J. Gronwald - Academia.edu (original) (raw)

Papers by J. Gronwald

Research paper thumbnail of Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

Research paper thumbnail of The risk of breast cancer in women with a CHEK2 mutation

Hereditary Cancer in Clinical Practice, 2012

Research paper thumbnail of Population Screening of CHEK2 Mutations in Poland

Hereditary Cancer in Clinical Practice, 2006

Research paper thumbnail of The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

British Journal of Cancer, 2008

Research paper thumbnail of Duration of tamoxifen use and the risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

Research paper thumbnail of Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

British Journal of Cancer, 2012

Research paper thumbnail of Management of ovarian and endometrial cancers in women belonging to HNPCC carrier families: review of the literature and results of cancer risk assessment in Polish HNPCC families

Hereditary cancer in clinical practice, 2015

Over half the cancer deaths in HNPCC families are due to extra-colonic malignancies that include ... more Over half the cancer deaths in HNPCC families are due to extra-colonic malignancies that include endometrial and ovarian cancers. The benefits of surveillance for gynecological cancers are not yet proven and there is no consensus on the optimal surveillance recommendations for women with MMR mutations. We performed a systematic review of the literature and evaluated gynecological cancer risk in a series of 631 Polish HNPCC families classified into either Lynch Syndrome (LS, MMR mutations detected) or HNPCC (fulfillment of the Amsterdam or modified Amsterdam criteria). Published data clearly indicates no benefit for ovarian cancer screening in contrast to risk reducing surgery. We confirmed a significantly increased risk of OC in Polish LS families (OR = 4,6, p < 0.001) and an especially high risk of OC was found for women under 50 years of age: OR = 32,6, p < 0.0001 (95% CI 12,96-81,87). The cumulative OC risk to 50 year of life was calculated to be 10%. Six out of 19 (32%) ea...

Research paper thumbnail of Molecular Analyses in Diagnosis of High Genetic Predispositions to Malignancies

Journal of Clinical Biochemistry and Nutrition, 2000

Research paper thumbnail of A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

Research paper thumbnail of Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies

Journal of Medical Genetics, 2005

Research paper thumbnail of Cancer risks in first degree relatives of BRCA1 mutation carriers: effects of mutation and proband disease status

Journal of Medical Genetics, 2005

Research paper thumbnail of A protein truncating BRCA1 allele with a low penetrance of breast cancer

Journal of Medical Genetics, 2004

Research paper thumbnail of Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States

Journal of Medical Genetics, 2002

Research paper thumbnail of Pathologic Complete Response Rates in Young Women With BRCA1-Positive Breast Cancers After Neoadjuvant Chemotherapy

Journal of Clinical Oncology, 2010

Purpose To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in... more Purpose To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in BRCA1 mutation carriers according to chemotherapy regimen. Patients and Methods From a registry of 6,903 patients, we identified 102 women who carried a BRCA1 founder mutation and who had been treated for breast cancer with neoadjuvant chemotherapy. Pathologic complete response was evaluated using standard criteria. Results Twenty-four (24%) of the 102 BRCA1 mutation carriers experienced a pCR. The response rate varied widely with treatment: a pCR was observed in one (7%) of 14 women treated with cyclophosphamide, methotrexate, and fluorouracil (CMF); in two (8%) of 25 women treated with doxorubicin and docetaxel (AT); in 11 (22%) of 51 women treated with doxorubicin and cyclophosphamide (AC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC), and in 10 (83%) of 12 women treated with cisplatin. Conclusion A low rate of pCR was observed in women with breast cancer and a BRCA1 mutat...

Research paper thumbnail of Risk of Breast Cancer in Women With a CHEK2 Mutation With and Without a Family History of Breast Cancer

Journal of Clinical Oncology, 2011

Purpose To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on he... more Purpose To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer. Patients and Methods Seven thousand four hundred ninety-four BRCA1 mutation–negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T). Results A truncating mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR was higher for women with a first- or second-degree relative with breast cancer (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95% CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of 6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relati...

Research paper thumbnail of Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Human Molecular Genetics, 2011

Research paper thumbnail of Long polymerase chain reaction in detection of germline deletions in the von Hippel-Lindau tumour suppressor gene

Research paper thumbnail of Common variants at 19p13 are associated with susceptibility to ovarian cancer

Nature genetics, 2010

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in th... more Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10⁻⁴ and P = 6 × 10⁻⁴, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10⁻⁹ and P = 4 × 10⁻¹¹, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

Research paper thumbnail of A high frequency of BRCA2 gene mutations in Polish families with ovarian and stomach cancer

European Journal of Human Genetics, 2003

Germ-line mutations in the BRCA2 gene are associated with a wide range of cancer types, including... more Germ-line mutations in the BRCA2 gene are associated with a wide range of cancer types, including the breast, ovary, pancreas, prostate and melanoma. In this study, we evaluated the importance of a family history of stomach cancer in predicting the presence of a BRCA2 mutation in Polish patients with ovarian cancer. A BRCA2 mutation was found in eight of 34 women with ovarian cancer and a family history of stomach cancer versus three of 75 women with ovarian cancer and a family history of ovarian cancer, but not of stomach cancer (odds ratio ¼ 7.4; 95% CI 1.8-30; P ¼ 0.004). The results of this study suggest that, in the Polish population, the constellation of ovarian and stomach cancer predicts the presence of a germ-line BRCA2 mutation and confirms that stomach cancer is part of the spectrum of BRCA2 mutations. It is expected that the penetrance of BRCA2 mutations for stomach cancer will vary from country to country, reflecting local environmental and lifestyle factors.

