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
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
Breast and ovarian cancers now account for one in three cancers in Indian women and their incidence is rising.Major differences in the clinical presentation of breast and ovarian cancers exist between India and the Un...Breast and ovarian cancers now account for one in three cancers in Indian women and their incidence is rising.Major differences in the clinical presentation of breast and ovarian cancers exist between India and the United Kingdom.For example,Indian patients with breast cancer typically present a decade earlier than in the UK.Reasons for this could be multifactorial,including differences in underlying biology,environmental risks,and other systematic factors including access to screening.One possible explanation lies in variable incidence or penetrance of germline mutations in genes such as BRCA1 and BRCA2.We performed a methodical database and literature review to investigate the prevalence and spectrum of high-risk cancer susceptibility genes in Indian patients with breast and ovarian cancers.We identified 148 articles,but most studies were small,with inconsistent inclusion criteria and based on heterogeneous technologies,so that mutation frequency could not be reliably ascertained.Data were also often lacking on penetrance,histopathology,and survival outcomes.After filtering out unsuitable studies,only 13 remained,comprising 1028 patients.Large-scale research studies are urgently needed to determine mutation prevalence,spectra,and clinico-pathological features,and hence derive guidelines for screening,treatment,and prevention specific to the Indian population.展开更多
背景与目的:携带BRCA1/2基因胚系突变的女性终生罹患卵巢癌、乳腺癌和其他癌症的风险增加,早期识别此部分高风险人群,并采取针对性的风险管理方案对降低癌症的发病率和死亡率非常重要,本研究旨在分析携带BRCA1/2基因胚系突变的遗传性乳...背景与目的:携带BRCA1/2基因胚系突变的女性终生罹患卵巢癌、乳腺癌和其他癌症的风险增加,早期识别此部分高风险人群,并采取针对性的风险管理方案对降低癌症的发病率和死亡率非常重要,本研究旨在分析携带BRCA1/2基因胚系突变的遗传性乳腺癌-卵巢癌综合征(hereditary breast-ovarian cancer syndrome,HBOC)患者一级亲属接受基因筛查的现状及影响因素。方法:采用便利抽样法选取2021年2月—2022年4月在复旦大学附属妇产科医院就诊的72例已确诊BRCA1/2基因胚系突变的HBOC女性患者及其316名一级亲属,采用问卷调查法了解HBOC患者一级亲属是否接受基因筛查的现状;并采用logistic回归分析相关的影响因素。结果:在72例HBOC女性患者中,93.1%(n=67)将基因筛查结果传达给了她们的一级亲属。在18岁以上的一级亲属中,32.3%(n=102)决定进行基因筛查和遗传风险管理。Logistic回归分析显示,患者疾病类型、卵巢癌国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)分期、受教育程度、一级亲属性别、受教育程度及患者与亲属的情感亲密度是一级亲属是否愿意接受基因筛查和遗传风险管理的显著影响因素(P<0.05)。结论:HBOC患者一级亲属接受基因筛查的现状不容乐观。鉴于乳腺癌患者、文化程度较低的患者,男性亲属、文化程度较低的亲属及与患者情感亲密度较低的亲属接受基因筛查的概率较低,我们应采取针对性的干预措施提高这部分亲属的自我基因筛查行为。展开更多
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.
基金Dr Abeer Shaaban is funded by the CRUK Birmingham Cancer Centre.
文摘Breast and ovarian cancers now account for one in three cancers in Indian women and their incidence is rising.Major differences in the clinical presentation of breast and ovarian cancers exist between India and the United Kingdom.For example,Indian patients with breast cancer typically present a decade earlier than in the UK.Reasons for this could be multifactorial,including differences in underlying biology,environmental risks,and other systematic factors including access to screening.One possible explanation lies in variable incidence or penetrance of germline mutations in genes such as BRCA1 and BRCA2.We performed a methodical database and literature review to investigate the prevalence and spectrum of high-risk cancer susceptibility genes in Indian patients with breast and ovarian cancers.We identified 148 articles,but most studies were small,with inconsistent inclusion criteria and based on heterogeneous technologies,so that mutation frequency could not be reliably ascertained.Data were also often lacking on penetrance,histopathology,and survival outcomes.After filtering out unsuitable studies,only 13 remained,comprising 1028 patients.Large-scale research studies are urgently needed to determine mutation prevalence,spectra,and clinico-pathological features,and hence derive guidelines for screening,treatment,and prevention specific to the Indian population.
文摘背景与目的:携带BRCA1/2基因胚系突变的女性终生罹患卵巢癌、乳腺癌和其他癌症的风险增加,早期识别此部分高风险人群,并采取针对性的风险管理方案对降低癌症的发病率和死亡率非常重要,本研究旨在分析携带BRCA1/2基因胚系突变的遗传性乳腺癌-卵巢癌综合征(hereditary breast-ovarian cancer syndrome,HBOC)患者一级亲属接受基因筛查的现状及影响因素。方法:采用便利抽样法选取2021年2月—2022年4月在复旦大学附属妇产科医院就诊的72例已确诊BRCA1/2基因胚系突变的HBOC女性患者及其316名一级亲属,采用问卷调查法了解HBOC患者一级亲属是否接受基因筛查的现状;并采用logistic回归分析相关的影响因素。结果:在72例HBOC女性患者中,93.1%(n=67)将基因筛查结果传达给了她们的一级亲属。在18岁以上的一级亲属中,32.3%(n=102)决定进行基因筛查和遗传风险管理。Logistic回归分析显示,患者疾病类型、卵巢癌国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)分期、受教育程度、一级亲属性别、受教育程度及患者与亲属的情感亲密度是一级亲属是否愿意接受基因筛查和遗传风险管理的显著影响因素(P<0.05)。结论:HBOC患者一级亲属接受基因筛查的现状不容乐观。鉴于乳腺癌患者、文化程度较低的患者,男性亲属、文化程度较低的亲属及与患者情感亲密度较低的亲属接受基因筛查的概率较低,我们应采取针对性的干预措施提高这部分亲属的自我基因筛查行为。
