Positive Family History Of Cancer Research Articles

CERVICAL CANCER SCREENING USING ACETIC ACID AMONG HIGH RISK WOMEN AND PLAN OF NURSING ACTION

Background: Screening for cervical cancer using visual inspection with acetic acid (VIA) has been advocated by WHO as a suitable, low cost and feasible alternative modality for control of cervical cancer in low resource setting. The aim of the study was to assess cervical cancer screening for high risk women using acetic acid and implement the plan of nursing action. A cross-sectional design was carried out in the Gynecological OPD at Zagazig University Hospitals. A purposive sample of 100 females was required to estimate sensitivity and specificity of acetic acid in identifying pre malignant epithelial cell changes of the cervix. The tools used for data collection were; a structured interview sheet, clinical assessment sheet and the plan for nursing action. The results revealed that, women at risk for cervical cancer were more likely to be >30 years and more, their age of marriage was <20 years, had positive family history of cancer. They were also multipara, had repeated cervical laceration, exposed to STIs especially chlamydia and menorrhagia was present in 29.0% of them. Meanwhile post-coital bleeding was reported by 19.0% of the participants. Positive result for premalignant cervical lesion was 26.0% for VIA. Sensitivity and specificity of VIA were found to be 100% and 89.16% respectively. The accuracy of VIA was 91.0% which means that VIA test was more accurate. It can be concluded that VIA can effectively identify more cases of cervical intraepithelial neoplasia. It has been proven to achieve high sensitivity with an acceptable specificity. VIA test offers hope for universal screening as an alternate method for low resource setting. It is recommended that; VIA should be actively advocated to improve detection rate of cervical lesions so that it should be performed in all the women attending outpatient gynecological clinics.

BRCAness Combined With a Family History of Cancer Is Associated With a Poor Prognosis for Breast Cancer Patients With a High Risk of BRCA Mutations

BackgroundThe inexpensive prediction of the characteristics of BRCA-mutated breast cancer as “BRCAness” using the somatic cells of patients with breast cancer could be useful for developing a therapeutic strategy. Our objective was to correlate BRCAness with the clinicopathologic features, including a family history (FH) of cancer, in breast cancer patients with a high risk of BRCA mutations. Patients and MethodsThe present study included 124 patients, including 55 with early-onset and 77 with triple-negative breast cancer, who had undergone resection at Kyushu University Hospital from 2005 to 2014. Early-onset breast cancer is defined as an onset in patients aged ≤ 40 years. BRCAness was performed using multiple ligation-dependent probe amplification. The patients’ FH of cancer was surveyed from first- to third-degree relatives. ResultsOf the 124 patients, the multiple ligation-dependent probe amplification assay results indicated that 59 tumors (47.6%) had BRCAness and 27 patients (21.8%) had a positive FH for cancer. The patients with BRCAness experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) compared with those without. Patients with FH had shorter RFS and OS compared to those without BRCAness. The patients were divided into those with and without BRCAness and those with and without a positive FH. The BRCAness with FH subgroup experienced significantly shorter RFS and OS. Multivariate analysis revealed that BRCAness and a positive FH were independent negative prognostic factors. ConclusionOur findings suggest that BRCAness tumors with a positive FH of cancer were associated with a poor prognosis in the BRCA-mutation high-risk group. We propose that BRCAness and a positive FH will serve to predict patients’ prognosis.

Family history of cancer as surrogate predictor for immunotherapy with anti-PD1/PD-L1 agents: preliminary report of the FAMI-L1 study.

Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed. In this preliminary report at multivariate analyses, positive family history of cancer showed a statistically significant relationship with a better objective response rate (p=0.0024), disease control rate (p=0.0161), median time to treatment failure (p=0.0203) and median overall survival (p=0.0221). Diagnosis of multiple neoplasms significantly correlates only to a better disease control rate, while interestingly non-early onset of cancer and sex (in favor of female patients) showed significant correlation with a better median overall survival (p=0.0268 and p=0.0272, respectively). This pilot study seems to individuate easily available patient's features as possible predictive surrogates of clinical benefit for anti-PD-1/PD-L1 treatments. These preliminary results need to be confirmed with a greater sample size, in prospective trials with immunotherapy.

