BRCA1 and BRCA2 Common Mutations in Iranian Breast Cancer Patients: a Meta Analysis

Forat-Yazdi, Mohammad,Neamatzadeh, Hossein,Sheikhha, Mohammad Hasan,Zare-Shehneh, Masoud,Fattahi, Mortaza Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Background: To date several common mutations in BRCA1 and BRCA2 associated with breast cancer have been reported in different populations. However, the common BRCA1 and BRCA2 mutations among breast cancer patients in Iran have not been described in detail. Materials and Methods: To comprehensively assess the frequency and distribution of the most common BRCA1 and BRCA2 mutations in Iranian breast cancer patients, we conducted this meta-analysis on 13 relevant published studies indentified in a literature search on PubMed and SID. Results: A total of 11 BRCA1 and BRCA2 distinct common mutations were identified, reported twice or more in the articles, of which 10 (c.2311T>C, c.3113A>G, c.4308T>C, c.4837A>G, c.2612C>T, c.3119G>A, c.3548A>G, c.5213G>A c.IVS16-92A/G, and c.IVS16-68A/G) mutations were in BRCA1, and 1 (c.4770A>G) was in BRCA2. The mutations were in exon 11, exon 13, intron 16, and exon 20 of BRCA1 and exon 11 of BRCA2. All have been previously reported in different populations. Conclusions: These meta analysis results should be helpful in understanding the possibility of any first true founder mutation of BRCA1/BRCA2 in the Iranian population. In addition, they will be of significance for diagnostic testing, genetic counseling and for epidemiological studies.

Association between the XRCC3 Thr241Met Polymorphism and Risk of Colorectal Cancer: a Meta Analysis of 5,193 Cases and 6,645 Controls

Namazi, Abolfazl,Abedinzadeh, Maryam,Nourbaksh, Parisa,Neamatzadeh, Hossein Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: Many studies have reported associations of the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism with colorectal cancer (CRC) risk, but the results remained controversial. Hence, we performed the present meta-analysis with different inheritance models. Materials and Methods: We searched the PubMed and Google scholar databases for studies relating to associations between XRCC3 Thr241Met polymorphism and risk of CRC. 16 studies with 5,193 cases and 6,645 controls were finally included into the meta-analysis. Results: We found that the XRCC3 Thr241Met polymorphism was associated with increased CRC risk only under a dominant genetic model (CC+CT vs. TT: OR 0.575, 95%CI 0.498-1.665, p<0.001, $P_{heterogeneity}=0.00$, $I^2=83%$). There was a significant association between XRCC3 Thr241Met polymorphism and CRC risk in Caucasian in the overall 8 studies under only in the heterozygote genetic model (CT vs. TT: OR=0.929, 95%CI =0.806-1.070, P=0.308, $P_{heterogeneity}=0.002$, $I^2=57%$). Four studies evaluated the XRCC3 Thr241Met polymorphism and CRC risk in Asians. Two genetic models of the XRCC3 polymorphism were significantly correlated with increasing risk in Asians (dominant model: CC+CT vs. TT: OR= 0.609, 95%CI=411-0.902, P=0.013, $P_{heterogeneity}=0.54$, $I^2=0.00%$; Allele model: C vs. T: OR=0.708, 95 %=CI 0.605-0.829, p=0.000, $P_{heterogeneity}=0.000$, $I^2=92%$). The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. Conclusions: In conclusion, this meta-analysis indicates that XRCC3 Thr241Met shows an increased CRC risk, particularly in Asians rather than Caucasians.

Association between MTHFR C677T Polymorphism and Risk of Prostate Cancer: Evidence from 22 Studies with 10,832 Cases and 11,993 Controls

Abedinzadeh, Mehdi,Zare-Shehneh, Masoud,Neamatzadeh, Hossein,Abedinzadeh, Maryam,Karami, Hormoz Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.11

Background: The MTHFR C677T polymorphism is a genetic alteration affecting an enzyme involved in folate metabolism, but its relationship to host susceptibility to prostate cancer remains uncertain. The aim of this study was to investigate the association between MTHFR C677T polymorphism and prostate cancer by performing a meta-analysis. Materials and Methods: Pubmed and Web of Science databases were searched for case-control studies investigating the association between MTHFR C677T polymorphism and prostate cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess any link. Results: A total of 22 independent studies were identified, including 10,832 cases and 11,993 controls. Meta-analysis showed that there was no obvious association between MTHFR C677T polymorphism and risk of prostate cancer under all five genetic models. There was also no obvious association between MTHFR C677T polymorphism and risk of prostate cancer in the subgroup analyses of Caucasians. In contrast, MTHFR C677T polymorphism was associated with increased risk for prostate cancer in Asians with the allele model (C vs G: OR=1.299, 95 %CI =1.121-1.506, P=0.001, $P_{heterogeneity}=0.120$, $I^2=45%$), additive genetic model (CC vs TT: OR =1.925, 95 % CI= 1.340-2.265, P=0.00, $P_{heterogeneity}=0.587$, $I^2=0.00%$), recessive model (CC vs TT+TC: OR= 1.708, 95 % CI=1.233-2.367, P=0.001, $P_{heterogeneity}=0.716$, $I^2=0.00%$), and heterozygote genetic model (CT vs TT: OR=2.193, 95 % CI =1.510-3.186, P=0.000, $P_{heterogeneity}=0.462$, $I^2=0.00%$). Conclusions: These results suggest that the MTHFR C677T polymorphism does not contribute to the risk of prostate cancer from currently available evidence in populations overall and Caucasians. However, the meta analysis indicates that it may play a role in prostate cancer development in Asians.

