The Key Role of Human Microbiota in Breast Cancer

Sound evidence recognizes the microbiota as one of the major players in human health and disease, including cancer. Every human being is an holobiont, a shared human and microbial ecosystem, in which microbial composition is individually set by behaviours and environmental factors during the first years of life. Thereafter it is modulated by diet, physical activity, emotions and drugs (in particularly antibiotics and chemotherapeutics). As a consequence, a shift in medicine is needed toward a more comprehensive practice that takes into account every individual's genoma and, in addition, his or her metagenome, known as microbiome: a "microbiota revolution". As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Specific microbes display unique features regulating their host niche in a number of body sites, which can result in an increased risk of cancer; in addition, gut microbiota composition plays a role in immune modulation within the intestinal barrier, affecting local and systemic inflammation, recognized drivers of cancer. Moreover, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and subsequentely may impact on the onset, progression and treatment of hormonal dependent cancers. Microbiota is also clearly involved in modulating the response to anticancer treatments, and above all to the emerging immunotherapy. Based on these premises, the microbiome is becoming a potential target, in order to enhance efficacy of antitumoral treatments as well as to lower their toxicity. The complex scenario that links microbiome composition to oncogenesis and response to anticancer treatments defines the frames of a new “oncobiotic” perspective.

Download Full-text

The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case–control studies

BMC Medical Genomics ◽

10.1186/s12920-021-00965-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Weiqing Liu ◽

Shumin Ma ◽

Lei Liang ◽

Zhiyong Kou ◽

Hongbin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Thyroid Cancer ◽

Cancer Risk ◽

Large Scale ◽

Meta Analysis ◽

Cochrane Library ◽

Cancer Type ◽

Increased Risk ◽

Risk Of Cancer

Abstract Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

Download Full-text

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

The International Journal of Biological Markers ◽

10.5301/jbm.2011.6266 ◽

2011 ◽

Vol 26 (1) ◽

pp. 43-49 ◽

Cited By ~ 3

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.

Download Full-text

Breast Cancer and Its Relationship with the Microbiota

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15081747 ◽

2018 ◽

Vol 15 (8) ◽

pp. 1747 ◽

Cited By ~ 58

Author(s):

Mariana Fernández ◽

Iris Reina-Pérez ◽

Juan Astorga ◽

Andrea Rodríguez-Carrillo ◽

Julio Plaza-Díaz ◽

...

Keyword(s):

Breast Cancer ◽

Dynamic Balance ◽

Human Microbiome ◽

Serum Levels ◽

Endogenous Hormones ◽

Human Beings ◽

Microbial Composition ◽

Metabolizing Enzymes ◽

Health And Disease ◽

Bacterial Genes

The microorganisms that live symbiotically in human beings are increasingly recognized as important players in health and disease. The largest collection of these microorganisms is found in the gastrointestinal tract. Microbial composition reflects both genetic and lifestyle variables of the host. This microbiota is in a dynamic balance with the host, exerting local and distant effects. Microbial perturbation (dysbiosis) could contribute to the risk of developing health problems. Various bacterial genes capable of producing estrogen-metabolizing enzymes have been identified. Accordingly, gut microbiota is capable of modulating estrogen serum levels. Conversely, estrogen-like compounds may promote the proliferation of certain species of bacteria. Therefore, a crosstalk between microbiota and both endogenous hormones and estrogen-like compounds might synergize to provide protection from disease but also to increase the risk of developing hormone-related diseases. Recent research suggests that the microbiota of women with breast cancer differs from that of healthy women, indicating that certain bacteria may be associated with cancer development and with different responses to therapy. In this review, we discuss recent knowledge about the microbiome and breast cancer, identifying specific characteristics of the human microbiome that may serve to develop novel approaches for risk assessment, prevention and treatment for this disease.

