СONTRIBUTION OF POLYMORPHIC VARIATION OF ТP53 AND XRCC1 GENES TO THE SUSCEPTIBILITY TO BREAST CANCER FOR WOMEN OF KYRGYZ AND BELARUSIAN NATIONALITY - A COMPARATIVE STUDY ON MULTIFACTOR DIMENSIONALITY REDUCTION METHODS

2018 ◽  
Vol 64 (1) ◽  
pp. 95-101
Author(s):  
Nazira Aldasheva ◽  
Vyacheslav Kipen ◽  
Zhaynagul Isakova ◽  
Sergey Melnov ◽  
Raisa Smolyakova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Rflp Analysis ◽  
Kyrgyz Republic ◽  
Increased Risk ◽  
Polymorphic Variants ◽  
The Republic

Basing on Multifactor Dimensionality Reduction method we showed that polymorphic variants p.Q399R (rs25487, XRCC1) and p.P72R (rs1042522, TP53) correlated with increased risk of breast cancer for women from the Kyrgyz Republic and the Republic of Belarus. Cohort for investigation included patients with clinically verified breast cancer: 117 women from the Kyrgyz Republic (nationality - Kyrgyz) and 169 - of the Republic of Belarus (nationality - Belarusians). Group for comparison included (healthy patients without history of cancer pathology at the time of blood sampling) 102 patients from the Kyrgyz Republic, 185 - from the Republic of Belarus. Respectively genotyping of polymorphic variants p.Q399R (rs25487, XRCC1) and p.P72R (rs1042522, TP53) was done by PCR-RFLP. Analysis of the intergenic interactions conducted with MDR 3.0.2 software. Both ethnic groups showed an increase of breast cancer risk in the presence of alleles for SNPs Gln p.Q399R (XRCC1) in the heterozygous state: for the group “Kyrgyz” - OR=2,78 (95% CI=[1,60-4,82]), p=0,001; for the group “Belarusians” - OR=1,85 (95% СІ=[1Д1-2,82], p=0,004. Carriers with combination of alleles Gln (p.Q399R, XRCC1) and Pro (p.P72R, TP53) showed statistically significance increases of breast cancer risk as for patients from the Kyrgyz Republic (OR=2,89, 95% CI=[1,33-6,31]), so as for patients from the Republic of Belarus (OR=3,01, 95% CI=[0,79-11,56]).

scholarly journals Transiently increased risk of breast cancer after childbirth: implications for fertility treatments and surrogacy

2020 ◽  
Vol 35 (6) ◽  
pp. 1253-1255
Author(s):  
Zeev Blumenfeld ◽  
Norbert Gleicher ◽  
Eli Y Adashi
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Small Degree ◽  
Short Term ◽  
Benefit Ratio ◽  
Professional Societies ◽  
Fertility Treatments ◽  
Increased Risk

Abstract Whereas longstanding dogma has purported that pregnancies protect women from breast cancer, a recent meta-analysis now mandates reconsideration since it reported an actual higher breast cancer risk for more than two decades after childbirth before the relative risk turns negative. Moreover, the risk of breast cancer appears higher for women having their first birth at an older age and with a family history and it is not reduced by breastfeeding. The process of obtaining informed consent for all fertility treatments, therefore, must make patients aware of the facts that every pregnancy, to a small degree, will increase the short-term breast cancer risk. This observation may be even more relevant in cases of surrogacy where women agree to conceive without deriving benefits of offspring from assuming the risk, thus creating a substantially different risk-benefit ratio. Consequently, it appears prudent for professional societies in the field to update recommendations regarding consent information for all fertility treatments but especially for treatments involving surrogacy.

Association of APC and MCC Polymorphisms with Increased Breast Cancer Risk in an Indian Population

2011 ◽  
Vol 26 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Nupur Mukherjee ◽  
Nilanjana Bhattacharya ◽  
Satyabrata Sinha ◽  
Neyaz Alam ◽  
Runu Chakravarti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Risk Of Cancer

