Publications by authors named "Oleg Oszurek"

19 Publications

  • Page 1 of 1

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

Clin Cancer Res 2020 10 17;26(20):5411-5423. Epub 2020 Jun 17.

Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.

Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.

Experimental Design: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting.

Results: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations.

Conclusions: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-0103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572656PMC
October 2020

Serum selenium level and cancer risk: a nested case-control study.

Hered Cancer Clin Pract 2019 23;17:33. Epub 2019 Dec 23.

3Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.

Background: Epidemiologic studies have demonstrated a relationship between selenium status and cancer risk among those with low selenium levels. It is of interest to prospectively evaluate the relationship between selenium and cancer among women who reside in a region with ubiquitously low selenium levels.

Methods: We performed a nested case-control study of baseline serum selenium levels and cancer risk using data and biological samples from 19,573 females that were participants in a biobanking initiative between 2010 and 2014 in Szczecin Poland. Cases included women with any incident cancer ( = 97) and controls ( = 184) were women with no cancer at baseline or follow-up. Serum selenium was quantified using mass spectroscopy.

Results: The odds ratio associated being below the cutoff of 70.0 μg/L compared to a level above 70.0 μg/L was 2.29 (95% CI 1.26-4.19;  = 0.007). The risks for women in the two middle categories were similar and suggests that the normal range be between 70 μg/L and 90 μg/L. There was evidence for an increased risk of cancer among women in the highest category of selenium levels (i.e., > 90 μg/L), but this association did not achieve statistical significance (OR = 1.63; 95%CI 0.63-4.19;  = 0.31).

Conclusions: Results from this study suggest that suggest that the optimum serum level of selenium in women living in Poland should be between 70 μg/L and 90 μg/L.
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http://dx.doi.org/10.1186/s13053-019-0131-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929308PMC
December 2019

Blood arsenic levels and the risk of familial breast cancer in Poland.

Int J Cancer 2020 05 26;146(10):2721-2727. Epub 2019 Aug 26.

Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

Arsenic is recognized as a potent carcinogen at high concentrations, but the relationship between environmental arsenic and breast cancer risk has not well been studied. Most research has focused on the effect of arsenic in populations with high endemic exposure, and not in populations with arsenic levels within normal limits. We sought to determine if blood arsenic levels predict the risk of breast and other cancers risk among women in northern Poland. The cohort consisted of 1,702 healthy women, aged 40 and above, identified between 2010 and 2017. Blood arsenic level was determined by inductively coupled plasma mass spectrometry. After an average of 4.5 years of follow-up (range 0.7-7.3 years), there were 110 incident cases of cancer diagnosed in the cohort, including 68 cases of breast cancer. Women in the highest quartile of arsenic had a highly significant 13-fold increased risk of developing breast cancer, compared to women in the lowest quartile (hazard ratio [HR] = 13.2; 95% confidence interval [CI] 4.02-43.0). Results were similar for arsenic and all incident cancers (HR quartile 4 vs. quartile 1 = 13.3; 95% CI 4.78-37.0). If confirmed, our study suggests that the blood arsenic level may be a useful predictive marker of cancer risk in women.
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http://dx.doi.org/10.1002/ijc.32595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154768PMC
May 2020

A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases.

Mod Pathol 2019 12 25;32(12):1834-1846. Epub 2019 Jun 25.

Department of Obstetrics and Gynecology, Sahlgrenska Cancer Center, Inst Clinical Scienses, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7/CK20/CDX2/PAX8. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1-50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.
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http://dx.doi.org/10.1038/s41379-019-0302-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207534PMC
December 2019

Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.

J Pathol Clin Res 2018 10 21;4(4):250-261. Epub 2018 Sep 21.

Cancer Control and Population Sciences, Duke Cancer Institute, Durham, NC, USA.

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.
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http://dx.doi.org/10.1002/cjp2.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174617PMC
October 2018

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer.

