• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4513-4518
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• 2014

The prevalence of BRCA1 gene mutations in breast cancer differs between diverse ethnic groups. Relatively little information is known about patterns of BRCA1 mutations in early-onset breast cancer in women of Uighur or Han descent, the major ethnic populations of the Xinjiang region in China. The aim of this study was to identify BRCA1 mutations in Uighur and Han patients with early-onset (age <35 years), and sporadic breast cancer for genetic predisposition to breast cancer. For detection of BRCA1 mutations, we used a polymerase chain reaction single-stranded conformation polymorphism approach, followed by direct DNA sequencing in 22 Uighur and 13 Han women with early-onset sporadic breast cancer, and 32 women with benign breast diseases. The prevalence of BRCA1 mutations in this population was 22.9% (8/35) among early-onset sporadic breast cancer cases. Of these, 31.8% (7/22) of Uighur patients and 7.69% (1/13) of Han patients were found to have BRCA1 mutations. In 7 Uighur patients with BRCA1 mutations, there were 11 unique sequence alterations in the BRCA1 gene, including 4 clearly disease-associated mutations on exon 11 and 3 variants of uncertain clinical significance on exon 11, meanwhile 4 neutral variants on intron 20 or 2. None of the 11 BRCA1 mutations identified have been previously reported in the Breast Cancer Information Core database. These findings reflect the prevalence of BRCA1 mutations in Uighur women with early-onset and sporadic breast cancer, which will allow for provision of appropriate genetic counseling and treatment for Uighur patients in the Xinjiang region.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5331-5336
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• 2014

Background: Early onset breast cancer is associated with poor outcomes but variable results have been reported. It is a significant problem in Pakistani women but remains under reported. Breast conservation plays an important role in surgical management of this younger patient group. The objective of this study was to determine the outcome of breast conservative therapy in patients with early onset breast cancer in our population and compare it with their older counterparts. Materials and Methods: A review of patients with invasive breast cancer who underwent breast conservation surgery at Shaukat Khanum Cancer Hospital from 1997 to 2009 was performed. Patients were divided into two groups i.e. Group I age ${\leq}40$ and Group II >40 years. A total of 401 patients with breast cancer were identified in Group I and 405 patients in Group II. Demographics, histopathological findings and receptor status of the two groups were compared. The Chi square test was used for categorical variables. Outcome was assessed on basis of 10 year locoregional recurrence free survival (LRRFS), disease free survival (DFS) and overall survival (OS). For survival analysis Kaplan Meier curves were used and significance was determined using the Log rank test. Cox regression was applied for multivariate analysis. Results: Median follow up was 4.31 (0.1-15.5) years. Median age at presentation was 34.6 years (17-40) and 51.9 years (41-82) for the two groups. Groups were significantly different from each other with respect to grade, receptor status, tumor stage and use of neoadjuvant therapy. No significant difference was present between the two groups for estimated 10 year LRRFS (86% vs 95%) (p=0.1), DFS (70% vs 70%) (p=0.5) and OS (75% vs 63%) (p=0.1). On multivariate analysis, tumor stage was an independent predictor of LRRFS, DFS and OS. Conclusions: Early onset breast cancer is associated with a distinct biology but does not lead to poorer outcomes in our population.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7955-7958
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• 2014

Breast cancer is the most common cancer among women in the world. In Iran, the incidence of breast cancer is on the increase. We here studied the association of rs1219648 in FGFR2 and rs1042522 in TP53 and their interaction in development of early onset sporadic breast cancer in Iranian Azeri population to evaluate epistatic effects on the risk of mammary neoplasia. We genotyped the two polymorphisms in 100 women with early onset breast cancer and 100 healthy women by PCR-RFLP. Allele frequency differences were tested using $chi^2$-test with 95% confident intervals. Our results indicated a statistically significant association (p<0.05) between rs1219648, but not rs1042522, and risk of breast cancer. We also found that the combination of FGFR2 major genotype and TP53 hetero genotype had protective effects against breast cancer, while the hetero allele of FGFR2 in combination with the minor genotype of TP53 was associated with a high risk. This study revealed an important crosstalk between two polymorphisms in FGFR2 and TP53 in development of breast cancer. These candidates risk variants should be further evaluated in studies with a larger sample size.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.149-153
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• 2016

