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Functional polymorphisms of ATP citrate lyase gene predicts clinical outcome of patients with advanced colorectal cancer.

Xie S, Zhou F, Wang J, Cao H, Chen Y, Liu X, Zhang Z, Dai J, He X - World J Surg Oncol (2015)

Bottom Line: Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS).Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively).The SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 169 West Changle Street, Xi'an, 710032, China. 58142293@qq.com.

ABSTRACT

Background: Previous studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers. Our current study aims to assess the effects of functional single nucleotide polymorphisms (SNPs) in ACLY gene on recurrence and survival of colorectal cancer (CRC) patients.

Methods: A total of 697 resected Chinese CRC patients were included in this study. Two functional single nucleotide polymorphisms in ACLY gene were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis.

Results: Multivariate Cox regression analysis showed that there was no significant association between SNPs in ACLY gene and the prognosis of total patient cohort. However, in patients with stage III + IV diseases, the two functional SNPs (rs2304497 and rs9912300) exhibited a significant association with the risks of death (HR = 0.47, 95% CI = 0.24-0.90 and HR = 0.59, 95% CI = 0.37-0.92, respectively) and recurrence (HR = 0.46, 95% CI = 0.24-0.86 and HR = 0.54, CI = 0.35-0.83, respectively). Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS). Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively). Compared with patients carrying zero unfavorable genotype, those carrying two unfavorable genotypes had a 2.24-fold and 2.33-fold increase of death and recurrence risks, respectively.

Conclusions: The SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.

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Related in: MedlinePlus

Kaplan-Meier curves of overall and recurrence-free survival. CRC patients with advanced stage diseases (A–D) and early stage diseases (E–H).
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Fig1: Kaplan-Meier curves of overall and recurrence-free survival. CRC patients with advanced stage diseases (A–D) and early stage diseases (E–H).

Mentions: We assessed the effect of two SNPs in ACLY gene on the death and recurrence in CRC patients using the multivariate Cox regression model (Table 2). After adjusting for gender, age, hospital site, tumor position, TNM stage, tumor differentiation, and treatment after surgery, no significant association was observed between SNPs and CRC patient outcomes. To further evaluate the modifying effect of host characteristics on association of SNPs in ACLY gene with the prognosis, we performed a stratified analysis in patients with early stage and advanced stage tumor. We found that in patients with advanced stage tumor (stage III + IV), the heterozygous variant (WV) and homozygous variant (VV) genotypes in both rs2304497 and rs9912300 reduced the death risk of CRC in the dominant model (HR = 0.47, 95% CI = 0.24–0.90 and HR = 0.59, 95% CI = 0.37–0.92, respectively). They also exhibited significant associations with recurrence risk (HR = 0.46; 95% CI = 0.24–0.86 and HR = 0.54; CI = 0.35–0.83, respectively). Kaplan-Meier analysis showed similar results, indicating that CRC patients with advanced stage carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better OS and RFS than those with corresponding homozygous wild-type (WW) genotype (Figure 1A–D).Table 2


Functional polymorphisms of ATP citrate lyase gene predicts clinical outcome of patients with advanced colorectal cancer.

Xie S, Zhou F, Wang J, Cao H, Chen Y, Liu X, Zhang Z, Dai J, He X - World J Surg Oncol (2015)

Kaplan-Meier curves of overall and recurrence-free survival. CRC patients with advanced stage diseases (A–D) and early stage diseases (E–H).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359538&req=5

Fig1: Kaplan-Meier curves of overall and recurrence-free survival. CRC patients with advanced stage diseases (A–D) and early stage diseases (E–H).
Mentions: We assessed the effect of two SNPs in ACLY gene on the death and recurrence in CRC patients using the multivariate Cox regression model (Table 2). After adjusting for gender, age, hospital site, tumor position, TNM stage, tumor differentiation, and treatment after surgery, no significant association was observed between SNPs and CRC patient outcomes. To further evaluate the modifying effect of host characteristics on association of SNPs in ACLY gene with the prognosis, we performed a stratified analysis in patients with early stage and advanced stage tumor. We found that in patients with advanced stage tumor (stage III + IV), the heterozygous variant (WV) and homozygous variant (VV) genotypes in both rs2304497 and rs9912300 reduced the death risk of CRC in the dominant model (HR = 0.47, 95% CI = 0.24–0.90 and HR = 0.59, 95% CI = 0.37–0.92, respectively). They also exhibited significant associations with recurrence risk (HR = 0.46; 95% CI = 0.24–0.86 and HR = 0.54; CI = 0.35–0.83, respectively). Kaplan-Meier analysis showed similar results, indicating that CRC patients with advanced stage carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better OS and RFS than those with corresponding homozygous wild-type (WW) genotype (Figure 1A–D).Table 2

Bottom Line: Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS).Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively).The SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 169 West Changle Street, Xi'an, 710032, China. 58142293@qq.com.

ABSTRACT

Background: Previous studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers. Our current study aims to assess the effects of functional single nucleotide polymorphisms (SNPs) in ACLY gene on recurrence and survival of colorectal cancer (CRC) patients.

Methods: A total of 697 resected Chinese CRC patients were included in this study. Two functional single nucleotide polymorphisms in ACLY gene were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis.

Results: Multivariate Cox regression analysis showed that there was no significant association between SNPs in ACLY gene and the prognosis of total patient cohort. However, in patients with stage III + IV diseases, the two functional SNPs (rs2304497 and rs9912300) exhibited a significant association with the risks of death (HR = 0.47, 95% CI = 0.24-0.90 and HR = 0.59, 95% CI = 0.37-0.92, respectively) and recurrence (HR = 0.46, 95% CI = 0.24-0.86 and HR = 0.54, CI = 0.35-0.83, respectively). Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS). Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively). Compared with patients carrying zero unfavorable genotype, those carrying two unfavorable genotypes had a 2.24-fold and 2.33-fold increase of death and recurrence risks, respectively.

Conclusions: The SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.

Show MeSH
Related in: MedlinePlus