Detection of germline deleterious mutations in prostate cancer patients with use of a validated 30-gene sequencing assay.

223 Background: Germline DNA repair gene alterations in men with metastatic prostate cancer (PC) unselected for family history of malignancy occur in a greater frequency compared to localized PC and the general population. We hypothesized that assessing heritable alterations in a broader panel of high-susceptibility genes, may be relevant for detecting familial associations with other cancers in PC patients. Methods: We examined a cohort of 52 PC patients (median age 60, range 45-80) with histologically confirmed PC (17 localized, 35 metastatic). Germline DNA was isolated from blood lymphocytes or buccal swabs, and targeted next-generation sequencing was conducted with use of a previously validated panel of 30 genes associated with an elevated risk for common cancers (Color Genomics). As a reference for gene aberration frequencies we used the Exome Aggregation Consortium (ExAC) database. Results: The majority of patients (48/52, 92%) had a positive family history of cancer in any relative. Nine deleterious pathogenic mutations were identified in germline DNA samples from 8/52 (15%) patients, affecting the following genes: APC (n = 2, 3.8%), BRCA2 (n = 2, 3.8%), CHEK2 (n = 3, 5.7%), ATM (n = 1, 1.9%), RAD51D (n = 1, 1.9%). APC mutations were significantly more frequent in our cohort compared to the ExAC database (0.3%, p &lt; 0.001). The frequency of DNA repair gene alterations (7/52, 13.5%) was also significantly higher compared to the ExAC database (0.3%, p &lt; 0.001). The median overall survival (OS) between patients with and without germline gene alterations was similar (81.5 versus 74 months, respectively). The presence of heritable gene alterations from the 30-gene panel was significantly more frequent in patients with a positive family history of any cancer (p &lt; 0.001) or prostate, breast, ovarian cancer (p = 0.001) in a first degree relative. Conclusions: The use of a targeted panel of high-susceptibility cancer-associated genes in PC not only confirms the enrichment of germline mutations in men with PC. It can also reveal associations of PC with other cancers which may portend implications for treatment and prognosis.

Abstract P4-06-14: Voice of cancer patients: Association of family history with genetic mutations in breast and ovarian cancer

Abstract There are specific guidelines for testing germline mutations in patients with breast cancer. Besides BRCA 1 and 2, germline mutations of multiple other genes are being recognized as risk factors for breast and ovarian cancers and hence more patients are being tested using multigene panels. Many patients share their experiences as freely shared messages in online forums. In this study, we use our automated system (VoCP) to analyze these messages to understand awareness of genetic testing in breast cancer patients and some factors that lead to their genetic testing. Method: We collected 15.13 million unique messages (by 987,189 users) from 37 unrestricted cancer forums that provide clinically relevant information. We built custom ontologies for genetic tests; breast, ovarian and other cancers; risk reducing mastectomy and oophorectomy; and screening. We then used VoCP that uses techniques from Big Data Science and Artificial Intelligence (e.g., deep learning, topic modeling, information retrieval, and natural language processing) to extract relevant information from these messages. Results: Out of 15.13 million, 30,074 messages from 7,838 distinct users were discussing genetic testing. Mutations that were discussed most include: · BRCA1/BRCA2 (28,130 messages); 954 patients were positive · PALB2 (218 messages); 114 were positive · CHEK2 (315 messages); 149 were positive · TP53 (180 messages); 55 were positive · BRIP1 (76 messages); 36 were positive · CDH1 (128 messages); 12 were positive · NBN (80 messages); 28 were positive · STK11 (48 messages); 2 were positive · RAD50/ RAD51C (39 messages/48 messages) Association with family history of cancer: 3,083 messages mentioned positive family history and some mentioned several cancers in their family; these messages discussed the following cancers: · Breast cancer: 2,243 massages · Ovarian cancer: 830 massages · Colon cancer: 247 messages · Pancreatic cancer: 121 massages · Prostate cancer: 206 massages · Lung cancer: 138 messages Out of 954 BRCA 1 and 2 positive patients, · 279 messages indicated their family members were tested for BRCA 1 and 2 · 156 messages indicated positive mutations were found in family members · 23 messages indicated that male members of family were also being tested Also, out of 954 BRCA 1 and 2 positive patients, · 333 mentioned opting for bilateral mastectomy and 117 talked about getting Prophylactic Bilateral Salpingo Oophorectomy · 309 messages talked about ovarian cancer once they found out that they have BRCA mutation Discussion:There is increasing awareness of genetic testing and germline mutations in addition to BRCA 1 and 2 in breast cancer. Positive family history of cancer is mentioned in 10% of patients seeking genetic testing. VoCP reliably provides meaningful insights from patients' point of view to their treatment and their concerns; it also gives insight into unmet needs where more resources and research should be focused. We plan to use VoCP for further segmenting these 30,074 messages to understand other attributes and awareness among such patients. Citation Format: Aggarwal S, Sharma R, Sharma R, Aggarwal A. Voice of cancer patients: Association of family history with genetic mutations in breast and ovarian cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-14.

