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Joanne Kotsopoulos,
Grzegorz Sukiennicki,
Magdalena Muszyńska,
Daniel Gackowski,
Krzysztof Kąklewski,
Katarzyna Durda,
Katarzyna Jaworska,
Tomasz Huzarski,
Jacek Gronwald,
Tomasz Byrski,
Oleg Ashuryk,
Tadeusz Dębniak,
Aleksandra Tołoczko-Grabarek, Małgorzata Stawicka,
Dariusz Godlewski,
Ryszard Oliński,
Anna Jakubowska,
Steven A Narod,
Jan Lubinski
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ABSTRACT: Few studies have evaluated the role of micronutrients or trace elements in breast cancer development among BRCA1 mutation carriers. To investigate a possible role of dietary and environmental exposures on cancer risk, we undertook an exploratory study, using a matched case-control design (n = 48 cases and 96 controls), to evaluate the relationships between plasma levels of 14 micronutrients and breast cancer risk among BRCA1 mutation carriers in Poland.
We estimated the univariate odds ratios (OR) and 95 % confidence intervals (CI) for breast cancer associated with plasma levels for each of 14 micronutrients.
Of the 14 analytes quantified, significant differences between cases and controls were seen for two (iron and retinol; p = 0.009 and p = 0.03, respectively). Women in the highest tertile of plasma iron had a 57 % lower risk, compared with those in the lowest quartile (OR = 0.43; 95 % CI 0.18-1.04; p for trend = 0.06). Increasing antimony levels were associated with an increased risk of breast cancer (p for trend = 0.05). Women in the highest tertile had a 2.43-fold increase in breast cancer risk compared with women in the lowest tertile (OR = 2.43; 95 % CI 1.00-5.91).
This study provides some preliminary evidence regarding a role of diet, specifically iron and antimony, in the etiology of BRCA1-associated breast cancer. Prospective studies are necessary to confirm these findings.
Cancer Causes and Control 05/2012; 23(7):1065-74. · 2.88 Impact Factor
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ABSTRACT: There is an increasing evidence that genetic factors play a role in the etiology of malignant tumors. Mutations of BRCA1 and BRCA2 genes are responsible for an increased risk of ovarian cancer. The role of mutations in NOD2 gene in this type of neoplasm is still under investigation.
The aim of this study was to determine: 1. incidence of NOD 2 3020insC constitutional mutation in a group of consecutive women with ovarian cancer, 2. risk of developing ovarian cancer in patients with NOD2 gene mutation, 3. clinical and pathological features of ovarian cancer in NOD2 gene mutation carriers.
Clinical and pathological data were collected from 257 non-selected patients with primary epithelial ovarian cancer. The researches identified NOD2 3020insC gene mutation. On the basis of patient source documentation we obtained the data concerning the age of patients at diagnosis, histopathological recognition, FIGO stage and morphological grade G.
19 out of 257 women were identified with germ-line 3020insC mutation of NOD2 gene (7.39%). An increased risk of ovarian cancer in NOD2 mutation carriers was not revealed (OR=1.01; p=0.928; 95% Cl=0.61-1.66). The mean age at diagnosis of patients with NOD2 mutation was 54.8 (SD=9.9), while for non-carriers it was 53.2 (SD=10.2). The difference between these frequencies was statistically irrelevant (p=0.550). Clinical and pathological profile of ovarian cancer was made. We assessed the following features: age at disease onset, histopathology, FIGO stage and morphological grade G. For NOD2 mutation carriers no statistically significant features of ovarian cancer were revealed.
1. Despite high frequency of constitutional mutations occurrence in NOD2 gene in women with ovarian cancer, genetic testing seem not to be justified in all women diagnosed with this disease. 2. Due to a lack of increased risk of ovarian cancer in NOD2 gene mutation carriers, proceedings for them may not differ from recommendations for general population. 3. It is difficult to determine characteristic clinical and pathological features of ovarian cancer for NOD2 gene mutation carriers.
