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PubMed2001

Genes, chromatin, and breast cancer: an epigenetic tale.

The production of heritable changes in gene expression is the driving force in the development and progression of breast cancer. Such changes can result from mutations or from epigenetic events such as hypermethylation of DNA and hypoacetylation of histones. Histone acetylation and DNA methylation are major determinants of chromatin structure, and chromatin structure is a primary regulator of gene transcription. Cancer cells frequently contain both mutated genes and genes with altered expression due to one or more epigenetic mechanisms. This review describes the epigenetic changes that disrupt normal chromatin architecture and modify the expression of key genes in breast cancer cells. The structural integrity of the latter genes is usually intact, but their expression has been substantially altered due to methylation in their promoter region or deacetylation of histones that interact with their promoter region or both mechanisms. Genes affected by epigenetic changes in breast cancers include HoxA5, p21WAF, gelsolin, BRCA1, BRCA2, E-cadherin, steroid hormone receptors, and retinoic acid receptor II. Because these epigenetic modifications are usually reversible by treatment with certain drugs, they represent vulnerabilities in the cancer cell that can be exploited as novel targets for new prevention and therapeutic strategies.

Breast Neoplasms↗

PubMed2026

Sociodemographic trends in prostate cancer: insights from the All of Us Research Program.

BACKGROUND: Prostate cancer disproportionately affects vulnerable populations. The All of Us Research Program (AoURP) is a database that aims to encapsulate the diversity of the United States. To explore the utility of this dataset in assessing prostate cancer disparities, we investigated whether treatment usage, disease progression, and genomic research participation vary across sociodemographic factors among AoURP participants with prostate cancer. METHODS: We identified AoURP participants with prostate cancer. Genomic research participation in AoURP, treatment usage, time-to-treatment, and time-to-metastasis were assessed by demographics and distance from a National Cancer Institute-designated comprehensive cancer center. Multivariable logistic regression and Cox proportional hazards regression were performed to evaluate treatment usage and time-to-treatment and time-to-metastasis, respectively. RESULTS: We observed lower genomic data availability in Black vs White patients (P < .001). In multivariable analyses, patients residing more than 80 miles from an NCI-designated comprehensive cancer center were less likely to receive androgen receptor pathway inhibitors (odds ratio [OR] = 0.30, 95% CI = 0.14 to 0.66; P = .002) and bone targeting agents (OR = 0.46, 95% CI = 0.30 to 0.70; P < .001) but more likely to undergo prostatectomy (OR = 1.97, 95% CI = 1.43 to 2.71; P < .001) than those residing less than 40 miles away. These patients also initiated treatment faster (hazard ratio [HR] = 1.54, 95% CI = 1.27 to 1.87; P < .001) and developed metastasis slower (HR = 0.58, 95% CI = 0.40 to 0.86; P = .006). Black patients were less likely to receive radiation (OR = 0.45, 95% CI = 0.23 to 0.88; P = .020), prostatectomy (OR = 0.65, 95% CI = 0.44 to 0.96; P = .028), and bone targeting agents (OR = 0.65, 95% CI = 0.45 to 0.93; P = .018) than White patients. CONCLUSIONS: Prostate cancer treatment usage, disease progression, and genomic research participation varied between demographic populations. As AoURP matures, additional studies may leverage future data releases to confirm these findings.

Aged↗

PubMed2006

Single nucleotide polymorphisms of the TGFB1 gene and lung cancer risk in a Korean population.

The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the transforming growth factor-beta 1 (TGFB1) gene and susceptibility to lung cancer and the clinical effect of the SNPs on lung cancer progression in a Korean population. Two polymorphisms in the promoter region of the TGFB1 (T-1572C, C-509T), and one SNP in codon 10 (T+869C) were determined using a SNaPshot primer extension assay in 194 Korean lung cancer patients and 283 normal controls. The polymorphic allele frequencies of A-1572G, C-509T, and T+869C were similar among lung cancer patients (0.52, 0.47, and 0.47, respectively) and controls (0.54, 0.46, and 0.44, respectively). When the data was stratified for smoking history, patients who smoked heavily and had heterozygous C-509T and T+869C genotypes showed an increased lung cancer risk (odds ratio OR = 3.77, confidence interval 95% CI = 1.25-11.30, P = 0.017; OR = 3.61, 95% CI = 1.21-10.74, P = 0.021 for each), after adjustment for age and sex. When heterozygous and homozygous variants for each SNPs were analyzed together, patients who were smokers and had variant genotypes also showed increased risk compared to the reference group. Further analyses to test the effect of the SNPs on the clinical parameters did not reveal an association of each polymorphic allele to the tumor stage or response to treatment. In addition, DNA fragments containing polymorphic genotype of the promoter region (-509T) showed increased transcriptional activity in luciferase assays using non-small cell lung cancer cell lines. In conclusion, this study suggests that heavy smokers in this Korean population who have specific polymorphic variants, which have been associated with increased transcriptional activity of TGFB1, might be more vulnerable to lung cancer.

