Involvement of microRNA-423 Gene Variability in Breast Cancer Progression in Saudi Arabia

Aim: microRNA-423 is an oncogenic factor which is frequently upregulated in cancer. However, associations withbreast cancer risk remain inconsistent. Therefore, we investigated the prevalence of microRNA-423 rs6505162C>Tgene variation with breast cancer susceptibility in Saudi women. Methodology: This study was conducted on 100breast cancer patients and 124 matched healthy individuals. Genotyping of the microRNA-423 rs6505162C/T genevariation was performed by using the amplification refractory mutation system PCR method (ARMS-PCR). Results:A significant difference was observed in the genotype distribution between the breast cancer cases and controls(p=0.0001), the frequencies of the genotypes CC,CT and TT being 25%, 52% and 23% in patients and 65%,20% and15% respectively, in controls. The microRNA-423 C>T variant was associated with an increased risk of breast cancerin codominant models for (OR = 6.73, 95 % CI, 3.50-12.97; RR 2.35(1.67-3.30, p=0.0001) the microRNA-423TTgenotype and (OR = 4.14, 95 % CI, 1.93-8.87; p=0.0003) microRNA-423CT (OR= 6.73, 95% CI, 3.50-12.97; p=0.0001)and also with the dominant model (OR 5.6(3.14-1.01), p=0.0001) CT+TT vs CC) with a non-significant association forthe recessive model (OR=1.75, 95%CI=0.08-3.44, P=0.139, TT vs CC+CT). The T allele significantly increased therisk of breast cancer (OR =2.63, 95 % CI, 1.77-3.91; p=0.001) compared to the C allele. Some 6.73 ,4.14 and 2.63 foldincreased risk of developing breast cancer was associated with TT and CT genotypes and the T allele of microRNA-423in the northwestern region of Saudi Arabia. Conclusion: Our findings indicate that the microRNA-423 TT genotypeand the T allele are associated with an increased susceptibility, metastasis and advanced stage of breast cancer in SaudiArabian patients. Further studies with larger sample sizes are necessary to confirm our findings.     

Estrogen Receptor Alpha Gene Polymorphisms and Breast Cancer Risk: a Case-control Study with Meta-analysis Combined

Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene(ESR-α) are associated with breast cancer risk. However, previous results from many molecular studies havebeen inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-αgene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms andbreast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium andhaplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysisof 24 published studies evaluating the association. No significant associations were found between the PvuIIpolymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observedamong carriers of the XbaI ‘G’ allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers ofthe ‘A’ allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the ‘CG’ haplotype(OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI ‘G’ allele was associated with anoverall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII‘C’ allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an associationbetween the PvuII ‘C’ and XbaI ‘G’ alleles and breast cancer risk was significant in Asians (‘C’ vs. ‘T’: OR =0.93, 95% CI = 0.85- 1.00; ‘G’ vs. ‘A’: OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, ourresults provide evidence that ESR-α polymorphisms are associated with susceptibility to breast cancer. Theseassociations may largely depend on population characteristics and geographic location.     

Predictors of Breast Cancer Screening Uptake: A Pre Intervention Community Survey in Malaysia

Introduction: Despite health education efforts to educate women on breast cancer and breast cancer screeningmodalities, the incidence of breast cancer and presentation at an advanced stage are still a problem in Malaysia.Objectives: To determine factors associated with the uptake of breast cancer screening among women in thegeneral population. Methods: This pre-intervention survey was conducted in a suburban district. All householdswere approached and women aged 20 to 60 years old were interviewed with pre-tested guided questionnaires.Variables collected included socio-demographic characteristics, knowledge on breast cancer and screeningpractice of breast cancer. Univariate and multivariate analysis were performed. Results: 41.5% of a total of381 respondents scored above average; the mean knowledge score on causes and risks factors of breast cancerwas 3.41 out of 5 (SD1.609). 58.5% had ever practiced BSE with half of them performing it at regular monthlyintervals. Uptake of CBE by nurses and by doctors was 40.7% and 37.3%, respectively. Mammogram uptakewas 14.6%. Significant predictors of BSE were good knowledge of breast cancer (OR=2.654, 95% CI: 1.033-6.816), being married (OR=2.213, 95% CI: 1.201-4.076) and attending CBE (OR=1.729, 95% CI: 1.122-2.665).Significant predictors for CBE included being married (OR=2.161, 95% CI: 1.174-3.979), good knowledge ofbreast cancer (OR=2.286, 95% CI: 1.012-5.161), and social support for breast cancer screening (OR=2.312, 95%CI: 1.245-4.293). Women who had CBE were more likely to undergo mammographic screening of the breast(OR=5.744, 95% CI: 2.112-15.623), p<0.005. Conclusion: CBE attendance is a strong factor in promoting BSEand mammography, educating women on the importance of breast cancer screening and on how to conduct BSE.The currently opportunistic conduct of CBE should be extended to active calling of women for CBE.     

