BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries....BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.展开更多
Background: Distinguishing between sub-clinical and aggressive forms of prostate cancer is difficult due to the heterogeneity of the disease. It is, however, important to identify aggressive forms to guide proper trea...Background: Distinguishing between sub-clinical and aggressive forms of prostate cancer is difficult due to the heterogeneity of the disease. It is, however, important to identify aggressive forms to guide proper treatment. This study compared gene expression profiles in cancer cells from hereditary and sporadic prostate cancer cases and attempted to correlate differentially regulated genes with clinico-pathological characteristics and prognosis. Materials and methods: The study population comprised patients diagnosed with clinically localized prostate cancer undergoing prostatectomy. Patients were divided into hereditary and sporadic cancer cases based on their family history. Fresh frozen biopsies from prostatectomy specimens were laser-dissected for RNA-extraction. Affymetrix HG-U133 Plus GeneChips were used to measure gene expression loaded onto Cluster 3.0 and Ingenuity Pathway Analysis softwares to examine the relationship among genes between groups. Differentially expressed genes were selected for protein expression analysis using immunohistochemistry on histological sections and tissue microarrays. Results: No single genes were signifycantly differentially expressed between hereditary and sporadic cases after adjustment for multiple testing. Using cluster analysis, four transcripts were found to be upregulated in hereditary prostate cancer tissue: CYR61, EGR3, KLF6 and SNF1LK. The intensity of CYR61, EGR2, KLF6 and SNF1LK immunostainings, however, were not significantly different in a separate sample of hereditary and sporadic prostate cancers. Furthermore, no correlations between CYR61, EGR2, KLF6, and SNF1LK staining intensities and the clinico-pathological variables or disease-free survival were detected, except for EGR3 that was significantly associated with T stage (p = 0.04). Conclusion: Overall, no single transcript level was significantly associated with hereditary prostate cancer. Cluster analysis suggested that the expression of CYR61, EGR3, KLF6 and SNF1LK were upregulated in cancer tissue from hereditary cases, but we were not able to confirm this on the protein level, and levels of these proteins were not found to correlate with clinico-pathological characteristics or biochemical recurrence.展开更多
Objective This study investigated the feasibility of screening residual normal ovarian tissues based on the expression of Bmi-1 and EZH2 in tissues adjacent to orthotopic ovarian carcinomas in nude mice. Methods The h...Objective This study investigated the feasibility of screening residual normal ovarian tissues based on the expression of Bmi-1 and EZH2 in tissues adjacent to orthotopic ovarian carcinomas in nude mice. Methods The human epithelial ovarian cancer cell line OVCAR3 was grown in subcutaneous tissues and the tumor tissues were orthotopically implanted. The expression levels of Bmi-1 and EZH2 were detected by immunohistochemical staining and RT-PCR in cancer tissues, proximal and remote tissues with respect to the cancer tissues, and normal ovarian tissues of nude mice.Results Thirty-five ovarian tissue samples with normal biopsy results were obtained from 40 cases of human epithelial ovarian cancer in the nude mice in which the tumor tissues were orthotopically implanted. Bmi-1 and EZH2 expression levels were lower in proximal paraneoplastic tissue samples than in cancer tissue samples(P < 0.05) and higher than in remote paraneoplastic tissue samples(P < 0.01). No significant difference was found in the expression levels of Bmi-1 and EZH2 using immunohistochemistry among residual normal ovarian tissues obtained from orthotopically implanted models that differed in severity. The expression of Bmi-1 and EZH2 was negative in 20 normal ovarian tissue samples.Conclusion The expression levels of Bmi-1 and EZH2 were reduced with increasing distance from the cancer tissues. Negative expression of these tumor-associated genes can be used as a standard for the screening of normal ovarian tissues adjacent to tumor tissues. Normal ovarian tissues can be obtained from the tissues adjacent to tumors.展开更多
Objective:As prostate cancer(Pr C)shows a BRCA mutation rate as high as 30%,it becomes crucial to find the optimal selection criteria for genetic testing.The primary objective of this study was to evaluate the BRCA mu...Objective:As prostate cancer(Pr C)shows a BRCA mutation rate as high as 30%,it becomes crucial to find the optimal selection criteria for genetic testing.The primary objective of this study was to evaluate the BRCA mutation rate in families with Pr C associated with breast and/or ovarian cancers;secondary aims were to compare the characteristics of families and BRCA-related Pr C outcome among BRCA1 and BRCA2 carriers.Methods:Following the Modena criteria for the BRCA test,we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score≥7 Pr Cs,by testing breast or ovarian cases and inferring the mutation in the prostate cases.The characteristics of families and BRCA-related Pr C outcomes were measured using the chi-square(χ^(2))test and Kaplan–Meier methods,respectively.Results:Among 6,591 families,580(8.8%)with a Gleason score≥7 Pr Cs were identified,of which 332(57.2%)met the Modena selection criteria for BRCA testing.Overall,215 breast or ovarian cancer probands(64.8%)were tested,of which 41 resulted positive for BRCA and one for CHEK2 genes(19.5%).No statistically significant differences were found in BRCA-related Pr C prognosis and in the characteristics of families among BRCA1,BRCA2 and non-tested patients.Ten of 23(44%)mutations in the BRCA2 gene fell in the prostate cancer cluster region(PCCR)at the 3′terminal of the 7914 codon.Conclusions:It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and Pr C.A trend toward a worse prognosis has been found in BRCA2 carriers.展开更多
