• 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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• 제17권sup3호
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• pp.135-141
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• 2016

Since the mean age of breast cancer in women living in developing countries, compared with those in developed countries, is lower by about 10 years, repetition of mammography can play an important role in reducing morbidity and mortality. Hence, this study aimed to investigate the relationship between family history of breast cancer and risk perception and its impact on repetition of mammography. In this cross-sectional study, 1,507 women aged 50 years and older, referred to the mammography center of Regions 1 and 6 in Tehran, Iran, were enrolled. Data were collected using a self-report questionnaire and analyzed using SPSS and LISREL. According to our findings, knowledge about the time interval of mammography was found to have the highest correlation with repetition of mammography (r=0.4). Among the demographic variables, marital status (${\beta}$= -0.1) and family history of breast cancer (${\beta}$=0.1) had the most direct and significant impact on repetition of mammography (P <0.05). Among the other variables studied, knowledge (${\beta}$=-0.5) had the highest direct and significant impact on repetition of mammography (P <0.05). Family history of breast cancer was one of the predictors of repetition of mammography, but the results did not prove any relationship with risk perception. Further studies are needed to assess the effect of risk perception and knowledge about time interval on the initiation and continuation of mammography.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.387-393
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• 2016

Background: CYP1A1 is a candidate gene for low-penetrance breast cancer susceptibility, as it plays an important role in the metabolism of carcinogens and estrogens. Purpose: The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in CYP1A1 and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history. Materials and Methods: Blood samples were collected from 112 breast cancer female patients and 115 age-matched controls who underwent breast cancer screening with imaging and showed negative results (BI-RADS I or BI-RADS II). Genotyping was performed using the PCR-RFLP technique. Results: No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p= 0.55; OR = 0.77; 95% CI= 0.32 - 1.83) nor with the M4 polymorphism (p= 0.95; OR= 0.95; 95% CI= 0.51 - 1.88). Analysis of subgroups defined by menopausal status or smoking history also revealed no association with these polymorphisms. Furthermore, the four identified haplotypes (AC; AA; GC and GA) were equally distributed among cases and controls, and haplotype analysis showed a strong linkage disequilibrium of both studied loci in either cases or controls (D'=1). Conclusions: Based on the study results, CYP1A1 M2 and M4 polymorphisms do not seem to play a major role in breast cancer risk among Jordanian females.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2433-2437
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• 2013

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumours. Associations between three VEGF gene polymorphisms (-634 G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, but the currently available results are inconclusive. Our aim was to investigate associations between three VEGF gene polymorphisms and breast cancer risk in Chinese Han patients. We performed a hospital-based case-control study including 680 female incident breast cancer patients and 680 female age-matched healthy control subjects. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the three VEGF gene polymorphisms. We observed that women carriers of +936 TT genotypes [odds ratio (OR) =0.46, 95% confidence interval (CI) = 0.28, 0.76; P=0.002] or 936 T-allele (OR=0.81, 95% CI= 0.68, 0.98; P=0.03) had a protective effect concerning the disease. Our study suggested that the +1612G/A polymorphism was unlikely to be associated with breast cancer risk. The -634CC genotype was significantly associated with high tumor aggressiveness [large tumor size (OR=2.63, 95% CI=1.15, 6.02; P=0.02) and high histologic grade (OR=1.47, 95% CI= 1.06, 2.03; P=0.02)]. The genotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Our study revealed that the VEGF -634 G/C and +936 C/T gene polymorphisms may be associated with breast cancer in Chinese Han patients.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.161-166
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• 2016

Iranian women are at high risk of low compliance with repeat mammography due to a lack of awareness about breast cancer, negative previous experiences, cultural beliefs, and no regular visits to a physician. Thus research is needed to explore factors associated with repeated mammography participation. Applying the concept of perceived risk as the guiding model, this study aimed to test the fit and strength of the relationship between perceived risk and physician recommendation in explaining repeat mammography. A total of 601 women, aged 50 years and older referred to mammography centers in region 6, were recruited via a convenience sampling method. Using path analysis, family history of breast cancer and other types of cancer were modeled as antecedent perceived risk, and physician recommendation and knowledge were modeled as an antecedent of the number of mammography visits. The model explained 49% of the variance in repeat mammography. The two factors of physician recommendation and breast self-examination had significant direct effects (P < 0.05) on repeat mammography. Perceived risk, knowledge, and family history of breast cancer had significant indirect effects on repeat mammography through physician recommendation. The results of this study provide a background for further research and interventions not only on Iranian women but also on similar cultural groups and immigrants who have been neglected to date in the mammography literature.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10225-10229
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• 2015

Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chain reaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patients and 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In case of the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) and homozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantly higher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancer risk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our results suggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188His polymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3051-3056
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• 2013

Background: Genetic aberrations of DNA repair enzymes are known to be common events associated with different cancer entities. The aim of the present study was to analyze genetic associations of rs1805404 (Asp81Asp) and rs1805414 (Ala284Ala) in the PARP1 gene with the risk of breast cancer in Saudi Arabia. Materials and Methods: These two SNP's were analyzed in a primary study group of breast cancer patients and healthy control subjects. Genotypes were determined by TaqMan SNP testing and analyzed using Chi-square or t test and logistic regression analysis with SPSS16.0 software. Results and Conclusions: Results showed that rs1805414 was associated with a significantly increased susceptibility to breast cancer, significant risk being observed for the TC, CC and TC+CC genotypes. In conclusion PARP1 rs1805414 SNP polymorphisms may be involved in the etiology of breast cancer in the Saudi population. In contrast, PARP1 rs1805404 did not show any significant association in overall in breast cancer samples when compared to healthy controls. Confirmation of our findings in larger populations of different ethnicities may provide evidence for a role of the PARP1 gene in breast carcinoma developnment.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1221-1233
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• 2016

Purpose: To investigate any potential association between wine and breast cancer risk. Materials and Methods: We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. Results: The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Conclusions: Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.323-335
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• 2016

Breast cancer risk assessment has developed during years and evaluation of genetic factor affecting risk of breast cancer is an important component of this risk assessment. The aim of this meta-analysis was to investigate the role of XRCC1 polymorphisms (Arg194Trp, Arg280His and Arg399Gln) in risk of breast cancer among different population and categories of menopausal status.PubMed, Medline, Web of Science, and PubMed Central were systematically searched to identify studies evaluating association between breast cancer and XRCC1 gene polymorphisms (Arg194Trp, Arg280His and Arg399Gln). Two authors independently extracted required information. Odds Ratios were pooled for four genetic inheritance models using both fixed and the DerSimonian and Laird random-effect models. Egger's test and contour-enhanced funnel plot was used to evaluate publication bias and small study effect. Additional subgroup analysis was performed for menopausal status, ethnicity, and source of controls. After evaluation and applying inclusion criteria on extracted studies, fifty three studies were included in this meta-analysis. For polymorphisms of Arg194Trp and Arg280His, no significant association was observed in all genetic models. Arg194Trp had a protective effect in post-menopausal status only in homozygote model (OR=0.57 [0.37-0.88]). Arg399Gln showed significant association with breast cancer in homozygote (OR=1.21 [1.10-1.34]), dominant (OR=1.09 [1.03-1.15]) and recessive (OR=1.21 [1.09- 1.35]) genetic models. Arg399Gln was associated with higher risk in post-menopausal status for homozygote and heterozygote models. Our findings suggest that XRCC1 gene polymorphisms modify breast cancer risk in different populations and different categories of menopausal status.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.847-853
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• 2014

There is a lot of debate on the relationship between vitamin D receptor polymorphisms and risk of breast cancer. Herein, we quantitatively analyzed the published case-control studies on this relationship by meta-analysis, performing a bibliographic search from Pubmed and CNKI up to July 31, 2013. The included case-control studies for Fok1, Bsm1, Taq1, Apa1, Cdx2 and Poly-A were 16, 19, 20, 10, 4, 6, respectively. Crude and adjusted odd ratios and 95% confidence intervals were calculated to present and compare the strength of any associations. The results of combined analyses indicated that Fok1, Bsm1, Apa1, Cdx2 and Poly-A were not significantly associated with the risk of breast cancer. In contrast, the tt genotype of Taq1 was a modest risk factor for breast cancer development (tt vs. TT: OR = 1.21, 95% CI: 1.01-1.44). To further confirm the above results, adjusted effects for the six polymorphisms were pooled based on adjusted ORs reported in the original studies. Adjusted ORs of Fok1, Apa1, Cdx2 and Poly-A were similar to the crude ORs. However, Bsm1 and Taq1 showed inconsistent results. For Bsm1, OR for BB vs. bb was 0.85, 95% CI: 0.74-0.98; for Taq1, OR for tt vs. TT was 1.03, 95% CI: 0.92-1.15, and not associated with risk. Subgroup analyses for crude ORs showed some association between Bsm1, Taq1 and breast cancer in Caucasians only, but for adjusted ORs, no associations were found. This meta-analysis suggests that the roles that Fok1, Apa1, Cdx2 and Poly-A polymorphisms play in breast cancer risk are negligible, with Bsm1 and Taq1 as possible exceptions. To be conservative, we still assumed that they may play a modest role in determining breast cancer risk. Further studies are needed to validate our findings.