Psychological distress in patients with chronic atrophic gastritis: the risk factors, protection factors, and cumulative effect

This study aimed to examine the psychological status among Chronic Atrophic Gastritis (CAG) patients and to find the cumulative effects of risk and protective factors. A sample of 101 CAG patients completed the investigation. Hierarchical linear regression was used to find risk and protective factors, and examine the cumulative effects in risk factor index (RFI) and protective factor index (PFI). Results showed that nine symptoms from SCL-90-R were severer among CAG patients than those in adult norm. Risk factors including positive family history of cancer and higher negative life events could predict higher GSI (β = 0.206, p = 0.023; β = 0.398, p < 0.001; R² = 0.203); more household resistant, positive coping and stronger resilience were protective factors and could predict GSI negatively (β = -0.188, p = 0.020; β = -0.350, p = 0.012; β = −0.066, p = 0.621; R² = 0.190). The GSI was positively correlated with RFI (β = 0.338, p < 0.001; R² = 0.113) and negatively related to PFI (β = −0.378, p < 0.001; R² = 0.133). In conclusion, CAG patients suffered from various psychological distress, and the protective factors should be enhanced cumulatively to protect against psychological distress.

Impact of age at diagnosis on clinicopathological outcomes of oral squamous cell carcinoma patients.

Objective:A recent trend in diagnosis of oral cancer in young age is observed, however its impact on various clinicopathological parameters needs to be explored. The aim of the current study was to compare and analyze impact of age at diagnosis with clinicopathological parameters of oral squamous cell carcinoma patients.Methods:In this cross sectional study conducted at Department of Oncology Ziauddin Hospital Karachi, we included histologically confirmed cases of oral squamous cell carcinoma. The patients were categorized as young age group (40yrs and younger) and old age group (41 yrs and above). A total of 115 patients diagnosed between 2013 and 2016 were enrolled in the study. The variables considered were age at diagnosis, sex, site of lesion, positive family history, tumor grade, stage, uric acid level and survival.Results:A statistically significant difference was observed between two age groups in overall survival, uric acid level and positive family history of cancer. No significant difference was observed in tumor location, grade and stage.Conclusion:Majority of oral cancer patients present at an advanced stage irrespective of age at diagnosis but young age has an overall improved survival. Moreover, a positive family history of cancer in young age group mandates further exploration of possible role of genetic polymorphisms which might be responsible for early onset of the disease.