Breast cancer is the most common cancer in Iran. In the recent years an upward trend has been observed in the Iranian population. Early detection by molecular approaches may reduce breast cancer morbidity and mortality. We provided consultation to 3,782 women diagnosed with early onset breast cancer during the past 15 years (1999-2014). To establish a data set for BRCA gene alterations of the Iranian families at risk, two hundred and fifty four women who met our criteria were analyzed. A total number of 46 alterations including 18 variants with unknown clinical significance (39.1%), 18 missense mutations (39.1%), 7 Indels (15.2%) and 3 large rearrangement sequences (6%) were identified. Further scanning of affected families revealed that 49% of healthy relatives harbor identical causative mutations. This is the first report of comprehensive BRCA analysis in Iranian women with early onset breast cancer. Our findings provide valuable molecular data to support physicians as well as patients for the best decision making on disease management.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8319-8324
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• 2014

Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intronexon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3'UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/BRCA2 and to identify specific 3'UTR variants that may be risk factors for cancer development. The 3'UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs $c.^*1287C$ >T (rs12516) (BRCA1) and $c.^*105A$ >C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3'UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism $c.^*1287C$ >T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP $c.^*1287C$ >T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2223-2227
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• 2016

Background: Breast cancer is the most common cancer among Iranian women. Since development of the disease in Iranian women occurs relatively early, the survival rate matters considerably. In different countries, survival of breast cancer patients varies considerably. Therefore, the one-year, three-year, five-year, and ten-year survival rates for breast cancer in Iran were assessed using a meta-analysis. Materials and Methods: This systematic review and meta-analysis was based on valid Iranian sources including SID, MAGIRAN and IRANMEDEX, along with reliable English databases, namely, PUBMED and SCOPUS. In domestic databases, a search was conducted based on key words of breast cancer and survival rate, and in international databases, with "breast cancer" and the equivalent of "neoplasm" of Mesh Word, "survival rate" and "Iran." Then all reviewed papers and theses which met the inclusion criteria were selected for investigation. To conduct the analysis STATA 11.2 software and random-effects models were used. Results: In 24 studies, 22,745 participants were included. The one-year, three-year, five-year and ten-year survival rates were 0.956, 0.808, 0.695 and 0.559, respectively. The minimum and maximum survival rates for 5-years were 0.48 and 0.87. The average age of the onset of the disease was 48.3. Conclusions: As in Iran, since the onset of the disease is at low age, in spite of the relatively high survival rate as compared to other cancers, prevention and screening programs at early age for early stage diagnosis seems necessary.

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.4945-4949
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• 2016

Background: Breast cancer is the commonest cancer in Egyptian females. Nrf2 is involved in oxidative stress while P73 functions in response to DNA damage. This study aimed to assess the role of Nrf2 promoter and P73 G4C14 to A4T14 SNPs in breast cancer in Egypt. Patients: Eighty-five female patients with breast tumours (41 malignant, 44 benign) were included. Nrf2 (rs6721961) and p73 (G4A) SNPs were determined by PCR- CTPP assay. Results: Genotype frequencies of the Nrf2 promoter SNP were 34.2% and 37.9% for AA in benign and malignant groups respectively, and 43.9% and 40.5% for CC and, 21.9 % and 21.6% for CA. Genotype frequencies for the P73 G4A SNP were 52.9% and 44.7% for GA in benign and malignant groups respectively, and 47.1% and 55.3% for GG. Discussion: Nrf2 genotypes in pre - and post-menopausal patients, showed significantly different distributions in the 2 patient groups, the AA genotype being significantly more common in pre-menopausal patients. The P73 G4A SNP showed no relation to age of disease onset. Conclusion: The Nrf2 (rs6721961) AA genotype might be related to early breast cancer onset. In contrast the P73 G4A polymorphism showed no relation to either disease risk or age at presentation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7467-7472
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• 2015

