Short article: Influence of regulatory NLRC5 variants on colorectal cancer survival and 5-fluorouracil-based chemotherapy.
Eur J Gastroenterol Hepatol
; 30(8): 838-842, 2018 08.
Article
in En
| MEDLINE
| ID: mdl-29762254
BACKGROUND: NLRC5 is an interferon γ-inducible protein, which plays a role in immune surveillance with a potential influence on cancer survival. OBJECTIVE: We aimed to evaluate the effect of potential regulatory variants in NLRC5 on overall survival and survival after 5-fluorouracil (5-FU)-based therapy of colorectal cancer (CRC) patients. PATIENTS AND METHODS: We carried out a case-only study in a Czech population of 589 cases; 232 received 5-FU-based therapy. Eleven variants within NLRC5 were selected using in-silico tools. Associations between polymorphisms and survival were assessed by Cox regression analysis adjusting for age at diagnosis, sex, and TNM stage. Survival curves were derived using the Kaplan-Meier method. RESULTS: Two variants showed a significant association with survival. All patients and metastasis-free patients at the time of diagnosis (pM0) who were homozygous carriers of the minor allele of rs27194 had a decreased overall survival (OSall and OSpM0) and event-free survival (EFSpM0) under a recessive model (OSall P=0.003, OSpM0 P=0.005, EFSpM0 P=0.01, respectively). OS was also decreased for all patients and for pM0 patients who carried at least one minor allele of rs289747 (OSall P=0.03 and OSpM0 P=0.003, respectively). Among CRC patients, who underwent a 5-FU-based adjuvant regimen, rs12445252 was associated with OSall, OSpM0 and EFSpM0, according to the dosage of the minor allele T (OSall P=0.0004, OSpM0 P=0.0001, EFSpM0 P=0.008, respectively). CONCLUSION: Our results showed that polymorphisms in NLRC5 may be used as prognostic markers of survival of CRC patients, as well as for survival in response to 5-FU treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
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Antineoplastic Combined Chemotherapy Protocols
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Biomarkers, Tumor
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Polymorphism, Single Nucleotide
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Intracellular Signaling Peptides and Proteins
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Fluorouracil
Type of study:
Etiology_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
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Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Eur J Gastroenterol Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2018
Document type:
Article
Country of publication:
United kingdom