[Identification of nucleotide changes of two known causative genes [BRCA2 and STK11] of hereditary breast cancer in an Iranian family using exome sequencing]

Since the identification of the two highly penetrant dominantly inherited genes, BRCA1/2, in the 1990s, a number of other genes have been identified which account for approximately 25% of the genetic basis for hereditary breast cancer. At least 75% are unidentified. The goal of this study is to investigate the presence or absence of a recessive pattern of inheritance in this heterogeneous disease whose possibility has been previously discussed by researchers. In this study we used exome sequencing as the most recent approach for identification of the genetic basis of any disease. The results of exome sequencing were confirmed by Sanger sequencing. Although we did not find any homozygous mutation in this family, however a heterozygous 4bp deletion that led to a frame shift mutation was identified in exon 11 of the BRCA2 gene. Also identified was a heterozygous single nucleotide polymorphism in exon 9 of the STK11 gene. The rs80359352 variation identified in this family is one of the frequent pathogenic mutations in the BRCA2 gene that has been reported in the BIC database. This variation has been previously observed in other ethnic populations such as Caucasians, Hispanics and the Chinese. In this study, for the first time, we report this mutation in Iranian population and its segregation in hereditary breast cancer

ER-negative /PR-positive breast carcinomas or technical artifacts in immunohistochemistry?

Evaluation of estrogen [ER] and progesterone [PR] receptors is important in the management and prognosis of breast cancer patients. Immunohistochemistry [IHC] is currently the worldwide accepted methodology for detection of ER/PR receptors in breast carcinomas. However, technical artifacts may alter the results. Since most authorities believe that there are no true ER-negative/PR-positive breast tumors, therefore we hypothesized that technical artifact in IHC might cause ER-negative/PR positive cases. The clinical records of 2432 patients treated by surgery at six community hospitals for different histologic subtypes of breast carcinoma were reviewed. Among them, 43 [1.8%] patients reported as ER-negative/PR-positive were re-evaluated in a reference laboratory. Expressions of ER and PR were evaluated by IHC on the same paraffin block used for the initial testing. The repeat study showed that of the 43 patients with the initial results of ER-negative/PR-positive, 24 [55.8%] were ER-positive/PR-positive, 15 [34.9%] were ER-negative/PR-negative, and 4 [9.3%] were ER-positive/PR-negative. In none of the 43 cases were the initial results [ER-negative/PR-positive] confirmed. Technical artifacts in IHC may alter ER/PR results in breast carcinomas. The technical factors affecting steroid receptor IHC ought to be properly controlled to provide reliable results

[Validation of food frequency questionnaire to assess folate intake status in breast cancer patients]

Inadequate folate intake could be associated with increased breast cancer risk. The aim of the present study was to assess the folate intake by designed Food Frequency Questionnaire [FFQ] using plasma folate concentration. This analytic cross-sectional study was conducted to evaluate the validity of the semi-quantitative FFQ [136 items] in 152 women with confirmed breast malignancy aged between 35 - 85 years old.. Folate plasma level was assessed by means of automated electrochemiluminescence. The Pearson and partial correlation coefficients were performed between the plasma level of folate and crude, total and energy-adjusted [residual] folate intakes. Area under ROC curve [AUC], sensitivity, specificity, positive and negative predictive values and odds ratio were fulfilled in two models in order to achieve validity assessment. The folate plasma level was significantly correlated with total intake of vegetables, bread and cereal groups [p=0.001] and also with total intake of fruits [p=0.001] and dairy products [p=0.026]. After adjusting for confounders, the folate plasma levels were correlated significantly with daily [beta=0.39], and residual [beta=0.41] folate intake levels [p=0.001]. The area under ROC curves in model I [folate plasma level <5.9 ng/ml] was 0.74 [95%CI=0.63-0.85] and for model II [folate plasma level <10.0 ng/ml] was estimated as 0.61[95%CI= 0.51- 0.71]. Model I indicated more appropriate predictive value [p=0.001] of folate intake assessment via FFQ. The results of this study showed that FFQ described in this study could be a valid and appropriate tool for assessing folate intake status in dietary content of breast cancer patients and also could be representative and valid for assessing the folate rich-food intake status

Sister chromatid exchange in peripheral blood lymphocytes as a possible breast cancer risk biomarker: a study of Iranian patients with breast cancer

Sister chromatid exchanges [SCEs] can be induced by various genotoxic treatments, suggesting that SCEs reflect a DNA repair process and it may be a good index for assessment of genomic instability. However, the occurrence of genetic instability and in particular, of spontaneous SCEs has been strongly linked to cancer. Several chromosomal regions and many genes have been implicated in breast cancer. Blood samples were obtained from 31 Iranian breast cancer patients and 11 healthy women. SCE was measured in peripheral blood lymphocytes by adding to Ham'sF10 medium in presence of PHA, BrdU [5-bromo-deoxy Uridine] fluorochrome Hoechst 33258, exposure to UV light and Giemsa staining. Then, SCE frequencies of patient and control groups were compared by the Mann-Withney U-test. Significantly difference was observed between two groups [p < 0.001]. This study indicates that SCE can be used as a risk biomarker for breast cancer

Penetrance of BRCA1/BRCA2 specific gene mutations in Iranian women with breast cancer

To estimate the penetrance of breast cancer genes 1 and 2 BRCA1/BRCA2 specific gene mutations in Iranian women with breast cancer. We conducted this study in the Department of Biostatistics, Tarbiat Modares University, Tehran, Iran between January and May 2008. The information was collected from the referral database of the Cancer Clinics, Day General Hospital, Tehran, Iran. We estimated the penetrance of breast cancer in carriers of BRCA1/2 specific gene mutations based on the modified kin-cohort method. Three hundred and forty-five probands were examined for specific mutations of BRCA1/2 genes. The estimated penetrance for the age groups among BRCA1/2 carriers was 31.9% < 50 years and 46.2% >/= 50 years. The reliable information of penetrance is considered important in genetic counseling. The low value of the estimated penetrance in this study might be attributed to the rare mutation in Iranian patients. Establishment and use of a kin-cohort gene databank is proposed as a solution for the preparation of the screening programs and the estimation of the penetrance to help reduce the risk of cancer