Comparison of cytohormonal status of postmenopausal women with cancer to age-matched controls

To determine whether the cytohormonal status of postmenopausal women with cancer involving the uterus and vagina differs from that of women free of cancer, 100 women 60 years of age or older with positive cervicovaginal smears were compared with an age-matched control group without malignant neoplasms. Epidermoid carcinoma was identified in 64 patients (average age: 67 years) and adenocarcinoma in 34 patients (average age: 69 years). One patient had leiomyosarcoma, and another had bladder carcinoma. The paucity of benign squamous cells in the smears precluded hormonal evaluation in 32% of the index cases; the smears from 10% of the controls were also indeterminate. Of the evaluable cases with epidermoid carcinoma of the cervix, a high maturation was noted in 46% as compared to 11% for the matched controls. In addition, high maturation was noted in 69% of those patients with endometrial adenocarcinoma as compared to 19% for the matched controls. None of the index cases were atrophic; 31% of the controls were. A history of exogenous estrogen usage was obtained in three patients with endometrial adenocarcinoma, all with high maturation, and in five controls, none with high maturation. These data appear to indicate a difference in the cytohormonal status of patients with cervical or endometrial carcinoma as compared to those without; consequently, cytologists should be especially attentive to smears showing high maturation from postmenopausal women.     

Evaluation of the two polymorphisms rs1801133 in MTHFR and rs10811661 in CDKN2A/B in breast cancer

The 5,10-Methylenetetrahydrofolate reductase (MTHFR) was the rate-limiting enzyme in the methyl cycle, which was encoded by the MTHFR gene. MTHFR played a key role in homocysteine plasma level and was associated with the risk of breast cancer. The cyclin-dependent kinase (CDK) inhibitor (CDKN2A/B) was the tumor suppressor in the cell cycle regulation. The single-nucleotide polymorphism was thought to be associated with the predisposition of breast cancer and in subsequent immune response in different populations. The current study was conducted on a peripheral blood sample of 100 Iranian women with breast carcinoma and 142 cancer-free healthy female volunteers. The TaqMan real-time polymerase chain reaction technique was applied for genotyping of participants. The correlation of both variants and demographic data were investigated with the risk of breast cancer. Our data showed that the MTHFR allele T and TT genotype had the higher prevalence in patients (P < 0.0001) than the control group. The frequency of risk C allele into the CDKN2A/B rs10811661 was 72%. The correlations of menarche and underlying hormonal disorder with the risk of breast cancer were investigated; also our results showed that the menopause status was statistically significant between patients and controls (P = 0.036). Our investigations demonstrated that the MTHFR rs180113 and CDKN2A/B rs10811661 had a significant correlation with the elevated risk of breast cancer and they might be potentially valuable to apply as a prognostic factor for individual health care.     

Polymorphisms of estrogen receptor alpha gene in endometrial cancer

It is hypothesized that polymorphisms of estrogen receptor-alpha (ERalpha) gene are involved in endometrial cancer. To test this hypothesis, the genotype distributions of six different loci (codon 10 T-->C, codon 87 G-->C, codon 243 C-->T, codon 325 C-->G, codon 594 G-->A, and intron 1 C-->G) of the ERalpha gene were investigated and their association with endometrial cancer was determined. The DNA from 113 cases of human endometrial cancer was analyzed by sequence-specific polymerase chain reaction. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. The frequency of variant genotype on codon 10 was significantly lower in endometrial cancer patients as compared to controls. Nine of 113 endometrial cancer patients (8.0%) showed genotype 10C/C compared to 27 of 200 healthy controls (13.5%). The relative risk of genotype 10C/C was calculated as 0.44, compared to wild-type. Forty-five of 113 endometrial cancer patients (39.8%) showed genotype T/C on codon 10 compared to 111 of 200 healthy controls (55.5%). The relative risk of genotype 10T/C was calculated as 0.67, compared to wild-type. The polymorphism on codon 87 was not detected both in endometrial cancer patients and in healthy control. Other loci, intron 1, and codons 243, 325, and 594, did not show a correlation with endometrial cancer. The frequency of alleles on codon 10 was also significantly lower in endometrial cancer patients as compared to controls. Sixty-three of 226 alleles (27.9%) of endometrial cancer patients showed allele C compared to 165 of 400 (41.2%) of healthy controls. The relative risk of allele 10C was calculated as 0.67, compared to wild-type. Other loci, intron 1, and codons 243, 325, and 594, did not show a difference between cancer patients and controls. All genotype and allelic distributions were in accordance with the Hardy-Weinberg equilibrium. The present study demonstrates for the first time a protective effect of 10C allele against endometrial cancer. Thus, inherited alterations in ERalpha may be associated with changes in estrogen metabolism and thereby may possibly explain inter-individual differences in disease incidences of endometrial cancer.     

GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients

Androgens have an anti-proliferative effect on endometrial cells. Human androgen receptor (AR) gene contains two polymorphic short tandem repeats of GGC and CAG, and a single-nucleotide polymorphism on exon 1 that is recognized by the restriction enzyme, StuI. Prior studies have shown that the lengths of the CAG repeat are inversely and linearly related to AR activity and associated with endometrial cancer. However, little is known about the GGC repeat and the StuI polymorphism of the AR gene. Thus, we investigated whether these AR polymorphisms are risk factors for endometrial cancer. To test this hypothesis, the genetic distributions of these polymorphisms were investigated in blood samples from endometrial cancer patients and healthy controls. The allelic and genotyping profiles were analyzed by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and direct DNA sequencing, and analyzed statistically. The GGC repeat was significantly longer in endometrial cancer patients as compared to normal healthy controls. In general, an increased risk of endometrial cancer was found with increasing GGC repeat. The relative risk for the 17 GGC repeat was greater than 4, as compared to controls. However, the StuI polymorphism was not significantly different between patients and controls. The findings suggest that increased numbers of GGC repeat on the AR gene may be a risk factor for endometrial cancer.     

Relationship between genetic anomalies of different levels and deviations in dermatoglyphic traits. Part 7: Dermatoglyphic peculiarities of females with cervical and endometrial carcinoma

This study was carried out to evaluate the effects of neoplastic diseases like carcinoma of the cervix and endometrial carcinoma, and was based on dermatoglyphic traits and their indices of intraindividual diversity (Div), fluctuating asymmetry (FIA) and directional asymmetry (DA). The results were compared with control groups of women and men, whose data have been detailed in our previous publications (Kobyliansky et al., 1999 a-d), and with analogous data of additional cancer groups available in the literature, like acute leukemia, bronchial cancer and breast cancer. The general aims of the study were as follows: (a) to obtain a dermatoglyphic characterization of discrete and quantitative traits and their Div, DA, FIA values in cancer patients, compared to healthy control groups, both female and male; (b) to test the hypothesis that in cancer patients there is an increased level of FIA as a result of an impaired developmental homeostasis; (c) to explore the possibility of using DT (dermatoglyphic traits) data of CW (women with cancer) to predict the probability of the appearance of cervical and endometrial carcinoma in apparently healthy females at a young age. The sample consisted of 94 Israeli-Jewish women of various groups, of which 54 had endometrial carcinoma and 40 had cervical carcinoma. The prints were collected in the Tel-Hashomer Hospital. The control group was a sample of 874 healthy subjects, half of them male and the other female, all from Jewish communities of European extractions (50%) as well as from Africa (50%). All controls were adults (over 18 years of age). Interpretation of prints was performed according to Cummins & Midlo (1961) and Penrose (1968) and included identification of patterns, ridge counts and the measurement of distances and angles in the palms, 79 DT for every individual were assessed. Significant differences were found for some of the studied traits between cancer patients and their healthy control groups. We encountered merely a low sexual dimorphism between the CW and the control males as compared to that between control males and females (with significant differences in 18% of the quantitative traits vs 64% in the control). The indices of diversity and asymmetry proved more suitable for discrimination, yielding the highest discrimination level between CW and control females. This finding suggested other data in the present study which points to a similarity between CW and control males.     

Effectiveness of mass screening for endometrial cancer

OBJECTIVE: To investigate the effectiveness of mass screening for endometrial cancer using Endocyte (Laboratoire CCD, Paris, France) endometrial smears. STUDY DESIGN: The study subjects were consecutive patients with documented endometrial cancer diagnosed between January 1, 1989, and December 31, 1997, at 22 hospitals in Japan. One hundred twenty-six cases were detected by mass screening and 1,069 diagnosed in outpatient clinics. We compared the stage of cancer at diagnosis and survival rate of patients in the two groups. RESULTS: Early stage was significantly more frequent in the screening group (P < .001); stage I comprised 88.1% of the screening group as compared with 65.3% of the outpatient group. Well-differentiated adenocarcinoma was significantly more frequent in the screening group (P < .01); grade 1 constituted 74.7% of the screening group as compared with 61.0% of the outpatient group. The five-year survival rate was significantly higher in the screening group than in the outpatient group (94.0% vs. 84.3%, P = .041). The crude hazard ratio (HR) of dying of endometrial cancer for the screening group as compared to the outpatient group was .47 (95% CI .22-.99, P = .048). HR became .96 (95% CI .45-2.08, P = .925) after adjustment for age, study area and cancer stage. CONCLUSION: The results suggest that an endometrial cancer screening program would lead to early detection and improved survival among women with endometrial cancer.     