Effect of Sociodemographic Characteristics on the Attitude and Practice of Adult Cancer Patients Treated in the General Hospitals, Tabuk Region, Saudi Arabia

its early stages, resulting in better prognosis and long-termsurvival. Moreover, compliance of cancer patients with treatment instructions is crucial for better prognosis. Little is known about the effect of sociodemographic factors on attitude and practice of cancer patients. Objective: The aim of this study was to assess the effect of sociodemographic status on the attitude and practice of adult patients with cancer towards the intent to start the treatment, the adherence to treatment regimen and the prognosis of the disease. Methods: this study was carried out inthe generalhospitals, Tabuk Region, Saudi Arabia. Participants were selected from the Oncology Center Outpatient Clinics. A questionnaire designed for cancer patients was used for data collection Background: many types of cancer are easily prevented through screening that can detect the disease during via direct interview. The questionnaire included questions to record sociodemographic factors, patient’s attitude (towards early diagnosis, treatment, and follow up), practice and general health status. Results: attitude score was significantly higher in the married respondents (p = 0.015). Practice score was higher in those aged less than 20 and above 60 years-old (p = 0.016), those who were in early stages of cancer (p = 0.004) and respondents with positive family history of cancer (p = 0.019). The attitude and practice scores were found to have a significant positive and moderate correlation (r = 0.487; p <0.001). Conclusion: the overall attitude and practice of the respondents towards cancer was fair in most of the points. However, their attitude and utilization of screening methods was less than satisfactory. This calls for an action to encourage Saudi population, particularly those at high risk, to seek and receive screening services. Explaining the benefits and the access to free screening services is crucial. Barriers that are responsible for this attitude and practice should be explored and addressed.

Knowledge, attitude, practice and barriers of cervical cancer screening among women living in mid-western rural, Nepal.

ObjectiveTo find out the knowledge, attitude, practice, and barriers of cervical cancer screening in mid-western rural, Nepal.MethodsA hospital-based cross-sectional study was conducted. Women aged 20 or more were interviewed using a structured questionnaire regarding the socio-demographic information, knowledge, attitude, practice, and barriers to the cervical cancer screening.ResultsTotal of 360 participants were recruited for this study, mean age was 30.13±10.4 years. More than 87% of participants had inadequate knowledge, but around 72% had a favorable attitude towards cervical cancer screening. There was a significant portion of women (86.4%) had never done any cervical cancer screening test. Despite being higher literacy rate of Brahmin and Chhetri ethnic group, they were less likely to attend the cervical cancer screening than Dalit and Janajati (p<0.001); and those who had a positive family history of cancer were more likely to attend the cervical cancer screening (p<0.001). Similarly, married women, who had adequate knowledge and or favorable attitude, were more likely to practice cervical cancer screening, though statistically not significant. Factors such as “No symptoms,” “Lack of awareness,” “Embarrassment,” etc. were the most common barriers for the cervical cancer screening.ConclusionThe adequate knowledge and practice of cervical cancer screening were meager among rural Nepalese women, but most of them had a favorable attitude. There is an imperative need for related awareness programs to promote the uptake of cervical cancer screening tests.

Anxiety, Depression and their Risk Factors in Cancer Moroccan Patients Undergoing Radiation Therapy: A Cross-Sectional Study

Purpose: To our knowledge, no study specifically assessed anxiety and depression in Moroccan cancer population undergoing radiotherapy. The objective of this study was to assess the prevalence of anxiety and depression in patients with cancer prior to the first session of radiotherapy and to identify predictor factors. Material and methods: It is a cross-sectional single center study. An interview was conducted using the Hospital Anxiety and Depression Scale. Results: 150 patients filled the study inclusion criteria. The mean age was 54.9 ± 12.8 years, 12% of patients were in current employment. 42% of the participants had a positive family history of cancer. Out of study participants, 58% scored abnormal on the anxiety scale and 52% on the depression scale. Statistically significant predictors of anxiety and depression were similar to those reported in published studies, such as the presence of family history of cancer, received radiotherapy in family, employment status and treatment intention. Conclusions: The results of this study suggest that a large proportion of cancer patients have psychiatric comorbidities. There is an urgent need for psychosocial support programs and psychological screening for patients diagnosed with cancer and candidate for radiation therapy.

