Genetic variant of <i>PRKAA1</i> and gastric cancer risk in an eastern Chinese population

Qiu, Li Xin; He, Jing; Cheng, Lei; Zhou, Fei; Wang, Mengyun; Sun, Meng; Zhou, Xiao Yan; Li, Jin; Guo, Wei; Wang, Ya Nong; Yang, Ya; Wang, Jiu Cun; Zhu, Xiao Dong; Wei, Qing

doi:10.18632/oncotarget.6124

Cited by 19 publications

(32 citation statements)

References 32 publications

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“…On chromosome 5p13 all GC associated variants were in high LD ( r 2 > 0.8) to the most associated marker (rs6872282) and in high LD ( r 2 > 0.8) to all risk SNPs previously reported at this locus in Asians and Europeans . Thus, together with previous findings, our data provide evidence that one or more of these SNPs represent(s) the true GC conferring variant(s) in both the Asian and European population.…”

Section: Discussionsupporting

confidence: 82%

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

et al. 2018

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Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine‐mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 × 10−04) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10−09). On chromosome 5p13 we found cis‐eQTL effects with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 × 10−11). On chromosome 8q24 we observed cis‐eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 × 10−47). In addition, we found trans‐eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 × 10−09). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk‐conferring GC pathomechanisms.

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Section: Discussionsupporting

confidence: 82%

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

et al. 2018

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“…Genetic polymorphisms in protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) are significantly associated with gastric cancer, according to genome-wide association study (GWAS) performed in Asians [14]. Identical associations were indicated in our previous study [15] and in several other studies performed in Korean and Chinese populations [16][17][18][19], and were reconfirmed in a recent GWAS performed with a European populations [20]. Although the definitive role of PRKAA1 has not yet been identified, 5′-AMP-activated protein kinase (AMPK) encoded by PRKAA1 can play a significant role in carcinogenesis, as it is involved in energy metabolism, cell cycle regulation, cell proliferation, and rapamycinpathway inhibition [21][22][23].…”

Section: Introductionmentioning

confidence: 80%

“…Quality and quantity requirements for genotyping DNA samples were determined by identifying intact DNA bands after 2% agarose gel electrophoresis, and their concentrations were measured at >20 ng/ μ L with a degree of purity >1.7. Genotype analysis was performed for the five single‐nucleotide polymorphisms (SNPs; rs10074991, rs13361707, rs154268, rs3805486, and rs6882903) associated with PRKAA1 using a GoldenGate assay (Illumina, San Diego, CA, USA). The call rates for the examined samples and SNPs were 100%, with all five SNPs meeting the Hardy–Weinberg equilibrium in the control group.…”

Section: Methodsmentioning

confidence: 99%

“…PRKAA1-related mechanisms associated with gastric carcinogenesis remain unknown. However, several studies consistently reported associations between PRKAA1 rs13361707 and gastric cancer [14,15,[17][18][19][20]. Additionally, a recent meta-analysis concerning PRKAA1 polymorphisms found that the PRKAA1 rs13361707 C allele was strongly associated with risk of noncardia gastric cancer [28].…”

Section: Nod2)mentioning

confidence: 99%

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Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans

et al. 2016

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Although several studies reported genetic polymorphisms in protein kinase AMP‐activated alpha 1 catalytic subunit (PRKAA1) and their associations with gastric cancer risk, few have evaluated associations between Helicobacter pylori infection and PRKAA1 gene‐environment interactions. Here, we evaluated the effects of interactions between H. pylori infection and PRKAA1 polymorphisms on gastric cancer risk in Koreans. In this hospital‐based case–control study, PRKAA1 genotypes were analyzed and H. pylori infection and CagA status were examined using a serologic method in 846 pairs of gastric cancer patients and controls matched for age and sex. H. pylori seropositivity was associated with a 1.43‐fold [95% confidence interval: 1.12–1.81] increase in the risk of gastric cancer, and CagA low‐positive titers during H. pylori infection increased the risk by 1.85‐fold (95% confidence interval, 1.38–2.48). Significant positive interaction between the PRKAA1 rs13361707 genotype and H. pylori infection was verified on an additive scale [relative excess risk due to interaction, 0.55; 95% confidence interval, 0.05–1.04; P = 0.030], and the gene‐environment interaction between PRKAA1 rs13361707 and CagA status was also statistically significant (relative excess risk due to interaction, 0.50; 95% confidence interval, 0.30–0.70; P < 0.001). Our results indicated that H. pylori infection, CagA status, and PRKAA1 polymorphisms were risk factors for gastric cancer in Koreans, and that the combination of two of these factors rather than their independent effects synergistically increased the risk.

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“…The DNA purity and concentrations were determined by spectrophotometer measurement of absorbance at 260 and 280 nm. Primers and probes were supplied by Applied Biosystems with four negative controls (without DNA template) and two duplicated samples included in each 384-plate for the quality control [ 35 ]. The assays were repeated for 5% of the samples, and the results were 100% concordant.…”

Section: Methodsmentioning

confidence: 99%

Genetic variants ofGADD45A, GADD45BandMAPK14predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer

et al. 2016

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The JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings.

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Genetic variant of PRKAA1 and gastric cancer risk in an eastern Chinese population

Cited by 19 publications

References 32 publications

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans

Genetic variants ofGADD45A, GADD45BandMAPK14predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer

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