A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer

Background

Over 500,000 women worldwide are diagnosed with ovarian or endometrial cancer each year. We have used a two-step strategy to identify plasma proteins that could be used to improve the diagnosis of women with an indication of gynecologic tumor and in population screening.

Methods

In the discovery step we screened 441 proteins in plasma using the proximity extension assay (PEA) and five Olink Multiplex assays (CVD II, CVD III, INF I, ONC II, NEU I) in women with ovarian cancer (n?=?106), endometrial cancer (n?=?74), benign ovarian tumors (n?=?150) and healthy population controls (n?=?399). Based on the discovery analyses a set of 27 proteins were selected and two focused multiplex PEA assays were developed. In a replication step the focused assays were used to study an independent set of cases with ovarian cancer (n?=?280), endometrial cancer (n?=?228), women with benign ovarian tumors (n?=?76) and healthy controls (n?=?57).

Results

In the discovery step, 27 proteins that showed an association to cancer status were identified. In the replication analyses, the focused assays distinguished benign tumors from ovarian cancer stage III–IV with a sensitivity of 0.88 and specificity of 0.92 (AUC?=?0.92). The assays had a significantly higher AUC for distinguishing benign tumors from late stage ovarian cancer than using CA125 and HE4 (p?=?9.56e?22). Also, population controls could be distinguished from ovarian cancer stage III–IV with a sensitivity of 0.85 and a specificity of 0.92 (AUC?=?0.89).

Conclusion

The PEA assays represent useful tools for identification of new biomarkers for gynecologic cancers. The selected protein assays could be used to distinguish benign tumors from ovarian and endometrial cancer in women diagnosed with an unknown suspicious pelvic mass. The panels could also be used in population screening, for identification of women in need of specialized gynecologic transvaginal ultrasound examination.

Funding

The Swedish Cancer Foundation, Vinnova (SWELIFE), The Foundation for Strategic Research (SSF), Assar Gabrielsson Foundation.

     

Incidence of genital mycoplasmas in women at the time of diagnostic laparoscopy

The cervicovaginal and endometrial isolation rates of Ureaplasma urealyticum and Mycoplasma hominis and relevant demographic data were obtained at the time of laparoscopy in 193 women from infertile marriage. For comparative purposes, fertile women undergoing laparoscopy for tubal ligation (n = 56) or other purposes (n = 64) were also cultured. Blacks were more likely than caucasians to be infected with either organism in all population types (p less than or equal to .05); however, no differences were noted in cervicovaginal carriage rates for blacks in different patient populations. M. hominis was isolated more frequently from tubal reanastomosis patients and less often from infertile patients, p less than or equal to .001. No differences were noted among the infertile subpopulations. Although the isolation rate of U. urealyticum from the different patient populations was similar, one subpopulation within the infertile population (male factor) was identified in which the prevalence of ureaplasmal infection of the female's lower genital tract was over twice as high (p less than or equal to .005) as in other infertile women. Yet there were no statistically significant differences in the demographic data of this subpopulation as compared to the population of infertile women as a whole. No other clinical subpopulation with single or multiple diagnoses not including male factor had an increased prevalence of infection. Eighty percent of infected, infertile couples had no clinical evidence of male factor infertility, indicating that only certain individuals are affected.This possibly explains why previous studies involving small numbers of patients without regard to clinical subpopulations have failed to show significant differences between infected and uninfected couples.(ABSTRACT TRUNCATED AT 250 WORDS)     

Migraine and Meditation: Characteristics of Cortical Activity and Stress Coping in Migraine Patients,Meditators and Healthy Controls—An Exploratory Cross-Sectional Study

The aim of this exploratory cross-sectional study was to investigate the characteristics of cortical activity and stress coping in migraine patients, meditation experienced subjects, and healthy controls. 45 meditation experienced subjects, 46 migraine patients, and 46 healthy controls took part in the study. Cortical activity was measured with the contingent negative variation (CNV), a slow cortical event-related potential. Stress coping was examined with the standardized Stress Coping Questionnaire SVF-78. A one-way analysis of variance was used to investigate possible differences between the groups. CNV-amplitude was significantly higher in migraineurs than in controls. The meditators showed significantly lowest amplitudes. Migraine patients used negative stress-coping strategies significantly more often than meditators and healthy controls. Especially the application of the strategy “rumination” was most frequent in migraine patients and least frequent in meditators. Moreover, frequent rumination was significantly correlated with high CNV-amplitudes. Cortical and stress processing in people with meditation experience was improved compared to migraine patients and healthy controls.     