Download Full-text

Mortality and Risk of Cancer After Prophylactic Bilateral Oophorectomy in Women With a Family History of Cancer

JNCI Cancer Spectrum ◽

10.1093/jncics/pky034 ◽

2018 ◽

Vol 2 (3) ◽

Cited By ~ 1

Author(s):

Julie Abildgaard ◽

Magnus Glindvad Ahlström ◽

Gedske Daugaard ◽

Dorte Lisbet Nielsen ◽

Anette Tønnes Pedersen ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Rate Ratio ◽

Bilateral Oophorectomy ◽

Family History Of Cancer ◽

Increased Risk ◽

History Of ◽

Risk Of Cancer ◽

The Impact ◽

History Of Cancer

Abstract Background Current international guidelines recommend systemic hormone therapy (HT) to oophorectomized women until the age of natural menopause. Despite an inherited predisposition to estrogen-dependent malignancies, the guidelines also apply to women oophorectomized because of a family history of cancer. The objective of this study was to investigate the impact of HT on mortality and risk of cancer in women oophorectomized because of a family history of cancer. Methods A nationwide, population-based cohort was used to study women oophorectomized because of a family history of cancer (n = 2002). Comparison cohorts included women from the background population individually matched on age (n = 18 018). Oophorectomized women were subdivided into three groups: oophorectomized at 1) age 45 years or younger not using HT, 2) age 45 years or younger using HT, 3) older than age 45 years, and their respective population comparison cohorts. Results Women oophorectomized at age 45 years or younger using HT had increased overall mortality (mortality rate ratio [MRR] = 3.45, 95% confidence interval [CI] = 1.53 to 7.79), mortality because of cancer (MRR = 5.67, 95% CI = 1.86 to 17.34), and risk of overall cancer (incidence rate ratio [IRR] = 3.68, 95% CI = 1.93 − 6.98), primarily reflected in an increased risk of breast cancer (IRR = 4.88, 95% CI = 2.19 − 10.68). Women oophorectomized at age 45 years or younger not using HT and women oophorectomized at older than age 45 years did not have increased mortality, mortality because of cancer, or risk of overall cancer, but they had increased risk of breast cancer (IRR = 2.64, 95% CI = 1.14 to 6.13, and IRR = 1.72, 95% CI = 1.14 to 2.59, respectively). Conclusions Use of HT in women oophorectomized at age 45 years or younger with a family history of cancer is associated with increased mortality and risk of overall cancer and breast cancer. Our study warrants further investigation to establish the impact of HT on mortality and cancer risk in oophorectomized women with a family history of cancer.

Download Full-text

Cancer Incidence in Patients With Acromegaly: A Cohort Study and Meta-Analysis of the Literature

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-02457 ◽

2018 ◽

Vol 103 (6) ◽

pp. 2182-2188 ◽

Cited By ~ 38

Author(s):

Jakob Dal ◽

Michelle Z Leisner ◽

Kasper Hermansen ◽

Dóra Körmendiné Farkas ◽

Mads Bengtsen ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Cohort Study ◽

Cancer Incidence ◽

Meta Analysis ◽

Population Based ◽

Incidence Rates ◽

Tract Cancer ◽

Increased Risk ◽

Risk Of Cancer

Abstract Context Acromegaly has been associated with increased risk of cancer morbidity and mortality, but research findings remain conflicting and population-based data are scarce. We therefore examined whether patients with acromegaly are at higher risk of cancer. Design A nationwide cohort study (1978 to 2010) including 529 acromegaly cases was performed. Incident cancer diagnoses and mortality were compared with national rates estimating standardized incidence ratios (SIRs). A meta-analysis of cancer SIRs from 23 studies (including the present one) was performed. Results The cohort study identified 81 cases of cancer after exclusion of cases diagnosed within the first year [SIR 1.1; 95% confidence interval (CI), 0.9 to 1.4]. SIRs were 1.4 (95% CI, 0.7 to 2.6) for colorectal cancer, 1.1 (95% CI, 0.5 to 2.1) for breast cancer, and 1.4 (95% CI, 0.6 to 2.6) for prostate cancer. Whereas overall mortality was elevated in acromegaly (SIR 1.3; 95% CI, 1.1 to 1.6), cancer-specific mortality was not. The meta-analysis yielded an SIR of overall cancer of 1.5 (95% CI, 1.2 to 1.8). SIRs were elevated for colorectal cancer, 2.6 (95% CI, 1.7 to 4.0); thyroid cancer, 9.2 (95% CI, 4.2 to 19.9); breast cancer, 1.6 (1.1 to 2.3); gastric cancer, 2.0 (95% CI, 1.4 to 2.9); and urinary tract cancer, 1.5 (95% CI, 1.0 to 2.3). In general, cancer SIR was higher in single-center studies and in studies with <10 cancer cases. Conclusions Cancer incidence rates were slightly elevated in patients with acromegaly in our study, and this finding was supported by the meta-analysis of 23 studies, although it also suggested the presence of selection bias in some earlier studies.