On average,over 25000 women are diagnosed with breast cancer under the age of 45 annually in the United States.Because an increasing number of young women delay childbearing to later life for various reasons,a growing...On average,over 25000 women are diagnosed with breast cancer under the age of 45 annually in the United States.Because an increasing number of young women delay childbearing to later life for various reasons,a growing population of women experience breast cancer before completing childbearing.In this context,preservation of fertility potential of breast cancer survivors has become an essential concept in modern cancer care.In this review,we will outline the currently available fertility preservation options for women with breast cancer of reproductive age,discuss the controversy behind hormonal suppression for gonadal protection against chemotherapy and highlight the importance of timely referral by cancer care providers.展开更多
It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet...It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization （IVF） after cancer treatment are also presented.展开更多
The number of reported new cancer cases is increasing every year. The probability of surviving cancer is high and is continually improving. The cancer treatment may induce ovarian or testicular failure by damaging ova...The number of reported new cancer cases is increasing every year. The probability of surviving cancer is high and is continually improving. The cancer treatment may induce ovarian or testicular failure by damaging ovarian follicles in females and spermatogonia in the males. Gonadal failure may affect all aspects of reproductive health, including pubertal development, hormone production, and sexual function in adult life. Therefore, the primary goal for cancer treatment is to ensure the highest possibility of cure and to maintain the reproductive health. The cancer patients should be provided with maximal chance to make an optimal decision without any significant impact and delay in cancer treatment. As a result of treatment innovations, the survival rates of young people have increased substantially;therefore, the need of fertility preservation has increased as well. The sperm cryopreservation and embryo cryopreservation have been standard methods of fertility preservation. Recently, the American Society for Reproductive Medicine has removed the experimental label from oocyte cryopreservation. However, other fertility preservation options including ovarian tissue and whole ovary cryopreservation and testicular tissue cryopreservation for pre-pubertal boys are still considered experimental. A coordinated approach by gynecologists, urologists, oncologists, pediatricians, surgeons, fertility specialists and counselors is required to make use of available fertility preservation options. Timely and complete information on the impact of cancer treatment on fertility and fertility preservation options should be presented to all patients when a cancer treatment is planned. The possibility of fertility preservation removes a huge concern and enables cancer patients to concentrate on their treatment and getting better. The purpose of this review is to present different options currently available to preserve fertility in men, women and adolescent children diagnosed with cancer and undergoing gonadotoxic therapy. All options are listed in two tables for quick reference. Most of the information is extracted from recent publications and presented in such a manner that it is valuable for cancer patients and professionals associated with fertility preservation.展开更多
Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on ou...Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.展开更多
文摘BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.
文摘Background: Distinguishing between sub-clinical and aggressive forms of prostate cancer is difficult due to the heterogeneity of the disease. It is, however, important to identify aggressive forms to guide proper treatment. This study compared gene expression profiles in cancer cells from hereditary and sporadic prostate cancer cases and attempted to correlate differentially regulated genes with clinico-pathological characteristics and prognosis. Materials and methods: The study population comprised patients diagnosed with clinically localized prostate cancer undergoing prostatectomy. Patients were divided into hereditary and sporadic cancer cases based on their family history. Fresh frozen biopsies from prostatectomy specimens were laser-dissected for RNA-extraction. Affymetrix HG-U133 Plus GeneChips were used to measure gene expression loaded onto Cluster 3.0 and Ingenuity Pathway Analysis softwares to examine the relationship among genes between groups. Differentially expressed genes were selected for protein expression analysis using immunohistochemistry on histological sections and tissue microarrays. Results: No single genes were signifycantly differentially expressed between hereditary and sporadic cases after adjustment for multiple testing. Using cluster analysis, four transcripts were found to be upregulated in hereditary prostate cancer tissue: CYR61, EGR3, KLF6 and SNF1LK. The intensity of CYR61, EGR2, KLF6 and SNF1LK immunostainings, however, were not significantly different in a separate sample of hereditary and sporadic prostate cancers. Furthermore, no correlations between CYR61, EGR2, KLF6, and SNF1LK staining intensities and the clinico-pathological variables or disease-free survival were detected, except for EGR3 that was significantly associated with T stage (p = 0.04). Conclusion: Overall, no single transcript level was significantly associated with hereditary prostate cancer. Cluster analysis suggested that the expression of CYR61, EGR3, KLF6 and SNF1LK were upregulated in cancer tissue from hereditary cases, but we were not able to confirm this on the protein level, and levels of these proteins were not found to correlate with clinico-pathological characteristics or biochemical recurrence.