The Investigation of Risk Factors Impacting Breast Cancer in Guilan Province

Introduction: Breast cancer is multifactorial therefore more recognition of risk factors is important in its prevention. Objective: This study was conducted in order to determine the factors influencing breast cancer in women referred to health centers in Guilan province in 2015-2016. Method: In a case- control study, 225 women with breast cancer were investigated. The control group consisted of 225 healthy women of the relatives (third-rank) whose phone numbers were obtained from the patients. Data were collected through telephone interviews. Results: The risk of breast cancer raised in women who have a family history of other cancers (OR= 3.5; 95% CI= 1.96-6.6) ,exposure to X-Ray (OR= 2.5; 95% CI=1.1-5.5), having more than 4 children (OR= 2.695% CI=1.2-4.8), age more than 36 years at first pregnancy(OR=2.3; 95% CI=0.7-5.1),primary levelof education (OR= 5.4;95% CI=2.8-11.2) and inadequate intake of fruit (OR=1.5; 95% CI=1-2.2). Also, presence of the following factors reduced breast cancer risk: regular menstruation (OR= 0.66; CI=0.4- 0.9), duration of breastfeeding more than 12 months, less than 6 months and 7-12 months (OR=0.23; 95% CI=0.09-0.59 , OR=0.29; 95% CI=0.17-0.49 and OR=0.03; 95% CI=0.01-0.08) and parity (OR=0.4; 95% CI=0.27-0.83) In multiple linear regression analysis of higher education (OR=0.16; 95% CI=0.03-0.77), using contraceptives for more than 16 years (OR=2.3; 95% CI=1.4-3.9), family history of other cancers (OR=6.1; 95% CI=1.9-19.3) and a history of X-Ray exposure (OR=4.4; 95% CI=1.07-18.1) were considered as predictive factors. Conclusion: The results of this study emphasize the importance of informing women about breast cancer risk factors. So, identification of these risk factors is required as important means of prevention and treatment of breast cancer.     

Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry

Epidemiologic studies of histologic types of breast cancer including mucinous, medullary, and tubular carcinomas have primarily relied on International Classification of Diseases-Oncology (ICD-O) codes assigned by local pathologists to define histology. Using data from the Breast Cancer Family Registry (BCFR), we compared histologic agreement between centralized BCFR pathology review and ICD-O codes available from local tumor registries among 3,260 breast cancer cases. Agreement was low to moderate for less common histologies; for example, only 55 and 26 % of cases classified as mucinous and medullary, respectively, by centralized review were similarly classified using ICD-O coding. We then evaluated risk factors for each histologic subtype by comparing each histologic case group defined by centralized review with a common set of 2,997 population-based controls using polytomous logistic regression. Parity [odds ratio (OR) = 0.4, 95 % confidence interval (95 % CI): 0.2-0.9, for parous vs. nulliparous], age at menarche (OR = 0.5, 95 % CI: 0.3-0.9, for age ≥13 vs. ≤11), and use of oral contraceptives (OCs) (OR = 0.5, 95 % CI: 0.2-0.8, OC use >5 years vs. never) were associated with mucinous carcinoma (N = 92 cases). Body mass index (BMI) (OR = 1.05, 95 % CI: 1.0-1.1, per unit of BMI) and high parity (OR = 2.6, 95 % CI: 1.1-6.0 for ≥3 live births vs. nulliparous) were associated with medullary carcinoma (N = 90 cases). We did not find any associations between breast cancer risk factors and tubular carcinoma (N = 86 cases). Relative risk estimates from analyses using ICD-O classifications of histology, rather than centralized review, resulted in attenuated, and/or more imprecise, associations. These findings suggest risk factor heterogeneity across breast cancer tumor histologies, and demonstrate the value of centralized pathology review for classifying rarer tumor types.     