Download Full-text

Reduced Rate of Infectious Complications Following Bloodless Autologous Peripheral Blood Stem Cell Transplants (APBSCT).

Blood ◽

10.1182/blood.v108.11.5453.5453 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5453-5453 ◽

Cited By ~ 1

Author(s):

Patricia A. Ford ◽

Barbara A. Matthews ◽

Nicole M. Brown

Keyword(s):

Breast Cancer ◽

High Dose Chemotherapy ◽

Infectious Complications ◽

High Dose ◽

Blood Transfusions ◽

Risk Of Infection ◽

Infection Rates ◽

Autologous Transplants ◽

Increased Risk ◽

Risk Of Cancer

Abstract While blood transfusions can be life saving, the associated risk of transfusing allogeneic blood is significant. The most common patient fears are transfusion-transmitted diseases such as HIV, Hepatitis B and C and West Nile Virus; however, the known risk of transmitting these diseases is quite small. More common complications are due to immunosuppression which can cause an increased risk of cancer recurrence in the oncologic patient and a significantly increased risk of infection. In trauma patients, it has been shown that the risk of infection increases with each additional unit of blood transfused. Currently, about 2.2 units of platelets and 3.3 units of red blood cells are administered following high-dose chemotherapy and an APBSCT. At the Center for Bloodless Medicine and Surgery at Pennsylvania Hospital, many procedures are now being completed without the use of blood products. We have previously reported the ability to perform bloodless APBSCT (Ballen, et al. J Clin Oncol2004;22:4087-4094). Knowing that blood transfusions can increase the risk of infection, we wanted to evaluate this transfusion-free population to determine if there was a correlation between infection rates and blood transfusions in the high risk transplant population. We performed a retrospective chart review of 46 patients with multiple myeloma (22), lymphoma (22) and breast cancer (2) who underwent a bloodless APBSCT in our center. Prior to transplantation, all patients recieved standard transplant doses of cyclophosphamide, carmustine and etoposide (BCV) or Melphalan. A PubMed search was performed and the closest data set in terms of patient demographics was a study by Pereira, et al. who report the rate of infectious complications in 75 patients with myeloma (30), lymphoma (30) and breast cancer (15) who were transfused liberally following high-dose chemotherapy and APBSCT (Pereira, et al. Eur J Haematol2006;76:102-108). In our bloodless patients, 37% of the patients had at least one infection, compared to Pereira and colleagues’ rate of 68% (see table). Our results are also reported in the average number of infections per patient. This comparison demonstrates a substantial reduction in the rate of infection in the bloodless population. While immunosuppression and the resulting increased infection rates have been correlated to blood transfusions in other patients populations, to the best of our knowledge this is the first report that suggests decreased infection rates in transfusion-free transplant patients. This data provides further evidence to support the practice of blood management strategies in order to reduce or eliminate blood transfusions. Patients with at least one infection All infections per person Bacterial per person Viral per person Fungal per person Unknown per person Autologous Transplants (Pereira, et al.) 68% .64 .53 .01 .07 .03 Bloodless Autologous Transplants 37% .41 .39 0 0 .02

Download Full-text

Morbidity and mortality in patients with hyperprolactinaemia: the PROLEARS study

Endocrine Connections ◽

10.1530/ec-17-0171 ◽

2017 ◽

Vol 6 (8) ◽

pp. 580-588 ◽

Cited By ~ 10

Author(s):

Enrique Soto-Pedre ◽

Paul J Newey ◽

John S Bevan ◽

Graham P Leese

Keyword(s):