Background: Breast cancer is known to be one of the most prevalent cancers among women in both developing and developed countries. The incidence of breast cancer in Pakistan has increased dramatically within the last few years and is the second country after Israel in Asia to have highest proportional cases of breast cancer. However, there are limited data for breast cancer available in the literature from Pakistan. Objectives: The study was conducted to bring to light the common clinical presentation of breast cancer and to evaluate the frequency of established risk factors in breast carcinoma patients and furthermore to compare the findings between premenopausal and postmenopausal women in Pakistan. Materials and Methods: A 6 months (from July 2012 to Dec 2012) cross sectional survey was conducted in Surgical and Oncology Units of Civil Hospital, Karachi. Data were collected though a well developed questionnaire from 105 female patients diagnosed with carcinoma of breast and analyzed using SPSS version 17. Institutional ethical approval was obtained prior to data collection. Results: Out of 105 patients, 43 were premenopausal and 62 were postmenopausal, 99 being married. Mean age at diagnosis was $47.8{\pm}12.4years$. A painless lump was the most frequent symptom, notived by 77.1%(n=81). Some 55.2% (n=58) patients had a lump in the right breast and 44.8%(n=47) in the left breast. In the majority of cases, the lump was present in upper outer quadrant 41.9% (n=44). Mean period of delay from appearance of symptoms to consulting a doctor was $5.13{\pm}4.8months$, from the shortest 1 month to the longest 36 months. Long delay (> 3 months) was the most frequent figure 41.9%. Considering overall risk factors most frequent were first pregnancy after 20 years of age (41%), physical breast trauma (28.6%), lack of breast feeding(21.9%), and early menarche <11 years (19%), followed by null parity (16.2%), consumption of high fat diet (15.2%), family history of breast cancer or any other cancer in first degree relatives (9.5% and 13.3%, respectively). Some of the less common factors were late menopause >54 years (8.6%), use of oral contraceptive pills (10.5%), use of hormone replacement therapy (4.7%),smoking (4.7%) and radiation (0.96%). Significant differences (p<0.005) were observed between pre and post menopausal women regarding history of physical breast trauma, practice of breast feeding and parity. Conclusions: A painless lump was the most frequent clinical presentation noted. Overall age at first child > 20 years, physical breast trauma, lack of breast feeding, early menarche <11 were the most frequent risk factors. Physical breast trauma, lower parity, a trend for less breast feeding had more significant associations with pre-menopausal than post-menopausal onset. Increase opportunity of disease prevention can be obtained through better understanding of clinical presentation and risk factors important in the etiology of breast cancer.

• Radiation Oncology Journal
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• 제26권1호
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• pp.65-73
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• 2008