Risk of colorectal cancer and clotting factor gene polymorphisms in Moroccan Population.

Venous thrombosis has been described as a common complication for cancer patients. The association between clotting factor gene polymorphisms and the risk of colorectal cancer has been evidenced. The aim of the present study was to investigate the association of G20210A factor II prothrombin (FII) and factor V Leiden ( FVL) G1691A with the risk of colorectal cancer(CRC). Genotyping of FVL and G20210A FII was performed using the polymerase chain reaction restriction fragment length polymorphism method on a sample of 76 patients with CRC as well as 182 controls. No significant difference in FVL gene variations was observed between cases and controls. However, with regard to the G20210A FII, the homozygous mutated genotype AA was associated with an increased risk of CRC. A significant association between the G20210A FII mutation and the risk of CRC was identified using recessive (OR=57.63, 95% CI: 3.33-997.26, P=0.0053), dominant (OR=27.87, 95% CI: 12.67 -61.28, P<0, 0001) and additive (OR=21.24, 95% CI: 10.45-43.16, P<0, 0001) models. No statistical difference was observed in parameters such as sex, age and positive family history for cancer. Our results did not support an effect of FVL gene on CRC risk and suggested that the G20210A FII prothrombin gene variant may be a risk factor for CRC in Moroccan population.

The characteristics of breast cancer patients with metachronous primary malignancies

Introduction. The risk of developing subsequent primary cancers varies from 1% to 18% and it depends on the type of first cancer and treatment methods applied. Considering the time of occurrence, multiple primary cancers generally fall into two categories: synchronous and metachronous. In breast cancer patients, 10.5% developed multiple primary cancers, from which 23.8% had synchronous, 79% had metachronous and the remaining 2.8% had both synchronous and metachronous malignancies. In patients with breast cancer, elevated risk is observed especially in the development of contralateral breast cancer, endometrial cancer, esophageal cancer, ovarian cancer and thyroid cancer. Aim. This paper presented the characteristics of breast cancer patients with metachronous primary malignancies in relation to the type of metachronous primaries (breast versus non-breast) and to analyse the impact of the type of metachronous cancers on survival rate. Material and methods. Among patients treated for breast cancer between 1963 and 2010, 354 patients (2.1%) developed metachronous primary malignancies and these made up 13.8% of all patients with multiple primary cancers. The mean age at diagnosis of the first breast cancer was 53 ± 11.5 years; positive family cancer history was noted in 127 patients (35.9%). Metachronous malignancies are defined as primaries following the diagnosis of breast cancer in a time interval greater than or equal to than 6 months. In our group, the mean time interval between the diagnosis of breast cancer and the appearance of metachronous malignancies was 100.9 ± 74.9 months (range: 6–543 months, median: 83 months). For comparison of the two groups (patients with second breast vs non-breast cancer) we used the Pearson’s Chi-square test for independence (for categorized variables) and variance analysis with Student’s t-test (for continuous variables). The survival rate was evaluated with the Kaplan-Meier method, and the log rank test was applied to assess the influ­ence of some factors on the evaluated results. The significance level at α = 0.05 was adopted for all statistical analyses. Results. The probability of occurrence of new cancer averaged from 38.1% to 67.8% for 5 and 10 years after diagnosis of first breast cancer, respectively. In our group, 380 cases of metachronous carcinomas were noted in 354 analysed patients. The most frequent metachronous malignancy was breast cancer (194 cases — 54.8%), which occurred as second (192 cases) or third (2 cases) cancer. Patients with contralateral breast cancer in comparison to other types of metachronous malignancies were significantly (p &lt; 0.05): younger (under 50 years: 56.2% vs 34.4%), premenopausal (69.6% vs 48.8%), had a lobular type of first breast cancer (6.7% vs 1.3%), and rarely received tamoxifen (25.3% vs 48.2%). The type of me­tachronous cancers significantly influenced survival rate: 10-year overall survival rates were 80.1% vs 67.8%, (p = 0.0271). Conclusions. The risk of occurrence of second malignancies in breast cancer survivors makes early detection of metachronous malignancies obligatory because it is an important factor which influences the quality of life in breast cancer survivors.

