Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history

The breast cancer susceptibility genes, BRCA1 and BRCA2, differ in their contribution to ovarian cancer. Recently, founder mutations in each of these genes were identified in Canadian breast cancer and breast ovarian cancer families of French ancestry. We have examined the prevalence of the founder mutations in a series of 113 French Canadian women with ovarian cancer unselected for family history. Germline mutations were found in eight of 99 invasive carcinomas and in none of the 14 tumors of borderline malignancy. Five cases carried the BRCA1 C4446T mutation and two cases carried the BRCA2 8765delAG mutation which are the most common mutations that have been described in French Canadian breast cancer and breast ovarian cancer families. All of these cases reported a family history of at least one first-degree relative with breast cancer, diagnosed below age 60 years, or with ovarian cancer. The identification of founder BRCA1 and BRCA2 mutations in ovarian cancer cases unselected for family history can facilitate carrier detection when the expected yield of a comprehensive screen may be low.     

Prevalence of founder BRCA1 and BRCA2 mutations in unselected French Canadian women with breast cancer

The frequency of BRCA1 and BRCA2 mutations in women with breast cancer varies according to the age at diagnosis, family history of cancer, and ethnicity/country of origin. We set out to estimate the frequency of seven previously described founder mutations in BRCA1 and BRCA2 in all eligible French Canadian women diagnosed with invasive breast cancer at one Montreal hospital over a 20-month period. One hundred and ninety-two patients were eligible and 127 (66.2%) provided blood for genetic testing. We identified 4 women who carried a founder mutation (3.1%, 95% confidence interval 0.9-7.9%) in this population. Interestingly, all the mutations were in BRCA2. The mean age at diagnosis for mutation carriers was 51.2 years (range 49.1-53.5). Two of these 4 cases were lobular invasive carcinomas and 2 were ductal carcinomas, histological grade 1 or 2. Despite a small tumor size (< or =20 mm), axillary nodal involvement was present in 3 women. Estrogen receptors were strongly expressed in all cases. Two of the 4 cases reported a strong family history of breast cancer, but a family history of site-specific breast cancer was a relatively poor indicator of the presence of BRCA2 mutations. The absence of BRCA1 mutations may be a result of chance, but may also reflect different geographical origins of the most common BRCA1 mutations within the French Canadian population.     

Contribution of the BRCA1 and BRCA2 mutations to breast cancer in Tunisia

Hereditary breast cancer accounts for 3–8% of all breast cancers, with mutations in the BRCA1 and BRCA2 genes responsible for up to 30% of these. To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, we studied 36 patients who had at least one first degree relative with breast and/or ovarian cancer Thirty-four 34 patients were suggestive of the BRCA1 mutation and two were suggestive of the BRCA2 mutation, based on the presence of male breast cancer detected in their corresponding pedigrees. Four mutations in BRCA1 were detected, including a novel frame-shift mutation (c.211dupA) in two unrelated patients and three other frameshift mutations – c.4041delAG, c.2551delG and c.5266dupC. Our study is the first to describe the c.5266dupC mutation in a non-Jewish Ashkenazi population. Two frameshift mutations (c.1309del4 and c.5682insA) were observed in BRCA2. Nineteen percent (7/36) of the familial cases had deleterious mutations of the BRCA1 or BRCA2 genes. Almost all patients with deleterious mutations of BRCA1 reported a family history of breast and/or ovarian cancer in the index case or in their relatives. Our data are the first to contribute to information on the mutation spectrum of BRCA genes in Tunisia, and we give a recommendation for improving clinical genetic testing policy.     

Contribution of BRCA1 and BRCA2 germline mutations to the incidence of early-onset breast cancer in Cyprus

