Family history of prostate and colorectal cancer and risk of colorectal cancer in the Women's health initiative.

BackgroundEvidence suggests that risk of colorectal and prostate cancer is increased among those with a family history of the same disease, particularly among first-degree relatives. However, the aggregation of colorectal and prostate cancer within families has not been well investigated.MethodsAnalyses were conducted among participants of the Women's Health Initiative (WHI) observational cohort, free of cancer at the baseline examination. Subjects were followed for colorectal cancer through August 31st, 2009. A Cox-proportional hazards regression modeling approach was used to estimate risk of colorectal cancer associated with a family history of prostate cancer, colorectal cancer and both cancers among first-degree relatives of all participants and stratified by race (African American vs. White).ResultsOf 75,999 eligible participants, there were 1122 colorectal cancer cases diagnosed over the study period. A family history of prostate cancer alone was not associated with an increase in colorectal cancer risk after adjustment for confounders (aHR =0.94; 95% CI =0.76, 1.15). Separate analysis examining the joint impact, a family history of both colorectal and prostate cancer was associated with an almost 50% increase in colorectal cancer risk (aHR = 1.48; 95% CI = 1.04, 2.10), but similar to those with a family history of colorectal cancer only (95% CI = 1.31; 95% CI = 1.11, 1.54).ConclusionsOur findings suggest risk of colorectal cancer is increased similarly among women with colorectal cancer only and among those with both colorectal and prostate cancer diagnosed among first-degree family members. Future studies are needed to determine the relative contribution of genes and shared environment to the risk of both cancers

Mouse models of colorectal cancer.

Colorectal cancer is one of the most common malignancies in the world. Many mouse models have been developed to evaluate features of colorectal cancer in humans. These can be grouped into genetically-engineered, chemically-induced, and inoculated models. However, none recapitulates all of the characteristics of human colorectal cancer. It is critical to use a specific mouse model to address a particular research question. Here, we review commonly used mouse models for human colorectal cancer

Atrial fibrillation and survival in colorectal cancer

BACKGROUND: Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer. PATIENTS AND METHODS: A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively. RESULTS: A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test). However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival. CONCLUSION: The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis

Downregulation of plasma MiR-142-3p and MiR-26a-5p in patients with colorectal carcinoma

Background: Colorectal cancer is one of the most commonly diagnosed cancers and cancer- related death worldwide. Identification of new specific biomarkers could be helpful to detection of this malignancy. Altered plasma microRNA expression has been identified in many cancers, including colorectal cancer. Objectives: The main objective of this study was to identify the circulating microRNAs with the most expression changes in colorectal cancer patients compared with neoplasm free healthy individuals. Materials and Methods: MicroRNA expression profiling was performed on plasma samples of 37 colorectal cancer patients and 8 normal subjects using microRNA microarray. Quantitative real-time reverse transcription polymerase chain reaction was used to validate the two selected altered microR NAs. Plasma samples from 61 colorectal cancer patients and 24 normal subjects were used in our validation study. Results: In profiling study we found a panel of six plasma microRNAs with significant downregulation. MicroRNA-142-3p and microRNA-26a-5p were selected and validated by polymerase chain reaction. Our results demonstrated that expression levels of plasma microRNA-142-3p and microRNA-26a-5p were significantly downregulated in patients with colorectal cancer when compared to control group. Conclusions: Our findings suggest that downregulation of plasma microRNA-142-3p and microRNA-26a-5p might serve as novel noninvasive biomarkers in the diagnosis of colorectal cancer, although more studies are needed to highlight the theoretical strengths. © 2015, Iranian Journal of Cancer Prevention

Colorectal Cancer Screening Behaviors among American Indians in the Midwest

Colorectal cancer is the second most diagnosed cancer among American Indians and is also the second leading cause of cancer death. We used a community-based participatory approach to conduct a mixed methods study to examine colorectal cancer screening behaviors. Here we report on the screening behaviors of our focus group participants (n=153). There were significant gender differences in the colorectal cancer screening rates for FOBT and colonoscopy. Although over 80% of participants reported having health insurance, only 35% of males over 50 years old and 57% of females reported ever having a colonoscopy. More research is needed to identify the causes of gender differences in colorectal cancer screening rates among American Indians. The results of the current study provide new information on the prevalence of colorectal cancer screening among American Indians living in the Midwestern (Kansas and Missouri) portion of the country

BH3 mimetic ABT-737 sensitizes colorectal cancer cells to ixazomib through MCL-1 downregulation and autophagy inhibition.