A prospective analysis of germline alterations (GA) in biliary tract cancer (BTC).

4085 Background: The incidence of hereditary cancer predisposition syndromes in patients (pts) with BTC is unknown. Cholangiocarcinoma has been reported in pts with germline mutations in BAP1, BRCA1/2, and mismatch repair genes. These associations are poorly characterized to date and the majority of pts do not undergo clinical germline analysis (CGA). Methods: Pts with BTC were offered consent to CGA between 01/2016 and 01/2017 under an IRB approved protocol (NCT01775072). Using the MSK-IMPACT platform, 76 genes associated with hereditary cancer predisposition were analyzed for germline variants and matched tumor samples were analysed for somatic alterations in &gt; 340 genes. Demographic and clinical data were collected. Results: 78 patients were accrued: Intrahepatic = 52, extrahepatic = 13, gallbladder = 13. Median age at diagnosis was 57 years (range 21-80), 45 (58%) had a positive family history of cancer in at least one 1st degree or two 2nd degree relatives. 7 patients had a personal history of cancer. A pathogenic or likely pathogenic GA was identified in 16 pts (20%). (See table). Conclusions: Prospective analysis of GAs in pts with BTC, unselected by family history or age, revealed potentially actionable findings in 20% of pts. CGA in pts with BTC may benefit patients and their families in view of screening and therapeutic implications. [Table: see text]

Homologous recombination deficiency and platinum rechallenge in platinum-resistant ovarian cancer patients.

5576 Background: Ovarian carcinomas show homologous recombination deficiency (HRD) in up to 50% of cases and in 15 to 20% of cases occur due to germline BRCA1 or BRCA2 mutations. BRCA mutated tumors are more sensitive to PARP inhibitors and platinum based chemotherapy. The objective of this study was to characterize a cohort of ovarian cancer patients regarding HRD and to evaluate the impact of these scores in prolonged platinum sensitivity. Methods: Thirty one ovarian cancer patients with platinum resistant recurrence reexposed to platinum based chemotherapy were selected. Paraffin embedded tumor samples from 14 patients were analyzed using ONCOSCAN assay (Affymetrix) to evaluate HRD scores. The association of the scores with response rate to platinum rechallenge, overall survival and clinical pathologic factors was evaluated. Results: From the cohort of 31 patients, 15 samples from 14 patients were analyzed for genomic alterations. Median scores were 19.5 for TAI, 12.5 for cnLOH+L, 26.0 for LST and 6.3 for HRD. High scores were found in 10 out of 14 (for cnLOH+L score) and 9 out of 14 (for LST score) patients. Seven of the 14 patients analyzed analyzed for genomic alterations had response, which suggested homologous recombination deficiency. No significant differences were observed between response rates for high versus low scores. Numerically, cnLOH+L, LST and HDR scores were higher in patients with response to treatment compared to those without response. Median overall survival was 13.4 months from the beginning of platinum rechallenge and no difference in survival according to scores was observed. Among the clinical pathologic factors, family history of breast or ovarian cancer or personal history of breast cancer was associated to higher response rate to platinum rechallenge. Conclusions: In conclusion,HRD scores showed to be potential markers of response to platinum rechallenge in the platinum resistant setting. Further studies are necessary to clarify the best cutoffs for each score, the impact of tumor heterogeneity and the analysis of tumor samples in the moment of treatment. Positive family history of cancer is a clinical factor predictvie of platinum rechallenge response.