Ginekologia polska 09/2008; 79(8):544-9. · 0.41 Impact Factor
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Cezary Cybulski,
Bohdan Górski,
Jacek Gronwald,
Tomasz Huzarski,
Tomasz Byrski,
Tadeusz Debniak,
Anna Jakubowska,
Dominika Wokołorczyk,
Bartłomiej Gliniewicz,
Andrzej Sikorski, [......],
Krzysztof Bar,
Robert Klijer,
Zdrojowy Romuald,
Bartosz Małkiewicz,
Andrzej Borkowski,
Tomasz Borkowski,
Marek Szwiec,
Michal Posmyk,
Steven A Narod,
Jan Lubiński
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ABSTRACT: Evidence to date that BRCA1 mutation carriers are at an increased risk of prostate cancer is mixed - both positive and negative studies have been published. To establish whether or not inherited variation in BRCA1 influences prostate cancer risk we genotyped 1793 men with prostate cancer in Poland and 4570 controls for three founder mutations (C61G, 4153delA and 5382insC). A BRCA1 mutation was present in 0.45% of the cases and 0.48% of the controls (odds ratio=0.9; P=1.0). The odds ratios varied substantially by mutation. The 5382insC mutation is the most common of the three founder mutations. It was detected only in one case (0.06%), whereas it was seen in 0.37% of controls (P=0.06). In contrast, the 4153delA was more common in prostate cancer cases (0.22%) than in controls (0.04%) (odds ratio=5.1; 95% confidence interval: 0.9-27.9; P=0.1). The C61G mutation was also found in excess in cases (0.17%) compared with controls (0.07%) (odds ratio=2.6; 95% confidence interval: 0.5-12.7; P=0.5). Eight men with prostate cancer carried a mutation. Only one of these carried the 5382insC mutation, compared with 17 of 22 individuals with mutations in the control population (P=0.003). These data suggest that the 5382insC mutation is unlikely to be pathogenic for prostate cancer in the Polish population. The presence of one of the other alleles was associated with an increased risk for prostate cancer (odds ratio=3.6; 95% confidence interval: 1.1-11.3; P=0.045); in particular for familial prostate cancer (odds ratio=12; 95% confidence interval: 2.9-51; P=0.0004). We consider that the risk of prostate cancer in BRCA1 carriers varies with the position of the mutation.
European Journal of Cancer Prevention 03/2008; 17(1):62-6. · 2.13 Impact Factor
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ABSTRACT: To study whether or not there is an adverse effect of early chest X-rays on breast cancer risk in breast cancer susceptibility gene 1 (BRCA1) carriers, we compared the histories of chest X-ray exposures before age 30 in 138 BRCA1 carriers with breast cancer with 158 age-matched women with breast cancer, but without a BRCA1 mutation. All cases were drawn from a national breast cancer research registry. Affected carriers reported more frequent chest X-ray use before age 20 than affected non-carriers (0.6 vs. 0.3; P = 0.01). Affected carriers had, on average, 1.8 chest X-rays before age 30 compared to an average of 1.0 for affected non-carriers (P = 0.002). The odds ratio for ever having had a chest X-ray below age 30, given a BRCA1 mutation, was 1.8 [95% confidence interval (CI) = 1.2-2.9; P = 0.01]. These observations support the hypothesis that early radiation exposure may be a risk factor for breast cancer in BRCA1 carriers.
Breast Cancer Research and Treatment 02/2008; 112(3):581-4. · 4.43 Impact Factor
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ABSTRACT: Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Nevertheless, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ERbeta, raised a question of its role in hereditary breast cancer. The aim of this study was to assess the frequency of ERalpha, ERbeta, PgR (progesterone receptor) and HER-2 expression in breast cancer patients with mutated BRCA1 gene and in the control group.
The study group consisted of 48 women with BRCA1 gene mutations confirmed by multiplex PCR assay. The patients were tested for three most common mutations of BRCA1 affecting the Polish population (5382insC, C61G, 4153delA). Immunostaining for ERalpha, ERbeta and PgR (progesterone receptor) was performed using monoclonal antibodies against ERalpha, PgR (DakoCytomation), and polyclonal antibody against ERbeta (Chemicon). The EnVision detection system was applied. The study population comprised a control group of 120 BC operated successively during the years 1998-99.