Risk Factor Analysis for Breast Cancer in Premenopausal and Postmenopausal Women of Punjab,India

Objective: Amritsar, the second largest town of agrarian state of Punjab, India reports high number of breast cancer cases every year. The present study investigated the etiology of breast cancer using various obesity indices and other epidemiological factors among breast cancer patients residing in and around Amritsar city. Methods: In this case control study, risk factors for breast cancer were analyzed in 542 female subjects: 271 females with breast cancer patients and 271 unrelated healthy females matched for age as control females. Results: Bivariate analysis for risk factors in cases and controls showed a lower risk (OR=0.65, 95% CI 0.43-0.99, p=0.04) in obese cases with BMI≥25kg/m2 as compared to subjects with normal BMI. Risk factor analysis showed that parameter which provided risk for cancer in postmenopausal women was obesity and in premenopausal women was parity. Postmenopausal women with BMI (overweight: OR=0.39, 95% CI 0.17-0.92, p=0.03; obese: OR= 0.26, 95% CI 0.13-0.52, p=0.00), WC (OR=0.17, 95% CI 0.05-0.52, p=0.00) and WHtR (p=0.02) had highr risk. Premenopausal women with 3 or less than 3 children had a higher risk (OR=5.54, 95 % CI 2.75-11.19, p=0.00) than postmenopausal women when compared to women with more than 3 children. Binary logistic regression analysis revealed that low parity (≤3) substantially increased the risk for breast cancer (OR=4.80, 95% CI 2.34-9.85, p=0.00) in premenopausal women. Conclusion: Obesity, parity associated breast cancer risk and reduced breastfeeding cumulatively predispose the premenopausal women of this region to higher risk of breast cancer.     

Breast Cancer Risk From Modifiable and Non-Modifiable Risk Factors among Women in Southeast Asia: A Meta-Analysis

Objective: The aim of this study was to determine breast cancer risk from modifiable and non-modifiable factors among women in Southeast Asia. Methods: This meta-analysis was performed on research articles on breast cancer risk factors in PubMed, ProQuest and EBSCO databases published between 1997 and October 2017. Pooled odds ratios (OR) are calculated using fixed and random-effect models. Data were processed using Review Manager 5.3 (RevMan 5.3). Results: From a total of 1,211 articles, 15 studies (1 cohort and 14 case control studies) met the criteria for systematic review. Meta-analysis results showed that of the known modifiable risk factors for breast cancer, parity (nulipara) had the highest odd ratio (OR = 1.85 [95% CI 1.47-2.32]) followed by body mass index (overweight) (OR = 1.61 [95% CI 1.43-1.80]) and use of oral contraceptives (OR = 1.27 [95% CI 1.07-1.51]). Of non-modifiable risk factors, family history of breast cancer had the highest odd ratio (OR = 2.53 [95% CI 1.25-5.09]), followed by age (≥ 40 years) (OR = 1.53 [95% CI 1.34-1.76]) and menopausal status (OR = 1.44 [95% CI 1.26-1.65]). Conclusion: This analysis confirmed associations between both modifiable risk factors (parity, body mass index and use of oral contraceptives) and non-modifiable risk factors (family history of breast cancer, age and menopausal status) with breast cancer.     

The Impact of Limited Language Proficiency in Screening for Breast Cancer

BackgroundThe prevalence of a culturally diverse population in the United States continues to grow. Nevertheless, the national impact of limited English proficiency (LEP) in breast cancer screening is still unknown.MethodsA retrospective review of the 2015 sample of the National Health Interview Survey database was performed. The cohort included women with and without LEP between 40 and 75 years. We evaluated differences in screening rates, baseline, socioeconomic, access to healthcare, and breast cancer risk factors with univariate and multivariate regression analyses.ResultsThe prevalence of LEP was 5.7% (N = 1825, weighted counts 3936,081). LEP women showed a statistically significant lower rate of overall screening mammograms (78% vs. 90%), fewer benign lumps removed (6.4% vs. 17%) and lower rates of access to healthcare variables. They showed a higher rate of nonprivate insurance and living below the poverty line, a lower rate of hormone replacement therapy (1.8% vs. 5.6%), older menarche (12.97 vs. 12.75) and a higher rate of current menstruation (36% vs. 24). LEP women were associated with a lower probability of having a screening mammogram in multivariate analysis (OR: 0.67, 95% CI: 0.51-0.87). When LEP was subdivided into Spanish and “other” languages, Spanish speakers were associated with a lower probability of a screening mammogram (OR 0.67, 95% CI 0.49-0.90) while controlling for the same covariates.ConclusionThe results from our study showed that LEP women are associated with a lower probability of having a screening mammogram. Particularly, the Spanish speakers were found as a vulnerable subgroup.     

