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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

Cumulative effect of unfavorable genotypes ofACLYgene. Effect on overall (A) and recurrence-free (B) survival of survival in CRC patients with advanced diseases analyzed by Kaplan–Meier curves.
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Fig2: Cumulative effect of unfavorable genotypes ofACLYgene. Effect on overall (A) and recurrence-free (B) survival of survival in CRC patients with advanced diseases analyzed by Kaplan–Meier curves.

Mentions: To further assess the cumulative effects of genetic variants on CRC overall survival in patients with advanced diseases, we did a joint analysis by including the two SNPs showing a significant association in single-SNP analysis (Table 2). The unfavorable genotypes were defined as the homozygous wild-type (WW) for both rs2304497 and rs9912300. When using group 1 (with zero unfavorable genotype) as reference, CRC patients in group 3 (with two unfavorable genotype) had a 2.24-fold increase of death (95% CI = 1.15–4.36; P = 0.17). A significant dose–response trend was observed (P for trend = 0.012) (Table 3). Furthermore, the risk of recurrence increased with the increasing number of unfavorable genotype (P for trend = 0.003). Kaplan–Meier analysis showed that there was a significantly decreased OS and RFS in patients carrying two unfavorable genotypes, compared with those carrying zero unfavorable genotype (log-rank P = 0.05 and P = 0.02, respectively, Figure 2A, B). We performed a stratified analysis to assess the effects of genetic variants on OS and RFS in patients with/without chemotherapy (Additional file 1: Table S1). No statistical significance was observed for SNP rs2304497 and rs9912300 in both subgroups. These results suggested that there might be no modifying effect of chemotherapy on the prognostic significance of both SNPs.Table 3


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)

Cumulative effect of unfavorable genotypes ofACLYgene. Effect on overall (A) and recurrence-free (B) survival of survival in CRC patients with advanced diseases analyzed by Kaplan–Meier curves.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Cumulative effect of unfavorable genotypes ofACLYgene. Effect on overall (A) and recurrence-free (B) survival of survival in CRC patients with advanced diseases analyzed by Kaplan–Meier curves.
Mentions: To further assess the cumulative effects of genetic variants on CRC overall survival in patients with advanced diseases, we did a joint analysis by including the two SNPs showing a significant association in single-SNP analysis (Table 2). The unfavorable genotypes were defined as the homozygous wild-type (WW) for both rs2304497 and rs9912300. When using group 1 (with zero unfavorable genotype) as reference, CRC patients in group 3 (with two unfavorable genotype) had a 2.24-fold increase of death (95% CI = 1.15–4.36; P = 0.17). A significant dose–response trend was observed (P for trend = 0.012) (Table 3). Furthermore, the risk of recurrence increased with the increasing number of unfavorable genotype (P for trend = 0.003). Kaplan–Meier analysis showed that there was a significantly decreased OS and RFS in patients carrying two unfavorable genotypes, compared with those carrying zero unfavorable genotype (log-rank P = 0.05 and P = 0.02, respectively, Figure 2A, B). We performed a stratified analysis to assess the effects of genetic variants on OS and RFS in patients with/without chemotherapy (Additional file 1: Table S1). No statistical significance was observed for SNP rs2304497 and rs9912300 in both subgroups. These results suggested that there might be no modifying effect of chemotherapy on the prognostic significance of both SNPs.Table 3

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