A genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk

He, Meian; Wu, Chen; Xu, Jianfeng; Guo, Huan; Yang, Handong; Zhang, Xiaomin; Sun, Jielin; Yu, Dianke; Zhou, Li; Peng, Tao; He, Ying; Gao, Yong; Yuan, Jing; Deng, Qifei; Dai, Xiayun; Tan, Aihua; Feng, Yingying; Zhang, Haiying; Min, Xinwen; Yang, Xiaobo; Zhu, Jiang; Zhai, Kan; Chang, Jiang; Qin, Xue; Tan, Wen; Hu, Yanling; Lang, Mingjian; Tao, Sha; Li, Yuanfeng; Li, Yang; Feng, Junjie; Li, Dongfeng; Kim, Seong-Tae; Zhang, Shijun; Zhang, Hongxing; Zheng, S. Lilly; Gui, Lixuan; Wang, Youjie; Wei, Sheng; Wang, Feng; Fang, Weili; Liang, Yuan; Zhai, Yun; Chen, Weihong; Miao, Xiaoping; Zhou, Gangqiao; Hu, Frank B.; Lin, Dong; Mo, Zengnan; Wu, Tangchun

doi:10.1136/gutjnl-2012-303434

Cited by 71 publications

(71 citation statements)

References 44 publications

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“…Out of these 17 SNPs, four SNPs were also trait-associated SNPs in the Asian population, which was significantly enriched in the Han Chinese eQTLs (p=0.0009) (see online supplementary table S3). Examples here included rs12506899 located in the α-fetoprotein gene ( AFP ), that was significantly associated with the cancer antigen 19-9 (CA19-9) in a GWAS conducted in a Han Chinese population 22. In our data this SNP was significantly associated with AFP gene expression (p=1.42×10 −10 ).…”

Section: Resultsmentioning

confidence: 55%

Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population

et al. 2014

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BackgroundElucidating the genetic basis underlying hepatic gene expression variability is of importance to understand the aetiology of the disease and variation in drug metabolism. To date, no genome-wide expression quantitative trait loci (eQTLs) analysis has been conducted in the Han Chinese population, the largest ethnic group in the world.MethodsWe performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue samples (n=64). The data were then compared with published eQTL data from a Caucasian population. We then performed correlations between these eQTLs with important pharmacogenes, and genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs), in particular those identified in the Asian population.ResultsOur analyses identified 1669 significant eQTLs (false discovery rate (FDR) < 0.05). We found that 41% of Asian eQTLs were also eQTLs in Caucasians at the genome-wide significance level (p=10−8). Both cis- and trans-eQTLs in the Asian population were also more likely to be eQTLs in Caucasians (p<10−4). Enrichment analyses revealed that trait-associated GWAS-SNPs were enriched within the eQTLs identified in our data, so were the GWAS-SNPs specifically identified in Asian populations in a separate analysis (p<0.001 for both). We also found that hepatic expression of very important pharmacogenetic (VIP) genes (n=44) and a manually curated list of major genes involved in pharmacokinetics (n=341) were both more likely to be controlled by eQTLs (p<0.002 for both).ConclusionsOur study provided, for the first time, a comprehensive hepatic eQTL analysis in a non-European population, further generating valuable data for characterising the genetic basis of human diseases and pharmacogenetic traits.

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Section: Resultsmentioning

confidence: 55%

Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population

et al. 2014

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“…Therefore, this study was conducted in two phases: at phase one, a genome-wide association study was conducted to identify the loci associated with the serum level of CEA in healthy Chinese men from a cohort that participated in the Fangchenggang Area Male Health and Examination Survey (FAMHES) (this part has been merged with other cohorts and partly published elsewhere [10], [11]). At phase two, the association between candidate SNPs found from phase one GWAS and preoperative CEA levels and prognosis of patients with CRC was analyzed.…”

Section: Introductionmentioning

confidence: 99%

Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China

et al. 2014

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BackgroundSerum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications.Methods and FindingsGenome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023).ConclusionsWe found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China.

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“…These genotypes were recently shown to strongly affect CA19-9 levels in PSC patients and influence the diagnostic performance of CA19-9. 7 Although two recent GWAS have reported an association between FUT2 and CEA, 9,17 in this study we have shown for the first time that this association is clinically relevant and that it positively influences the diagnostic performance of CEA. Our results showed that CEA levels increased with the number of A alleles in the case of the rs601338 variant of FUT2.…”

Section: Discussionmentioning

confidence: 87%

“…8 A recent genome-wide association study (GWAS) revealed an association between serum CEA levels and genes for fucosyltransferases and AB0 blood group. 9 The enzymes FUT2 and FUT3 are capable of catalyzing the fucosylation of glycoproteins. Both enzymes are known for their importance in synthesizing CA19-9.…”

Section: Introductionmentioning

confidence: 99%

A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis

et al. 2016

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Background: Primary sclerosing cholangitis (PSC) patients are at increased risk of biliary tract cancer, and carcinoembryonic antigen (CEA) serum levels might be used for screening. Objective: To examine cancer screening with CEA in PSC patients and analyse how serum CEA levels are affected by genetic variants of fucosyltransferase (FUT) 2 and 3. Methods: In a retrospective cohort analysis we evaluated CEA levels in 226 PSC patients, including 19 with biliary malignancy, and investigated how FUT2 and FUT3 SNPs affected CEA levels. Receiver-operating-characteristic (ROC) analysis was performed and cut-off values were determined based on Youden's index. A control cohort contained 240 patients, including 28 with biliary malignancy. Results: Median CEA concentration was lower in cancer-free patients (1.4 ng/mL) than in cancer patients (2.0 ng/mL, P ¼ 0.014). ROC analysis revealed an area under the curve (AUC) of 0.671, the optimal cut-off was 3.2 ng/mL. The FUT2 variant rs601338 (G428A) correlated with CEA levels, and the effect was most prominent in a subgroup of patients genetically incapable of expressing CA19-9. The AUC improved if ROC analysis was performed separately for wild-type (AUC: 0.731) and homozygous mutant (AUC: 0.816) G428A. The influence of FUT2 on CEA was confirmed in the control cohort. Conclusions: CEA is interesting for biliary-malignancy screening in PSC patients, especially in patients who do not express CA19-9. This is the first study to show that the combined use of CEA measurement and FUT genotyping is clinically beneficial and that it might enhance the early detection of biliary malignancy in clinical practice. This approach could also be effective when screening for other common gastrointestinal malignancies.

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A genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk

Abstract: This study identified several loci associated with CA19-9, CEA and AFP concentrations. The ABO variants were associated with risk of OSCC and pancreatic cancers and AFP variants with risk of hepatocellular cancer.

Cited by 71 publications

References 44 publications

Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population

Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population

Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China

A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis

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