Breast Cancer ◽

Cardiovascular Disease ◽

Bone Fractures ◽

Morbidity And Mortality ◽

Serum Prolactin ◽

Matched Cohort ◽

Pituitary Tumours ◽

Drug Induced ◽

Increased Risk ◽

Risk Of Cancer

Purpose High serum prolactin concentrations have been associated with adverse health outcomes in some but not all studies. This study aimed to examine the morbidity and all-cause mortality associated with hyperprolactinaemia. Methods A population-based matched cohort study in Tayside (Scotland, UK) from 1988 to 2014 was performed. Record-linkage technology was used to identify patients with hyperprolactinaemia that were compared to an age–sex-matched cohort of patients free of hyperprolactinaemia. The number of deaths and incident admissions with diabetes mellitus, cardiovascular disease, cancer, breast cancer, bone fractures and infectious conditions were compared by the survival analysis. Results Patients with hyperprolactinaemia related to pituitary tumours had no increased risk of diabetes, cardiovascular disease, bone fractures, all-cause cancer or breast cancer. Whilst no increased mortality was observed in patients with pituitary microadenomas (HR = 1.65, 95% CI: 0.79–3.44), other subgroups including those with pituitary macroadenomas and drug-induced and idiopathic hyperprolactinaemia demonstrated an increased risk of death. Individuals with drug-induced hyperprolactinaemia also demonstrated increased risks of diabetes, cardiovascular disease, infectious disease and bone fracture. However, these increased risks were not associated with the degree of serum prolactin elevation (Ptrend > 0.3). No increased risk of cancer was observed in any subgroup. Conclusions No excess morbidity was observed in patients with raised prolactin due to pituitary tumours. Although the increased morbidity and mortality associated with defined patient subgroups are unlikely to be directly related to the elevation in serum prolactin, hyperprolactinaemia might act as a biomarker for the presence of some increased disease risk in these patients.

Download Full-text

Effects of alcohol consumption in general, and wine in particular, on the risk of cancer development: a review

OENO One ◽

10.20870/oeno-one.2020.54.4.3569 ◽

2020 ◽

Vol 54 (4) ◽

pp. 813-832

Author(s):

Pierre-Louis Teissedre ◽

Zurine Rasines-Perea ◽

Jean-Claude Ruf ◽

Creina Stockley ◽

Arina Oana Antoce ◽

...

Keyword(s):

Breast Cancer ◽

Alcohol Consumption ◽

Alcoholic Beverages ◽

International Agency ◽

Upper Aerodigestive Tract ◽

Body Tissues ◽

Increased Risk ◽

Different Types ◽

Lifestyle Pattern ◽

Risk Of Cancer

Since 1988, alcohol has been classified as a Group 1 carcinogen, the highest level of risk, by the International Agency for Research on Cancer (IARC). In fact, alcohol consumption is the third leading risk factor for disease and mortality in Europe. It accounts for 4.65 % of the global burden of both injury and disease, making it one of the most preventable causes of injury and death. Tissues in closest contact with alcohol when it is ingested, such as those of the oral cavity, pharynx, esophagus and larynx, have at greater risk of becoming cancerous than other body tissues. The consumption of alcohol is also associated with an increased risk of stomach, colon, rectum, liver, female breast and ovarian cancers. Conversely, recent studies suggest that red wine components inhibit colony formation of human breast cancer and esophageal carcinoma cells, suggesting that wine-derived phenolic compounds may be inhibitory, in contrast to the alcohol component of wine. Because of a lack of systematic studies dealing with the different types of cancer and alcoholic beverages and wine in particular, in this narrative review we summarize the general risk of cancer linked to the consumption of alcoholic beverages, including wine, according to type of cancer, with 140 extracted relevant references from 1966 to 2020. Mostly epidemiological studies concerning large cohorts have been selected. For the cancers of the upper aerodigestive tract, liver, colorectum, breast cancer, pancreatic, prostate, an excessive consumption and/or misuse of alcoholic beverages is correlated with increased risk. Conversely a probable decreased risk has been found for renal/kidney cancers, as well as for Non-Hodgkin lymphomas, such as thyroid lymphomas, associated with the moderate consumption of alcoholic beverages. There is no evidence of ovarian, gastric, head and neck, and lung cancer being linked to the moderate consumption of alcoholic beverages. Cancer is a multifactorial disease, and many factors contribute to effects on health status, usually being both genetic and environmental. Habits (smoking, dietary/lifestyle pattern/ habits, physical activity), should also be taken into account when defining appropriate consumption frequencies for different types of alcoholic drink (wine, beer, spirits). Further research is needed related to wine consumption in the context of a healthy dietary and lifestyle pattern given health-promoting constituents of wine and its effects on cancer incidence.

