scholarly journals Association Analysis between SNPs in LATS1 and LATS2 and Non-Cardia Gastric Cancer

2020 ◽  
Author(s):  
Licong Ma ◽  
Xuyang Tian ◽  
Fang Gao ◽  
Wenjie Dong ◽  
Tong Dang ◽  
...  

Abstract Background: Many studies have found that large tumor suppressor kinase 1 (LATS1) and LATS2 play important roles in many diseases, but studies have been rare on the relationship between these genes and non-cardia gastric cancer (GC). We performed a case-control association study to investigate the associations between single nucleotide polymorphisms (SNPs) in LATS1 and LATS2 genes and Helicobacter pylori (H. pylori) infection as well as the risk of non-cardia GC. Methods: First, H. pylori infection was determined by the serological test using enzyme-linked immunoassay. Then genotyping of SNPs was performed for 808 samples by the Taqman method. Finally, unconditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age and gender, for the association of each SNP with the infection of H. pylori, the risk of non-cardia gastric cancer, as well as the expression of LATS1 and LATS2 proteins in non-cardia GC tissues, using the codominant, dominant, recessive, overdominant, and additive inheritance models, respectively. Results: The statistical results showed that LATS2 rs9552315 was associated with H. pylori infection, and the CC+CT genotype could reduce the risk of H. pylori infection (odds ratio [OR]: 0.549, 95% confidence interval [CI]: 0.339–0.881, P<0.05) compared with the TT genotype in a dominant model. LATS1 rs9393175 was associated with the risk of non-cardia GC, and the AG genotype reduced the risk of non-cardia GC (OR: 0.702, 95% CI: 0.516–0.952, P<0.05) compared with the GG+AA genotype in an overdominant model. LATS2 rs9509492 was associated with the risk of GC in an additive model. No associations were found between five SNPs and expression of LATS1 and LATS2 proteins in non-cardia GC tissue. Conclusions: LATS2 rs9552315 CT genotype may be a protective factor against infection of H. pylori. LATS1 rs9393175 AG genotype and LATS2 rs9509492 GG genotype may be protective factors for non-cardia GC.

2019 ◽  
Author(s):  
Licong Ma ◽  
Xuyang Tian ◽  
Fang Gao ◽  
Wenjie Dong ◽  
Tong Dang ◽  
...  

Abstract Background: Many studies have found that large tumor suppressor kinase 1 (LATS1) and LATS2 play important roles in many diseases, but studies have been rare on the relationship between these genes and non-cardia gastric cancer (GC). We performed a case-control association study to investigate the associations between single nucleotide polymorphisms (SNPs) in LATS1 and LATS2 genes and Helicobacter pylori infection as well as the risk of non-cardia GC. Methods: First, H. pylori infection was determined by an enzyme-linked immunoassay. Then genotyping of SNPs was performed for 808 samples by the Taqman method. Finally, appropriate statistical methods were used to analyze the relationship between the SNPs of LATS1 and LATS2 genes and H. pylori infection, the risk of non-cardia GC, and the level of protein expression. Results: The statistical results showed that LATS2 rs9552315 was associated with H. pylori infection, and that the CC+CT genotype could reduce the risk of H. pylori infection (odds ratio [OR]: 0.549, 95% confidence interval [CI]: 0.339–0.881, P<0.05) compared with the TT genotype in a dominant model. LATS1 rs9393175 was associated with risk of non-cardia GC, and the AG genotype reduced the risk of non-cardia GC (OR: 0.702, 95% CI: 0.516–0.952, P<0.05) compared with the GG+AA genotype in an overdominant model. LATS2 rs9509492 was associated with the risk of GC in an additive model. No associations were found between five SNPs and expression of LATS1 and LATS2 proteins. Conclusions: LATS2 rs9552315 CT genotype may be a protective factor against infection of H. pylori. LATS1 rs9393175 AG genotype and LATS2 rs9509492 GG genotype may be protective factors for non-cardia GC.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Nu Ma ◽  
Ting-Yu Xie ◽  
Xue-Yi Chen