In Cyprus, the prevalence of breast cancer associated with BRCA1 and BRCA2 mutations in young women is unknown. In this study, we present the results of mutational analysis of the BRCA1 and BRCA2 genes in 26 Cypriot women diagnosed with breast cancer by the age of 40. The entire coding regions, including splice sites, of the BRCA1 and BRCA2 genes were sequenced using cycle sequencing. We identified four pathogenic mutations: two in BRCA1 [c.1840A>T (K614X), c.5310delG (5429delG)] and two in BRCA2 [c.3531-3534delCAGC (3758del4), c.8755delG (8984delG)] in six of 26 unrelated patients. The BRCA2 mutation c.3531-3534delCAGC (3758del4) is novel and the BRCA1 mutation c.1840A>T (K614X) is reported for the first time in Cypriot patients. The BRCA2 Cypriot founder mutation c.8755delG (8984delG) was detected in three unrelated patients. Additionally, we identified one novel BRCA1 missense mutation, two novel polymorphisms and three novel intronic variants of which BRCA1 c.4185+3A>G (IVS12+3A>G) may be pathogenic. Of the six BRCA1/2 mutation carriers, only four had a family history. These results show that the prevalence of BRCA1 and BRCA2 mutations in Cypriot women diagnosed with early-onset breast cancer is high. We conclude that Cypriot women with early-onset breast cancer should be offered BRCA1/2 testing irrespective of their family history.     

BRCA1 and BRCA2 mutations in Russian familial breast cancer

We have screened index cases from 25 Russian breast/ovarian cancer families for germ‐line mutations in all coding exons of the BRCA1 and BRCA2 genes, using multiplex heteroduplex analysis. In addition we tested 22 patients with breast cancer diagnosed before age 40 without family history and 6 patients with bilateral breast cancer. The frequency of families with germline mutations in BRCA was 16% (4/25). One BRCA1 mutation, 5382insC, was found in three families. The results of present study, and those of a separate study of 19 breast‐ovarian cancer families, suggest that BRCA1 5382insC is a founder mutation in the Russian population. Three BRCA2 mutations were found in patients with breast cancer without family history: two in young patients and one in patients with bilateral breast cancer. Four novel BRCA2 mutations were identified: three frameshift (695insT, 1528del4, 9318del4) and one nonsense (S1099X). © 2002 Wiley‐Liss, Inc.     

Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer

We ascertained 184 Ashkenazi Jewish women with breast/ovarian cancer (171 breast and 13 ovarian cancers, two of the former also had ovarian cancer) in a self-referral study. They were tested for germline founder mutations in BRCA1 (185delAG, 5382insC, 188del11) and BRCA2 (6174delT). Personal/family histories were correlated with mutation status. Logistic regression was used to develop a model to predict those breast cancer cases likely to be germline BRCA1/BRCA2 mutation carriers in this population. The most important factors were age at diagnosis, personal/family history of ovarian cancer, or breast cancer diagnosed before 60 years in a first degree relative. A total of 15.8% of breast cancer cases, one of 13 ovarian cancer cases (7.7%), and both cases with ovarian and breast cancer carried one of the founder mutations. Age at diagnosis in carriers (44.6 years) was significantly lower than in non-carriers (52.1 years) (p<0.001), and was slightly lower in BRCA1 than BRCA2 carriers. Thirty three percent of carriers had no family history of breast or ovarian cancer in first or second degree relatives. Conversely, 12% of non-mutation carriers had strong family histories, with both a first and a second degree relative diagnosed with breast or ovarian cancer. The predicted values from the logistic model can be used to define criteria for identifying Ashkenazi Jewish women with breast cancer who are at high risk of carrying BRCA1 and BRCA2 mutations. The following criteria would identify those at approximately 10% risk: (1) breast cancer <50 years, (2) breast cancer <60 years with a first degree relative with breast cancer <60 years, or (3) breast cancer <70 years and a first or second degree relative with ovarian cancer.     

Prevalence of founder mutations in the BRCA1 and BRCA2 genes among unaffected women from the Bahamas

Population‐based testing for BRCA1/2 mutations detects a high proportion of carriers not identified by cancer family history‐based testing. We sought to determine whether population‐based testing is an effective approach to genetic testing in the Bahamas, where 23% of women with breast cancer carry one of seven founder mutations in the BRCA1 or BRCA2 gene. We determined the prevalence of founder BRCA mutations in 1847 Bahamian women without a personal history of breast or ovarian cancer, unselected for age or family history. We found that 2.8% (20/705) of unaffected women with a family history of breast/ovarian cancer and 0.09% (1/1089) of unaffected women without a family history carry a BRCA mutation. A total of 38% of unaffected women with a known mutation in the family were found to carry the familial mutation. We previously suggested that all Bahamian women with breast or ovarian cancer be offered genetic testing. These current data suggest that additionally all unaffected Bahamian women with a family history of breast/ovarian cancer should be offered genetic testing for the founder BRCA mutations.     

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation‐positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer.     