The adenomatous polyposis coli (APC) and mutated in colorectal cancer (MCC) genes are key regulatory genes of the Wnt/β-catenin signaling pathway, which are independently involved in maintaining low levels of β-catenin in the cell. In addition to genetic and epigenetic alterations, some genetic polymorphisms in the genes associated with the Wnt signaling pathway have been reported to be associated with an increased risk of cancer, including breast cancer. In the present study we analyzed the association of genotype and haplotype status of two single nucleotide polymorphisms (SNPs), rs2229992 and rs11283943, in the APC and MCC genes, respectively, with an increased risk of breast carcinogenesis in a breast cancer and control population from eastern India. We observed a significant association of the rs11283943 SNP with increased breast cancer risk. Two specific haplotypes involving the minor allele of rs11283943 were found to be associated with an increased breast cancer risk. Kaplan-Meier curves showed a significant association of the 2–2 genotype (genotype homozygous for the rs11283943 minor allele) with decreased survival (p=0.045) of the breast cancer patients in our study, in particular patients with early-onset BC.

scholarly journals Biological Aging Marker p16INK4a in T Cells and Breast Cancer Risk

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3122
Author(s):  
Jie Shen ◽  
Renduo Song ◽  
Bernard F. Fuemmeler ◽  
Kandace P. McGuire ◽  
Wong-Ho Chow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mrna Expression ◽  
Cellular Senescence ◽  
Human Cancer ◽  
Biological Aging ◽  
Increased Risk ◽  
Discovery Stage

Prior research has demonstrated that altered telomere length, a well-known marker for biological aging, is associated with various types of human cancer. However, whether such association extends to additional hallmarks of biological aging, including cellular senescence, has not been determined yet. In this two-stage study, we assessed the association between p16INK4a mRNA expression in T cells, a marker of cellular senescence, and breast cancer risk. The discovery stage included 352 breast cancer patients and 324 healthy controls. p16INK4a mRNA expression was significantly higher in individuals who were older, Black, and had family history of cancer than their counterparts in both cases and controls. p16INK4a mRNA expression also differed by marital status, annual income, and smoking status in cases. In the discovery stage, we found that increased p16INK4a mRNA expression was associated with 1.40-fold increased risk of breast cancer (OR = 1.40; 95%CI: 1.21, 1.68; p < 0.001). A marginally significant association was further observed in the validation stage with 47 cases and 48 controls using pre-diagnostic samples (OR = 1.28; 95%CI: 0.98, 2.97; p = 0.053). In addition, we found that p16INK4a mRNA expression was higher in tumors with selected aggressive characteristics (e.g., poorly differentiated and large tumors) than their counterparts. In summary, our results demonstrate that higher p16INK4a mRNA expression in T cells is a risk factor for breast cancer and further support the role of biological aging in the etiology of breast cancer development. Novelty and Impact Statements: The results from this study provide evidence that cellular senescence, a process of biological aging, plays a role in breast cancer etiology. In addition, our results also support that social demographics may modify cellular senescence and biological aging.

scholarly journals Pubertal timing and breast density in young women: a prospective cohort study

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Lauren C. Houghton ◽  
Seungyoun Jung ◽  
Rebecca Troisi ◽  
Erin S. LeBlanc ◽  
Linda G. Snetselaar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Density ◽  
Young Women ◽  
Geometric Mean ◽  
Age At Onset ◽  
Breast Development ◽  
Increased Risk ◽  
Pubertal Tempo

Abstract Background Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. Methods From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006–2008, 182 participants then aged 25–29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. Results The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2–86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2–26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9–17.5%)). Conclusions Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.

scholarly journals Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) variants and breast cancer risk in Burkina Faso

2019 ◽  
Vol 10 (1) ◽  
pp. 175-183 ◽  
Author(s):  
Isabelle Touwendpoulimdé Kiendrebeogo ◽  
Abdou Azaque Zoure ◽  
Pegdwendé Abel Sorgho ◽  
Albert Théophane Yonli ◽  
Florencia Wendkuuni Djigma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Sporadic Breast Cancer ◽  
Disease Stage ◽  
Breast Cancer Patients ◽  
Glutathione S Transferase ◽  
Increased Risk ◽  
Increased Susceptibility

