Browsing by Author "Irmejs, Arvids"

Now showing 1 - 13 of 13
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    BRCA1/2 mutation screening in high-risk breast/ovarian cancer families and sporadic cancer patient surveilling for hidden high-risk families
    (2013-06-14) Berzina, Dace; Nakazawa-Miklasevica, Miki; Zestkova, Jekaterina; Aksenoka, Karina; Irmejs, Arvids; Gardovskis, Andris; Kalniete, Dagnija; Gardovskis, Janis; Miklasevics, Edvins; Onkoloģijas institūts
    Background: The estimated ratio of hereditary breast/ovarian cancer (HBOC) based on family history is 1.5% in Latvia. This is significantly lower than the European average of 5-10%. Molecular markers like mutations and SNPs can help distinguish HBOC patients in the sporadic breast and ovarian cancer group.Methods: 50 patients diagnosed with HBOC in the Latvian Cancer Registry from January 2005 to December 2008 were screened for BRCA1 founder mutation-negatives and subjected to targeted resequencing of BRCA1 and BRCA2 genes. The newly found mutations were screened for in the breast and ovarian cancer group of 1075 patients by Real Time-PCR/HRM analysis and RFLP.Results: Four BRCA2 mutations including three novel BRCA2 frameshift mutations and one previously known BRCA2 frameshift mutation and one BRCA1 splicing mutation were identified. Two of the BRCA2 mutations were found in a group of consecutive breast cancer patients with a frequency of 0.51% and 0.38%.Conclusions: Molecular screening of sequential cancer patients is an important tool to identify HBOC families.
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    Challenges in the management of a patient with Cowden syndrome : Case report and literature review
    (2012-04-14) Melbarde-Gorkuša, Inga; Irmejs, Arvids; Berziņa, Dace; Štrumfa, Ilze; Aboliņš, Arnis; Gardovskis, Andris; Subatniece, Signe; Trofimovičs, Genadijs; Gardovskis, Janis; Miklaševičs, Edvins; Pārmantotā vēža pētniecības nodaļa
    We would like to present a patient with a classical phenotype of a rare disorder - Cowden syndrome, its diagnostics and management challenges. A breast surgeon has to be aware of this rare condition when treating a patient with breast manifestations of Cowden syndrome and has to refer the patient to a clinical geneticist for further evaluation. Sequencing of the PTEN gene showed the Asp24Gly mutation. According to the latest literature data, the lifetime risk of breast cancer for Cowden syndrome patients is 81% and surgery is a justified option to reduce the risk of breast cancer. Bilateral risk-reducing mastectomy with immediate reconstruction was performed to eliminate further risk of breast cancer. 3 years after the risk-reducing breast surgery the patient is satisfied with the outcome. This is to our best knowledge the first reported Cowden syndrome case with follow-up data after risk-reducing measures have been taken.
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    Clinical, molecular and geographical features of hereditary breast/ovarian cancer in Latvia
    (2005-06-15) Gardovskis, Andris; Irmejs, Arvids; Milosevics, Edvins; Borosenko, Viktors; Bitina, Marianna; Melbarde-Gorkusa, Inga; Vanags, Andrejs; Kurzawski, Grzegorz; Suchy, Janina; Górski, Bohdan; Gardovskis, Janis; Department of Surgery
    Introduction. The aim of the study is to evaluate the incidence and phenotype-genotype characteristics of hereditary breast and ovarian cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by this syndrome. Material and methods. In 2002-2004 in two Latvian oncology hospitals (Liepãja Oncology Hospital and Daugavpils Oncology Hospital) cancer family histories were collected from 287 consecutive patients with breast and ovarian cancer. In all cases, when it was possible to obtain the blood sample, DNA testing for founder mutations in the BRCA1 gene was performed. Results. Among 287 family cancer histories analysed in 8 (2.8%) cases criteria of hereditary breast cancer (HBC) were fulfilled and in 5 (1.7%) cases hereditary breast and ovarian cancer (HBOC) was diagnosed. In 50 (17.4%) cases we have suspicion of hereditary breast cancer (HBC susp.) and in 8 (2.8%) cases - suspicion of hereditary breast and ovarian cancer (HBOC susp.). We have one (0.3%) case with hereditary ovarian cancer (HOC). DNA testing of founder mutations in the BRCA1 gene (exon 20 (5382 insC) exon 5 (300T/G), exon 11, 17 (4153delA)) for 178/287 (62%) patients was performed. In 9/287 (4.9%) cases we found a mutation in the BRCA1 gene. 4 mutations were detected in exon 11, 17 (4153delA) and 4 mutations in exon 20 (5382 insC) and 1 in exon 5. Conclusions. Existing pedigree/clinical data suggest that in Latvia the clinical frequency of hereditary breast and ovarian cancer is around 5% of consecutive breast and ovarian cancer patients and suspicion of the syndrome is observed in another 20% of cases. Frequency of BRCA1 founder mutations is 5% of all consecutive breast and ovarian cancers. Considerable geographical differences in the clinical and molecular frequency of hereditary breast ovarian cancer have been observed in Latvia.