Base Sequence↗

PubMed1999

Suicidal thoughts in cancer patients: clinical experience in psycho-oncology.

Because cancer is a life-threatening illness, its impact on the patient's emotional well-being, such as suicidal thoughts, has become a significant problem in public health as well as in clinical oncology. Factors such as the pain and hopelessness are suggested as making cancer patients more vulnerable to suicide. On the other hand, euthanasia and physician-assisted suicide are now important medical and social issues all over the world. However, little is known about the relationship between the characteristics of cancer patients and suicidal thoughts. The present study investigated the characteristics of patients who were referred to the Psychiatry Division, National Cancer Center Hospital East, due to risk of suicide or suicide attempts. Fourteen patients were referred, representing 3.9% of all consultations. Most of these patients suffered from advanced cancer and poor physical functioning. The most frequent psychiatric diagnosis was mood disorder (57%), and the next was delirium (29%). In patients with mood disorders (8 cases), suicidal thoughts disappeared after psychiatric treatment in 5 cases, but not in 3 cases. Those three patients survived a significantly shorter time than the others after psychiatric consultation. These empirical data might indicate that most suicidal thoughts experienced by cancer patients are not rational, and a careful evaluation, including psychiatric assessment, should be conducted in such patients.

Aged↗

PubMed2001

Osteoporosis in survivors of acute lymphoblastic leukemia.

Osteoporosis is currently receiving increasing attention as an important late effect in survivors of childhood cancer and its treatment because of their quality of life and its negative effect on the survivors' ability to perform developmentally appropriate activities. Survivors of childhood cancer are especially vulnerable because they are affected during childhood and adolescence, a time when peak bone mass should be achieved. This paper reviews decreased bone density in acute lymphoblastic leukemia (ALL), which is the most common childhood cancer and has a cure rate approaching 80%. Osteopenia/osteoporosis has been observed in all phases of the disease: at diagnosis, during treatment, and throughout the post-treatment period for as long as 20 years. Among the findings that have been described are musculoskeletal pain, disturbed gait, fractures, kyphosis, lordosis, and growth failure. Risk factors not specifically related to ALL include smoking, ingestion of carbonated beverages, and family history of "brittle bone" or fractures. Patients should be counseled in regard to diet, exercise, smoking cessation, and avoidance of carbonated beverages. There are a number of options for specific drug therapy; however, the administration of bisphosponates to children and adolescents must be approached with caution. Research is needed to determine how extensive the problem is and how to best prevent and treat the osteopenia/osteoporosis associated with ALL.

Humans↗

PubMed2026

Dynamic and Ongoing De Novo L1 Retrotransposition Contributes to Genome Plasticity and Intrapatient Heterogeneity in Ovarian Cancer.

UNLABELLED: Long interspersed element-1 (L1) retrotransposons are the only protein-coding active transposable elements in the human genome. Although typically silenced in normal cells, they are highly expressed in many human epithelial cancers, including high-grade serous ovarian cancer (HGSC), and can integrate into the genome through retrotransposition. De novo L1 insertions are known to contribute to genomic instability and cancer evolution in epithelial malignancies, including HGSC, suggesting that they might also play a role in intrapatient tumor heterogeneity. In this study, we quantified de novo L1 insertions in clinical HGSC specimens and uncovered high heterogeneity in total L1 insertion events (L1 burden) between patients. HGSC tumors with high L1 burden were highly proliferative, whereas tumors with low or no L1 insertions showed enrichment of immune response and cell death pathways. Although the overall L1 burden was similar across different tumor sites within the same patient, the specific L1 insertions (L1 profiles) diverged significantly more than their single-nucleotide variants profiles. Taken together, these findings demonstrate that L1 activity and retrotransposition are highly dynamic in vivo and can contribute substantially to tumor genome plasticity, especially at late stages of cancer progression. The patient-specific propensity of acquiring L1 insertions (L1 burden) could be driven by molecular properties of the progenitor tumor. Retrotransposition-associated DNA damage and/or replication stress could be a potential molecular vulnerability for precision cancer medicine approaches. SIGNIFICANCE: L1 retrotransposition is a dynamic process that continues at late stages of high-grade serous ovarian cancer and can substantially contribute to intrapatient tumor heterogeneity.