Research paper thumbnail of NOD2 variants and the risk of malignant melanoma

European Journal of Cancer Prevention, 2005

Research paper thumbnail of Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

Research paper thumbnail of The risk of breast cancer in women with a CHEK2 mutation

Hereditary Cancer in Clinical Practice, 2012

Research paper thumbnail of Population Screening of CHEK2 Mutations in Poland

Hereditary Cancer in Clinical Practice, 2006

Research paper thumbnail of The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

British Journal of Cancer, 2008

Research paper thumbnail of Duration of tamoxifen use and the risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

Research paper thumbnail of Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

British Journal of Cancer, 2012

Research paper thumbnail of Management of ovarian and endometrial cancers in women belonging to HNPCC carrier families: review of the literature and results of cancer risk assessment in Polish HNPCC families

Hereditary cancer in clinical practice, 2015

Over half the cancer deaths in HNPCC families are due to extra-colonic malignancies that include ... more Over half the cancer deaths in HNPCC families are due to extra-colonic malignancies that include endometrial and ovarian cancers. The benefits of surveillance for gynecological cancers are not yet proven and there is no consensus on the optimal surveillance recommendations for women with MMR mutations. We performed a systematic review of the literature and evaluated gynecological cancer risk in a series of 631 Polish HNPCC families classified into either Lynch Syndrome (LS, MMR mutations detected) or HNPCC (fulfillment of the Amsterdam or modified Amsterdam criteria). Published data clearly indicates no benefit for ovarian cancer screening in contrast to risk reducing surgery. We confirmed a significantly increased risk of OC in Polish LS families (OR = 4,6, p < 0.001) and an especially high risk of OC was found for women under 50 years of age: OR = 32,6, p < 0.0001 (95% CI 12,96-81,87). The cumulative OC risk to 50 year of life was calculated to be 10%. Six out of 19 (32%) ea...

Research paper thumbnail of Molecular Analyses in Diagnosis of High Genetic Predispositions to Malignancies

Journal of Clinical Biochemistry and Nutrition, 2000

Research paper thumbnail of A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

Research paper thumbnail of Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies

Journal of Medical Genetics, 2005

Research paper thumbnail of Cancer risks in first degree relatives of BRCA1 mutation carriers: effects of mutation and proband disease status

Journal of Medical Genetics, 2005

Research paper thumbnail of A protein truncating BRCA1 allele with a low penetrance of breast cancer

Journal of Medical Genetics, 2004

Research paper thumbnail of Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States

Journal of Medical Genetics, 2002

Research paper thumbnail of Pathologic Complete Response Rates in Young Women With BRCA1-Positive Breast Cancers After Neoadjuvant Chemotherapy

Journal of Clinical Oncology, 2010

Purpose To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in... more Purpose To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in BRCA1 mutation carriers according to chemotherapy regimen. Patients and Methods From a registry of 6,903 patients, we identified 102 women who carried a BRCA1 founder mutation and who had been treated for breast cancer with neoadjuvant chemotherapy. Pathologic complete response was evaluated using standard criteria. Results Twenty-four (24%) of the 102 BRCA1 mutation carriers experienced a pCR. The response rate varied widely with treatment: a pCR was observed in one (7%) of 14 women treated with cyclophosphamide, methotrexate, and fluorouracil (CMF); in two (8%) of 25 women treated with doxorubicin and docetaxel (AT); in 11 (22%) of 51 women treated with doxorubicin and cyclophosphamide (AC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC), and in 10 (83%) of 12 women treated with cisplatin. Conclusion A low rate of pCR was observed in women with breast cancer and a BRCA1 mutat...

Research paper thumbnail of Risk of Breast Cancer in Women With a CHEK2 Mutation With and Without a Family History of Breast Cancer

Journal of Clinical Oncology, 2011

Purpose To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on he... more Purpose To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer. Patients and Methods Seven thousand four hundred ninety-four BRCA1 mutation–negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T). Results A truncating mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR was higher for women with a first- or second-degree relative with breast cancer (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95% CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of 6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relati...

Research paper thumbnail of Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Human Molecular Genetics, 2011

Research paper thumbnail of Long polymerase chain reaction in detection of germline deletions in the von Hippel-Lindau tumour suppressor gene

Research paper thumbnail of Common variants at 19p13 are associated with susceptibility to ovarian cancer

Nature genetics, 2010

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in th... more Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5 × 10⁻⁴ and P = 6 × 10⁻⁴, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3 × 10⁻⁹ and P = 4 × 10⁻¹¹, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

Research paper thumbnail of A high frequency of BRCA2 gene mutations in Polish families with ovarian and stomach cancer

European Journal of Human Genetics, 2003

Germ-line mutations in the BRCA2 gene are associated with a wide range of cancer types, including... more Germ-line mutations in the BRCA2 gene are associated with a wide range of cancer types, including the breast, ovary, pancreas, prostate and melanoma. In this study, we evaluated the importance of a family history of stomach cancer in predicting the presence of a BRCA2 mutation in Polish patients with ovarian cancer. A BRCA2 mutation was found in eight of 34 women with ovarian cancer and a family history of stomach cancer versus three of 75 women with ovarian cancer and a family history of ovarian cancer, but not of stomach cancer (odds ratio ¼ 7.4; 95% CI 1.8-30; P ¼ 0.004). The results of this study suggest that, in the Polish population, the constellation of ovarian and stomach cancer predicts the presence of a germ-line BRCA2 mutation and confirms that stomach cancer is part of the spectrum of BRCA2 mutations. It is expected that the penetrance of BRCA2 mutations for stomach cancer will vary from country to country, reflecting local environmental and lifestyle factors.

Research paper thumbnail of NOD2 variants and the risk of malignant melanoma

European Journal of Cancer Prevention, 2005