Association Between Polymorphisms in Gastric Cancer Related Genes and Risk of Gastric Cancer: A Case-Control Study.
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ABSTRACT:
SUBMITTER: Pu Y
PROVIDER: S-EPMC8166284 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMalignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumours. Susceptible genetic background, accumulation of genetic changes, and environmental factors play an important role in gastric carcinogenesis. Single nucleotide polymorphisms (SNPs) in mitotic segregation genes could be responsible for inducing the slow process of accumulation of genetic changes, leading to genome instability.Patients and methodsWe performed a case-control study of polymorphisms in mitotic kinases TTK rs151658 and BUB1B rs1031963 and rs1801376 to assess their effects on gastric cancer risk. We examined the TTK abundance in gastric cancer tissues using immunoblot analysis.ResultsC/G genotype of rs151658 was more frequent in patients with diffuse type of gastric cancer and G/G genotype was more common in intestinal types of gastric cancers (p = 0.049). Polymorphic genotype A/A of rs1801376 was associated with higher risk for developing diffuse type of gastric cancer in female population (p = 0.007), whereas A/A frequencies were increased in male patients with subserosa tumour cell infiltration (p = 0.009). T/T genotype of rs1031963 was associated with well differentiated tumours (p = 0.035). TT+CT genotypes of rs1031963 and GG+AG genotypes of rs1801376 were significantly associated with gastric cancer risk (dominant model; OR = 2,929, 95% CI: 1.281-6.700; p = 0.017 and dominant model; OR = 0,364, 95% CI: 0.192-0.691; p = 0.003 respectively).ConclusionsOur results suggest that polymorphisms in mitotic kinases TTK and BUB1B may contribute to gastric tumorigenesis and risk of tumour development. Further investigations on large populations and populations of different ethnicity are needed to determine their clinical utility.
| S-EPMC5024654 | biostudies-literature
Project description:The human gut hosts a diverse community of bacteria referred to as the gut microbiome. We investigated the association between the relative abundance of gastric microbiota and gastric cancer (GC) risk in a Korean population. The study participants included 268 GC patients and 288 controls. DNA was extracted from gastric biopsies, and 16S rRNA gene analysis was performed. Unconditional logistic regression models were used to observe the associations. Of the participants, those who had the highest level (highest tertile) of relative Helicobacter pylori and Propionibacterium acnes abundances showed a significantly higher risk for GC after adjusting for potential confounding variables (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.17-2.97, p for trend = 0.017 and OR = 4.77, 95% CI = 2.94-7.74, p for trend <0.001, respectively). Subjects who carried Prevotella copri had a significantly higher risk of GC than noncarriers (OR = 2.54, 95% CI = 1.42-4.55, p for trend = 0.002). There was a lower risk of GC in subjects carrying Lactococcus lactis than in noncarriers (OR = 0.21, 95% CI = 0.10-0.44, p for trend <0.001). H. pylori, P. acnes and P. copri are strong risk factors, whereas L. lactis is a protective factor, for GC development in Koreans. Further microbiome studies are warranted to verify the findings of the current study.
| S-EPMC6753194 | biostudies-literature
Project description:BackgroundNumerous epidemiological studies have evaluated the association between TGFBR1 polymorphisms and the risk of cancer, however, the results remain inconclusive. To derive a more precise estimation of the relation, we conducted a comprehensive meta-analysis of all available case-control studies relating the TGFBR1*6A and IVS7+24G>A polymorphisms of the TGFBR1 gene to the risk of cancer.MethodsEligible studies were identified by search of electronic databases. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were applied to assess the associations between TGFBR1*6A and IVS7+24G>A polymorphisms and cancer risk.ResultsA total of 35 studies were identified, 32 with 19,767 cases and 18,516 controls for TGFBR1*6A polymorphism and 12 with 4,195 cases and 4,383 controls for IVS7+24G>A polymorphism. For TGFBR1*6A, significantly elevated cancer risk was found in all genetic models (dominant OR = 1.11, 95% CI = 1.04~1.18; recessive: OR = 1.36, 95% CI = 1.11~1.66; additive: OR = 1.13, 95% CI = 1.05~1.20). In subgroup analysis based on cancer type, increased cancer risk was found in ovarian and breast cancer. For IVS7+24G>A, significant correlation with overall cancer risk (dominant: OR = 1.39, 95% CI = 1.15~1.67; recessive: OR = 2.23, 95% CI = 1.26~3.92; additive: OR = 1.43, 95% CI = 1.14~1.80) was found, especially in Asian population. In the subgroup analysis stratified by cancer type, significant association was found in breast and colorectal cancer.ConclusionsOur investigations demonstrate that TGFBR1*6A and IVS7+24G>A polymorphisms of TGFBR1 are associated with the susceptibility of cancer, and further functional research should be performed to explain the inconsistent results in different ethnicities and cancer types.