Mayo Clin Proc 2018 03;93(3):307-320

Department of Medical Oncology, Mayo Clinic, Rochester, MN.

Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.

Patients And Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).

Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively).

Conclusion: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes.
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http://dx.doi.org/10.1016/j.mayocp.2017.10.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870793PMC
March 2018

Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer.

JAMA Oncol 2017 12;3(12):e173290

Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Germany and Institute of Pathology, University of Heidelberg, Heidelberg, Germany

Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.

Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer.

Design, Setting, And Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years.

Exposures: Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines.

Main Outcomes And Measures: Overall survival time.

Results: The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form.

Conclusions And Relevance: This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.
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http://dx.doi.org/10.1001/jamaoncol.2017.3290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744673PMC
December 2017

BRCA1 founder mutations compared to ovarian cancer in Belarus.

Fam Cancer 2014 Sep;13(3):445-7

Department of Obsetetrics and Gynecology, Grodno State Medical University, Grodno, Belarus.

In Belarus and other Slavic countries, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases, but the data on contribution of these mutations to ovarian cancers are limited. To estimate the proportion of ovarian cancers in Belarus, which are dependent on BRCA1 Slavic founder mutations, we sought the presence of three most frequent mutations (BRCA1: 5382insC, C61G and, 4153delA) in 158 consecutive unselected cases of ovarian cancer. One of the three founder mutations was present in 25 of 158 unselected cases of ovarian cancer (15.8 %). We recommend that all cases of ovarian cancer in Belarus be offered genetic testing for these founder mutations. Furthermore, genetic testing of the Belarusian population will provide the opportunity to prevent a significant proportion of ovarian cancer.
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http://dx.doi.org/10.1007/s10689-014-9721-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164833PMC
September 2014

Ten-year survival in patients with BRCA1-negative and BRCA1-positive breast cancer.

J Clin Oncol 2013 Sep 12;31(26):3191-6. Epub 2013 Aug 12.

Tomasz Huzarski, Tomasz Byrski, Jacek Gronwald, Bohdan Górski, Pawel Domagała, Cezary Cybulski, Oleg Oszurek, and Jan Lubiński, Pomeranian Medical University, Szczecin; Marek Szwiec, Regional Oncology Center, Opole; Karol Gugała, District Specialist Hospital, Olsztyn; Malgorzata Stawicka, Regional Oncology Center, Poznań; Zbigniew Morawiec, Regional Oncology Center, Łódź; Tomasz Mierzwa, Regional Oncology Hospital; Hanna Janiszewska, Nicolaus Copernicus University, Bydgoszcz; Ewa Kilar, District Specialist Hospital, Świdnica; Elzbieta Marczyk, Regional Oncology Center, Kraków; Beata Kozak-Klonowska and Monika Siołek, Regional Oncology Center, Kielce; Dariusz Surdyka, St John's Cancer Center, Lublin; Rafal Wiśniowski, Regional Oncology Hospital, Bielsko Biała; Michal Posmyk, Regional Oncology Center, Białystok, Poland; and Ping Sun and Steven A. Narod, Women's College Research Institute, Toronto, Ontario, Canada.

Purpose: To estimate 10-year overall survival (OS) rates for patients with early-onset breast cancer, with and without a BRCA1 mutation, and to identify prognostic factors among those with BRCA1-positive breast cancer.

Patients And Methods: A total of 3,345 women with stage I to III breast cancer, age ≤ 50 years, were tested for three founder mutations in BRCA1. Information on tumor characteristics and treatments received was retrieved from medical records. Dates of death were obtained from the vital statistics registry. Survival curves for the mutation-positive and -negative subcohorts were compared. Predictors of OS were determined using the Cox proportional hazards model.