Health Beliefs and Breast Cancer Screening Behaviors among Iranian Female Health Workers

Shiryazdi, Seyed Mostafa,Kholasehzadeh, Golrasteh,Neamatzadeh, Hossein,Kargar, Saeed Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: Breast cancer is a serious health problem. Early detection is crucial for optimal treatment and reducing mortality. Objective: The aim of this study was to evaluate health beliefs concerning performance of breast self- examination (BSE) and mammography in a sample of Iranian female health workers. Materials and Methods: This cross-sectional study was performed among 441 female health care workers (physicians=88, nurses=163, midwives=38, officers=68, and others=84) in 3 different health centers in Yazd, Iran. Data were collected using a self administered questionnaire which included demographic characteristics and thenPersian version of the Champion's Health Belief Model Scale (CHBMS). Results: The mean age of the participants was $34.7{\pm}13.7$. It was found that 41.9% of the workers performed BSE in the past and 14.9% of them regularly, but only 10.6% of them had undergone a mammogram. Perceived barriers to BSE (F=6.351, P=0.021) and mammography (F=5.214, p=0.022) were significantly higher in officers than physicians, nurses or midwives. Perceived barriers were lower among those who had performed BSE and mammography, but not significant (p=0.34 and p=0.56, respectively). Furthermore, perceived susceptibility and perceived benefits of the workers who had BSE and mammography were significantly higher than who did not (p<0.05). Perceived seriousness was not a significant variable in BSE and mammography (p=0.71 and p=0.43, respectively). Conclusions: The health beliefs of health workers concerning the perceived susceptibility of breast cancer and the perceived benefits BSE and mammography significantly impact their screening practices.

Association of XRCC1 Arg399Gln Polymorphism with Colorectal Cancer Risk: A HuGE Meta Analysis of 35 Studies

Forat-Yazdi, Mohammad,Gholi-Nataj, Mohsen,Neamatzadeh, Hossein,Nourbakhsh, Parisa,Shaker-Ardakani, Hossein Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: Non-synonymous polymorphisms in XRCC1 hase been shown to reduce effectiveness of DNA repair and be associated with risk of certain cancers. In this study we aimed to clarify any association between XRCC1 Arg399Gln and colorectal cancer (CRC) risk by performing a meta-analysis of published case-control studies. Materials and Methods: PubMed and Google Scholar were searched to explore the association between XRCC1 and CRC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias was assessed by Egger's and Begg's tests. Results: Up to January 2015, 35 case control studies involving 9,114 CRC cases and 13,948 controls were included in the present meta-analysis. The results showed that the Arg399Gln polymorphism only under an allele genetic model was associated with CRC risk (A vs. G: OR 0.128, 95% CI 0.119-0.138, p<0.001). Also, this meta-analysis suggested that the XRCC1 Arg399Gln polymorphism might associated with susceptibility to CRC in Asians (A vs G: OR 0.124, 95% CI 0.112-0.138, p<0.001) and Caucasian (A vs G: OR 0.132, 95% CI 0.119-0.146, p<0.001) only under an allele genetic model. Conclusions: This meta-analysis confirms the association between XRCC1 Arg399Gln polymorphism and CRC risk and suggests that the heterogeneity is not strongly modified by ethnicity and deviation from the Hardy-Weinberg equilibrium.

BreastLight Apparatus Performance in Detection of Breast Masses Depends on Mass Size

Shiryazdi, Seyed Mostafa,Kargar, Saeed,Taheri-Nasaj, Hossein,Neamatzadeh, Hossein Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Background: Accurate measurement of breast mass size is fundamental for treatment planning. We evaluated performance of BreastLight apparatus in detection breast of masses with this in mind. Materials and Methods: From July 2011 to September 2013, a total of 500 women referred to mammography unit in Yazd, Iran for screening were recruited to this study. Performance of BreastLight in detection breast masses regard their sizeing, measured with clinical breast examination (CBE), mammography and sonography, was assessed. Sonographic and mammography examinations were performed according to breast density among women in two groups of women younger (n=105) and older (n=395) than 30 years. Size correlations were performed using Spearman rho analysis. Differences between mass size as assessed with the different methods (mammography, sonography, and clinical examination) and the BreastLight detection were analyzed using $X^2$-trend test. Results: Performance of the BreastLight in detection of lesions smaller than or equal to 1 cm assessed by CBE, mammography and sonography was 4.4%,7.7% and 12.5% and for masses larger than 4 cm was 65%, 100% and 57.1%, respectively. The performance of BreastLight in detection was significantly increased with larger masses (p<0.001). Conclusions: We conclude that clinical measurement of breast cancer size is as accurate as that from mammography or ultrasound. Accuracy can be improved by the use of a simple formula of both clinical and mammographic measurements.