목적: 40세 이하의 젊은 여성 유방암 환자는 나이 든 여성 보다 BRCA1과 BRCA2 배선돌연변이의 빈도가 상대적으로 높다. 유방암 가족력이 있거나 젊은 나이에 유방암을 진단받은 백인 여성들의 BRCA1/2 돌연변이 암에 대한 연구에서 면역조직화학적으로 BRCA1/2 돌연변이 음성인 암과 다른 특성이 발견되었다. 이 연구의 목적은 유방암 가족력과 관계없이 젊은 나이에 유방암이 발생한 한국 여성을 대상으로 BRCA1/2 돌연변이 유뮤에 따라, 그리고 BRCA1과 BRCA2 각각의 돌연변이에 따라 면역조직화학적 특성으로 상호간의 구별이 가능한지, 면역조직화학적 검사로 BRCA1/2 돌연변이의 가능성을 알아보는 것이 가능한지를 조사하는데 있으며 BRCA와 관련된 암의 예후인자로서의 역할도 분석하였다. 대상 및 방법: BRCA1/2 검사를 시행한 40세 이하의 한국인 젊은 여성 유방암 환자의 유방암 수술 후 병리조직을 찾아서 조직미세배열법으로 슬라이드를 만들었다. 이 검체들의 병리조직, 등급, 림프절 전이, T 병기, 에스트로겐 수용체, 프로게스테론 수용체 및 HER-2 상태와 BRCA1/2의 관계를 비교하였다. 그리고 이 환자들의 BRCA 돌연변이 상태와 면역조직학적, 병리학적 상태와 예후 인자로서의 역할도 조사하였다. 결과: BRCA1/2 돌연변이를 조사한 101명 중 14명에서 16개의 돌연변이가 있었으며(13.9%), 유방암-난소암 가족력이 있는 경우(4/14, 28.6%), 양측성 유방암이 있는 경우(3/9, 33.3%)에 BRCA1/2 돌연변이 빈도가 높았다. 에스트로겐 수용체 음성인 경우 BRCA1/2 양성이 19.4%(12/62)로 에스트로겐 수용체 양성 비율 5.1%(2/37)에 비해 유의하게 높았고(p=0.038), HER-2 음성인 경우 BRCA1/2 돌연변이 음성 비율이 16.5%(13/79)로 양성 비율 4.5%(1/22)에 비해 높은 경향을 보였으며(p=0.073), 프로게스테론 수용체는 차이가 없었다. 에스트로겐 수용체, 프로게스테론 수용체 및 HER-2 모두 음성인 경우(triple negative)는 BRCA1/2 돌연변이 비율이 24.2%(8/33)로 매우 높았다. 종양의 크기, 림프절 전이 상태, HER-2 상태는 단변량 변수와 다변량 변수 모두에서 무병 생존에 유의한 영향을 미치는 인자 이었으나 BRCA1/2 돌연변이 상태는 무병생존에 유의한 인자가 아니었다. 결론: 면역조직화학적으로 에스트로겐 수용체나 HER-2 음성을 보이는 젊은 유방암 환자에서 BRCA1/2 돌연변이 발생이 유의하게 높았으며, 프로게스테론 수용체까지 모두 음성인 경우 BRCA1/2 돌연변이가 있을 확률이 24.2%로 높아서 유방암 유전자 돌연변이 가능성을 예측하는데 도움을 줄 수 있다. 한국인 젊은 여성 유방암 환자에서 BRCA1/2 돌연변이 상태가 무병생존에 유의한 인자는 아니었으나 좀 더 많은 환자와 긴 추적관찰 기간의 추가적인 연구가 필요하다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1175-1179
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• 2015

Background: Expression of matrix metalloproteinases (MMPs) is up-regulated in human cancers. The aim of present study was to investigate the role of MMP-9 C-1562T polymorphism and its interaction with MMP-2 C-735T polymorphism in susceptibility to breast cancer in a population from Western Iran with Kurdish ethnic background. Materials and Methods: The study sample of 205 individuals consisted of 101 breast cancer patients and 104 healthy subjects. MMP-9 C-1562T and MMP-2 C-735T variants were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Among 67.4% of studied patients the breast cancer developed in the third and forth decades of the life. The frequency of MMP-9 T allele was 17.3% in patients and 10.1% in controls. The presence of T allele significantly increased the risk of breast cancer by 1.87-fold [OR=1.87 (95% CI 1.05-3.33, p=0.035)]. The frequency of MMP-9 CT+TT genotype tended to be higher in those patients with a family history of cancer in first degree-relatives (36.8%) than those without a family history (28.3%, p=0.37). We observed an interaction between the MMP-9 -1562 T allele with MMP-2 -735 C allele that significantly increased the risk of breast cancer [OR=1.42 (95% CI 1.02-1.98, p=0.036)]. Conclusions: The present study demonstrated that MMP-9 C-1562T polymorphism alone and in combination with MMP-2 C-735T polymorphism increased the risk of breast cancer that might be a useful biomarker in identifying women at risk of developing breast cancer. Also, this study revealed that in most women from Western Iran breast cancer presents in third and fourth decades of life.