• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.4
• /
• pp.1355-1360
• /
• 2012

Background: The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of breast cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice. Materials and Methods: We systematically searched PubMed, Embase, Elsevier and Springer for relevant articles published before Nov 2011. Summary odds ratio (OR) and 95% confidence interval (95% CI) incidence rates were calculated using a random-effects model with STATA (version 10.0) software. Results: A total of fifteen case-control studies, including 19,621 cases and 27,001 controls based on the search criteria, were included for analysis. A significant association was found between carrying the CHEK2 I157T variant and increased risk of unselected breast cancer (OR = 1.48, 95% CI = 1.31-1.66, P < 0.0001), familial breast cancer (OR = 1.48, 95% CI = 1.16-1.89, P < 0.0001), and early-onset breast cancer (OR = 1.47, 95% CI = 1.29-1.66, P < 0.0001). We found an even stronger significant association between the CHEK2 I157T C variant and increased risk of lobular type breast tumors (OR = 4.17, 95% CI = 2.89-6.03, P < 0.0001). Conclusion: Our research indicates that the CHEK2 I157T variant may be another important genetic mutation which increases risk of breast cancer, especially the lobular type.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.7
• /
• pp.3615-3617
• /
• 2016

Background: Breast cancer molecular analysis by linkage analysis has the advantage of facilitating early diagnosis in asymptomatic genetic carriers, with a view to the preventive follow-up of these subjects and genetic counseling. The aim of this study was to evaluate BRCA1 gene D17S855 and D17S1322 markers in breast cancer patients. Materials and Methods: A series of 85 BC patients and 85 unrelated healthy women were recruited for haplotype analysis performed using two short tandem repeat markers located within the BRCA1 gene locus. Each marker was amplified with PCR genomic DNA from each individual and fluorescently end-labeled primers. Results: Both D17S855 and D17S1322 markers included 12 kinds of alleles. Results indicate that most of the BC patients shared two common 121-150 (11.2%, RR=1.56 and p=0.02) and 121-146 (5.6%, RR=1.9 and p=0.02) haplotypes. Conclusions: Our results should be helpful to understand the haplotype phase in the BRCA1 gene and establish a genetic screening strategy in the Iranian population.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.2247-2254
• /
• 2016

Background: The incidence of breast cancer is rising in Oman, and the disease is diagnosed at late stages, when treatment success is limited. Omani women might benefit from better awareness, so that breast cancer can be detected early and treated. This study was conducted to assess Omani women's levels of breast cancer awareness and early detection practice, and explore factors which might influence these levels. Materials and Methods: A mixed methods study was conducted in 2014, including a quantitative survey of 1,372 and a qualitative assessment of 19 Omani women, aged ${\geq}20years$ from five Omani governorates using convenient sampling. Demographic information and scores for awareness levels were used in a multivariate regression model to investigate factors associated with awareness. Thematic analysis and interpretive description were used to analyse the qualitative data. Results: The overall means for early detection and general awareness scores were 0.58 (SD 0.24) and 0.46 (SD 0.21), respectively. General awareness was significantly associated with age, education, income and familiarity with cancer patients (p<0.05), while early detection was significantly associated with age, marital status and education. A majority of women (59.5%) agreed with a belief in 'evil eye' or envy as a risk factor for breast cancer. Women discussed various factors which may empower or inhibit awareness, including the cultural-religion-fatalistic system, personal-familial-environmental system, and healthcare-political-social system. Conclusions: The overall low scores for awareness and early detection, and the survey of local beliefs highlight a severe necessity for a contextually-tailored breast cancer awareness intervention programme in Oman.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.7
• /
• pp.4339-4345
• /
• 2013

Background: The purpose of this study was to evaluate the prevalence of BRCA1 (MIM: 113705) founder mutations in familial breast cancer (BC) patients with high risks in Iran. BRCA1 is among the cancer susceptibility genes best known for high penetrance mutations. BRCA1 genotyping is now used to determine patient counseling, management decisions, and prognosis of this syndrome. Materials and Method: Thirty nine patients with clinical BC and 29 high risk healthy women, related to the patients, participated in the study. DNA from blood samples was extracted and analyzed by PCR and SSCP methods in order to find 185delAG and 5382insC founder mutations. In addition, a 251bp fragment of BRCA1's exon 11 was amplified and analyzed for determination of new mutations. Results: The data indicated the presence of 185delAG and 5382insC founder mutations in both groups studied. Two out of 39 BC patients (5.1%) and one out of 29 relatives (3.4%) were suspected to be carriers of 185delAG mutations. However, we found only one patient (2.6%) to be a carrier of a 5382insC mutation. Also, 2 women (5.1%) of the patient group and 3 n (10.3%) of relatives group were identified as carriers of unclarified mutations in the 251bp fragment of the BRCA1 gene. The carriers of BRCA1 founder mutations have a high lifetime risk of breast cancer. Conclusions: Therefore, these data are useful in counseling of individuals with a significant family history of breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.1539-1546
• /
• 2016