Background. Our previous data suggested that three single-nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, of the lysyl oxidase-like 1 gene (LOXL1) are significantly associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). The following study investigated other SNPs that potentially effect XFS/XFG. Methods. A total of 216 Uygur patients diagnosed with XFS/XFG, and 297 Uygur volunteers were admitted to the First Affiliated Hospital at Xinjiang Medical University between January 2015 and October 2017. Blood samples were collected by venipuncture. Alleles and genotypes of LOXL1, TBC1D21, ATXN2, APOE, CLU, AFAP1, TXNRD2, CACNA1A, ABCA1, GAS7, and CNTNAP2 were analyzed by direct sequencing. Results. The allele G of rs41435250 of LOXL1 was a risk allele for XFS/XFG (P<0.001), whereas the allele G of rs893818 of LOXL1 was a protective allele for XFS/XFG (P<0.001). After adjusting all data for age and gender, the following results were obtained: the frequency of genotype CC for rs7137828 of ATXN2 was significantly higher in XFS/XFG patients than in controls (P=0.027), while no significance was found with reference to the frequency of genotype TT. The frequency of genotype GG for rs893818 of LOXL1 (P<0.001) and the frequency of genotype AA were both significantly higher in XFS/XFG groups compared to the control group (P<0.001). In addition, the frequency of genotype TT for rs41435250 of LOXL1 was higher in XFS/XFG patients than in controls (P=0.003), while no significant difference was found with reference to the frequency of genotype GG after adjusting for age and gender. In addition, the haplotypes G-A/T-G/G-G for rs41435250 and rs893818 were significantly associated with XFS/G. Conclusions. With reference to LOXL1, the rs41435250 resulted as a risk factor and rs893818 as a protective factor for XFS/XFG in the Uygur populations. Meanwhile, the rs16958445 of TBC1D21 and the rs7137828 of ATXN2 have also shown to be associated with pathogenesis of XFS/XFG.


Genes ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 20 ◽  
Author(s):  
Patricio Gonzalez-Hormazabal ◽  
Maher Musleh ◽  
Marco Bustamante ◽  
Juan Stambuk ◽  
Raul Pisano ◽  
...  

The RAS/RAF/MEK/ERK pathway regulates certain cellular functions, including cell proliferation, differentiation, survival, and apoptosis. Dysregulation of this pathway leads to the occurrence and progression of cancers mainly by somatic mutations. This study aimed to assess if polymorphisms of the RAS/RAF/MEK/ERK pathway are associated with gastric cancer. A case-control study of 242 gastric cancer patients and 242 controls was performed to assess the association of 27 single nucleotide polymorphisms (SNPs) in the RAS/RAF/MEK/ERK pathway genes with gastric cancer. Analyses performed under the additive model (allele) showed four significantly associated SNPs: RAF1 rs3729931 (Odds ratio (OR) = 1.54, 95%, confidence interval (CI): 1.20–1.98, p-value = 7.95 × 10−4), HRAS rs45604736 (OR = 1.60, 95% CI: 1.16–2.22, p-value = 4.68 × 10−3), MAPK1 rs2283792 (OR = 1.45, 95% CI: 1.12–1.87, p-value = 4.91 × 10−3), and MAPK1 rs9610417 (OR = 0.60, 95% CI: 0.42–0.87, p-value = 6.64 × 10−3). Functional annotation suggested that those variants or their proxy variants may have a functional effect. In conclusion, this study suggests that RAF1 rs3729931, HRAS rs45604736, MAPK1 rs2283792, and MAPK1 rs9610417 are associated with gastric cancer.


2021 ◽  
Vol 10 ◽  
Author(s):  
Jimi Kim ◽  
Hyejin Kim ◽  
Jeonghee Lee ◽  
Il Ju Choi ◽  
Young-Il Kim ◽  
...  

BackgroundChronic gastritis along with Helicobacter pylori (H. pylori) infection has been implicated in inflammatory response-related genes linked to the causation of gastric cancer. Glutathione S-transferase Pi (GSTP1) plays a role in regulating oxidative stress and detoxification against carcinogenesis. In this study, we aimed to determine whether an antioxidant-rich diet is associated with gastric cancer risk and identify how this association could be altered by GSTP1 genetic variants.MethodsThis study included 1,245 participants (415 cases and 830 controls) matched for age and sex. The dietary antioxidant capacity was estimated based on the oxygen radical absorbance capacity (ORAC) incorporated with a semiquantitative food frequency questionnaire. Five single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695, rs749174, rs1871042, rs4891, and rs947895) were selected among the exome array genotype data.ResultsHigh dietary ORAC was inversely associated with gastric cancer (hydrophilic ORAC OR T3vs. T1, 95% CI = 0.57, 0.39–0.82, P = 0.004; lipophilic ORAC = 0.66, 0.45–0.95, P = 0.021; total phenolics = 0.57, 0.39–0.83, P = 0.005). The polymorphism rs1871042 increased the risk of gastric cancer (OR, 95% CI = 1.55, 1.10–2.16, P = 0.01, CT+TT vs. CC). A remarkably reduced risk of gastric cancer was observed among those who had a high dietary ORAC according to rs1871042 polymorphism (hydrophilic ORAC OR T3vs. T1, 95% CI = 0.36, 0.17–0.78, P for trend = 0.013; lipophilic ORAC = 0.58, 0.37–0.93, P for trend = 0.021; total phenolics = 0.38, 0.17–0.83, P for trend = 0.019).ConclusionsOur findings indicate that dietary ORAC intake may be inversely associated with the risk of gastric cancer altered by genetic variants of GSTP1, providing new intervention strategies for gastric cancer patients.


Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 270
Author(s):  
Gabriel Herrera-Maya ◽  
Gilberto Vargas-Alarcón ◽  
Oscar Pérez-Méndez ◽  
Rosalinda Posadas-Sánchez ◽  
Felipe Masso ◽  
...  

Recent studies have shown that P-selectin promotes the early formation of atherosclerotic plaque. The aim of the present study was to evaluate whether the SELP gene single nucleotide polymorphisms (SNPs) are associated with presence of acute coronary syndrome (ACS) and with plasma P-selectin levels in a case-control association study. The sample size was estimated for a statistical power of 80%. We genotyped three SELP (SELP Ser290Asn, SELP Leu599Val, and SELP Thr715Pro) SNPs using 5’ exonuclease TaqMan assays in 625 patients with ACS and 700 healthy controls. The associations were evaluated with logistic regressions under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The genotype contribution to the plasma P-selectin levels was evaluated by a Student’s t-test. Under different models, the SELP Ser290Asn (OR = 0.59, pCCo-Dominant = 0.047; OR = 0.59, pCDominant = 0.014; OR = 0.58, pCOver-Dominant = 0.061, and OR = 0.62, pCAdditive = 0.015) and SELP Thr715Pro (OR = 0.61, pCDominant = 0.028; OR = 0.63, pCOver-Dominant = 0.044, and OR = 0.62, pCAdditive = 0.023) SNPs were associated with a lower risk of ACS. In addition, these SNPs were associated with low plasma P-selectin levels. In summary, this study established that the SELP Ser290Asn and SELP Thr715Pro SNPs are associated with a lower risk of developing ACS and with decreased P-selectin levels in plasma in a Mexican population.


2020 ◽  
Author(s):  
Jimi Kim ◽  
Hyejin Kim ◽  
Jeonghee Lee ◽  
Il Ju Choi ◽  
Young-Il Kim ◽  
...  

Abstract Background Chronic gastritis along with Helicobacter pylori (H. pylori) infection has been implicated in inflammatory response-related genes linked to the causation of gastric cancer (GC). Glutathione S-transferase Pi (GSTP1) plays a role in regulating oxidative stress and detoxification against carcinogenesis. In this study, we aimed to determine whether an antioxidant-rich diet was associated with GC risk and to identify how the association could be altered by GSTP1 genetic variants. Methods The study was conducted with 1,245 participants (415 cases and 830 controls) matched for age and sex. Dietary antioxidant capacity was estimated based on oxygen radical absorbance capacity (ORAC) incorporated with a semiquantitative food frequency questionnaire. Five single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695, rs749174, rs1871042, rs4891, and rs947895) were selected among the exome array genotype data. Results High dietary ORAC showed inverse associations with GC (hydrophilic ORAC OR T3 vs. T1, 95% CI = 0.57, 0.39–0.82, P = 0.004; lipophilic ORAC = 0.66, 0.45–0.95, P = 0.021; total phenolics = 0.57, 0.39–0.83, P = 0.005). The polymorphism of rs1871042 increased GC risk (OR, 95% CI = 1.55, 1.10–2.16, P = 0.01, CT + TT vs. CC). A remarkably reduced risk of GC was observed among those who had a high dietary ORAC according to rs1871042 polymorphism (hydrophilic ORAC OR T3 vs. T1, 95% CI = 0.36, 0.17–0.78, P for trend = 0.013; lipophilic ORAC = 0.58, 0.37–0.93, P for trend = 0.021; total phenolics = 0.38, 0.17–0.83, P for trend = 0.019). Conclusions Our findings indicate that the association between dietary ORAC intake and GSTP1 polymorphisms as they pertain to the risk of GC may present new intervention strategies for GC patients.


2019 ◽  
Author(s):  
Ketian Wang ◽  
Liangyue Pang ◽  
Luoping Yin ◽  
Xia Li ◽  
Jianming Zhang ◽  
...  

