KCNB1 GENE POLYMORPHISMS AND RELATED INDEL AS PREDICTOR BIOMARKERS OF TREATMENT RESPONSE FOR COLORECTAL CANCER – TOWARD A PERSONALIZED MEDICINE
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Date
2020-06
Authors
Barbirou, Mouadh
Sghaier, Ikram
Bedoui, Sinda
Ben Abderrazek, Rahma
Kraiem, Hazar
Farah, Azer
Hassiki, Rym
Mokrani, Amina
Mezlini, Amel
Almawi, Wassim Y
Journal Title
Journal ISSN
Volume Title
Publisher
International Society of Oncology and BioMarkers
Abstract
The KCNB1 gene variants were differentially associated with cancers. However, their association with colorectal cancer
has not yet been explored. We investigated the contribution of the KCNB1 gene variants rs3331, rs1051295, and indel
(insertion/deletion) rs11468831 Polymorphism as predictors of the treatment response in colorectal cancer patients. A
retrospective study, which involved 291 Tunisian colorectal cancer patients (aged 60.0 6 13.1 years), who were stratified into responder and non-responder groups, according to TNM stages and their responsiveness to chemotherapy
based on fluorouracil. KCNB1 genotyping was performed with amplification-refractory mutation system–polymerase
chain reaction, and was confirmed by Sanger sequencing. Sex-specific response was found and colorectal cancer females
are less likely to achieve a positive response during the chemotherapy strategy, compared to males. Weight and body
mass index, tumor size, and tumor localization are considered as predictive factors to treatment responsiveness.
Carriage of rs11468831 Ins allele was significantly associated with successful therapy achievement (p adjusted\ 0.001).
Stratification of colorectal cancer patients’ response according to tumor localization and TNM stages reveals negative
association of rs3331 Major allele to treatment response among the patients with advanced cancer stages (subgroup
G2). The presence of rs3331 (homozygous minor) C/C genotype was positively associated with decline in carcinoembryonic antigen (p = 0.043) and CA19-9 (p = 0.014) serum levels. On the other hand, the presence of rs1051295
(homozygous minor) A/A genotype was correlated with marked decline in CA19-9 serum levels. KCNB1 haplotype did
not reveal any association between haplotypes and treatment response. The results obtained suggest that gender-specific
strategies for screening treatment and prevention protocols as well as KCNB1 variants may constitute an effective model
for ongoing personalization medicine.
Description
Keywords
CA19-9, CEA, gender, TNM stages, colorectal cancer, KCNB1, personalized medicine, treatment response, Research Subject Categories::MEDICINE
Citation
Barbirou, M., Sghaier, I., Bedoui, S., Ben Abderrazek, R., Kraiem, H., Farah, A., Hassiki, R., Mokrani, A., Mezlini, A., Almawi, W. Y., Loueslati-Yacoubi, B., & Bouhaouala-Zahar, B. (2020). KCNB1 gene polymorphisms and related indel as predictor biomarkers of treatment response for colorectal cancer – toward a personalized medicine. Tumor Biology, 42(6), 101042832092523. https://doi.org/10.1177/1010428320925237