A case of contralateral breast cancer and skin cancer associated with NBN heterozygous pathogenic variant c.698_701delAACA.

Approximately 39.6% of people will be diagnosed with cancer during their lifetime. Several factors including, lifestyle, environment and genetics may play a role in its development. Understanding these causes will greatly improve treatment methods, prevention, and survival rates of these patients. Our patient, who has a positive family history of cancer, presented with contralateral breast cancer and multiple skin malignancies. Genetic testing revealed a frameshift variant in NBN. This gene encodes the protein, nibrin, which is involved in maintaining genomic stability. Several reports have identified heterozygous NBN frameshift (c.2028delT, c.2097dupT, c.657-661delACAAA) and splice site variants (c.1397+delG) in patients with breast cancer. However, our report is the first to describe a heterozygous c.698_701delAACA NBN variant in a patient with breast cancer. Since NBN is involved in DNA integrity, loss of functional protein due to pathogenic variants significantly increases the risk of various cancers. Given the family and personal history of our patient, in connection with previous reports of NBN pathogenic variants predisposition to cancer, this variant is predicted to be pathogenic and clinically significant.

Можливості клінічного використання тестування на поліморфні варіанти генів ESR1 та CYP2D6*4 у хворих на рак грудної залози та ендометрія

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

Behavioral risk factors of breast cancer in Bangui of Central African Republic: A retrospective case-control study.

Breast cancer is recognized as a major public health problem in developing countries; however, there is very little evidence of behavioral factors associated with breast cancer risk. This study was conducted to identify lifestyles as risk factors for breast cancer among Central African women. A case-control study was conducted with 174 cases confirmed histologically by the pathology unit of the National Laboratory and 348 age-matched controls. Data collection tools included a questionnaire with interviews and medical records of patients. Data were analyzed using SPSS software version 20. Odd ratio (OR) and 95% confidence intervals (95% CI) were obtained by unconditional logistic regression. In total, 522 women were studied with a mean age of 45.8 (SD = 13.4) years. By unconditional logistic regression model, women with breast cancer were more likely to have attained illiterate and elementary education level [11.23 (95% CI, 4.65–27.14) and 2.40 (95% CI, 1.15–4.99)], married [2.09 (95% CI, 1.18–3.71)], positive family history [2.31 (95% CI, 1.36–3.91)], radiation exposure [8.21 (95% CI, 5.04–13.38)], consumption charcuterie [10.82 (95% CI, 2.39–48.90)], fresh fish consumption [4.26 (95% CI, 1.56–11.65)], groundnut consumption [6.46 (95% CI, 2.57–16.27)], soybean consumption [16.74 (95% CI, 8.03–39.84)], alcohol [2.53 (95% CI, 1.39–4.60)], habit of keeping money in bras[3.57 (95% CI, 2.24–5.69)], overweight [5.36 (95% CI, 4.46–24.57)] and obesity [3.11(95% CI, 2.39–20.42)]. However, decreased risk of breast cancer was associated with being employed [0.32 (95% CI, 0.19–0.56)], urban residence [0.16 (95% CI, 0.07–0.37)], groundnut oil consumption [0.05 (95% CI, 0.02–0.14)], wine consumption [0.16 (95% CI, 0.09–0.26)], non habit of keeping cell phone in bras [0.56 (95% CI, 0.35–0.89)] and physical activity [0.71(95% CI, 0.14–0.84)]. The study showed that little or no education, marriage, positive family history of cancer, radiation exposure, charcuterie, fresh fish, groundnut, soybean, alcohol, habit of keeping money in bras, overweight and obesity were associated with breast cancer risk among Central African women living in Bangui. Women living in Bangui should be more cautious on the behavioral risk associated with breast cancer.