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism is Associated with Breast Cancer Risk: A Meta-Analysis

Background: A number of case-control studies were conducted to investigate the association of angiotensinconverting enzyme insertion/deletion (ACE I/D) polymorphism with breast cancer. But the results remain controversial.This meta-analysis aims to comprehensively evaluate the association of ACE I/D polymorphism with breast cancer.Method: A comprehensive literature search on PubMed, Google Scholar, SCOPUS and ISI Web of Knowledgedatabases for studies published up to June 01, 2018 was performed. Summary odds ratios (ORs) and 95% confidenceintervals (CI) were estimated. Publication bias of literatures was evaluated using funnel plots and Egger’s test. Results:A total of 20 studies including 2846 breast cancer cases 9299 controls meeting the predefined criteria were involved inthe meta-analysis. Overall, the ACE I/D polymorphisms was significantly associated with breast cancer under the allelemodel (I vs. D: OR= 0.803, 95% CI 0.647-0.996, p=0.046), the homozygote model (II vs. DD: OR= 0.662, 95% CI0.462-0.947, p=0.024), the heterozygote model (ID vs. DD: OR= 0.707, 95% CI 0.528-0.946, p=0.020), the dominantmodel (II+ID vs. DD: OR= 0.691, 95% CI 0.507-0.941, p=0.019). In the subgroup analysis by ethnicity, a significantassociation was found among Asian and Caucasian populations, but not among mixed populations. Conclusions: Thismeta-analysis suggests that ACE I/D polymorphism may be associated with increased risk of breast cancer, especiallyamong Asian and Caucasians. However, well-designed studies with larger sample size and more ethnic groups areneeded to further validate the results.     

Meta-Analysis of Association between PALB2 Polymorphisms and Breast Cancer

Background: Previous studies have assessed associations between single nucleotide polymorphisms (SNPs) ofthe Partner and localizer of BRCA2 (PALB2) gene and risk of breast cancer. However, the results of these studiesare not consistent. Materials and Methods: We designed a meta-analysis to obtain a more reliable appraisal ofthe association between SNPs in the PALB2 gene and the susceptibility to breast cancer. We searched PubMed, Googlescholar and Embase databases and selected six studies with sufficient data to estimate the pooled odds ratios (ORs)and 95% confidence intervals (CIs). Results: Statistical analyses showed that the rs120963 was associated with breastcancer risk in allelic (OR (95% CI) = 1.33 (1.18-1.49)), homozygous (OR (95% CI) = 1.74 (1.31-2.32)), dominant(OR (95% CI) = 1.42 (1.22, 1.65)) and recessive (OR (95% CI) = 1.54 (1.17, 2.03)) models. The rs249954 andrs16940342 were associated with breast cancer risk in allelic (OR (95% CI) = 1.13 (1.04, 1.23) and 1.12 (1.01, 1.24)respectively) and dominant (OR (95% CI) = 1.23 (1.09, 1.39) and 1.18 (1.04, 1.33) respectively) models. The rs249935and rs447529 SNPs were associated with breast cancer in homozygous (OR (95% CI) = 0.67 (0.46, 0.97) and 0.51(0.30, 0.89) respectively) and recessive (OR (95% CI) = 0.65 (0.45, 0.95) and 0.51 (0.30, 0.88) respectively) models.Conclusions: The current meta-analysis shows the associations between five SNPs of PALB2 and breast cancer riskand confirms the results of previous studies regarding the role of this gene in the pathogenesis of breast cancer.     