Download Full-text

PREDICTORS AND PREMORBID CONDITIONS OF THE DEVELOPMENT OF FEMALE GENITAL CANCER, IN PARTICULAR ENDOMETRY CANCER AND BREAST CANCER

Клінічна та профілактична медицина ◽

10.31612/2616-4868.3(17).2021.09 ◽

2021 ◽

Vol 3 (17) ◽

pp. 75-83

Author(s):

A. Petruk ◽

O. Lytvak ◽

A. Khabrat

Keyword(s):

Breast Cancer ◽

Type 2 Diabetes ◽

Amino Acids ◽

Tissue Growth ◽

Biologically Active ◽

Genital Cancer ◽

Increased Risk ◽

Risk Of Cancer ◽

Female Genital

Objective: to review a new potential diagnostic criteria for predictors and premorbid conditions of female genital cancer, including endometrial cancer and breast cancer. Materials and methods. Bibliographic, information-analytical methods were used in the work. Sources of information were data from the scientific literature on the topic of the study, modern gadleins, a review of randomized controlled trials. Results. The results of epidemiological studies suggest that the increased risk of cancer of the female reproductive system is the presence of obesity and type 2 diabetes. Potential mechanisms of their association are hyperinsulinemia, hyperglycemia, chronic inflammation, and insulin resistance. Because insulin is a major regulator of cell metabolism and is a tissue growth factor, hyperinsulinemia increases the risk of cancer. Hyperinsulinemia is associated with increased secretion of androgens by the ovaries and decreased levels of the protein that binds sex hormones, leading to higher concentrations of biologically active estrogens, which are also known to be risk factors for female genital cancer. In recent years, PFAA profiles have been found to be significantly altered in cancer and type 2 diabetes. Because cancer cells require certain amino acids to synthesize DNA, tumor growth factors, build new blood vessels, and duplicate all of their protein content, changes in PFAA profiles can be used as biomarkers of disease and different types of cancer at different stages. Conclusions. With the growing incidence of cancer, the issue of early diagnosis and detection of cancer in the pre-clinical stages remains relevant. Protein metabolism in cancer remains unclear and requires further research using a larger sample size. In addition, the biological mechanisms by which amino acids may contribute to the risk and progression of cancer or other premorbid conditions need to be elucidated. Determining the exact mechanism underlying changes in PFAA profiles has great potential for cancer diagnosis and treatment.

Download Full-text

The Relationship between Pre-miR-3131 3-bp Insertion/Deletion Polymorphism and Susceptibility and Clinicopathological Characteristics of Patients with Breast Cancer

MicroRNA ◽

10.2174/2211536608666190906111830 ◽

2020 ◽

Vol 9 (3) ◽

pp. 216-223

Author(s):

Mahsa Azizi ◽

Nahid Rahimi ◽

Gholamreza Bahari ◽

Seyed Mehdi Hashemi ◽

Mohammad Hashemi

Keyword(s):

Breast Cancer ◽

Case Control Study ◽

Late Onset ◽

Meta Analysis ◽

Clinicopathological Characteristics ◽

Increased Risk ◽

Pcr Rflp ◽

Risk Of Cancer ◽

The Relationship ◽

Control Study

Aims: This study aimed at examining the effect of 3-bp pre-miR-3131 insertion/deletion (ins/del) polymorphism on Breast Cancer (BC) risk. Objectives: Totally 403 women including 199 BC patients and 204 women who have no cancer were included in this case-control study. Genotyping of miR-3131 3-bp ins/del polymorphism was performed by mismatch PCR-RFLP method. Methods: The findings expressed that the pre-miR-3131 3-bp ins/del variant was not related to the risk of BC in all genetic tested models. While, the ins/del genotype was related to late onset BC (OR=2.53, 95%CI=1.27-4.84, p=0.008). Results: Pooled results from the meta-analysis indicated to that the pre-miR-3131 ins/del is related to with an increased risk of cancer in heterozygous (OR=1.26, 95%CI=1.06-1.51, p=0.01), dominant (OR=1.33, 95%CI=1.14-1.54, p=0.0002), and allele (OR=1.24, 95%CI=1.06-1.45, p=0.006) genetics models. Conclusion: It is concluded that, our findings did not support a relationship between pre-miR-3131 ins/del polymorphism and the risk of BC. While, this variant was significantly related to late onset BC. Combined results of this study with previous studies indicated that this polymorphism increased the risk of cancer. More studies in a study with larger population with variety of ethnicities are required to verify our findings.

Download Full-text