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Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma.

ABSTRACT: Genetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single-nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case-control, candidate gene association study of 370 CCA patients and 740 age-, sex-, and residential area-matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log-additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log-rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX-2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX-2 has been shown to contribute to cholangiocarcinogenesis, the COX-2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival.

SUBMITTER: Chaiteerakij R

PROVIDER: S-EPMC4618630 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma.

Chaiteerakij Roongruedee R Juran Brian D BD Aboelsoud Mohammed M MM Harmsen William S WS Moser Catherine D CD Giama Nasra H NH Allotey Loretta K LK Mettler Teresa A TA Baichoo Esha E Zhang Xiaodan X Therneau Terry M TM Lazaridis Konstantinos N KN Roberts Lewis R LR

Cancer medicine 20150815 10

Genetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single-nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case-control, candidate gene association study of 370 CCA patients and 740 age-, sex-, and residential area-matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log-additive genotype effects of SNPs on CCA risk ...[more]

PMID: 26276523

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Project description:BACKGROUND:Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy. METHODS:SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan-Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS. RESULTS:The CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p?=?0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p?=?0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p?=?0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p?=?0.006 and p?=?0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p?=?0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p?=?0.02). However, there was no significant association between the SNPs and 5-year RFS. CONCLUSIONS:Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.

Dataset Information

Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma.

Publications

Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma.

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