Polymorphisms of p53 codon 72 and MDM2 promoter 309 and the risk of endometrial cancer

Genetic polymorphisms of p53 and its negative regulator murine double minute 2 homolog (MDM2) have been shown to be closely associated with tumorigenesis in a variety of human cancers. In the present study, single nucleotide polymorphism (SNP) at p53 codon 72 and MDM2 promoter 309 was examined for germline DNA samples from 102 endometrial cancer cases and 95 controls using polymerase chain reaction-based fragment analysis. There were no significant differences in the genotype and allele prevalence between control subjects and endometrial cancer patients for p53 codon 72. The GG genotype frequency of MDM2-SNP309 was statistically higher in endometrial cancer patients than that in normal healthy women when compared with the TG genotype ( P = 0.0088). However, no statistically significant differences were found between the TT and TG or GG genotype frequencies and allele prevalence. Interestingly, the combination of the homozygous Arg/Arg genotype of p53 codon 72 and homozygous GG genotype of MDM2 SNP309 polymorphisms was significantly associated with the risk of endometrial cancer (odds ratio = 3.28, 95% confidence interval = 1.13 to 9.53, P = 0.0212). The homozygous variants of wild p53 codon 72 and mutant MDM2 promoter 309 may cooperatively increase the risk of endometrial cancer in a Japanese population.     

Children's Reactions to and Memory for a Stressful Event: Influences of Age,Anatomical Dolls,Knowledge, and Parental Attachment

This article investigated how age and cancer are associated with goal commitment in recently diagnosed cancer patients and healthy controls. One hundred and thirty-two cancer patients and 132 healthy control group members generated a list of present goals and assessed perceived difficulty of goals, effort for goal attainment, influence of health on goal attainment, and anticipated time of goal attainment. In regression analyses, main effects of cancer status on life goals were found, indicating among cancer patients a lower total number of goals; a focus on social, transcendental, and health-related rather than achievement-related goals; higher perceived difficulty of goals; lower effort to attain one's goals; stronger perceived negative health effects on goal attainment; and a stronger focus on short-term rather than long-term goals. In addition, main effects of age indicated an age-associated reduction in the number of goals and a shift away from achievement-related goals toward easier and short-term goals and higher effort for goal attainment. Further, age differences in goal variables were stronger in healthy controls than in cancer patients.     

The immunological status of breast cancer patients during treatment with a new antiestrogen,toremifene

Summary The immune status of breast cancer patients was followed during antiestrogen treatment for at least 1 year or until progression of the disease. Twelve postmenopausal women with advanced estrogen-receptor-positive breast cancer were treated with a novel antiestrogen, toremifene. Immune functions were determined before the start of the treatment and at 3, 6, and 12 months. For NK cell cytotoxicity testing there were 74 healthy controls and for T cell subset measurements 28 healthy controls. No statistically significant changes in the T cell subsets or NK cell cytotoxicity were observed during treatment. However, throughout toremifene treatment patients had fewer CD4 cells (T helper lymphocytes) than did the controls. Cancer patients had higher pretreatment B cell values than the controls,P = 0.01, but during the first months of toremifene treatment B cell values decreased and remained within the normal range thereafter. A positive effect on mitogen-stimulation tests with phytohemagglutinin (PHA) and concanavalin A (ConA) was observed during the first months of treatment (P = 0.01 for PHA and 0.03 for log [ConA] and a stabilization at the higher level thereafter. These results indicate that toremifene has a stimulatory effect on cell-mediated immunity in breast cancer patients.     

Type A personality as a mediator of stress and strain in employed women

A survey of 136 employed women was conducted. Type A personality, demographic variables, job characteristics and attitudes, health habits, and physical and psychological symptoms of strain were assessed. Average Type A score was higher than the normative mean (57th percentile). Compared with Type Bs, the Type A women had been in their current jobs for a shorter time, worked longer hours, and were less satisfied with their jobs. None of the health habit behaviors was related to Type A score. Small but substantial proportions of the sample complained that they often or always experienced a variety of physical and psychological symptoms. The former were not related to Type A score, but Type A women did tend to report more nervousness in all situations and more dysphoria of all kinds at work. Correlations between job dissatisfaction and rated job stress with symptoms were calculated separately for Type As and Type Bs. Substantial correlations were found for the Type As but not the Type Bs. Dissatisfaction and stress were related to more frequent symptom complaints in the Type As. Correlations of health habits and symptoms were also computed for Type As and Bs separately. Implications for future research are discussed.     