Humans↗

PubMed1995

Sibling adaptation to childhood cancer collaborative study: siblings' perceptions of the cancer experience.

Investigated responses of siblings (N = 254) of children with cancer to structured interviews designed to elicit thoughts and feelings about effects of cancer on self and family. Siblings indicated distress about family separations and disruptions, lack of attention, focus of family on the ill child, negative feelings in themselves and family members, cancer treatments and their effects, and fear of death. Siblings also reported becoming more compassionate, families becoming closer, and having experiences they otherwise would not have had. Age and gender differences in responses indicated distinctive perceptions of and vulnerability to the cancer experience. Older siblings were far more likely to report positive effects than younger siblings suggesting that level of maturity can moderate the stress of an ill child within the family.

Adaptation, Psychological↗

PubMed2006

Consenting of the vulnerable: the informed consent procedure in advanced cancer patients in Mexico.

BACKGROUND: A topic of great concern in bioethics is the medical research conducted in poor countries sponsored by wealthy nations. Western drug companies increasingly view Latin America as a proper place for clinical research trials. The region combines a large population, modern medical facilities, and low per capita incomes. Participants from developing countries may have little or non alternative means of treatment other than that offered through clinical trials. Therefore, the provision of a valid informed consent is important. METHODS: To gain insight about some aspects of the informed consent procedure in a major cancer centre in Mexico, we conducted a three-step evaluation process: 1) a ten point multiple choice survey questionnaires, was used to explore some aspects of the patients' experiences during the informed consent process, 2) researchers' knowledge about specific aspects of the informed consent was evaluated in this study using survey questionnaires; and 3) the comprehensibility, readability and number of pages of the consent forms were analysed. The socioeconomic and educational level of the patients, were also considered. Results were reported using a numerical scale. RESULTS: Thirty five patients, 20 doctors, and 10 individuals working at the hospital agreed to participate in the study. Eighty three percent of the patients in the study were classified as living in poverty; education level was poor or non existent, and 31% of the patients were illiterate. The consent forms were difficult to understand according to 49% of the patients, most doctors agreed that the forms were not comprehensible to the patients. The average length of the IC documents analysed was 14 pages, and the readability average score was equivalent to 8th grade. CONCLUSION: The results presented in this work describe some relevant characteristics of the population seen at public health care institutions in Mexico. Poverty, limited or no education, and the complexity of the information provided to the patients may question the validity of the informed consent procedure in this group of patients.

Attitude↗

PubMed2001

Psychological and screening profiles of first-degree relatives of prostate cancer patients.

The purpose of the present study was to systematically compare the psychological and screening profiles of first-degree relatives (FDRs) of prostate cancer patients versus non-FDRs. FDRs (n = 56) and non-FDRs (n = 100), recruited through prostate cancer index cases and newspaper advertisements, completed questionnaires via mail. FDRs reported feeling at greater risk for prostate cancer, estimated that they were at higher average lifetime risk for the disease, agreed more strongly that prostate cancer is inherited, and that less can be done to prevent the development of the disease. Increased age, but not FDR status, was associated with more frequent screening behavior. Taken together, the results indicate that FDRs are characterized by greater perceived vulnerability to prostate cancer and lower expectations about disease prevention. Yet, they are no more likely to be screened than non-FDRs. These findings underscore the importance of developing, and evaluating, evidence-based health communication protocols to promote screening adherence among at-risk patients.

Adult↗

PubMed1991

Depression and chronic fatigue in cancer patients.

Fatigue is a very common symptom among cancer patients. It is crucial to diagnose those patients for whom the fatigue is a symptom of depression, and to treat them appropriately. The key to providing complete and satisfying care is to identify and address the psychologic, social, and medical vulnerabilities of each cancer patient. No one is in a better position to accomplish that than the primary physician.

Depression↗

PubMed2026

Epithelial tumor suppressor deletion promotes neuroendocrine differentiation in bladder cancer and reveals homoharringtonine as a candidate vulnerability.