Specific patterns of the hereditary breast and ovarian cancer (HBOC) syndrome are related to mutations in the BRCA1 gene. One hundred unrelated breast cancer patients were interviewed to obtain clinical symptoms and signs, pedigree and familial history of HBOC syndrome related cancer. Subsequently, data were calculated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk prediction model. Patients with high score of BOADICEA were offered genetic testing. Eleven patients with high score of BOADICEA, 2 patients with low score of BOADICEA, 2 patient's family members and 15 controls underwent BRCA1 genetic testing. Mutation screening using PCR-HRM was carried out in 22 exons (41 amplicons) of BRCA1 gene. Sanger sequencing was subjected in all samples with aberrant graph. This study identified 10 variants in the BRCA1 gene, consisting of 6 missense mutations (c.1480C>A, c.2612C>T, c.2566T>C, c.3113A>G, c.3548 A>G, c.4837 A>G), 3 synonymous mutations (c.2082 C>T, c.2311 T>C and c.4308T>C) and one intronic mutation (c.134+35 G>T). All variants tend to be polymorphisms and unclassified variants. However, no known pathogenic mutations were found.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.3229-3235
• /
• 2013

Background: Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk. Methods: We genotyped seven mutations in BRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breast cancer patients and 80 healthy controls. Results: We found significant associations in the analyses of CHEK2- 1100delC (p=0.001) and BRCA1-5382insC (p=0.021) mutations in breast cancer patients compared to controls. The highest risk was observed among breast cancer patients carrying both CHEK2-1100delC and BRCA2- Met784Val mutations (OR=0.093; 95%CI 0.021-0.423; p=0.001). We identified one previously undescribed BRCA2 and a CHEK2 four-marker haplotype of A-C-G-C which was overrepresented ($X^2$=7.655; p=0.0057) in the patient group compared to controls. Conclusion: In this study, we identified a previously undescribed BRCA2 and CHEK2 A-C-G-C haplotype in association with the breast cancer in our population. Our results further suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to an unexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role in the development and prognosis of breast cancer.

• Molecules and Cells
• /
• v.38 no.3
• /
• pp.251-258
• /
• 2015

Germline mutations in the breast cancer type 2 susceptibility gene (BRCA2) are linked to familial breast cancer and the progressive bone marrow failure syndrome Fanconi anaemia. Established Brca2 mouse knockout models show embryonic lethality, but those with a truncating mutation at the C-terminus survive to birth and develop thymic lymphoma at an early age. To overcome early lethality and investigate the function of BRCA2, we used T cell-specific conditional Brca2 knockout mice, which were previously shown to develop thymic lymphoma at a low penetrance. In the current study we showed that the number of peripheral T cells, particularly na$\ddot{i}$ve pools, drastically declined with age. This decline was primarily ascribed to improper peripheral maintenance. Furthermore, heterozygous mice with one wild-type Brca2 allele manifested reduced T cell numbers, suggesting that Brca2 haploinsufficiency might also result in T cell loss. Our study reveals molecular events occurring in Brca2-deficient T cells and suggests that both heterozygous and homozygous Brca2 mutation may lead to dysfunction in T cell populations.

• Toxicological Research
• /
• v.14 no.2
• /
• pp.123-127
• /
• 1998

BRCA1 is a tumor suppresser gene in familial cases of breast cancer. It has been controversial whether the subcellular localization of BRCA1 is located in nuclei or cytoplasm in normal human breast cells. We found that a p220 protein was expressed in Type II Normal human breast epithelial cells (NHBEC) but not in Type I NHBEC in Western blot analysis using the 17F8 (3A2) antibody. Immunostaining using the same antibody revealed positive staining in nuclei, cytoplasm and perinuclei of Type II cells and negative staining in Type I NHBEC. The p220 protein, however, was expressed in SV40 immortalized Type I NHBEC and tumorigenic cells derived from them after x-ray and neu oncogene treatment. The subcelluar localization was mostly cytoplasmic and punctate in the nuclei. The breast carcinoma cell lines, MCF-7 and T47D, also expressed the p220 protein. Using RT-PCR, we observed the expression of BRCA1 mRNA in both Type I and Type II NHBEC. This result indicated that there might be mechanisms involved in post-translational or translational regulation of BRCA1 gene. It is speculated that the absence of BRCA1 protein expression in Type I NHBEC might playa role in their susceptibility to neoplastic transformation.