Genetic variants of SDF-1 and CXCR4 genes in endometrial carcinoma

In this study, we aimed to investigate a possible association between the Stromal cell-derived factor-1 (SDF-1) and CXCR4 polymorphisms and the risk of developing endometrial carcinoma. SDF-1 3??A and CXCR4 gene polymorphisms was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism in 139 healthy individuals and 113 patients with endometrial carcinoma. In our study groups SDF-1 3??A AA genotype frequency was higher in patients that of controls and individuals who had AA genotype showed a 2.6-fold increased risk for endometrial cancer. The carriers of CXCR4 T allele were higher in patients compared with controls and individuals who had TT genotype had a 2.5-fold high risk for endometrial carcinoma. Our finding suggest that there was no significant association between the (SDF-1) and CXCR4 polymorphisms and endometrium cancer risk. Further studies in a larger population are needed to better elucidate the role of (SDF-1) and CXCR4 gene polymorphisms in the risk of endometrial carcinogenesis. To the best of our knowledge, this is the first study to show such an association.     

Bone Health History in Breast Cancer Patients on Aromatase Inhibitors

A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI) users before breast cancer (BC) diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC). Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001). Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.     

Chromium homeostasis in patients with type II (NIDDM) diabetes.

The purpose of this study was to assess chromium handling in non-insulin dependent diabetic patients (NIDDM) compared to healthy volunteers. Chromium handling was evaluated using fasting blood and second morning void urine samples from 93 NIDDM patients and 33 healthy volunteers. Significant differences in chromium homeostasis were seen between patients and controls. NIDDM patients had mean levels of plasma chromium around 33% lower and urine values almost 100% higher than those found in health. Healthy volunteers showed a significant negative correlation between fasting levels of plasma chromium and insulin. This was not evident in NIDDM patients. In the early years of onset of NIDDM, plasma chromium values were inversely correlated with plasma glucose. This was lost in patients with diabetes of more than 2 years duration. We suggest large losses of chromium over many years may exacerbate an already compromised chromium status in NIDDM patients and might contribute to the developing insulin resistance seen in patients with type 2 diabetes.     

Self-Assessed General Health and Dental Status Among the Elderly in a Swedish County

A random sample of non-institutionalized elderly people in Örebro County, Sweden, has been examined. The present paper reports on the general health conditions obtained from interviews in this population and on the relation between general health and dental status. Eighty-one percent of the clinically examined subjects considered that they were healthy or fairly healthy. A higher percentage of women as compared to men regarded themselves to be moderately or very ill. Women also used more drugs than men did. Only 6% did not feel strong enough for extensive dental treatment. Physically handicapped people used dental services less than the rest of the population did. Otherwise, general health seemed to have limited influence on the use of dental services. Subjects with better dental status reported less frequent illness, chronic diseases, and medication as compared to subjects with poorer dental status. The self-assessed general health, also in the presence of age, sex, and residence variables, showed significant correlation with the dental status but not if socio-economic variables were also included in a regression model.     

Association of Metformin Use with Outcomes in Advanced Endometrial Cancer Treated with Chemotherapy

There is increasing evidence that metformin, a commonly used treatment for diabetes, might have the potential to be repurposed as an economical and safe cancer therapeutic. The aim of this study was to determine whether stage III-IV or recurrent endometrial cancer patients who are using metformin during treatment with chemotherapy have improved survival. To test this we analyzed a retrospective cohort of subjects at two independent institutions who received chemotherapy for stage III-IV or recurrent endometrial cancer from 1992 to 2011. Diagnosis of diabetes, metformin use, demographics, endometrial cancer clinico-pathologic parameters, and survival duration were abstracted. The primary outcome was overall survival. The final cohort included 349 patients, 31 (8.9%) had diabetes and used metformin, 28 (8.0%) had diabetes but did not use metformin, and 291 (83.4%) did not have diabetes. The results demonstrate that the median overall survival was 45.6 months for patients with diabetes who used metformin compared to 12.5 months for patients with diabetes who did not use metformin and 28.5 months for patients without diabetes (log-rank test comparing the three groups P = 0.006). In a model adjusted for confounders, the difference in survival between the three groups remained statistically significant (P = 0.023). The improvement in survival among metformin users was not explained by better baseline health status or more aggressive use of chemotherapy. Overall, the findings in this retrospective cohort of endometrial cancer patients with stage III-IV or recurrent disease treated with chemotherapy indicate that patients with diabetes who were concurrently treated with metformin survived longer than patients with diabetes who did not use metformin.