Nutrient Patterns and Risk of Breast Cancer in Uruguay

Objectives. To explore the role of nutrient patterns in the etiology of breast cancer (BC) among Uruguayanwomen. Methods. A principal component analysis was conducted. The study included 442 newly diagnosedcases of BC and 442 hospitalized controls. Results. Two dietary patterns derived from factor analysis and werelabeled as high-meat and antioxidants patterns. Whereas the high-meat pattern was directly associated withBC risk (OR for the highest versus the lowest quartile = 3.50, 95 % CI 1.94-6.30, p-value for trend <0.0001),the antioxidants pattern displayed a protective effect (OR=0.44, 95 % CI 0.27-0.74). Its negative associationwas stronger for postmenopausal than for premenopausal women (OR=0.63, 95% CI 0.51-0.79 vs. OR=0.89,95% CI 0.50-1.56, respectively). Both strata were heterogeneous (p=0.004). The high-meat pattern was moreassociated with BC risk among patients with family history of BC compared with participants without it, butresults did not differ by histology. In contrast, the antioxidants pattern was more associated with non-ductalcancers (OR=0.50 [95 % CI 0.35-0.69]) than with ductal cancers (OR=0.72, 95 % CI 0.58-0.88, heterogeneityp-value=0.03). Conclusions. Results support an association between the high-meat and antioxidant dietarypatterns and BC risk. Furthermore, findings suggest that gene-environmental interactions may be importantin BC etiology.     

Breast density as a determinant of interval cancer at mammographic screening

The association of breast density (% of breast volume involved by fibro-glandular densities) with the risk of interval cancer (IC) was investigated by reviewing a consecutive series of 346 cancers detected at screening (SDC) during 1996-1999 and of 90 ICs, reported as negative in the same period and diagnosed in the following 2 years, and comparing them to a random sample of 360 healthy controls. The probability of IC was significantly associated with breast density, whatever grouping (0/1-25/26-74/>74%; 0-25/26-60/61-74/>74%; 0-25/26-74/>74%) was considered (chi(2)=30.67-34.08, P<0.<0.01): 27.8% of all ICs were classified in the >74% density class, as compared to 7% of SDC and 5% of healthy controls. No significant association to IC was observed for Wolfe pattern (P2/Dy vs N1/P1: chi(2)=0.30, P=0.960), number of used mammographic views (single oblique vs oblique+craniocaudal: chi(2)=0.02, P=0.90) or screening round (first vs repeat: chi(2)=1.41, P=0.23). Multivariate analysis confirmed the independent association of breast density to IC, the highest risk being observed for >74% density class (OR vs 0% class=13.4, 95% CI 2.7-65.6, OR vs all other density classes=5.1, 95% CI 2.6-10.0). Age showed an independent association too, older women having a lower risk of IC (OR=0.52 95% CI 0.3-09). Breast density (>74%) resulted as being a major determinant of IC. Special screening protocols (shorter rescreening interval, routine use of ultrasonography) might be suggested for these subjects in order to improve screening sensitivity and efficacy.     

Association of IL-10 rs1800871 and rs1800872 Polymorphisms with Breast Cancer Risk: A Systematic Review and Meta-Analysis

Background: The rs1800871 and rs1800872 polymorphisms of interleukin 10 (IL-10) gene has been indicated tobe associated with breast cancer (BC) risk, but study results are still debatable. To derive a more precise evaluation, weperformed a comprehensive meta-analysis. Methods: Multiple electronic databases were searched to identify studiesassessing the IL-10 rs1800871 and rs1800872 polymorphisms with BC risk. Results: A total of 21 case-control studieswith 6054 cases and 6355 controls were included in this met-analysis. There was a significant association between thers1800871 polymorphism and BC risk (CT vs. TT: OR= 1.17, 95% CI 1.01-1.35, p=0.02; and CC+CT vs. TT: OR= 1.29,95% CI 1.00-1.66, p=0.04). Moreover, increased BC risks were also associated with the rs1800872 polymorphism (Cvs. A: OR= 1.29, 95% CI 1.04-1.60, p=0.01; CC vs. AA: OR= 1.54, 95% CI 1.03-2.30, p=0.03; CC+CA vs. AA: OR=1.43, 95% CI 1.01-2.01, p=0.03; and CC vs. CA+AA: OR= 1.23, 95% CI 1.01-1.51, p=0.04). A pooling of the studieswas also conducted by ethnicity, but failed to show an association of IL-10 rs1800871 and rs1800872 polymorphismwith BC risk in Asians and Caucasians. Conclusions: Our results are inconsistent with previous meta-analysis suggeststhat IL-10 rs1800871 and rs1800872 polymorphisms might contribute to BC susceptibility in overall population, butnot by ethnicity.     