Abstract The aim of this study was to identify genetic factors under additive and dominance models that contribute to caries susceptibility, and to investigate into the interactions between these genes. A cross-sectional study was conducted among 1055 adolescents in Foshan, South China. The International Caries Detection and Assessment System (ICDAS) was used to identify caries. Demographic and environmental variables were analyzed. Twenty-three single nucleotide polymorphisms (SNPs) in 14 genes were identified from saliva samples. Regression analysis was used for the evaluation of direct and epistasis of genes under the hypothesis of an additive model and using the minor allele as the reference allele. After the adjustment by environmental factors, the G allele in AMBN (rs13115627) was a protective factor for caries under both additive model (P=0.007; OR=0.728; 95% CI, 0.579-0.916) and dominance model (P=0.021; OR=0.728; 95% CI, 0.556-0.953). No interactions between selected genes met the Bonferroni correction significance cutoff for multiple testing. Our results suggests that gender, one-child family, Cariostat score and Plaque Index have independent protective effects on dental caries. The polymorphisms in AMBN (rs13115627), under both additive and dominance models alters caries susceptibility of Adolescents in South China. No epistatic effect has been found between selected genes.


2016 ◽  
Vol 39 (4) ◽  
pp. 1537-1552 ◽  
Author(s):  
Chuanjun Zhuo ◽  
Mingjing Shao ◽  
Ce Chen ◽  
Chongguang Lin ◽  
Deguo Jiang ◽  
...  

Objective: Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population. Methods: Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis. Results: For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05). Conclusion: Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Rasa Liutkeviciene ◽  
Alvita Vilkeviciute ◽  
Greta Gedvilaite ◽  
Kriste Kaikaryte ◽  
Loresa Kriauciuniene

Background. To determine the impact of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 genotypes on the development of age-related macular degeneration (AMD) in the Lithuanian population. Methods. A total of 916 subjects were examined: 309 patients with early AMD, 301 patients with exudative AMD, and 306 healthy controls. The genotyping of HTRA1 rs11200638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 was carried out using the RT-PCR method. Results. Our study showed that single-nucleotide polymorphisms rs3793784 and rs11200638 were associated with increased odds of early and exudative AMD, and the variant in KCTD10 (rs56209061) was found to be associated with decreased odds of early and exudative AMD development after adjustments for age and gender in early AMD analysis and after adjustments only for age in exudative AMD. The haplotype containing two minor alleles C-A and the G-A haplotype in rs3793784-rs11200638 were statistically significantly associated with an increased risk of exudative AMD development after adjustment for age, while the G-G haplotype showed a protective role against early and exudative AMD and the haplotype C-G in rs3793784-rs11200638 was associated with a decreased risk only of exudative AMD development. Conclusions. Our study identified two markers, rs11200638 and rs3793784, as risk factors for early and exudative AMD, and one marker, rs56209061, as a protective factor for early and exudative AMD development. The haplotypes constructed of rs3793784-rs11200638 were found to be associated with AMD development, as well.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Yong Li ◽  
Zhen-Jian Zhuo ◽  
Haiyan Zhou ◽  
Jiabin Liu ◽  
Zhenghui Xiao ◽  
...  

Neuroblastoma is the most common seen solid neural tumor in children less than age one. As mutation in the miR-34b/c gene is observed in several types of human malignancies, there likely to be similar events that contribute to the pathogenesis of neuroblastoma. We hypothesize that polymorphism in the miR-34b/c gene might predispose to neuroblastoma. Here, we conducted this replication study by genotyping rs4938723 T>C from miR-34b/c in Hunan children (162 subjects with neuroblastoma and 270 control subjects) and examined its effect on the risk of neuroblastoma. We determined such association using logistic regression, adjusted for age and gender. Relative to those with TT genotype, subjects with C allele had reduced neuroblastoma risk (TC vs. TT: adjusted OR=0.46, 95%CI=0.30‐0.71; additive model: adjusted OR=0.64, 95%CI=0.47‐0.88; TC/CC vs. TT: adjusted OR=0.49, 95%CI=0.33‐0.73). Stratified analysis revealed that rs4938723 TC/CC carriers were less likely to develop neuroblastoma for patients in the subgroups of age≤18 months, age>18 months, females, males, tumors in retroperitoneal, tumors in other sites, and clinical stages II, III, IV, and III+IV. Our findings verified miR-34b/c rs4938723 C variant allele as a protective factor for the risk of neuroblastoma. Further investigation of how miR-34b/c rs4938723 T>C might modify neuroblastoma risk is warranted.


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