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Colon cancer [keywords]
- Cohort study of risk factors for breast cancer in post menopausal women. [Journal Article]
- Epidemiol Health 2013.:e2013003.
The present study assessed more than 800 potential risk factors to identify new predictors of breast cancer and compare the independence and relative importance of established risk factors.Data were collected by the Women's Health Initiative and included 147,202 women ages 50 to 79 who were enrolled from 1993 to 1998 and followed for 8 years. Analyses performed in 2011 and 2012 used the Cox proportional hazard regression to test the association between more than 800 baseline risk factors and incident breast cancer.Baseline factors independently associated with subsequent breast cancer at the p<0.001 level (in decreasing order of statistical significance) were breast aspiration, family history, age, weight, history of breast biopsies, estrogen and progestin use, fewer live births, greater age at menopause, history of thyroid cancer, breast tenderness, digitalis use, alcohol intake, white race, not restless, no vaginal dryness, relative with prostate cancer, colon polyps, smoking, no breast augmentation, and no osteoporosis. Risk factors previously reported that were not independently associated with breast cancer in the present study included socioeconomic status, months of breast feeding, age at first birth, adiposity measures, adult weight gain, timing of initiation of hormone therapy, and several dietary, psychological, and exercise variables. Family history was not found to alter the risk associated with other factors.These results suggest that some risk factors not commonly studied may be important for breast cancer and some frequently cited risk factors may be relatively unimportant or secondary.
- Identification of putative immunologic targets for colon cancer prevention based on conserved gene expression from pre-invasive to malignant lesions. [JOURNAL ARTICLE]
- Cancer Prev Res (Phila) 2013 May 16.
The length of time required for pre-invasive adenoma (AD) to progress to carcinoma, the immunogenicity of colorectal cancer (CRC), and the identification of high risk populations make development and testing of a prophylactic vaccine for the prevention of CRC possible. We hypothesized that genes upregulated in AD relative to normal tissue, which maintained increased expression in CRC, would encode proteins suitable as putative targets for immunoprevention. We evaluated existing AD and CRC microarray datasets and identified 160 genes that were ≥ 2-fold up-regulated in both AD and CRC relative to normal colon tissue. We further identified 23 genes that demonstrated protein over-expression in colon AD and CRC based on literature review. Silencing the most highly up-regulated genes, CDH3, CLDN1, KRT23, and MMP7, in AD and CRC cell lines resulted in a significant decrease in viability (p<0.0001) and proliferation (p<0.0001) as compared to controls and an increase in cellular apoptosis (p<0.05 for CDH3, KRT23). Results were duplicated across cell lines representing microsatellite instability (MSI), CpG island methylator (CIMP) and chromosomal instability (CIN) phenotypes suggesting immunologic elimination of cells expressing these proteins could impact the progression of all CRC phenotypes. To determine whether these proteins were immunogens, we interrogated sera from early stage CRC patients and controls and found significantly elevated CDH3 (p=0.006), KRT23 (p=0.0007), and MMP7 (p<0.0001) serum IgG in cases as compared to controls. These data demonstrate a high throughput approach to the identification of biologically relevant putative immunologic targets for CRC and identified 3 candidates suitable for vaccine development.
- The Chemopreventive Efficacies of Nonsteroidal Anti-inflammatory Drugs: the Relationship of Short-term Biomarkers to Long-term Skin Tumor Outcome. [JOURNAL ARTICLE]
- Cancer Prev Res (Phila) 2013 May 16.
The UVB component of sunlight, which causes DNA damage and inflammation, is the major cause of nonmelanoma skin cancer (NMSC), the most prevalent of all cancers. Nonsteroidal anti-inflammatory drugs (NSAIDs) and coxibs have been shown to be effective chemoprevention agents in multiple preclinical trials, including NMSC, colon and urinary bladder cancer. NSAIDs, however, cause gastrointestinal irritation, which led to the recent development of nitric oxide (NO) derivatives that may partially ameliorate this toxicity. This study compared the efficacy of several NSAIDs and NO-NSAIDs on UV-induced NMSC in SKH-1 hairless mice and determined whether various short-term biomarkers were predictive of long-term tumor outcome with these agents. Naproxen at 100 (p>.05) and 400 ppm (p<.01) in the diet reduced tumor multiplicity by 26 and 63% respectively. The NO-naproxen at slightly lower molar doses shows similar activities. Aspirin at 60 or 750 ppm in the diet reduced tumor multiplicity by 19 and 50%; while the equivalent doses (108 and 1350 ppm) were slightly less effective. Sulindac at 25 and 150 ppm in the diet doses far below the Human Equivalent Dose, was the most potent NSAID with reductions of 50 and 94% respectively. In testing short-term biomarkers we found that agents that reduce UV-induced prostaglandin E2 synthesis and/or inhibit UV-induced keratinocyte proliferation yielded long-term tumor efficacy.