基金Supported by a grant from the Health Department of Hainan Province(No.QW2013-040)
文摘Objective This study investigated the feasibility of screening residual normal ovarian tissues based on the expression of Bmi-1 and EZH2 in tissues adjacent to orthotopic ovarian carcinomas in nude mice. Methods The human epithelial ovarian cancer cell line OVCAR3 was grown in subcutaneous tissues and the tumor tissues were orthotopically implanted. The expression levels of Bmi-1 and EZH2 were detected by immunohistochemical staining and RT-PCR in cancer tissues, proximal and remote tissues with respect to the cancer tissues, and normal ovarian tissues of nude mice.Results Thirty-five ovarian tissue samples with normal biopsy results were obtained from 40 cases of human epithelial ovarian cancer in the nude mice in which the tumor tissues were orthotopically implanted. Bmi-1 and EZH2 expression levels were lower in proximal paraneoplastic tissue samples than in cancer tissue samples(P < 0.05) and higher than in remote paraneoplastic tissue samples(P < 0.01). No significant difference was found in the expression levels of Bmi-1 and EZH2 using immunohistochemistry among residual normal ovarian tissues obtained from orthotopically implanted models that differed in severity. The expression of Bmi-1 and EZH2 was negative in 20 normal ovarian tissue samples.Conclusion The expression levels of Bmi-1 and EZH2 were reduced with increasing distance from the cancer tissues. Negative expression of these tumor-associated genes can be used as a standard for the screening of normal ovarian tissues adjacent to tumor tissues. Normal ovarian tissues can be obtained from the tissues adjacent to tumors.
文摘Objective:As prostate cancer(Pr C)shows a BRCA mutation rate as high as 30%,it becomes crucial to find the optimal selection criteria for genetic testing.The primary objective of this study was to evaluate the BRCA mutation rate in families with Pr C associated with breast and/or ovarian cancers;secondary aims were to compare the characteristics of families and BRCA-related Pr C outcome among BRCA1 and BRCA2 carriers.Methods:Following the Modena criteria for the BRCA test,we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score≥7 Pr Cs,by testing breast or ovarian cases and inferring the mutation in the prostate cases.The characteristics of families and BRCA-related Pr C outcomes were measured using the chi-square(χ^(2))test and Kaplan–Meier methods,respectively.Results:Among 6,591 families,580(8.8%)with a Gleason score≥7 Pr Cs were identified,of which 332(57.2%)met the Modena selection criteria for BRCA testing.Overall,215 breast or ovarian cancer probands(64.8%)were tested,of which 41 resulted positive for BRCA and one for CHEK2 genes(19.5%).No statistically significant differences were found in BRCA-related Pr C prognosis and in the characteristics of families among BRCA1,BRCA2 and non-tested patients.Ten of 23(44%)mutations in the BRCA2 gene fell in the prostate cancer cluster region(PCCR)at the 3′terminal of the 7914 codon.Conclusions:It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and Pr C.A trend toward a worse prognosis has been found in BRCA2 carriers.
文摘On average,over 25000 women are diagnosed with breast cancer under the age of 45 annually in the United States.Because an increasing number of young women delay childbearing to later life for various reasons,a growing population of women experience breast cancer before completing childbearing.In this context,preservation of fertility potential of breast cancer survivors has become an essential concept in modern cancer care.In this review,we will outline the currently available fertility preservation options for women with breast cancer of reproductive age,discuss the controversy behind hormonal suppression for gonadal protection against chemotherapy and highlight the importance of timely referral by cancer care providers.
文摘It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization （IVF） after cancer treatment are also presented.
文摘The number of reported new cancer cases is increasing every year. The probability of surviving cancer is high and is continually improving. The cancer treatment may induce ovarian or testicular failure by damaging ovarian follicles in females and spermatogonia in the males. Gonadal failure may affect all aspects of reproductive health, including pubertal development, hormone production, and sexual function in adult life. Therefore, the primary goal for cancer treatment is to ensure the highest possibility of cure and to maintain the reproductive health. The cancer patients should be provided with maximal chance to make an optimal decision without any significant impact and delay in cancer treatment. As a result of treatment innovations, the survival rates of young people have increased substantially;therefore, the need of fertility preservation has increased as well. The sperm cryopreservation and embryo cryopreservation have been standard methods of fertility preservation. Recently, the American Society for Reproductive Medicine has removed the experimental label from oocyte cryopreservation. However, other fertility preservation options including ovarian tissue and whole ovary cryopreservation and testicular tissue cryopreservation for pre-pubertal boys are still considered experimental. A coordinated approach by gynecologists, urologists, oncologists, pediatricians, surgeons, fertility specialists and counselors is required to make use of available fertility preservation options. Timely and complete information on the impact of cancer treatment on fertility and fertility preservation options should be presented to all patients when a cancer treatment is planned. The possibility of fertility preservation removes a huge concern and enables cancer patients to concentrate on their treatment and getting better. The purpose of this review is to present different options currently available to preserve fertility in men, women and adolescent children diagnosed with cancer and undergoing gonadotoxic therapy. All options are listed in two tables for quick reference. Most of the information is extracted from recent publications and presented in such a manner that it is valuable for cancer patients and professionals associated with fertility preservation.
文摘Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.