Venereal Transmission of Cancer: A Study

Miasms have a tendency to remain dormant for years and they are the fundamental cause of chronic diseases. Two of the three known miasms—Sycosis and Syphilis—are venereal. This means they can infect the DNA as well as can get transmitted sexually. Cancer is a complex miasmatic disease. To understand the possibility of its venereal transmission and also when a partner's family have a positive family history of cancer, a study was done on 54 known cases of cancer. The cancer patients were surveyed under three categories: (1) a history of past or present addiction, (2) a history of cancer in one's own family, (3) a history of cancer in the spouse or in his or her family. Analysis showed that, along with addiction and heredity, occurrence of cancer is also found to be associated significantly when there is a positive history of cancer in spouse or in his or her family. This is a soft statistical proving to Dr. Hahnemann's concept of venereal nature of chronic diseases.

Potential risk of esophageal squamous cell carcinoma due to nucleotide excision repair XPA and XPC gene variants and their interaction among themselves and with environmental factors

The association of nucleotide excision repair (NER) gene polymorphisms with esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of the current study was to assess the association of repair gene xeroderma pigmentosum A (XPA) (rs-1800975) and xeroderma pigmentosum C (XPC) (rs-2228000) polymorphisms with ESCC risk as well as modifying effects of environmental factors. The genotyping was done in 450 confirmed ESCC cases and equal number of individually matched controls by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. Conditional logistic regression models were used to assess the genotypic associations and interactions. A high ESCC risk was found in subjects who carried the homozygous minor allele of XPA (odds ratio (OR) = 3.57; 95% confidence interval (CI) = 1.76-7.23), and the risk was higher when analysis was limited to participants who were ever smokers (OR = 4.22; 95% CI = 2.01-8.88), lived in adobe houses (OR = 8.42; 95% CI = 3.74-18.95), consumed large volumes of salt tea (OR = 7.42; 95% CI = 3.30-16.69), or had a positive family history of cancer (FHC) (OR = 9.47; 95% CI = 4.67-19.20). In case of XPC, a homozygous minor allele also showed strong association with ESCC risk (OR = 4.43; 95% CI = 2.41-8.16). We again observed a very strong effect of the above environmental factors in elevating the risk of ESCC. Further, the variant genotypes of both genes in combination showed an increased risk towards ESCC (OR = 7.01; 95% CI = 3.14-15.64) and such association was synergistically significant. Salt tea consumption showed an interaction with genotypes of XPA and XPC. However, an interaction with FHC was significant in the case of XPA genotype only. XPA and XPC genotypes are associated with an increased risk of ESCC, and such association was reasonably modulated by different exposures.

Risk Factors for Endometrial Cancer: Results from a Hospital-Based Case-Control Study

Objectives:The purpose of this investigation was to examine the association between endometrial cancer and possible etiological agents.Methods:A case-control study was conducted in Iran between March 2012 and May 2016. The demographic and reproductive factors of 205 women with endometrial cancer were compared, and 590 healthy cases were participated in the control group. For each endometrial cancer case, there were three controls, who were matched in terms of age and residence. The data were considered significant at p ≤0.05.Results:After adjusting the variables, the nulliparity (OR 6.23, 95% CI 2.86-13.59), the nulligravidity (OR 5.94, 95% CI 2.51-14.06), the positive family history of reproductive cancer (OR 4.97, 95% CI 2.33-10.59), the infertility history (OR 2.38, 95%CI 1.32-4.31), the obesity (BMI ≥25) (OR 1.71, 95% CI 1.16-2.52), the early menarche age (<12 years) (OR 2.10, 95% CI 1.17-3.75), and the hormonal contraception use (OR 1.69, 95% CI 1.15-2.49) were found to be associated with an increased risk of endometrial cancer. Nevertheless, the education level, the job of women, the marital age, the leisure activities, and the breast feeding were not found to be associated with the endometrial cancer after adjusting the variables.Conclusion:Scheduling of the screening program is vitally indispensable to identify endometrial cancer in women with nulliparity, nulligravidity and the positive family history of cancer. In addition, women with early menarche, those with the history of infertility, the obese ones, and those who use contraception pills need to be particularly aware of the potential risks.