Paraoxonase 1 (PON1) Q192R Gene Polymorphism and Cancer Risk: A Meta-Analysis Based on 30 Publications

Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated inthe development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidatethe association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-controlstudies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associationby STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of theoverall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain canceretc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q:OR=0.605, 95% CI=0.378-0.967, Pheterogeneity=0.000; RR vs QQ: OR=0.494, 95% CI=0.275-0.888, Pheterogeneity=0.002;RQ vs QQ: OR=0.465, 95% CI=0.259-0.835, Pheterogeneity=0.000; and RR+RQ vs QQ: OR=0.485, 95% CI=0.274-0.857,Pheterogeneity=0.000), and associated with prostate cancer in homozygote (RR vs QQ: OR=0.475, 95% CI=0.251-0.897, Pheterogeneity=0.001) and recessive models (RR vs RQ+QQ: OR=0.379, 95% CI=0.169-0.853, Pheterogeneity=0.000),while an increased risk was identified in lymphoma (R vs Q: OR=1.537, 95% CI=1.246-1.896, Pheterogeneity=0.944;RR vs QQ: OR=2.987, 95% CI=1.861-4.795, Pheterogeneity=0.350; RR+RQ vs QQ: OR=1.354, 95% CI=1.021-1.796,Pheterogeneity=0.824; and RR vs RQ+QQ: OR=2.934, 95% CI=1.869-4.605, Pheterogeneity=0.433), and an increased risk inprostate cancer under heterozygote comparison (RQ vs QQ: OR=1.782, 95% CI=1.077-2.950, Pheterogeneity=0.000)and dominant models (RR+RQ vs QQ: OR=1.281, 95% CI=1.044-1.573, Pheterogeneity=0.056). When subgroupanalysis that performed by the control source (hospital based or population based), a decreased risk of the overallcancers was revealed by homozygote (RR vs QQ: OR=0.601, 95% CI=0.366-0.987, Pheterogeneity=0.000) and dominantmodels (RR vs RQ+QQ: OR= 0.611, 95% CI=0.384-0.973, Pheterogeneity=0.000) in hospital based group. Stratifyingby ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q: OR=0.788,95% CI=0.626-0.993, Pheterogeneity=0.000) was uncovered in Caucasian. In summary, these findings suggested thatPON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it mightincrease cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies willbe continued on this issue of interest.     

Breast carcinoma screening and risk perception among women at increased risk for breast carcinoma: results from a national survey

BACKGROUND: The Gail model is validated to estimate breast carcinoma risk. The authors assessed the association of Gail risk scores with screening and cancer risk perception. METHODS: Using the 2000 National Health Interview Survey, the authors studied women ages 41-70 without a cancer history. Gail scores > or = 1.66% defined increased risk. The authors used logistic regression to assess associations between breast carcinoma risk and previous and recent (< or = 1 year) mammography and clinical breast examination (CBE). RESULTS: Of 6410 women, 15.7% had increased risk. High-risk women more frequently reported previous mammograms (94% vs. 85%; P < 0.0001), previous CBE (93% vs. 88%; P < 0.0001), recent mammograms (70% vs. 54%; P < 0.0001), recent CBE (71% vs. 61%; P < 0.0001), and high cancer risk perception (20% vs. 9%; P < 0.0001). However, 30% of high-risk women had not received a recent mammogram. After adjustment for sociodemographic factors, access to care factors, and cancer risk perception, high-risk women remained more likely to have received recent mammography (adjusted odds ratio [OR], 1.45, 95% confidence interval [95% CI], 1.19-1.77), recent CBE (OR, 1.32; 95% CI, 1.08-1.61]), and previous mammography than average-risk women. The authors observed an interaction between risk and age, with women ages 41-49 years more frequently reporting previous mammography (OR, 4.79; 95% CI, 1.55-4.81) than average-risk, same-age women. For women age > or = 50 years, the odds of previous mammography were similar regardless of risk. CONCLUSIONS: In a nationally representative sample, 15.7% of women had increased breast carcinoma risk using the Gail model. High-risk women perceived higher cancer risk and more often received screening. However, nearly one in three high-risk women did not receive recent screening and most of these women did not perceive increased risk.     