The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances MLN2238 induced apoptosis and negatively regulates autophagy. Co-administration of BH3 mimetic ABT-737 with MLN2238 synergistically kills colorectal cancer cells through MCL-1 neutralization and autophagy inhibition. Furthermore, the synergistic killing effect of the combination therapy is correlated with P53 status in colorectal cancer. These data highlight that the combination of ABT-737 with MLN9708 is a promising therapeutic strategy for human colorectal cancer

[Prognosis of colorectal cancer and socio-economic inequalities].

It is well established that socio-economic status is a major prognostic factor for many cancers, including colorectal cancer. The aims of this review are (i) to report epidemiological data showing how socio-economic status influences colorectal cancer survival, (ii) to attempt to describe the mechanisms underlying these survival inequalities, and (iii) to assess their impact on survival of colorectal cancer

Increased prevalence of colorectal adenomas in women with breast cancer

Background: The frequency of colorectal adenomas and carcinomas was investigated in a large cohort of women with breast cancer in comparison with matched controls, since data on the occurrence of second tumors in women with breast cancer is controversial. Design: In a cohort study, 188 consecutive women (median age 57 years) with primary breast cancer and 376 age-matched women who served as controls were examined by total colonoscopy. Breast cancer patients and controls were compared for the frequency of colorectal adenomas and carcinomas. Results: Women with breast cancer showed a higher risk of colorectal adenomas than controls (14.9 vs. 9.3%, p = 0.047, OR 1.7, 95% Cl 1.0-2.9). This increased prevalence resulted primarily from an increased prevalence in the age group 65-85 (31 vs. 10%, p = 0.004, OR 3.8, 95% Cl 1.6-9.3). Colorectal carcinomas were found infrequently in both groups (2 in each group). Women with breast cancer receiving anti-estrogen therapy showed a trend towards a lower risk of adenomas compared to women without anti-estrogen therapy (3.7 vs. 17.2%, p = 0.053, OR 0.16, 95% Cl 0.0-1.1). Conclusions: Women with breast cancer above the age of 65 years have an increased risk of colorectal adenomas compared to women without breast cancer. Women with a diagnosis of breast cancer should especially be encouraged to participate in colorectal cancer-screening programs which, in most countries, call for screening of all average-risk individuals over the age of 50 years

CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype.

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has a mild phenotype

The Effect of Race/Ethnicity on the Age of Colon Cancer Diagnosis

ABSTRACT BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer in the United States. Notably, racial/ethnic disparities exist in both incidence and mortality. PURPOSE: The aim of this case study was to investigate the impact of race/ethnicity on age at diagnosis of colorectal cancer in a defined population in Suffolk County, NY. METHODS: Data were retrospectively collected on race/ethnicity, health insurance status, age at diagnosis, stage at diagnosis, gender, smoking status, alcohol intake, tumor location, and body mass index for colorectal cancer patients with medical records in the Stony Brook University Medical Center database (2005-2011). Population-based data on Hispanic and non-Hispanic Whites were obtained from the Surveillance, Epidemiology, and End Results registry of New York State for an overlapping time period. Permutation-based ANCOVA and logistic regression with stepwise variable selection were conducted to identify covariates and first-order interactions associated with younger age at diagnosis and cancer stage as a dependent categorical variable. RESULTS: Of 328 colorectal cancer patients, Hispanics were diagnosed at a median younger age of 57y vs. 67y than non-Hispanic Whites (FDR = 0.001). Twenty-six percent of Hispanics were diagnosed with colorectal cancer prior to the recommended age (50y) for colorectal cancer surveillance compared to 11% of non-Hispanic Whites (FDR =0.007). Analysis of New York State registry data corroborated our findings that Hispanic colorectal cancer patients were diagnosed at a median younger age than non-Hispanic Whites. Permutation-based ANCOVA identified race/ethnicity and health insurance as significantly associated with age of diagnosis (P=0.001). Logistic regression selected (younger) age at diagnosis as being significantly associated with stage IV disease. The limitations of the case study reside in the use of self-reporting of race and ethnicity and in the small sample sizes. CONCLUSIONS: Hispanics may be at higher risk for colorectal cancer (y) and younger age at diagnosis is associated with advanced disease