| S-EPMC3414489 | biostudies-literature
Project description:The transforming growth factor-β (TGFβ) pathway plays an important role in various types of human cancer. However, the role of TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms in gastric cancer is controversial. We aimed to investigate the associations between these polymorphisms and gastric cancer susceptibility, clinicopathological parameters and survival. A case-control study was conducted in 1,010 gastric cancer patients and 1,500 healthy controls. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. Compared with the TT genotype, the TGFB1 -509 C allele (CT/CC) was significantly associated with a reduced risk of gastric cancer (OR, 0.71; 95% CI, 0.58-0.87; p=0.001) and certain subtypes of gastric cancer including intestinal type (OR, 0.70; 95% CI, 0.57-0.87; p=0.001), poorly differentiated (OR, 0.67; 95% CI, 0.54-0.85; p=0.001) and stage TNM III+IV (OR, 0.73; 95% CI, 0.58-0.92; p=0.008). Compared with the TGFBR2 -875 GG genotype, carriers of the A allele (AA/AG) had a significantly decreased gastric cancer risk (OR, 0.58; 95% CI, 0.62-0.91; P<0.001). A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles was associated with a further decreased risk of gastric cancer (OR, 0.42; 95% CI, 0.32-0.57, p<0.001). No significant correlation was observed between polymorphisms and survival of gastric cancer patients. Our results suggest that both the TGFB1 -509 and TGFBR2 -875 polymorphisms contribute to a decreased gastric cancer risk. The TGFB1 -509 polymorphism affects certain subtypes of gastric cancer according to clinicopathological parameters. A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles conferred a further decreased gastric cancer risk. These findings provide clues to the biological mechanisms that underline tumor heterogeneity.
| S-EPMC3410591 | biostudies-literature
Project description:MicroRNAs (miRNAs) are small non-coding RNA molecules, which participate in diverse biological processes and may regulate tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to diverse functional consequences, including cancer development, by altering miRNA expression. Numerous studies have shown the association between miRNA SNPs and cancer risk; however, the results are generally debatable and inconclusive, mainly due to limited statistical power. To assess the relationship between the five most common SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs2292832, and miR-27a rs895919) and the risk cancer development, we performed a meta-analysis of 66 published case-control studies. Crude odds ratios at 95% confidence intervals were used to investigate the strength of the association. No association was observed between rs2910164 and cancer risk in the overall group. However, in stratified analysis, we found that either the rs2910164 C allele or the CC genotype was protective against bladder cancer, prostate cancer, cervical cancer, and colorectal cancer, whereas it was a risk factor for papillary thyroid carcinoma and squamous cell carcinoma of the head and neck (SCCHN). Further, rs11614913 was found to be significantly associated with decreased cancer risk, in particular, for bladder cancer, gastric cancer, and SCCHN. For miR-499, a significant association was found between the rs3746444 polymorphism and cancer risk in pooled analysis. In subgroup analysis, similar results were mainly observed for breast cancer. Finally, no association was found between rs2292832 and rs895919 polymorphisms and cancer risk in the overall group and in stratified analysis. In summary, miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 are risk factors for cancer development, whereas mir-149 rs2292832 and miR-27a rs895919 are not associated with cancer risk.