Lack of Association between the CDH1 -160C>A Polymorphism and Risk of Gastrointestinal Cancer - a Meta-Analysis

Sahami-Fard, Mohammad Hossein,Yazd, Ehsan Farashahi,Khazaei, Zahra,Neamatzadeh, Hossein Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

E-cadherin (CDH1) genetic variations alter gene transcriptional activity of epithelial cells in vitro and may cause susceptibility to various cancers. Associations of CDH1 -160C>A polymorphism with various cancers have been widely reported. However, the results are controversial and inconsistent. To derive a more accurate estimation of the relationship, a meta-analysis was performed with regard to gastrointestinal (GI) cancer risk. Eligible studies were identified through a search of PubMed database until December 2015. Associations between the CDH1 -160C>A polymorphism and GI cancer risk was considered by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 31 studies including 11,606 cases and 12,655 controls were involved in this meta-analysis. Overall, this meta-analysis showed no association between CDH1 -160C>A polymorphism and GI cancer risk (A vs. C: OR = 1.08, 95%CI = 0.98-1.18, P = 0.086;CA vs. CC: OR = 1.09, 95%CI = 0.97-1.22, P = 0.118; AA vs. CC: OR = 1.10, 95%CI = 0.89-1.35, P = 0.356; AA vs. CC + CA: OR = 1.06, 95%CI = 0.96-1.18, P = 0.207; CA+AA vs. CC: OR = 1.01, 95%CI = 0.84-1.22, P = 0.89). In subgroup analysis, similar results were found. In conclusion, this meta-analysis has demonstrated that there is a lack of association of the CDH1-160C>A polymorphism with GI cancer susceptibility.

CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer Patients

Yazdi, Mohammad Forat,Rafieian, Shiva,Gholi-Nataj, Mohsen,Sheikhha, Mohammad Hasan,Nazari, Tahereh,Neamatzadeh, Hossein Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there is considerable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understanding the current state of evidence in this area and its limitations is important for the care of patients who require endocrine therapy for breast cancer. Materials and Methods: A total of 101 patients with breast cancer who received tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene by nested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poor metabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neu status, and stage 3. Results: The mean age of the patients with the disease recurrence was $50.8{\pm}6.4$ and in non recurrent patients was $48.2{\pm}6.8$. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6% (n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifen-treated patients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolic variants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6 genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women with breast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreased likelihood of recurrence. Conclusions: This study for the first time demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvant tamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor of breast cancer outcome in Her2-neu positive women receiving tamoxifen.

DNMT3B -149 C>T and -579 G>T Polymorphisms and Risk of Gastric and Colorectal Cancer: a Meta-analysis

Khoram-Abadi, Khadijeh Mirzaee,Forat-Yazdi, Mohammad,Kheirandish, Shahnaz,Saeidi, Nasim,Zarezade, Zeinab,Mehrabi, Nahid,Neamatzadeh, Hossein Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

Background: Numerous studies have investigated associations of DNA methyltransferase (DNMT) -149 C>T and -579 G>T polymorphisms with gastric cancer (GC) and colorectal cancer (CRC) susceptibility; however, the findings are inconsistent prompting the present meta-analysis. Materials and Methods: Related studies were identified from PubMed, Google scholar, and SID until 10 October 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Results: Eleven studies were included based on the search criteria for CRC and GC related to the DNMT3B 149 C>T (3,353 cases and 4,936 controls) and DNMT3B 579 G>T (1,387 cases and 2,064 controls) polymorphisms. There was no significant association overall between DNMT3B -149 and 579 polymorphisms and the risk of cancer. In the stratified analysis by cancer type, DNMT3B 579G>T polymorphism was associated with the risk of CRC and GC. While the DNMT3B -149C/T polymorphism was related with a significantly increased risk of CRC in two tested models, dominant (GG+GT vs. TT: OR 0.51, 95 % CI 0.38-0.69; P = 0.00, Pheterogeneity=0.69, $I^2=0%$) and heterozygote (GT vs. TT: OR 0.50, 95 % CI 0.37-0.69; P=0.00, Pheterogeneity=0.41, $I^2=0%$), no evidence of any association with GC risk was observed as in the pooled analyses. Conclusions: More studies are needed to assess associations of DNMT3B -149C/T and DNMT3B 579G>T polymorphisms with cancer in different ethnicities with large population sizes to generate comprehensive conclusions.