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1.
Single nucleotide polymorphisms as prognostic and predictive factors of adjuvant chemotherapy in colorectal cancer of stages I and II
Matej Horvat, Uroš Potočnik, Katja Repnik, Rajko Kavalar, Borut Štabuc, 2016, pregledni znanstveni članek

Opis: Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant.
Ključne besede: single nucleotide polymorphism, colorectal cancer, adjuvant chemotherapy
Objavljeno: 14.06.2017; Ogledov: 354; Prenosov: 220
.pdf Celotno besedilo (1,27 MB)
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2.
Polymorphism of the IL13 gene may be associated with uterine leiomyomas in Slovenian women
Jovan Krsteski, Staša Jurgec, Maja Pakiž, Igor But, Uroš Potočnik, 2016, izvirni znanstveni članek

Opis: Uterine leiomyomas (ULM) are a common cause of solid pelvic tumors in women. Their etiopathogenesis remains unclear. Interleukins (ILs) and their receptors can influence tumor biology of ULM. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) exhibited in the genes IL4 (rs2070874), IL4R (rs1801275), IL12RB1 (rs11575934), IL12B (rs6887695), IL13 (rs20541) and IL23R (rs7517847) as risk factors for ULM in Slovenian women and to identify associations between corresponding clinical parameters and the analyzed SNPs. In addition, solitary and multiple ULM were compared to identify clinical and/or genetic parameters influencing their occurrence. We conducted a case-control study that included 181 women with leiomyomas and 133 control subjects. Genotyping of selected SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and high resolution melting (HRM) techniques. The TT genotype of rs20541 (IL13) was significantly associated with decreased risk of ULM compared to both the CC and CT genotypes [p = 0.018; odds ratio (OR) = 0.184; 95% confidence interval (95% CI) = 0.048-0.7121. Using genetic and clinical data to develop a predictive model with logistic regression, we found that adenomyosis, higher age at diagnosis, family history of ULM occurrence, earlier menarche, lower number of pregnancies and lower age at first sexual intercourse, the G allele and genotypes AG and GG of rs1801275 (IL4R) were associated with an increased risk of multiple ULM occurrence. We also found an association between rs20541 (IL13) and 17ß-estradiol serum levels in patients with multiple ULM (p 0.003). Our study showed, for the first time, that rs20541 (IL13) may contribute to susceptibility of ULM development and that rs1801275 (IL4R) can predispose patients to develop multiple ULM.
Ključne besede: genetic risk, uterine leiomyomas, ULM, single nucleotide polymorphism (SNP), IL13 gene
Objavljeno: 30.03.2017; Ogledov: 532; Prenosov: 205
.pdf Celotno besedilo (478,01 KB)
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3.
Single nucleotide polymorphisms in genes MACC1, RAD18, MMP7 and SDF-1[alpha] as prognostic factors in resectable colorectal cancer
Matej Horvat, Uroš Potočnik, Katja Repnik, Rajko Kavalar, Vesna Zadnik, Stojan Potrč, Borut Štabuc, 2016, izvirni znanstveni članek

Opis: Background: Colorectal cancer (CRC) represents one of the most common malignancies worldwide. Research has indicated that functional gene changes such as single nucleotide polymorphism (SNP) influence carcinogenesis and metastasis and might have an influence on disease relapse. The aim of our study was to evaluate the role of SNPs in selected genes as prognostic markers in resectable CRC. Patients and methods: In total, 163 consecutive patients treated surgically for CRC of stages I, II and III at the University Medical Centre in Maribor in 2007 and 2008 were investigated. DNA was isolated from formalin-fixed paraffin-embedded CRC tissue from the Department of Pathology and SNPs in genes SDF-1alpha, MMP7, RAD18 and MACC1 were genotyped using polymerase chain reaction followed by high resolution melting curve analysis or restriction fragment length polymorphism. Results: We found worse disease-free survival (DFS) for patients with TT genotype of SNP rs1990172 in gene MACC1 (p = 0.029). Next, we found worse DFS for patients with GG genotype for SNP rs373572 in gene RAD18 (p = 0.020). Higher frequency of genotype GG of MMP7 SNP rs11568818 was found in patients with T3/T4 stage (p = 0.014), N1/N2 stage (p = 0.041) and with lymphovascular invasion (p = 0.018). For MACC1 rs1990172 SNP we found higher frequency of genotype TT in patients with T3/T4 staging (p = 0.024). Higher frequency of genotype GG of RAD18 rs373572 was also found in patients with T1/T2 stage with disease relapse (p = 0.041). Conclusions: Our results indicate the role of SNPs as prognostic factors in resectable CRC.
Ključne besede: single nucleotide polymorphism, colorectal cancer, MACC1, RAD18, MMP7, SDF-1a
Objavljeno: 05.04.2017; Ogledov: 356; Prenosov: 52
.pdf Celotno besedilo (698,90 KB)
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