| S-EPMC3835861 | biostudies-literature
Project description:BackgroundThe previous published data on the association between the X-ray repair cross-conplementation group 1 (XRCC1) polymorphisms and thyroid cancer risk remained controversial. Hence, we performed a meta-analysis on all available studies that provided 1729 cases and 3774 controls (from 11 studies) for XRCC1 Arg399Gln, 1040 cases and 2487 controls for Arg194Trp (from 7 studies), and 1432 cases and 3356 controls for Arg280His (from 8 studies).Methodology/principal findingsPubMed, CNKI, and EMBASE database were searched to identify relevant studies. Overall, no significant association was found between XRCC1 Arg399Gln (recessive model: OR = 0.95, 95% CI = 0.77-1.15; dominant model: OR = 0.89, 95% CI = 0.75-1.05; homozygote model: OR = 0.92, 95% CI = 0.69-1.23; Heterozygote model: OR = 0.91, 95% CI = 0.80-1.03; additive model: OR = 0.93, 95% CI = 0.81-1.07), Arg194Trp (recessive model: OR = 1.41, 95% CI = 0.62-3.23; dominant model: OR = 1.01, 95% CI = 0.77-1.34; homozygote model: OR = 1.42, 95% CI = 0.55-3.67; Heterozygote model: OR = 1.03, 95% CI = 0.85-1.26; additive model: OR = 1.08, 95% CI = 0.81-1.42), and Arg280His (recessive model: OR = 1.08, 95% CI = 0.56-2.10; dominant model: OR = 1.01, 95% CI = 0.84-1.22; homozygote model: OR = 1.00, 95% CI = 0.51-1.96; Heterozygote model: OR = 1.04, 95% CI =0.75-1.42; additive model: OR = 1.03, 95% CI = 0.86-1.23) and thyroid cancer risk when all the eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significant association was still not found in these three genetic polymorphisms.Conclusions/significanceIn summary, this meta-analysis indicates that XRCC1 Arg399Gln, Arg280His, and Arg194Trp are not associated with thyroid cancer.
| S-EPMC4161346 | biostudies-literature
Project description:Functional variants in inducible T cell costimulator (ICOS) gene are predicted to be associated with the susceptibility of colorectal cancer (CRC). In this study, we enrolled 2,606 participants (involving 1,003 CRC cases and 1,303 healthy controls) and conducted a case-control study to explore the potential relationship of ICOS rs4404254 T>C and rs10932029 T>C polymorphisms with the risk of CRC. A custom-by-design 48-Plex SNPscan Kit was used to obtain the genotypes of ICOS rs4404254 T>C and rs10932029 T>C variants. We found that ICOS rs10932029 T>C polymorphism was associated with risk of CRC in several subgroups (female subgroup: CC vs. TT: adjusted OR = 6.49, 95% CI 1.36-30.90, P = 0.019 and CC vs. CT/TT: adjusted OR = 6.38, 95% CI 1.34-30.32, P = 0.020; < 61 years subgroup: CC vs. TT: adjusted OR = 4.23, 95% CI 1.10-16.24, P = 0.036 and CC vs. CT/TT: adjusted OR = 4.20, 95% CI 1.10-16.09, P = 0.036; never smoking subgroup: CC vs. TT: adjusted OR = 2.82, 95% CI 1.04-7.64, P = 0.041 and CC vs. CT/TT: adjusted OR = 2.83, 95% CI 1.05-7.66, P = 0.041 and BMI ≥ 24 subgroup: CC vs. TT: adjusted OR = 6.81, 95% CI 1.39-33.30, P = 0.018 and CC vs. CT/TT: adjusted OR = 6.79, 95% CI 1.39-33.11, P = 0.018). In addition, we found that ICOS rs4404254 T>C polymorphism was associated with the susceptibility of CRC in never smoking subgroup (CC/TC vs. TT: adjusted OR = 1.23, 95% CI 1.01-1.51, P = 0.045). In summary, our findings suggest that ICOS rs10932029 T>C and ICOS rs4404254 T>C polymorphisms may be associated with the risk of CRC. In the future, a fine-mapping study with a functional evaluation is needed to explore the relationship between ICOS polymorphisms and the risk of CRC.
| S-EPMC6958277 | biostudies-literature
Project description:BackgroundMutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom syndrome). Thus, genetic variants of BLM and proteins that form complexes with BLM, such as TOP3A and RMI1, might affect cancer risk as well.MethodsIn this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in RMI1, TOP3A, and BLM and their associations with cancer risk in acute myeloid leukemia/myelodysplatic syndromes (AML/MDS; N = 152), malignant melanoma (N = 170), and bladder cancer (N = 61). Two population-based control groups were used (N = 119 and N = 156).ResultsBased on consistency in effect estimates for the three cancer forms and similar allelic frequencies of the variant alleles in the control groups, two SNPs in TOP3A (rs1563634 and rs12945597) and two SNPs in BLM (rs401549 and rs2532105) were selected for analysis in breast cancer cases (N = 200) and a control group recruited from spouses of cancer patients (N = 131). The rs12945597 in TOP3A and rs2532105 in BLM showed increased risk for breast cancer. We then combined all cases (N = 584) and controls (N = 406) respectively and found significantly increased risk for variant carriers of rs1563634 A/G (AG carriers OR = 1.7 [95%CI 1.1-2.6], AA carriers OR = 1.8 [1.2-2.8]), rs12945597 G/A (GA carriers OR = 1.5 [1.1-1.9], AA carriers OR = 1.6 [1.0-2.5]), and rs2532105 C/T (CT+TT carriers OR = 1.8 [1.4-2.5]). Gene-gene interaction analysis suggested an additive effect of carrying more than one risk allele. For the variants of TOP3A, the risk increment was more pronounced for older carriers.ConclusionThese results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk.