中国早发性乳腺癌患者中BRCA1基因突变分析

目的研究中国早发性乳腺癌患者中BRCA1基因致病性突变的发生情况以及家族史在突变携带者识别中的作用。方法研究对象为来自中国4个乳腺癌临床医疗中心的188例早发性乳腺癌病例(发病年龄≤40岁),其中39例(20.1%)有乳腺/卵巢癌家族史。从外周静脉血提取基因组DNA,对BRCA1基因的全部编码区和外显子/内含子拼接区进行PCR扩增。其中22例通过单链构象多态方法进行突变初筛,166例用变性高效液相色谱分析进行初筛;对发现的异常片段通过DNA直接测序的方法进行确认。对发现重复出现突变的样本,选取5个与BRCA1基因连锁的标记(D17S855、D17S1322、D17S1323、D17S1326和D17S1327)进行等位基因型分析。结果在15例(8.0%)患者中发现有12个BRCA1基因的致病性突变,其中BRCA11100delAT和5589del8突变分别在3个和2个患者中发现。在39例同时伴有乳腺/卵巢癌家族史的病例中共发现有9例(23.1%)携带突变。有(无)乳腺癌家族史的早发性乳腺癌病例间BRCA1基因的突变率的差异有统计学意义(P=0.001)。重复出现的突变在所有检测病例中出现的频率为2.7%,在所有检测到的突变中占33.3%。两个来自中国北方的BRCA11100delAT突变携带病例有相同的等位基因型,而与来自上海地区的此突变携带者的等位基因型在D17S1322位点上有所差异。两例5589del8突变携带者在所检测的5个STR位点上有完全相同的等位基因型。结论这是到目前为止较大规模的关于中国早发性乳腺癌人群的BRCA1基因突变的研究,有助于增加对中国早发性乳腺癌人群中BRCA1基因致病性突变分布的全面认识。在中国早发性乳腺癌人群中,BRCA1基因致病性突变在肿瘤的发生中有比较重要的意义,尤其在伴有乳腺/卵巢癌家族史病例中该基因突变的意义尤为突出。两个重复出现的突变可能在中国人群中有始祖效应,在进行全基因检测前对其先进行检测可能非常合算。     

中国上海家族性乳腺癌BRCA1和BRCA2基因的突变

目的研究上海地区家族性乳腺癌中BRCA1／BRCA2基因的突变位点及携带情况。方法研究对象来自35个汉族家族性乳腺癌家系，家系中至少有一个一级亲属乳腺癌患病史。共35例患者，其中13例发病年龄≤加岁。由静脉血提取基因组DNA，对BRCA1／BRCA2基因的全部编码序列进行扩增。扩增产物突变分析先由变性高效液相色谱分析进行筛查，之后进行DNA直接测序证实。结果在BRCA1基因中发现有4个突变位点，其中2个为新发现位点——拼接点突变（IVS17-1G〉T；IVS21＋1G〉C）；另两个为已报道的致病突变位点——移码突变（1100delAT；5640delA）。BRCA2基因的1个致病突变位点位于11号外显子上，为移码突变（5802delAATT）。另外，共发现有12个新的单核苷重复多态位点，都未引起氨基酸编码改变；其中，8个在BRCA1基因上，4个在BRCA2基因上。在家族性乳腺癌中，BRCA1突变频率（11．4％）高于BRCA2基因（2．9％）。结论新发现的2个BRCA1基因的拼接点突变可能是中国上海人群家族性乳腺癌的特有突变位点；在我国上海地区人群中，BRCA1基因突变起着比BRCA2基因更大的作用；该研究丰富了中国人群中BRCA基因的突变谱，并为未来的临床基因检测提供了筛查模式。     

Family history, BRCA mutations and breast cancer in Vietnamese women

The purpose of this report is to estimate the proportions of familial and hereditary breast cancers among unselected cases of breast cancer in Vietnam. Two hundred and ninety-two unselected cases of incident breast cancer were recruited from the National Cancer Hospital, Hanoi, the largest cancer centre in Vietnam. Family histories were collected for 292 cases and a DNA sample was obtained for 259 cases. DNA samples were screened for mutations in the large exons of BRCA1 and BRCA2 using the protein truncation test and by allele-specific testing for 17 founder mutations which have been reported in other Asian populations. Complete gene sequencing was performed on two cases of familial breast cancer. Seven of 292 cases reported a relative with breast cancer and one patient reported a relative with ovarian cancer. A pathogenic BRCA mutation was detected in 2 of 259 cases; one BRCA1 carrier was diagnosed at age 51 and one BRCA2 carrier was diagnosed at age 42. Neither case reported a relative with breast or ovarian cancer. A family history of breast cancer is very uncommon among Vietnamese breast cancer patients. The frequency of pathogenic BRCA mutations in Vietnamese breast cancer patients is among the lowest reported worldwide.     