Breast Cancer Risk From Modifiable and Non-Modifiable Risk Factors among Palestinian Women: A Systematic Review and Meta-Analysis

Objective: Breast cancer (BC) is known as one of the deadliest forms of cancer, and it is increasing globally. Identifying risk factors for BC is a key point in developing preventive strategies to reduce its occurrence. Herein, we aimed to conduct a systematic review and meta-analysis focus on the risk factors for BC in Palestine. Material and Methods: We performed a systematic search via PubMed, MEDLINE, SCOPUS, Science Direct, Cochrane library, Emerald Insight, and Google scholar for identifying studies published on BC risk factors up to March 2021. Pooled odds ratios (OR) are calculated using fixed and random-effect models. Data were processed using Review Manager 5.4 (RevMan 5.4). Results: From a total of 73 articles, seven case-control studies met the criteria for systematic review. Meta-analysis results showed that of the known modifiable risk factors for BC, diabetes mellitus (DM) had the highest odds ratio (OR = 4.97, 95% CI 3.00- 8.25) followed by hypertension (OR = 3.21, 95% CI 1.96-5.23), obesity (BMI >30 Kg/m2) (OR = 2.90, 95% CI 2.00- 4.21), and passive smoking (OR = 1.50, 95% CI 1.12- 2.02). Controversially, breastfeeding (OR = 0.37, 95% CI 0.23- 0.61) was protective factor in BC. Of non-modifiable risk factors for BC has reached menopause had the highest odds ratio (OR = 3.74, 95% CI 2.64- 5.29), followed by family history of BC (OR = 2.63, 95% CI 1.07-6.44) and age (≥ 40 years) (OR = 2.49, 95% CI 1.43-4.34). Conclusions: The most significant predictors of BC in Palestine were DM, hypertension, passive smokers, age (>40), reached menopause, and family history of BC. Almost all these risk factors are consistent with known risk factors for breast cancer in other parts of the world.     

Breast Cancer Risk and the Combined Effect of Environmental Estrogens

OBJECTIVE: The present study aimed to determine whether the combined effects of environmental estrogens measured as the total effective xenoestrogen burden (TEXB-alpha) are a risk factor for breast cancer over and above the risk potentially linked to specific pesticides. METHODS: We measured the levels of 16 organochlorine pesticides as well as TEXB in adipose tissue of 198 women at the time of breast cancer diagnosis. These were compared with findings in 260 age and hospital matched control women without breast cancer. RESULTS: The median levels of p,p'-DDE (1,1-dichloro-2,2-bis( p -chlorophenyl)ethylene), aldrin, endosulfan ether and lindane (the pesticides detected in > 40% of the study population) were higher in cases than controls, although the differences did not reach statistical significance. After adjusting for potential confounders, the odds ratio (OR) for breast cancer in women with detectable levels of aldrin was 1.55 (95% confidence interval (CI) 1.00-2.40). Among the postmenopausal women, the OR for aldrin and lindane was 1.84 (95% CI 1.06-3.18) and 1.76 (95% CI 1.04-2.98), respectively. Among cases with body mass index (BMI) below the median (28.6 kg/m2), the OR was 3.42 (95% CI 1.22-9.58) for women in the highest quartile of TEXB-alpha versus those in the lowest. The subgroup of leaner postmenopausal women showed an increased risk (OR: 5.67; 95% CI 1.59-20.21) for those in the highest tertile versus those in the lowest. CONCLUSIONS: We found an increased risk for breast cancer in the leaner women, especially in the leaner postmenopausal subgroup, related to the TEXB-alpha. The pesticides aldrin and lindane are also individually associated with risk.     

MDM2 启动子区309 位点基因多态性与乳腺癌风险的关系*

目的:采用病例- 对照研究检测MDM2 启动子区309 位点T>G 单核苷酸多态（SNP 309）在中国女性人群中的频率分布,分析其与中国女性乳腺癌发病风险的关系。方法:提取病例组698 例原发性乳腺癌患者及对照组525 例健康人的外周血单核细胞DNA,采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP ）分析法,检测MDM2 启动子区309 位点基因多态性,确定此位点三种基因型,即T/T、T/G、G/G 基因型。统计分析病例组和对照组人群MDM2 SNP 309 各基因型频率分布,及各基因型与乳腺癌发病风险的相关性。结果:在研究的病例组与对照组整体人群中,经年龄、月经状态、家族史及生育史等因素校正后,与MDM2 SNP 309 T/T基因型比较,T/G 型及G/G 型与乳腺癌的发病风险无显著相关性（T/G,adjusted OR= 1.2,95%CI:0.8～1.6,P=0.30;G/G,adjusted OR= 1.0,95%CI:0.7～1.5,P=0.88）。 进一步分层分析后显示:在绝经后人群中,与T/T基因型比较,T/G 基因型及G/G 基因型显著增加乳腺癌的发病风险（T/G,adjusted OR= 1.8,95%CI:1.2～3.0,P=0.011;G/G,adjusted OR= 1.9,95%CI:1.2～3.3,P=0.014）。 提示绝经后人群携带T/G 型、G/G 型者比携带T/T基因型者患乳腺癌的风险分别升高约1.8、1.9 倍。在绝经前人群中,各基因型与乳腺癌的发病风险无显著相关性（P>0.05）。 结论:MDM2 启动子309 位点突变型G 等位基因携带者显著增加绝经后女性乳腺癌的发病风险。      