| S-EPMC2685436 | biostudies-literature
Project description:Folate has essential roles in DNA synthesis, repair and methylation. Folate metabolism-related gene variants may modulate the levels of this vitamin and affect the cancer risk. Thus, whether these polymorphisms play an important role in carcinogenesis, particularly colorectal cancer (CRC) development, has been a subject interest. The present study investigated the association between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS) and the reduced folate carrier 1 (RFC1) genes and CRC risk. Polymorphisms in MTHFR (677C>T and 1298A>C), TS [1494del6 and the TS enhancer region (TSER)] and RFC1 (-43T>C, 80G>A and 696C>T) were characterized using polymerase chain reaction-restriction fragment length polymorphism in 477 CRC cases and 514 controls. Although no polymorphisms were significantly associated with the CRC risk in the overall sample, significant associations between folate metabolism-related polymorphisms and CRC risk were identified in the stratified analyses. The MTHFR 677CT/1298AC and MTHFR 1298AC+CC/TSER 2R3R genotypes in the presence of plasma folate levels ≤4.12 ng/ml were associated with significantly increased CRC risk. In addition, individuals with the MTHFR 677TT/TSER 3R3R or MTHFR 677/TSER 3R3R/TS 1494 0bp6bp+6bp6bp genotypes and diabetes mellitus (DM) were at an increased risk for CRC. Therefore, the data suggest that i) MTHFR polymorphisms combined with low plasma folate levels and ii) polymorphisms in folate metabolism-related genes combined with metabolic syndrome risk factors (hypertension and DM) increase the odds of developing CRC.
| S-EPMC4471578 | biostudies-literature
Project description:Many studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln, Arg194Trp, Arg280His, -77T>C, and X-ray repair cross-complementing group 3 (XRCC3) T241M polymorphisms with lung cancer risk, but the results remained controversial. Hence, we performed a meta-analysis to investigate the association between lung cancer risk and XRCC1 Arg399Gln (14,156 cases and 16,667 controls from 41 studies), Arg194Trp (7,426 cases and 9,603 controls from 23 studies), Arg280His (6,211 cases and 6,763 controls from 16 studies), -77T>C (2,487 cases and 2,576 controls from 5 studies), and XRCC3 T241M (8,560 cases and 11,557 controls from 19 studies) in different inheritance models. We found that -77T>C polymorphism was associated with increased lung cancer risk (dominant model: odds ration [OR]?=?1.45, 95% confidence interval [CI]?=?1.27-1.66, recessive model: OR?=?1.73, 95% CI?=?1.14-2.62, additive model: OR?=?1.91, 95% CI?=?1.24-1.94) when all the eligible studies were pooled into the meta-analysis. In the stratified and sensitive analyses, significantly decreased lung cancer risk was observed in overall analysis (dominant model: OR?=?0.83, 95% CI?=?0.78-0.89; recessive model: OR?=?0.90, 95% CI?=?0.81-1.00; additive model: OR?=?0.82, 95% CI?=?0.74-0.92), Caucasians (dominant model: OR?=?0.82, 95% CI?=?0.76-0.87; recessive model: OR?=?0.89, 95% CI?=?0.80-0.99; additive model: OR?=?0.81, 95% CI?=?0.73-0.91), and hospital-based controls (dominant model: OR?=?0.81, 95% CI?=?0.76-0.88; recessive model: OR?=?0.89, 95% CI?=?0.79-1.00; additive model: OR?=?0.80, 95% CI?=?0.71-0.90) for XRCC3 T241M. In conclusion, this meta-analysis indicates that XRCC1 -77T>C shows an increased lung cancer risk and XRCC3 T241M polymorphism is associated with decreased lung cancer risk, especially in Caucasians.
| S-EPMC3753326 | biostudies-literature