AbstractBackground and objectiveBreast cancer remains the most common cause of cancer mortality in women. The aim of this study was to investigate associations between genetic variability in GSTM1 and GSTT1 and susceptibility to breast cancer.MethodsGenomic DNA was extracted from blood samples for 80 cases of histologically diagnosed breast cancer and 100 control subjects. Genotyping analyses were performed by PCR-based methods. Associations between specific genotypes and the development of breast cancer were examined using logistic regression to calculate odds ratios [1] and 95% confidence intervals (95%CI).ResultsNo correlation was found between GSTM1-null and breast cancer (OR = 1.83; 95%CI 0.90-3.71; p = 0.10), while GSTT1-null (OR = 2.42; 95%CI 1.17-5.02; p= 0.01) was associated with increased breast cancer risk. The GSTM1/GSTT1 double null was not associated with an increased risk of developing breast cancer (OR = 2.52; 95%CI 0.75-8.45; p = 0.20). Furthermore, analysis found no association between GSTM1-null (OR =1.12; 95%CI 0.08-15.50; p = 1.00) or GSTT1-null (OR = 1.71; 95%CI 0.13-22.51; p = 1.00) and the disease stage of familial breast cancer patients or sporadic breast cancer patients (GSTM1 (OR = 0.40; 95%CI 0.12-1.32; p = 0.20) and GSTT1 (OR = 1.41; 95%CI 0.39-5.12; p = 0.75)). Also, body mass index (BMI) was not associated with increased or decreased breast cancer risk in either GSTM1-null (OR = 0.60; 95%CI 0.21-1.68; p = 0.44) or GSTT1-null (OR = 0.60; 95%CI 0.21-1.68; p =0.45).ConclusionOur results suggest that only GSTT1-null is associated with increased susceptibility to breast cancer development.

scholarly journals Review of: Are breast density and bone mineral density independent risk factors for breast cancer?

2005 ◽  
Vol 8 (11) ◽  
Author(s):  
J. L. Hopper
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Bone Mineral Density ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Correlation Coefficient ◽  
Breast Density ◽  
Mammographic Breast Density ◽  
Mineral Density ◽  
Increased Risk

Citation of original article:K. Kerlikowske, J. Shepherd, J. Creasman, J. A. Tice, E. Ziv, S. R. Cummings. Are breast density and bone mineral density independent risk factors for breast cancer. Journal of the National Cancer Institute 2005; 97(7): 368–74.Abstract of the original articleBackground: Mammographic breast density and bone mineral density (BMD) are markers of cumulative exposure to estrogen. Previous studies have suggested that women with high mammographic breast density or high BMD are at increased risk of breast cancer. We determined whether mammographic breast density and BMD of the hip and spine are correlated and independently associated with breast cancer risk. Methods: We conducted a cross-sectional study (N = 15 254) and a nested case-control study (of 208 women with breast cancer and 436 control subjects) among women aged 28 years or older who had a screening mammography examination and hip BMD measurement within 2 years. Breast density for 3105 of the women was classified using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) categories, and percentage mammographic breast density among the case patients and control subjects was quantified with a computer-based threshold method. Spearman rank partial correlation coefficient and Pearson's correlation coefficient were used to examine correlations between BI-RADS breast density and BMD and between percentage mammographic breast density and BMD, respectively, in women without breast cancer. Logistic regression was used to examine the association of breast cancer with percentage mammographic breast density and BMD. All statistical tests were two-sided. Results: Neither BI-RADS breast density nor percentage breast density was correlated with hip or spine BMD (correlation coefficient = −.02 and −.01 for BI-RADS, respectively, and −2.06 and .01 for percentage breast density, respectively). Neither hip BMD nor spine BMD had a statistically significant relationship with breast cancer risk. Women with breast density in the highest sextile had an approximately threefold increased risk of breast cancer compared with women in the lowest sextile (odds ratio: 2.7; 95% confidence interval: 1.4–5.4); adjusting for hip or spine BMD did not change the association between breast density and breast cancer risk. Conclusion: Breast density is strongly associated with increased risk of breast cancer, even after taking into account reproductive and hormonal risk factors, whereas BMD, although a possible marker of lifetime exposure to estrogen, is not. Thus, a component of breast density that is independent of estrogen-mediated effects may contribute to breast cancer risk.

scholarly journals Methylation-Based Biological Age and Breast Cancer Risk

2019 ◽  
Vol 111 (10) ◽  
pp. 1051-1058 ◽  
Author(s):  
Jacob K Kresovich ◽  
Zongli Xu ◽  
Katie M O’Brien ◽  
Clarice R Weinberg ◽  
Dale P Sandler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cox Regression ◽  
Disease Risk ◽  
Statistical Tests ◽  
Biological Age ◽  
Cancer Case ◽  
Increased Risk