Mutational analysis of BRCA1 and BRCA2 in Mediterranean Spanish women with early-onset breast cancer: identification of three novel pathogenic mutations

In Spain, the contribution of BRCA mutations to the population incidence of early-onset breast cancer was unknown. We carried out a mutational analysis of the BRCA1 and BRCA2 genes in 124 Spanish women diagnosed with breast cancer before the age 41 and who were not selected for a family history of this disease. The genetic study was performed by PCR-SSCP analysis and DNA sequencing. We identified 6 pathogenic BRCA mutations in 7 unrelated probands (5.6%; 95% CI=2.3% to 11.3%): 1 BRCA1 (c.2080delA) and 5 BRCA2 (p.Y3006X, p.Q1994X, c.9204_9217del14, c.9254_9258del5 and c.295+2T>C). Three out of 6 mutations were novel (BRCA2 p.Y3006X, c.9204_9217del14, and c.295+2T>C), and two further mutations had not been previously found in Spain (BRCA1 c.2080delA and BRCA2 p.Q1994X). The one remaining (BRCA2 c.9254_9258del5) was detected in two probands of our sample. Additionally, we identified two new missense mutations: BRCA1 p.P1812A and BRCA2 p.G2044A. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of BRCA mutations, some of which appear as founding mutations. We categorized patients into familial or non-familial groups on the basis of her family history of breast/ovarian cancer; this analysis indicated that among Spanish women with early-onset breast cancer, an even moderate family history is a good predictor of being a BRCA mutation carrier.     

Family history as a predictor of uptake of cancer preventive procedures by women with a BRCA1 or BRCA2 mutation

Women with a BRCA1 or BRCA2 mutation are at an elevated risk of developing breast and ovarian cancer; however, it is unclear to what extent family history influences the uptake of cancer prevention options.Women with a BRCA1/2 mutation completed a follow-up questionnaire that assessed uptake of cancer preventive options. The pedigree of each woman was reviewed, and information was recorded on cancers diagnosed in relatives. Five hundred and seventeen women were included in the study. Women with a sister with breast cancer were more likely to have a prophylactic mastectomy than those without a sister with breast cancer [odds ratios (OR) = 2.4, p = 0.003]. Uptake of prophylactic mastectomy was significantly lower in women with a mother with ovarian cancer compared with those whose mother did not have ovarian cancer (OR = 0.4, p = 0.01). Having a mother or sister with ovarian cancer significantly predicted the uptake of prophylactic oophorectomy (OR = 1.6, p = 0.04). Women with a BRCA2 mutation were less likely to have a prophylactic oophorectomy than those with a BRCA1 mutation (OR = 0.49, p = 0.0004). Among women with a BRCA1 or BRCA2 mutation, family history predicts the uptake of prophylactic mastectomy and prophylactic oophorectomy.     

High incidence of mutations in <Emphasis Type="Italic">BRCA1 and BRCA2</Emphasis> genes in ovarian cancer

The incidence of mutations in the BRCA1 and BRCA2 genes in the studied sampling of 74 patients with ovarian cancer was 19%. The incidence of mutations in the Russian sampling of patients, formed without consideration for the family history, is one of the highest in European countries. Retrospective analysis showed that 9% patients carrying mutation had no family history of ovarian or breast cancer. The majority of mutations (86%) were detected in BRCA1 gene, where 5382insC mutation predominated (58%). These data suggest the possibility and advisability of screening for mutations in the BRCA1/2 genes in patients with ovarian cancer, particularly because this population includes patients without family history of ovarian and/or breast cancer. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 7, pp. 93–95, July, 2007     

Characterization of ten novel and 13 recurring BRCA1 and BRCA2 germline mutations in Italian breast and/or ovarian carcinoma patients. Mutations in brief no. 178. Online