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    Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia
    (2015) Serrano-Fernandez, Pablo; Dymerska, Dagmara; Kurzawski, Grzegorz; Derkacz, Róza; Sobieszczańska, Tatiana; Banaszkiewicz, Zbigniew; Roomere, Hanno; Oitmaa, Eneli; Metspalu, Andres; Janavičius, Ramunas; Elsakov, Pavel; Razumas, Mindaugas; Petrulis, Kestutis; Irmejs, Arvids; Miklaševičs, Edvins; Scott, Rodney J.; Lubiński, Jan; Rīga Stradiņš University
    The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC) raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668), already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition. Material and Methods. DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls), Latvia (81 cases and controls), Lithuania (123 cases and controls), and Poland (795 cases and controls). Results. Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (corrected P value = 0.018 for the Estonian, corrected P value = 0.0034 for the Lithuanian, and corrected P value = 0.0076 for the Polish sample). Conclusions. The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers.
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    Discussion on the use of taxanes for treatment of breast cancers in BRCA1 mutations carriers
    (2007-09-15) Irmejs, Arvids; Purkalne, Gunta; Bitina, Marianna; Gardovskis, Andris; Gardovskis, Janis; Onkoloģijas institūts
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    Epidemiologic, clinical, and molecular characteristics of hereditary prostate cancer in Latvia
    (2011) Abele, Andris; Vjaters, Egils; Irmejs, Arvids; Trofimovičs, Genadijs; Miklaševičs, Edvins; Gardovskis, Janis; Onkoloģijas institūts
    Background and Objective. Prostate cancer is one of the most commonly diagnosed malignancy affecting men in Latvia. The aim of this study was to evaluate the epidemiological features and molecular basis of hereditary prostate cancer in Latvia. Material and Methods. A total of 1217 newly diagnosed prostate cancer patients were recruited in our study. Data were analyzed according to clinical diagnostic criteria for hereditary prostate cancer. Molecular testing for the founder mutation 657del5 of the NBS1 gene was performed for the first 280 prostate cancer patients and 173 control cases, and for the founder mutations 300T/G, 4153delA, and 5382insC of the BRCA1 gene for 112 prostate cancer patients with a history of breast or ovarian cancer in their families. Results. Of the 1217 families, 14 (1.2%; 95% CI, 0.7%-1.9%) matched clinical diagnostic criteria for definitive hereditary prostate cancer, and of the 1217 families, 196 (16.1%; 95% CI, 14.1%-18.3%) for suspected hereditary prostate cancer. The founder mutation of the NBS1 gene was detected in 1 (0.4%, 95% CI, 0.1%-2.0%) of the 280 cases in the prostate cancer group and in 1 (0.6%; 95% CI, 0.1%-3.2%) of the 173 cases in the control group. The mutation 5382insC of the BRCA1 gene was detected in 2 (1.8%; 95% CI, 0.5%-6.3%) of the 112 cases analyzed in the prostate cancer group. No other BRCA1 founder mutations were detected. Conclusions. Our study did not reveal predisposition genes for hereditary prostate cancer as the founder mutations of the BRCA1 and NBS1 genes are rarely detected in Latvia, but showed the importance of evaluation risk individually as a positive family history of cancer was associated with the earlier onset of prostate cancer.