Neuroendocrine bladder carcinoma (NEBC) is a highly aggressive malignancy with unresolved lineage determinants and limited preclinical models, hindering mechanistic investigation and therapeutic development. Here, we sought to assess whether bladder epithelial-derived models are competent to acquire neuroendocrine lineage programs under defined tumor suppressor alterations and to identify candidate therapeutic vulnerabilities in these systems. We integrated genomic and transcriptomic analyses of human NEBC with genetically engineered mouse models, epithelial-derived bladder organoids, and patient-derived NEBC models. Human NEBC exhibited dominant RB1 and TP53 alterations and an epithelial transcriptional continuum consistent with lineage plasticity. In vivo, intravesical Adeno-Cre-mediated tumor suppressor deletion predominantly generated sarcoma-like tumors, whereas epithelial-restricted organoid models recapitulated the molecular and neuroendocrine features of human NEBC, supporting epithelial lineage competence for neuroendocrine differentiation. Patient-derived models and human NEBC specimens further supported epithelial identity in NEBC. Using these complementary platforms, drug screening identified homoharringtonine (HHT) as a candidate therapeutic vulnerability in the tested NEBC systems. HHT suppressed neuroendocrine marker expression, induced apoptosis, and attenuated IL6-JAK-STAT3 signaling. Together, these findings describe complementary epithelial-derived NEBC models and support further investigation of HHT as a candidate therapeutic vulnerability.

Journal Article↗

PubMed2004

Then and now: quality of life of young breast cancer survivors.

BACKGROUND: Women under age 50, a quarter of all cases of breast cancer, are especially vulnerable to physical and psychosocial late effects of their treatment due to having more aggressive treatment and their relative youth. METHODS: In person interviews were conducted with the population-based sample: 185 women who were under 50 at diagnosis and were cancer-free 5 years later. Quality of life in the physical, psychological, social, and spiritual domains was assessed and compared with results obtained a few months after diagnosis. RESULTS: Five years after diagnosis, 92% rated their health as good or excellent, and only 10% said their health had been getting worse. Between baseline and 5 years, there were significant improvements in surgical symptoms, body image, worry about the future, patient-physician communication, intrusiveness of treatment, and all of the SF-36 measures except for general health. There were significant decreases in emotional support and the size of one's social network. More women were now menopausal (75% due to treatment) and there were fewer children at home. There were no significant changes in employment status, marital/partner status, sexual activity, sexual problems, self-esteem, and attendance at religious services or frequency of prayer. In multivariate models, a greater increase in physical quality of life was associated with reporting fewer chronic conditions, being employed, having been treated by chemotherapy and fewer had no children under age 18 living at home. A greater increase in mental quality of life was associated with fewer chronic conditions and a smaller decrease in emotional support. CONCLUSIONS: Five years after diagnosis, young breast cancer survivors who remained cancer-free enjoyed good health and improved quality of life. Nonetheless, physical, social, and psychological concerns must be addressed so that young breast cancer survivors will continue to be resilient as they age.

Adult↗

PubMed2002

Breast cancer and the language of risk, 1750-1950.

The language of risk, in relation to disease, is usually viewed as having developed in the post-war era, but in fact it has a much longer history. Focusing on the period from the mid-eighteenth century to the mid-twentieth century, this article examines evolving beliefs about what makes women vulnerable to breast cancer and traces the history of certain 'risk factors', such as the presence of benign breast disease, the experience of injury to the breast, the influence of unhappy emotions, the onset of menopause, and a family history of cancer. It situates beliefs about breast cancer within their social and cultural contexts, examining ideas concerning the relationship between mind and body, the impact of new medical knowledge, the social meanings of cancer, definitions of femininity and images of the female body, and women's own views on what places them at risk. It concludes that an historical perspective adds an important dimension to our contemporary understanding of the concept of medical risk.

Breast Neoplasms↗

PubMed1996

Pathogenesis and prevention of stomach cancer.

In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the N-nitrosamide hypothesis should be dismissed as the etiology of stomach cancer, and why the contemporarily available principles and practice of intervention strategies to rapidly decrease the surprisingly high prevalence rate of Helicobacter pylori infection are impractical at this moment, are explained. In order to introduce an alternative provisional strategy of the "planned triumph" for the population vulnerable to stomach cancer, vitamin C is defined as an anti-inflammatory agent on the basis of the pathogenesis of Helicobacter pylori infection.

Animals↗

PubMed2002

Separating the apples and oranges in the fruit cocktail: the mixed results of psychosocial interventions on cancer survival.