Germline mutations in the BRCA1 and BRCA2 genes are associated with approximately 80% of families with a high incidence of breast and/or ovarian cancers (OMIM database reference numbers: 113705, 600185). Furthermore, constitutional mutations in the these genes have been reported in women with early-onset breast carcinoma and without family history of cancer. We analyzed by protein truncation test (PTT) and single strand conformation polymorphism (SSCP) followed by sequence analysis, BRCA1 exons 11 and 20 and BRCA2 exons 10 and 11 in 142 Italian cancer patients. These included six male breast cancer cases, 61 women with breast carcinoma diagnosed before 36 years old and selected independently of family history of breast cancer and 75 familial breast and/or ovarian cancer patients. In a previous report, we described 11 different BRCA1 mutations in a subset of 70 cases. Here, we report the characterization of 23 additional mutations, 14 in BRCA1 and 9 in BRCA2, subsequently identified. Ten mutations were not previously described, while the other 13 were recurrent. Of the 61 women with early-onset breast cancer, 11 carried a germline mutation in BRCA1 (18.0%) and four in BRCA2 (6.6%). These frequencies indicate that BRCA1/BRCA2 genetic tests should be advised to women with breast cancer diagnosed at early age, independently of family history of cancer.     

Probability of BRCA1/2 mutation varies with ovarian histology: results from screening 442 ovarian cancer families

While there are many reports in the literature of mutation testing of BRCA1 and BRCA2 in breast/ovarian cancer families, the question of which type of ovarian cancers are relevant still pertains. We have undertaken whole gene screening including multiple ligation-dependent probe amplification in an affected individual within 442 unrelated non-Jewish families containing at least one reported ovarian cancer diagnosed less than 50 years or at any age with family history of breast or ovarian cancer for mutations in BRCA1 and BRCA2. A total of 166 mutations were identified 110 (25%) in BRCA1 and 56 (13%) in BRCA2 . In families without confirmation of ovarian diagnosis, the detection rate drops significantly. In families fulfilling Breast Cancer Linkage Consortium (BCLC) criteria with confirmed ovarian cancer cases, the mutation detection frequency was 80%. If only BCLC families with unconfirmed ovarian cancers were included, the detection rate dropped to 36% when a relevant ovarian cancer diagnosis was not confirmed. In BCLC families containing only one ovarian cancer, BRCA2 accounted for 45% of identified mutations. No mutations were identified in affected individuals with borderline or mucinous tumours. Detection rates dropped below the 10/20% international thresholds in a number of families with unconfirmed ovarian cancers. Borderline/mucinous pathology substantially reduces the likelihood of identifying a BRCA1/2 mutation. Strenuous efforts should be made to confirm ovarian pathology if the lack of confirmation or refuting the diagnosis would decrease a family's likelihood of mutation detection below screening thresholds. In the UK, a higher proportion of families harbour BRCA2 pathogenic mutations than predicted from previous studies.     

BRCA1 and BRCA2 mutations among 233 unselected Finnish ovarian carcinoma patients.

Germline mutations of BRCA1 and BRCA2 predispose to hereditary breast-ovarian cancer syndrome. In Finland, 20 different BRCA1/2 mutations have been identified, and 13 of them are founder mutations that account for the vast majority of Finnish BRCA1/2 families. The purpose of our study was to determine the prevalence of BRCA1/2 mutations in unselected Finnish ovarian carcinoma patients and to evaluate the relationship between mutation carrier status and personal/family history of cancer. Two hundred and thirty-three patients were screened for all the 20 BRCA1/2 mutations known in the Finnish population. Additionally, a subgroup of patients with personal history of breast cancer and/or family history of breast and/or ovarian cancer was screened for novel BRCA1/2 mutations. Thirteen patients (5.6%) had mutations: eleven in BRCA1 and two in BRCA2. All the mutation-positive patients were carriers of the previously known Finnish BRCA1/2 mutations, and seven recurrent founder mutations accounted for 12 of the 13 mutations detected. A logistic regression analysis was used to determine the odds of mutation for ovarian carcinoma patients. The most significant predictor of a mutation was the presence of both breast and ovarian cancer in the same woman, but family history of breast cancer was also strongly related to mutation carrier status. Although BRCA1/2 mutation testing is not warranted in the general Finnish ovarian cancer patient population, patients who have also been diagnosed with breast cancer or have family history of breast or breast and ovarian cancer could benefit from referral to genetic counselling and mutation testing.     

Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer

To investigate the role of BRCA1 and BRCA2 mutations in Korean patients with sporadic breast cancer, 793 breast cancer patients were analyzed by denaturing high performance liquid chromatography and direct sequencing. The 793 breast cancer patients enrolled in this study had no family history of affected first- or second-degree relatives with breast and/or ovarian cancer. Seventy-nine different sequence variations were identified, of which 34 were novel. Fifteen deleterious mutations were detected in 20 out of 793 patients (2.5%): 11 frameshift mutations and 4 nonsense mutations (seven in BRCA1 and eight in BRCA2), and no recurrent or founder mutations were observed in BRCA mutation screening. However, three mutations (K467X, 3972delTGAG, and R2494X in BRCA2) were identified in other studies of the Korean population. Of 793 patients, the clinicopathological information was obtained in 135 patients, who included 20 deleterious mutation-positive and 115 deleterious mutation-negative groups. The median age at diagnosis, histologic type, histologic grade and T stage did not show statistically significant difference between these two groups. BRCA-mutation-associated tumors showed lower estrogen receptor, progesterone receptor, and HER-2/neu but higher p53 expression. Although poor prognostic features were noted in BRCA-associated tumors, we did not find statistically significant differences. The present study will be helpful in the evaluation of the need for the genetic screening of germline BRCA mutations and reliable genetic counseling for sporadic breast cancer patients.     

海南西部地区乳腺癌患者 BRCA1 / 2 基因突变状态分析

目的 不同的区域及种族的 BRCA1 / 2 基因突变频率差异较大, 着重分析海南西部地区乳腺癌患 者 BRCA1 / 2 基因的突变状态及对患者预后的影响。 方法 选取 2015 年 10 月 ~ 2020 年 12 月在海南西部中 心医院住院并确诊为原发性乳腺癌的 256 例患者为研究对象, 采用变性高效液相色谱法 ( denaturing high performance liquid chromatography, DHPLC) 筛查乳腺癌患者是否存在 BRCA1 / 2 基因突变, 分析 BRCA1 / 2 基 因突变状态及 BRCA1 / 2 基因突变患者的临床特征, 并随访分析患者 5 年生存情况, COX 回归分析影响患者 预后的因素。 结果 256 例乳腺癌患者中共检出 53 例患者发生 BRCA1 / 2 基因突变, 其中 BRCA1 突变率 12. 11 % (31 / 256), BRCA2 突变率 8. 59 % (22 / 256), 其中有害变异率为 7. 03 % (18 / 256)。 BRCA1 / 2 基 因突变患者家族病史、 妇科疾病史、 乳腺疾病史、 雌激素受体 (estrogen receptor, ER)、 原癌基因 (CerbB2) 蛋白阳性比例以及临床病理分级、 临床分期与未突变患者比较差异有统计学意义 (P< 0. 05)。 患者总 体生存率为 83. 59 % , BRCA1 / 2 基因突变者生存率低于未突变者 (P< 0. 05), COX 回归分析显示, BRCA1 / 2 基因突变、 乳腺疾病史、 临床分期、 CerbB-2 阳性、 CEA、 CA199 均是影响乳腺癌患者生存的危险因素 (P< 0. 05)。 结论 通过 DHPLC 可有效筛查海南西部地区乳腺癌患者 BRCA1 / 2 基因的有害变异, BRCA1 / 2 基因突变与临床病理特征及预后密切相关。     

BRCA1 and BRCA2 mutation analysis of early-onset and familial breast cancer cases in Mexico

The entire coding regions of BRCA1 and BRCA2 were screened for mutations by heteroduplex analysis in 51 Mexican breast cancer patients. One BRCA1 and one BRCA2 truncating mutation each was identified in the group of 32 (6%) early-onset breast cancer patients (< or =35 years). Besides these two likely deleterious mutations, eight rare variants of unknown significance, mostly in the BRCA2 gene, were detected in six of 32 (19%) early-onset breast cancer cases and in three of 17 (18%) site-specific breast cancer families, one containing a male breast cancer case. No mutations or rare sequence variants have been identified in two additional families including each an early-onset breast cancer case and an ovarian cancer patient. The two truncating mutations (BRCA1 3857delT; BRCA2 2663-2664insA) and six of the rare variants have never been reported before and may be of country-specific origin. The majority of the alterations appeared to be distinct, with only one of them being observed in more than one family.