Results: Of the 3,345 patients enrolled onto the study, 233 (7.0%) carried a BRCA1 mutation. The 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4% to 86.4%); for noncarriers, it was 82.2% (95% CI, 80.5% to 83.7%). The adjusted hazard ratio (HR) associated with carrying a BRCA1 mutation was 1.81 (95% CI, 1.26 to 2.61). Among BRCA1 carriers with a small (< 2 cm) node-negative tumor, the 10-year survival rate was 89.9%. Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted HR, 4.1; 95% CI, 1.8 to 8.9). Oophorectomy was associated with improved survival in BRCA1 carriers (adjusted HR, 0.30; 95% CI, 0.12 to 0.75).

Conclusion: The 10-year survival rate among women with breast cancer and a BRCA1 mutation is similar to that of patients without a BRCA1 mutation. Among women with a BRCA1 mutation, survival was much improved after oophorectomy.
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http://dx.doi.org/10.1200/JCO.2012.45.3571DOI Listing
September 2013

Carcinoma in the inactive bladder - the dilemma of the forgotten organ.

Cent European J Urol 2012 19;65(1):38-9. Epub 2012 Mar 19.

Department of Urology and Urological Oncology, Pomeranian Medical University, Szczecin, Poland.

Etiologic factors affecting bladder tumor have been well confirmed and it is widely recognized that carcinogenic substances in urine may play an important role in a pathogenesis. Carcinoma developing in a defunctionalized bladder, although uncommon, does occur. We report a case of a transitional cell carcinoma (TCC) found in a remaining bladder of a male patient and a review of the most relevant literature.
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http://dx.doi.org/10.5173/ceju.2012.01.art12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921762PMC
February 2014

CHEK2 mutations and HNPCC-related colorectal cancer.

Int J Cancer 2010 Jun;126(12):3005-9

International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, il. Połabska 4, Szczecin, Poland.

Recently, the 1100delC variant of cell cycle checkpoint kinase 2 (CHEK2) has been reported to confer a colorectal cancer risk in hereditary non-polyposis-colorectal cancer (HNPCC) and HNPCC-related families in the Netherlands. To investigate whether CHEK2 mutations confer increased cancer risk in HNPCC and HNPCC-related families in Poland, we genotyped 463 probands from HNPCC and HNPCC-related families, and 5,496 controls for 4 CHEK2 alleles (1100delC, IVS2+1G>A, del5395, I157T). All 463 probands were screened for mutations in the HNPCC-related genes MSH2, MLH1 and MSH6. A positive association was observed for HNPCC-related cancer and the I157T missense CHEK2 mutation (OR = 1.7; p = 0.007), but not for the truncating alleles (OR = 1.0; p = 1.0). The association with the I157T was seen both for the 117 cases who fulfill Amsterdam criteria (OR = 1.9; p = 0.1) and for the 346 cases who do not fulfill the criteria (OR = 1.6; p = 0.03). One hundred forty-five of the 463 families had a mutation in MSH2, MLH1 or MSH6 (MMR-positive families). A positive association between the CHEK2 I157T mutation and HNPCC-related cancer was observed only for MMR-negative cases (OR = 2.1; p = 0.0004), but not for MMR-positive cases (OR = 0.8; p = 0.9). The association with I157T was particularly strong for MMR-negative cases with familial colorectal cancer (2 or more first-degree relatives affected) (OR = 2.5; p < 0.0001). We conclude that the I157T variant of CHEK2 increases the risk of colorectal cancer among MMR-negative, HNPCC/HNPCC-related families in Poland.
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http://dx.doi.org/10.1002/ijc.25003DOI Listing
June 2010

Hereditary breast and ovarian cancer.

Hered Cancer Clin Pract 2008 Jun 15;6(2):88-98. Epub 2008 Jun 15.

International Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

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http://dx.doi.org/10.1186/1897-4287-6-2-88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735784PMC
June 2008

CDKN2A-positive breast cancers in young women from Poland.

Breast Cancer Res Treat 2007 Jul 24;103(3):355-9. Epub 2006 Oct 24.

Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, ul Połabska 4, Szczecin, Poland.