The results of our investigation showed that BRCA1 mutation carriers were more likely to have ERalpha-negative breast cancer than those in the control group. Only 14.5% of BRCA1-related cancers were ERalpha-positive compared with 57.5% in the control group (P < 0.0001). On the contrary, the expression of ERbeta protein was observed in 42% of BRCA1-related tumors and in 55% of the control group. An interesting finding was that most hereditary cancers (75% of the whole group) were triple-negative: ERalpha(-)/PgR(-)/HER-2(-) but almost half of this group (44.4%) showed the expression of ERbeta.
In the case of BRCA1-associated tumors the expression of ERbeta was significantly higher than the expression of ERalpha. This may explain the effectiveness of tamoxifen in preventing contralateral breast cancer development in BRCA1 mutation carriers.
BMC Cancer 02/2008; 8:100. · 3.01 Impact Factor
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ABSTRACT: Abstract
Background
Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Nevertheless, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ERβ, raised a question of its role in hereditary breast cancer. The aim of this study was to assess the frequency of ERα, ERβ, PgR (progesterone receptor) and HER-2 expression in breast cancer patients with mutated BRCA1 gene and in the control group.
Methods
The study group consisted of 48 women with BRCA1 gene mutations confirmed by multiplex PCR assay. The patients were tested for three most common mutations of BRCA1 affecting the Polish population (5382insC, C61G, 4153delA). Immunostaining for ERα, ERβ and PgR (progesterone receptor) was performed using monoclonal antibodies against ERα, PgR (DakoCytomation), and polyclonal antibody against ERβ (Chemicon). The EnVision detection system was applied. The study population comprised a control group of 120 BC operated successively during the years 1998–99.
Results
The results of our investigation showed that BRCA1 mutation carriers were more likely to have ERα-negative breast cancer than those in the control group. Only 14.5% of BRCA1 -related cancers were ERα-positive compared with 57.5% in the control group ( P < 0.0001). On the contrary, the expression of ERβ protein was observed in 42% of BRCA1 -related tumors and in 55% of the control group. An interesting finding was that most hereditary cancers (75% of the whole group) were triple-negative: ERα(-)/PgR(-)/HER-2(-) but almost half of this group (44.4%) showed the expression of ERβ.
Conclusion
In the case of BRCA1 -associated tumors the expression of ERβ was significantly higher than the expression of ERα. This may explain the effectiveness of tamoxifen in preventing contralateral breast cancer development in BRCA1 mutation carriers.
BMC Cancer. 01/2008;
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Janusz Menkiszak,
Jacek Gronwald,
Bohdan Górski,
Anna Jakubowska,
Tomasz Huzarski,
Tomasz Byrski,
Małgorzata Foszczyńska-Kłoda,
Olga Haus,
Hanna Janiszewska,
Magdalena Perkowska, [......],
Katarzyna Lamperska,
Elwira Strózyk,
Dariusz Godlewski, Małgorzata Stawicka,
Bernard Waśko,
Marek Bebenek,
Andrzej Rozmiarek,
Izabella Rzepka-Górska,
Steven A Narod,
Jan Lubiński
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ABSTRACT: There is increasing evidence that hereditary factors play a greater role in ovarian cancer than in any of the other common cancers of adulthood. This is attributable, to a large extent, to a high frequency of mutations in the BRCA1 or BRCA2 genes. In Poland, 3 common founder mutations in BRCA1 account for the majority of families with identified BRCA mutations. Our study was conducted in order to estimate the prevalence of any of 3 founder BRCA1 mutations (5382insC, C61G and 4153delA) in 364 unselected women with ovarian cancer, and among 177 women with ovarian cancer and a family history of breast or ovarian cancer. A mutation was identified in 49 out of 364 unselected women with ovarian cancer (13.5%) and in 58 of 177 women with familial ovarian cancer (32.8%). The majority of women with ovarian cancer and a BRCA1 mutation have no family history of breast or ovarian cancer. The high frequency of BRCA1 mutations in Polish women with ovarian cancer supports the recommendation that all Polish women with ovarian cancer should be offered testing for genetic susceptibility, and that counseling services be made available to them and to their relatives. It is important that mutation surveys be conducted in other countries prior to the introduction of national genetic screening programs.
International Journal of Cancer 11/2003; 106(6):942-5. · 5.44 Impact Factor