In past reviews of the literature on psychosocial interventions for cancer patients, different reviewers have reached disparate conclusions about the ability of a psychosocial intervention to have an impact on cancer survival. This article highlights some of the basis for differences of opinion, including the range of psychosocial interventions provided to patients and the challenges inherent in conducting research studies of this type. Social workers who work with cancer patients at vulnerable times need to understand what the current evidence shows can be gained from participation in a psychosocial intervention. Several key questions have been identified that can provide the basis for future rigorous studies. The role of the social worker in participating and shaping research on the relationship of psychosocial intervention and cancer survival is also discussed.

Humans↗

PubMed2004

The motivating impact of informing women smokers of a link between smoking and cervical cancer: the role of coherence.

This research assessed the role of having a coherent explanation of the link between smoking and cervical cancer in motivating women to stop smoking. In the 1st study, women were given a leaflet with either a detailed or a minimal explanation of the link or no leaflet. The leaflets were similarly effective at providing a coherent explanation. In a cross-sectional analysis, having a coherent explanation moderated the relationship between perceived vulnerability and intention: Higher perceived vulnerability to cervical cancer was associated with greater intention to quit smoking only amongst women with a more coherent explanation of the link between smoking and cervical cancer. This finding was replicated in a 2nd study. These results are consistent with H. Leventhal et al.'s (1997) self-regulatory model, which suggests that motivation to change behavior depends not only on perceiving a threat but also on having a coherent model linking the behavior with the threat.

Adult↗

PubMed2002

Arsenic poisoning in groundwater: health risk and geochemical sources in Bangladesh.

Of the 2508 water samples analyzed in 10 districts of Bangladesh, 51%, on an average, contained arsenic levels of 0.05 to 2.50 mg/l. 95% of nail, 96% of hair, and 94% of urine samples contained arsenic above the normal level. Approximately 3.58 million people out of a total of 17.92 million who are drinking water containing arsenic levels >0.20 mg/l are potentially exposed to high risk of health hazard. Eight thousand and five hundred arsenic patients are identified; they are suffering from various skin lesions, gangrene in leg, skin, lung, bladder, liver, and renal cancer. A big portion of the total population is highly vulnerable to various internal cancers. Lowest arsenic concentration in drinking water producing dermatological disease is found to be 0.103 mg/l. However, the exposure time to develop arsenicosis varies from case to case reflecting its dependence on arsenic level in drinking water and food, nutritional status, genetic variant of human being, and compounding factors. This study has determined the high intensity of fluorescent humic substances in drinking water containing elevated concentrations of arsenic and very low concentrations of heavy metals. The synergistic/antagonistic effect of fluorescent compounds present in drinking water may aggravate the toxicity of arsenic. Geochemical study suggests that arsenic may be released from both reductive dissolution of Fe and Mn (oxy)hydroxide and microbial oxidation of organic matter.

Arsenic Poisoning↗

PubMed2004

Breast cancer treatment in older women: impact of the patient-physician interaction.

OBJECTIVES: To assess the impact of the patient-physician interaction on breast cancer care in older women. DESIGN: Cross-sectional survey. SETTING: Los Angeles County, California. PARTICIPANTS: Two hundred twenty-two consecutively identified breast cancer patients aged 55 and older who were within 6 months of breast cancer diagnosis and/or 1 month posttreatment. MEASUREMENTS: Dependent variables were patient breast cancer knowledge, treatment delay, and receipt of breast-conserving surgery (BCS). Key independent variables were five dimensions of the patient-physician interaction by patient report, including physician provision of tangible and interactive informational support, physician provision of emotional support, physician participatory decision-making style, and patient perceived self-efficacy in the patient-physician interaction. Age and ethnicity were additional important independent variables. RESULTS: In multiple logistic regression models, only physician interactive informational support had significant relationships with all three dependent variables, controlling for a wide range of patient sociodemographic and case-mix characteristics, visit length, number of physicians seen, social support, and physician sociodemographic and practice characteristics. Specifically, informational support positively predicted patient breast cancer knowledge (adjusted odds ratio (AOR)=1.18, 95% confidence interval (CI)=1.00-1.38), negatively predicted treatment delays (AOR=0.80, 95% CI=0.67-0.94), and positively predicted receipt of BCS (AOR=1.29, 95% CI=1.07-1.56). Age and ethnicity were not significant predictors in these models. CONCLUSION: One specific domain of the patient-physician interaction, interactive informational support, may provide an avenue to ensure adequate breast cancer knowledge for patient treatment decision-making, decrease treatment delay, and increase rates of BCS for older breast cancer patients, thereby potentially mitigating known healthcare disparities in this vulnerable population of breast cancer patients.

Age Factors↗