Abstract Background Age is one of the strongest predictors of cancer, chronic disease, and mortality, but biological responses to aging differ among people. Epigenetic DNA modifications have been used to estimate “biological age,” which may be a useful predictor of disease risk. We tested this hypothesis for breast cancer. Methods Using a case-cohort approach, we measured baseline blood DNA methylation of 2764 women enrolled in the Sister Study, 1566 of whom subsequently developed breast cancer after an average of 6 years. Using three previously established methylation-based “clocks” (Hannum, Horvath, and Levine), we defined biological age acceleration for each woman by comparing her estimated biological age with her chronological age. Hazard ratios and 95% confidence intervals for breast cancer risk were estimated using Cox regression models. All statistical tests were two-sided. Results Each of the three clocks showed that biological age acceleration was statistically significantly associated with increased risk of developing breast cancer (5-year age acceleration, Hannum’s clock: hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.00 to 1.21, P = .04; Horvath’s clock: HR = 1.08, 95% CI = 1.00 to 1.17, P = .04; Levine’s clock: HR = 1.15, 95% CI = 1.07 to 1.23, P < .001). For Levine’s clock, each 5-year acceleration in biological age corresponded with a 15% increase in breast cancer risk. Although biological age may accelerate with menopausal transition, age acceleration in premenopausal women independently predicted breast cancer. Case-only analysis suggested that, among women who develop breast cancer, increased age acceleration is associated with invasive cancer (odds ratio for invasive = 1.09, 95% CI = 0.98 to 1.22, P = .10). Conclusions DNA methylation-based measures of biological age may be important predictors of breast cancer risk.

Barriers to breast cancer risk screening

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1505-1505
Author(s):  
A. Zwaagstra ◽  
K. Hoskins
Keyword(s):  
Breast Cancer ◽  
Risk Assessment ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Practice Nurse ◽  
Assessment Tool ◽  
Advanced Practice ◽  
Advanced Practice Nurse ◽  
Risk Screening ◽  
Increased Risk

1505 Background: The U. S. Preventive Services Task Force has recommended that physicians assess and discuss breast cancer risk with their female patients. With this recommendation comes the need to develop strategies for providing breast cancer risk-screening and a need to identify potential barriers to the successful implementation of a risk-screening strategy. Methods: A personalized breast cancer risk profile was offered to all women presenting for a screening mammogram at a community hospital. The profile included a Gail model estimate and analysis of family cancer history to detect hereditary breast cancer syndromes utilizing a pedigree assessment tool developed by the authors. Women with 5 year Gail estimates ≥ 1.66%, lifetime Gail estimate ≥ 15% or increased score with the pedigree assessment tool were considered at increased breast cancer risk. Women in the increased risk cohort received written notification of their risk status and were advised to undergo formal risk assessment either through a free consultation with an advanced practice nurse with expertise in cancer risk assessment or with their primary physician. We analyzed compliance with this recommendation over the 6 month period of time after subjects received the risk notification letter. Results: For the three month study period, 242 women met criteria for the increased risk cohort. Of these, 201 (83%) failed to follow through with the advanced practice nurse for formal risk assessment. Surveys were mailed to all 201 non-compliant subjects to identify reasons for non-compliance and 80 surveys were returned (40%). Reasons given for failure to follow- through with formal risk assessment included: self-perception of “average” breast cancer risk (75%), recent normal screening mammogram (55%), primary care physician had not referred them (18%), absence of breast symptoms (15%), and time constraints (15%). Only 11 subjects (14%) indicated that they had discussed risk results with their physician. Conclusions: The majority of women in our study who requested breast cancer risk estimates failed to act on that information. These results could have implications for design and implementation of a successful breast cancer risk-screening program, and point to the need for better patient education and involvement of primary care physicians in the risk assessment process. No significant financial relationships to disclose.

FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma

Blood ◽  
2012 ◽  
Vol 119 (4) ◽  
pp. 1029-1031 ◽  
Author(s):  
Yussanne P. Ma ◽  
Flora E. van Leeuwen ◽  
Rosie Cooke ◽  
Annegien Broeks ◽  
Victor Enciso-Mora ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Hodgkin Lymphoma ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Control Series ◽  
Cancer Risk Factors ◽  
Increased Risk

Abstract Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL, we analyzed 2 independent case-control series, from the United Kingdom and The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26-2.02; P = .000111). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.

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