly different (X2 = 16.04, P<0.01). The frequency of the CYP2E1 (c1/c1) genotype in GCC cases and controls was 60.4% and 40.1%, respectively. The CYP2E1 (c1/c1) genotype was associated with an increased risk for GCC (the adjusted (OR) was 2.37, 95% confidence interval (CI): 1.52-3.70). Subjects who carried the CYP2E1 (c1/c1) genotype and were habitual smokers were at a significantly higher risk of developing GCC (OR = 4.68,95%CT. 2.19-10.04) compared with those who had the CYP2E1 (c1/c2 or c2/c2) genotype and did not smoke. CONCLUSION: These results suggest that the CYP2E1 genotype may influence individual susceptibility to development of GCC, and that the risk increases significantly in smokers.

Association between polymorphism rs6983267 and gastric cancer risk in Chinese population

AIM: To explore the association between single nucleotide polymorphisms (SNPs) at 8q24 and gastric cancer risk. METHODS: A case-control investigation including 212 gastric cancer patients and 377 healthy controls was conducted. The genotypes of SNPs (rs6983267, rs7008482 and rs10808555) were examined and established through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to evaluate the association between SNPs and gastric cancer. RESULTS: The genotype frequencies of rs6983267 in gastric cancer patients were obviously different from those in the control (P = 0.005). GT genotype of rs6983267 was associated with an increased risk of gastric cancer compared with GG genotype (adjusted odds ratio = 2.01, 95% confidence interval: 1.28-3.14). Further stratified analysis indicated that rs6983267 GT genotype facilitated the risk of gastric cancer of non-cardiac and intestinal type (OR: 2.638, 95% CI: 1.464-4.753; OR: 1.916, 95% CI: 1.166-3.150, respectively). CONCLUSION: This study demonstrates for the first time that rs6983267 is involved in susceptibility to gastric cancer, although further large-sample investigations are still needed.