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    Genotype-phenotype correlations among BRCA1 4153delA and 5382insC mutation carriers from Latvia
    (2011-10-27) Plakhins, Grigorijs; Irmejs, Arvids; Gardovskis, Andris; Subatniece, Signe; Rozite, Santa; Bitina, Marianna; Keire, Guntars; Purkalne, Gunta; Teibe, Uldis; Trofimovics, Genadijs; Miklasevics, Edvins; Gardovskis, Janis; Pārmantotā vēža pētniecības nodaļa
    Background: Mutations in the high penetrance breast and ovarian cancer susceptibility gene BRCA1 account for a significant percentage of hereditary breast and ovarian cancer cases. Genotype-phenotype correlations of BRCA1 mutations located in different parts of the BRCA1 gene have been described previously; however, phenotypic differences of specific BRCA1 mutations have not yet been fully investigated. In our study, based on the analysis of a population-based series of unselected breast and ovarian cancer cases in Latvia, we show some aspects of the genotype-phenotype correlation among the BRCA1 c.4034delA (4153delA) and c.5266dupC (5382insC) founder mutation carriers.Methods: We investigated the prevalence of the BRCA1 founder mutations c.4034delA and c.5266dupC in a population-based series of unselected breast (n = 2546) and ovarian (n = 795) cancer cases. Among the BRCA1 mutation carriers identified in this analysis we compared the overall survival, age at diagnosis and family histories of breast and ovarian cancers.Results: We have found that the prevalence of breast and ovarian cancer cases (breast: ovarian cancer ratio) differs significantly among the carriers of the c.5266dupC and c.4034delA founder mutations (OR = 2.98, 95%CI = 1.58 to 5.62, P < 0.001). We have also found a difference in the prevalence of breast and ovarian cancer cases among the 1st and 2nd degree relatives of the c.4034delA and c.5266dupC mutation carriers. In addition, among the breast cancer cases the c.4034delA mutation has been associated with a later age of onset and worse clinical outcomes in comparison with the c.5266dupC mutation.Conclusions: Our data suggest that the carriers of the c.4034delA and c.5266dupC founder mutations have different risks of breast and ovarian cancer development, different age of onset and prognosis of breast cancer.
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    High expression of miR-214 is associated with a worse disease-specific survival of the triple-negative breast cancer patients
    (2015-02-08) Kalniete, Dagnija; Nakazawa-Miklaševiča, Miki; Štrumfa, Ilze; Abolinš, Arnis; Irmejs, Arvids; Gardovskis, Janis; Miklaševičs, Edvins; Onkoloģijas institūts; Rīga Stradiņš University
    Background: Hereditary triple-negative breast cancer patients have better recurrence-free survival than triple-negative sporadic ones. High expression of some of the miRNAs is related to worse overall and disease-free survival of triple-negative breast cancer patients. The attempt to associate expression level of some miRNA in triple-negative hereditary and sporadic breast cancers to disease specific survival was performed in this study. Material and methods: Study group was made of 18 triple-negative breast cancer patients harboring the BRCA1 gene mutations and 32 triple-negative sporadic breast cancer patients. Quantitative amount of mir-10b, mir-21, mir-29a, mir-31, and mir-214 by real-time PCR was assessed. The disease-specific survival in relation of high and low levels of some of the miRNAs was analyzed using Log-rank (Mantel-Cox) test. Results: MiR-214 showed significantly higher expression level in sporadic tissues than in hereditary ones (p=0.0005). Triple-negative breast cancer patients with high level of miR-214 showed significantly worse disease-specific survival than patients with low level (p=0.0314). Conclusions: Our finding suggests that miR-214 possibly could be used as a potential prognostic biomarker for triple-negative breast cancer patients.