• Journal of Nutrition and Health
• /
• v.40 no.4
• /
• pp.334-346
• /
• 2007

The present study examined the reproductive factors and food intake pattern which influence on the breast cancer risk in Daegu${\cdot}$Gyungbuk area. The case subjects were 103 patients newly diagnosed as breast cancer at Kyungpook National University Hospital. The control subjects were 159 healthy women selected by frequency matching of age and menopausal status in the same community. The survey was conducted by individual interviews using questionnaires which include general and reproductive characteristics, dietary habits, and food frequency. The odds ratios were calculated by using unconditional logistic regression after adjusting for confounding variables. The mean age of the subjects was 50 yrs, and mean body mass index was significantly high in the patient group than in the control. The patient group had a significantly higher familial history of breast cancer and a significantly shorter breast-feeding period compared to the control group. It has been found no significant relationship between extrinsic hormone use such as oral contraceptives or estrogen replacement therapy and breast cancer risk. In regard of food habits, a high preference for the cooking method of steaming rather than frying, panbroiling or roasting was significantly associated with lower relative risk of breast cancer. The higher intake frequencies of fruits for all subjects, and seaweeds only for postmenopausal subjects were related with a significantly lower relative risk of breast cancer. The results of the study suggest that the possible risk factors for the breast cancer occurrence include high BMI, family history, less breast feeding experience, preference for the cooking method of frying, and less consumption of fruits and seaweeds. This study provides an useful data for nutrition education to prevent breast cancer for the residents in Daegu${\cdot}$Gyungbuk area.

• Radiation Oncology Journal
• /
• v.26 no.1
• /
• pp.65-73
• /
• 2008

Purpose: Women with breast cancer diagnosed at an age of 40 years or younger have a greater prevalence of germline BRCA1 and BRCA2 mutations than the prevalence of women with breast cancer diagnosed at older ages. Several immunohistochemical characteristics have been identified in breast cancers from studies of Caucasian women with BRCA1/2 mutations having familial or early-onset breast cancers. The aim of this study is to determine whether early-onset breast cancer in BRCA1 or BRCA2 mutation carriers, who were not selected from a family history, could be distinguished by the use of immunohistochemical methods and could be distinguished from breast cancer in women of a similar age without a germline BRCA1 or BRCA2 mutation. We also analyzed the prognostic difference between BRCA1/2 related and BRCA1/2 non-related patients by the use of univariate and multivariate analysis. Materials and Methods: Breast cancer tissue specimens from Korean women with early-onset breast cancers were studied using a tumor tissue microarray. Immunohistochemical staining of estrogen receptor(ER), progesterone receptor(PR) and HER-2, as well as the histology and grade of these specimens, were compared. The prognostic impact of immunohistochemical and histological factors as well as the BRCA1/2 mutation status was investigated separately. Results: There were 14 cases and 16 deleterious BRCA1/2 mutations among 101 patients tested. A family history(4/14) and bilateral breast cancers(3/9) were high risk factors for BRCA1/2 mutations. BRCA1/2-associated cancers demonstrated more expression of ER-negative(19.4% versus 5.1%, p=0.038) and HER-2 negative than BRCA1/2 negative tumors, especially for tumors with BRCA1 tumors The BRCA1/2 mutation rate for patients with triple negative tumors(negative expression of ER, PR and HER-2) was 24.2%. Tumor size, nodal status, and HER-2 expression status were significantly associated with disease free survival, as determined by univariate and multivariate analysis, but the BRCA1/2 status was not a prognostic factor. Conclusion: Breast cancer that occurs in women with a germline BRCA1 or BRCA2 mutations have recognizable immunohistochemical features, which may be useful in identifying individuals that are more likely to carry germline mutations. Although the BRCA1/2 mutation status was not a prognostic factor in Korean women with early-onset breast cancer, more cases with a longer follow-up period are needed for further study.