Effects of Menstrual and Reproductive Factors on the Risk of Breast Cancer: Meta-analysis of the Case-Control Studies in Japan

To elucidate the magnitude of the effect of menstrual and reproductive factors on breast cancer occurrence among Japanese women, we reviewed eight case-control studies previously conducted in Japan and used a quantitative method (meta-analysis) to summarize the data. While individual studies have different methods and populations, the estimated odds ratios (ORs) in the studies were statistically homogeneous for all study variables. It was confirmed that early age at menarche, late age at first birth, and premenopausal status are significantly associated with risk of breast cancer; an estimated combined OR of 0.68 (95% confidence interval (CI): 0.59-0.77) was obtained for women with onset of menstruation after age 16 compared to those before age 14. Nulliparous women had higher risk than women with first birth before age 25 (OR=1.56 95%, CI: 1.27-1.91). The OR for women with first birth after age 35 was 2.26 (95% CI: 1.85-2.77) compared to women at first birth before age 25. Premenopausal women had a higher risk than women with menopause before age 50 (OR=2.21, 95% CI: 1.53-3.20). We also found a significant protective effect of high parity after controlling for age at first birth and the other menstrual factors. The OR estimate for 3 or more births compared to nulliparity was 0.68 (95% CI: 0.54-0.86). The meta-analysis provided quantitative estimates of breast cancer risk among Japanese women with improved precision.     

TP53 Polymorphisms in Sporadic North Indian Breast Cancer Patients

Background: The purpose of this study was to evaluate the potential association of five (p.P47S, p.R72P, PIN3 Ins16bp, p.R213R and r.13494g>a) polymorphisms of TP53 with the risk of developing breast cancer in North Indian Punjabi population. Methods: We screened DNA samples of 200 sporadic breast cancer patients (197females and 3 males) and 200 unrelated healthy, gender and age matched individuals for the polymorphisms. Results: For the p.P47S polymorphism, we observed the PP genotype in 99.5% of the patients and PS genotype in only 1 patient. All the controls had the wild type PP genotype. The frequency of RR, RP and PP genotype of p.R72P was 23.5% vs 33.5%, 51.5% vs 45.5% and 25% vs 21% in patients and controls respectively. Heterozygous (RP) genotype was increased in breast cancer patients as compared to controls (51.5 vs 45.5%) and showed1.61 fold significantly increased risk for breast cancer (OR=1.61, 95% CI, 1.01-2.58, p=0.04). In breast cancer patients the frequencies of A1A1, A1A2 and A2A2 genotypes of PIN3 Ins16bp polymorphism were 67%, 26% and 7% respectively whereas in controls the genotype frequencies were 68.5%, 27.5% and 4% respectively, with no significant difference. For p.R213R (c.639A>G), all individuals had homozygous wild type genotype. The frequencies of GG, GA and AA genotypes of TP53 r.13494g>a polymorphism were 62 vs 67.5%, 33 vs 28%and 5 vs 4.5% in patients and controls respectively, again without significant difference. We observed that RPA1A1 genotype combination of p.R72P and PIN3 Ins16bp and RP-GG combination of p.R72P and r.13494g>a polymorphism showed significant risk of breast cancer (OR=1.65, 95%CI: 0.98-2.78, p=0.05; OR=1.72, 95%CI: 1.01-2.92, p=0.04). Conclusion: The results of present study indicated that among the five TP53 polymorphisms investigated, the p.R72P polymorphism, and the RP-A1A1 and RP-GG genotype combination contribute to breast cancer susceptibility in North Indians.