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    Lifestyle Factors and Breast Cancer in Females with PTEN Hamartoma Tumor Syndrome (PHTS)
    (2024-03) Hendricks, Linda A.J.; Verbeek, Katja C.J.; Schuurs-Hoeijmakers, Janneke H.M.; Mensenkamp, Arjen R.; Brems, Hilde; de Putter, Robin; Anastasiadou, Violetta C.; Villy, Marie Charlotte; Jahn, Arne; Steinke-Lange, Verena; Baldassarri, Margherita; Irmejs, Arvids; de Jong, Mirjam M.; Links, Thera P.; Leter, Edward M.; Bosch, Daniëlle G.M.; Høberg-Vetti, Hildegunn; Tveit Haavind, Marianne; Jørgensen, Kjersti; Mæhle, Lovise; Blatnik, Ana; Brunet, Joan; Darder, Esther; Tham, Emma; Hoogerbrugge, Nicoline; Vos, Janet R.; Onkoloģijas institūts
    Females with PTEN Hamartoma Tumor Syndrome (PHTS) have breast cancer risks up to 76%. This study assessed associations between breast cancer and lifestyle in European female adult PHTS patients. Data were collected via patient questionnaires (July 2020–March 2023) and genetic diagnoses from medical files. Associations between lifestyle and breast cancer were calculated using logistic regression corrected for age. Index patients with breast cancer before PHTS diagnosis (breast cancer index) were excluded for ascertainment bias correction. In total, 125 patients were included who completed the questionnaire at a mean age of 44 years (SD = 13). This included 21 breast cancer indexes (17%) and 39 females who developed breast cancer at 43 years (SD = 9). Breast cancer patients performed about 1.1 times less often 0–1 times/week physical activity than ≥2 times (ORtotal-adj = 0.9 (95%CI 0.3–2.6); consumed daily about 1.2–1.8 times more often ≥1 than 0–1 glasses of alcohol (ORtotal-adj = 1.2 (95%CI 0.4–4.0); ORnon-breastcancer-index-adj = 1.8 (95%CI 0.4–6.9); were about 1.04–1.3 times more often smokers than non-smokers (ORtotal-adj = 1.04 (95%CI 0.4–2.8); ORnon-breastcancer-index-adj = 1.3 (95%CI 0.4–4.2)); and overweight or obesity (72%) was about 1.02–1.3 times less common (ORtotal-adj = 0.98 (95%CI 0.4–2.6); ORnon-breastcancer-index-adj = 0.8 (95%CI 0.3–2.7)). Similar associations between lifestyle and breast cancer are suggested for PHTS and the general population. Despite not being statistically significant, results are clinically relevant and suggest that awareness of the effects of lifestyle on patients’ breast cancer risk is important.
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    Nationwide study of clinical and molecular features of hereditary non-polyposis colorectal cancer (HNPCC) in Latvia
    (2007-01) Irmejs, Arvids; Borosenko, Viktors; Melbarde-Gorkusa, Inga; Gardovskis, Andris; Bitina, Marianna; Kurzawski, Grzegorz; Suchy, Janina; Gorski, Bohdan; Gardovskis, Janis; Onkoloģijas institūts
    Background: The mutational spectrum of mismatch repair (MMR) genes in the Baltic States has been reported to be quite similar to that in Poland; however during a country-wide study considerable differences in the population of Latvia were discovered. This study was undertaken to investigate the clinical and molecular features of HNPCC in Latvia. Materials and Methods: Family cancer histories were collected, from January 2000 until October 2003, for 702 consecutive hospital based colorectal cancer (CRC) cases. In families suspected of having a history consistent with hereditary non-polyposis colorectal cancer (HNPCC), DNA testing for MLH1, MSH2 and MSH6 genes was performed. Immunohistochemical examination of the normal and the cancer tissue from large bowel tumors was undertaken for MSH2 and MSH6 protein expression in 182 out of 702 (26%) of the cases. Results: Among the 702 CRC patients only 1 (0.14%) fulfilled the Amsterdam criteria. Thirteen (1.9%) cases matched the criteria for suspected HNPCC and 10 (1.4%) cases matched the late onset HNPCC criteria. Altogether in 7 out of 702 (1%) cases MMR gene mutations were detected: 2 in MLH1, 3 in MSH2 and 2 in MSH6 gene. Only one out of the seven mutations was registered in the Human Genome Mutation Database and the ICG (International Collaborational Group)-HNPCC mutation data base. Negative MSH2 and MSH6 protein expression was detected in 4 (2.2%) and 18 out of 182 (9.9%) cases respectively. Conclusion: The role of the classical Amsterdam criteria in diagnosing HNPCC in CRC patients from Latvia is very limited and diagnostic criteria for suspected HNPCC are the most effective. The frequency of constitutional mutations within the MMR genes is 1% of all newly diagnosed CRC cases and the spectrum of mutations is potentially characteristic.