- Triplex-forming oligonucleotides targeting c-MYC potentiate the anti-tumor activity of gemcitabine in a mouse model of human cancer. [JOURNAL ARTICLE]
- Mol Carcinog 2013 May 16.
Antimetabolite chemotherapy remains an essential cancer treatment modality, but often produces only marginal benefit due to the lack of tumor specificity, the development of drug resistance, and the refractoriness of slowly proliferating cells in solid tumors. Here, we report a novel strategy to circumvent the proliferation-dependence of traditional antimetabolite-based therapies. Triplex-forming oligonucleotides (TFOs) were used to target site-specific DNA damage to the human c-MYC oncogene, thereby inducing replication-independent, unscheduled DNA repair synthesis (UDS) preferentially in the TFO-targeted region. The TFO-directed UDS facilitated incorporation of the antimetabolite, gemcitabine (GEM), into the damaged oncogene, thereby potentiating the anti-tumor activity of GEM. Mice bearing COLO 320DM human colon cancer xenografts (containing amplified c-MYC) were treated with a TFO targeted to c-MYC in combination with GEM. Tumor growth inhibition produced by the combination was significantly greater than with either TFO or GEM alone. Specific TFO binding to the genomic c-MYC gene was demonstrated, and TFO-induced DNA damage was confirmed by NBS1 accumulation, supporting a mechanism of enhanced efficacy of GEM via TFO-targeted DNA damage-induced UDS. Thus, coupling antimetabolite chemotherapeutics with a strategy that facilitates selective targeting of cells containing amplification of cancer-relevant genes can improve their activity against solid tumors, while possibly minimizing host toxicity. © 2013 Wiley Periodicals, Inc.
- Fever of unknown origin as the first manifestation of colonic pathology. [Journal Article]
- Clin Med 2013 Apr; 13(2):141-5.
Fever of unknown origin (FUO) is an entity caused by more than 200 diseases. Haematologic neoplasms are the most common malignant cause of FUO. Fever as a first symptom of colonic tumour pathology, both benign and malignant, is a rare form of presentation. Our work is a descriptive study of a series of 23 patients with colonic tumoral pathology who presented with fever of unknown origin. The mean age was 67.6 years; 56.5% of patients were men and 43.5% were women. Primary malignant neoplasia was the most common diagnosis. Blood cultures were positive in 45% of the samples. Coagulase-negative staphylococci were the most common cause of bacteraemia. Nine of 10 faecal occult blood tests performed were positive. Fever secondary to colon neoplasms, both benign and malignant, usually presents with a bacteraemic pattern, with positive results for blood-culture tests in a high percentage of cases.
- Quality of life estimate in stomach, colon, and rectal cancer patients in a hospital in China. [JOURNAL ARTICLE]
- Tumour Biol 2013 May 17.
The objective of this study was to investigate the outcome and coping patterns of patients with stomach, colon, and rectal cancer in a hospital in China. Health-related quality of life was assessed in 118 stomach, colon, and rectal cancer patients in Chinese People's Liberation Army General Hospital, Beijing, China, using the generic version of the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire Core 30 Items, Self-rated Anxiety Scores (SAS), Self-rated Depression Scores (SDS), Medical Coping Modes of Questionnaire (MCMQ), and Social Support Requirement Scale (SSRS) questionnaires. The overall QOL was 50.7 ± 6.5, 48.1 ± 7.7, and 47.6 ± 6.4, respectively, for stomach, colon, and rectal cancer groups. Correlations between QOL and SAS and SDS in stomach cancer patients were significantly higher than observed in the cohort of colon or rectal cancer patients (Spearman coefficient of 0.366 and 0.129, respectively). Cluster analysis of MCMQ data revealed four identifiable patterns (resign, confront, avoid-confront, and avoid-resign) of coping in the study group. Subjective support was significantly higher than objective support (p < 0.05); however, extent of using the support was significantly lower than either objective (p < 0.05) or subjective support (p < 0.01). SAS and SDS were negatively correlated to SSRS scores (p < 0.01 and p < 0.05, respectively). Stomach, colon, and rectal cancer patients had anxiety and depression stemming from their cancer diagnosis and postdiagnosis treatment, and sex dependency was prevalent in SSRS response. Coping patterns were reliable indicators of psychosocial side effects in patients with stomach, colon, and rectal cancers.
- Value-based healthcare in Lynch syndrome. [JOURNAL ARTICLE]
- Fam Cancer 2013 May 17.