Purpose: To investigate the contribution of CDKN2A A148T common variant to early-onset breast cancer in Poland, and to establish the characteristic features of these cancers.

Experimental Design: We studied 3,069 women diagnosed with breast cancer under the age of 51 and 3,493 population controls. CDKN2A variant were detected using RFLP-PCR and confirmed by genomic sequencing. Clinical and pathological features of CDKN2A-positive cases and CDKN2A-negative cases were compared.

Results: A148T variant was identified in 157 of 3,069 women with breast cancer (5.1%). Overall, the odds ratio for early-onset breast cancer, given a CDKN2A variant was 1.4 (95% CI 1.075-1.725; P = 0.012). Breast tumors in women with the CDKN2A variant were more commonly intraductal cancers (DCIS) with micro-invasion (14.8% vs. 8.5%; P = 0.035). Carriers and non-carriers were similar with respect to tumor size, laterality, multicentricity, nodal status, family history and estrogen-receptor status.

Conclusion: The CDKN2A A148T variant seems to contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of A148T variant appear to be similar to those of breast cancers in the population at large.
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http://dx.doi.org/10.1007/s10549-006-9382-xDOI Listing
July 2007

CHEK2-positive breast cancers in young Polish women.

Clin Cancer Res 2006 Aug;12(16):4832-5

International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

Purpose: To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers.

Experimental Design: We studied 3,228 women diagnosed with breast cancer under the age of 51 years and 5,496 population controls. CHEK2 mutations were detected by RFLP-PCR or allele-specific oligonucleotide-PCR assays. Clinical and pathologic features of CHEK2-positive cases and CHEK2-negative cases were compared.

Results: A truncating CHEK2 mutation (1100delC or IVS2+1G>A) was seen in 47 of 3,228 cases and in 34 of 5,496 controls (odds ratio, 2.4; P = 0.0001). The CHEK2 I157T missense mutation was present in 207 of 3,228 cases, compared with 264 of 5,496 controls (odds ratio, 1.4; P = 0.002). Breast cancers in women with a CHEK2 mutation were more commonly of lobular histology (21.5% versus 15.8%; P = 0.05), of size >2 cm (54.8% versus 43.5%; P = 0.01), or of multicentric origin (28.7% versus 19.5%; P = 0.01) than were cancers from women without a CHEK2 mutation. Bilateral cancers were equally common in both subgroups.

Conclusion: Three founder alleles in CHEK2 contribute to early-onset breast cancer in Poland. Breast tumors which arise in carriers of CHEK2 mutations seem to be similar to those of breast cancers in the population at large.
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http://dx.doi.org/10.1158/1078-0432.CCR-06-0158DOI Listing
August 2006

CDKN2A common variant and multi-organ cancer risk--a population-based study.

Int J Cancer 2006 Jun;118(12):3180-2

Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.

The population frequencies of the CDKN2A common variants remain undetermined. In Poland, there is a common variant of the CDKN2A: an alanine to threonine substitution (A148T), which has been detected in other populations. We have recently showed that it is significantly overrepresented among Polish melanoma patients when compared to general population. Herein, we ascertained the prevalence of the A148T variant in 3,583 unselected cancer cases and 3,000 random control subjects from the same Polish population. We evaluated eleven different malignancies, representing the majority of all common cancer sites. Positive association with A148T variant was observed for lung cancer (OR, 2.0; p = 0.0052). A similar trend, although nonsignificant after the Bonferroni correction, was observed for colorectal cancer (OR, 1.5; p = 0.5499). These results suggest that A148T variant may be associated with a multi-organ cancer risk in the Polish population.
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http://dx.doi.org/10.1002/ijc.21760DOI Listing
June 2006

Population Screening of CHEK2 Mutations in Poland.

Hered Cancer Clin Pract 2006 Jan 15;4(1):57. Epub 2006 Jan 15.

International Hereditary Cancer Center - Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

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http://dx.doi.org/10.1186/1897-4287-4-1-57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401924PMC
January 2006
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