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    Pilot study on low penetrance breast and colorectal cancer predisposition markers in Latvia
    (2006-03-15) Irmejs, Arvids; Miklasevics, Edvins; Boroschenko, Viktors; Gardovskis, Andris; Vanags, Andrejs; Melbarde-Gorkusa, Inga; Bitina, Marianna; Suchy, Janina; Gardovskis, Janis; Pārmantotā vēža pētniecības nodaļa
    Introduction: It has not been established whether CHEK2 and NOD2 variants are present in Latvia and whether inherited variation in these genes influences cancer risk in this population. Aim of the study: To evaluate the role of CHEK2 and NOD2 mutations in breast and colorectal cancers in the population of Latvia. Materials and methods: Peripheral venous blood samples were collected from 185 breast cancer and 235 colorectal cancer consecutive hospital-based cases from 11/2003 to 06/2005. The population control group included blood samples from the clamped distal part of the umbilical cord from 978 consecutive anonymous newborns born between 03/2005 and 08/2005. All cases and controls were tested for the presence of NOD2 3020insC mutation and CHEK2 I157T mutation. Results: NOD2 3020insC was present in 7.7% (18/235) of CRC cancers, in 9.2% (17/185) of breast cancers and in 7.7% (75/974) of controls. CHEK2 I157T variant was found in 7.6% (14/185) of breast cancer cases, 10.2% (24/235) of colon cancer cases and in 6.4% (63/978) of population controls. NOD2 3020insC variant was associated with increased risk of breast cancer (OR=2.5, p<0.05) for cases diagnosed at age between 51 and 60 years. CHEK2 I157T variant was associated with increased risk of colorectal cancer (OR=1.7, p<0.05) with the highest OR=2.0 for cases diagnosed at age >70 yrs. Conclusions: NOD2 3020insC and CHEK2 I157T variants may be associated with increased risk of colorectal and breast cancers in Latvia.
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    Platinum-based neoadjuvant chemotherapy in BRCA1-positive breast cancer : A retrospective cohort analysis and literature review
    (2018-04-27) Sæther, Nikolai Havn; Skuja, Elina; Irmejs, Arvids; Maksimenko, Jelena; Miklasevics, Edvins; Purkalne, Gunta; Gardovskis, Janis; Rīga Stradiņš University
    Background: There is increasing evidence of high platinum sensitivity in BRCA-associated breast cancer. However, evidence from randomized trials is lacking. The aim of this study was to analyze the results of platinum-based chemotherapy for BRCA1-positive breast cancer in a neoadjuvant setting. Methods: A retrospective study was performed by obtaining information from patient files. The results were compared with the available data from a literature review. Results: Twelve female patients with BRCA1 gene mutations who had stage I to III breast cancers were eligible for evaluation. They received platinum-based neoadjuvant chemotherapy between 2011 and 2016. Eleven patients received a combination of cisplatin and doxorubicin, and one patient received carboplatin and docetaxel. All patients underwent mastectomy after chemotherapy. Ten patients (83%) achieved pathological complete remission (pCR). The observed pCR rate was comparable to existing results found in similar studies. Conclusion: The results of the study confirm the high pCR rate in BRCA1-positive breast cancer after platinum-based neoadjuvant chemotherapy. Larger randomized studies and longer follow-up times are necessary to evaluate the role of platinum-based therapies in BRCA1-positive breast cancer.