Lynch syndrome (LS), one of the most frequent forms of hereditary colorectal cancer (CRC), is caused by a defect in one of the mismatch repair (MMR) genes. Carriers of MMR defects have a strongly increased risk of developing CRC and endometrial cancer. Over the last few years, value-based healthcare has been introduced as an approach to the cost-effective delivery of measurable patient value over complete cycles of care. This requires all involved stakeholders to formulate and validate 'patient value' for Lynch syndrome, as well as to identify targets and associated costs. The aim of this study was to develop a value-based care model for Lynch syndrome that can determine patient value and associated costs, and to design a coordinated care pathway from existing guidelines. All specialists in our hospital involved in the management of LS patients evaluated the care delivered to these patients at their department and formulated outcome measures relevant to patient value. Patients were then invited to complete a questionnaire that assessed the importance of these measures on a scale of 1-10. Six high-value outcomes were identified: (1) prevention of cancer or detection of early stage cancer (2) rapid results from MMR gene mutation testing (3) rapid investigation of the colon and uterus (4) no/little pain during colonoscopy and gynaecologic examination/biopsy (5) the offer of psychological help and (6) registration with the Dutch Lynch syndrome registry. A total of 38 (59 %) out of 62 patients completed the questionnaire. The relevance of all outcomes was confirmed by the patients and mean scores varied from 7.2 to 9.9. Patients underscored the relevance of both proper patient education and the efficiency of surveillance during their care cycle. Value-based care delivery for Lynch syndrome includes the implementation of six parameters related to prevention and early detection of cancer, a short cycle time and registration to ensure continuation of care. Estimated costs are <euro> 3320 for the first cycle of care (<euro> 3550 including gynaecologic surveillance) and approximately 720 per subsequent annual cycle (<euro> 950 including gynaecologic surveillance).
- Preoperative carcinoembryonic antigen as an outcome predictor in colon cancer. [JOURNAL ARTICLE]
- J Surg Oncol 2013 May 16.
OBJECTIVE:Several reports have shown that certain pre-operative CEA intervals can be predictive of long-term outcomes and have subsequently implied that preoperative CEA may be useful to assess the risk of recurrence or death as a continuous number for individual cases. This analysis assesses if this hypothesis is valid after correction for confounders.
METHODS:All colon cancer patients operated on at Massachusetts General Hospital from 2004 through 2011 were considered for retrospective review. Association between outcomes and preoperative CEA was measured in intervals and as a linear relationship.
RESULTS:Of the 1,071 patients operated for colon adenocarcinoma, 621 (57.9%) had a preoperative CEA drawn and were included in the analysis. In models using intervals, preoperative CEA did show association with (disease-free) survival, but this was shown to be chiefly a surrogate for metastatic presentation. In linear approaches adjusted for metastatic presentation, CEA loses all correlations with metastatic disease (P = 0.84), survival (P = 0.11), survival duration (P = 0.42) and disease-free interval (P = 0.94).
CONCLUSIONS:Extrapolating the predictive value of certain preoperative CEA intervals to a continuous approach for use in a case-for-case basis is unjustified. Preoperative CEA may be a useful risk estimator but has limited significance for predictions of long-term outcomes in individual cases. J. Surg. Oncol. 2013;9999:XX-XX. (c) 2013 Wiley Periodicals, Inc.
- Risk of Subsequent Primary Tumor Development in Melanoma Patients. [JOURNAL ARTICLE]
- Pathol Oncol Res 2013 May 17.
Incidence of subsequent malignant tumor development in 740 patients with primary cutaneous melanoma verified between 2006 and 2010 at the Semmelweis University was studied retrospectively and was compared to data of sex and age matched Hungarian population. The follow-up period was 1499 person-years for the whole group from the diagnosis of index melanoma with an average of 2 years. Standardized incidence rate (SIR) was established as the ratio of observed and expected values. The risk of all subsequent malignancies was 15- and 10-fold higher in males (SIR: 15.42) and in females (SIR: 10.55) with melanoma, than in the general population. The increased cancer risk resulted mainly from the significantly higher skin tumor development: SIR values were 160.39 and 92.64 for additional invasive melanoma and 342.28 and 77.04 for subsequent in situ melanoma in males and females, respectively. Non-melanoma skin cancers also notably contributed to the higher risk, the SIR was elevated in both genders to the same extent (males: 17.12, females: 17.55). The risk was also significantly higher for extracutaneous tumor development like chronic lymphocytic leukemia, colon and kidney cancer (both genders), non-Hodgkin's lymphoma, cervical cancer (females), and bladder carcinoma (males). These data underline the importance of patient education and the necessity of frequent medical follow up, including a close-up dermatological screening of melanoma survivors for further malignancies.