Association of Gankyrin and Stemness Factor Expression in Human Colorectal Cancer

Background

It is widely accepted that the adenoma-carcinoma sequence represents the process by which most colorectal cancers (CRCs) arise. Although gankyrin is overexpressed in CRC tissues, its roles in the initiation step of colorectal carcinogenesis remain largely unexplored.

Aim

We investigated the expression of gankyrin and stemness factors in human colorectal adenomas, precancerous lesions, as well as CRC tissues to assess its involvement in colorectal carcinogenesis.

Methods

Expression of several molecules including gankyrin and certain stemness factors was compared in 50 pairs of adenoma and surrounding normal mucosa using real-time quantitative polymerase chain reaction and in 30 CRC tissues using immunohistochemistry.

Results

In CRC specimens, expression of CD133, a cancer stem cell marker, was significantly correlated with gankyrin expression. Gankyrin knockdown decreased the expression of vascular endothelial growth factor (VEGF) and stemness factors such as Nanog and Oct-4 in colorectal cancer cells. Expression of gankyrin and these stemness factors was significantly higher in adenomas than in the surrounding normal mucosa. Importantly, a significant correlation was observed between the expression of gankyrin, VEGF, and Nanog in colorectal adenomas.

Conclusion

In CRC development, gankyrin would control stem cell behavior by regulating the expression of stemness factors.     

Is Colonoscopic Screening Necessary for Patients with Gastric Adenoma or Cancer?

Background

Since colorectal adenoma or cancer is commonly associated with gastric adenoma or cancer, early colorectal adenoma detection can affect the survival of gastric adenoma or cancer patients.

Aims

The purpose here was to investigate the colorectal adenoma or cancer prevalence and evaluate the necessity for screening colonoscopy in gastric adenoma or cancer patients.

Patients and methods

From September 2005 through August 2010, 857 patients younger than 70 years who had gastric adenoma or cancer were enrolled. Healthy age- and sex-matched controls were selected from the general screening population. The prevalence and risk of colorectal adenoma or cancer were compared between the participants and the controls.

Results

Data from 416 patients in the gastric neoplasm group (123 with gastric adenoma and 293 with gastric cancer) and 416 healthy control group participants were included in the statistical analysis. The presence of gastric adenoma or cancer was an independent risk factor for colorectal neoplasm (OR = 1.348, 95 % CI = 1.001–1.815). Patients with diffuse type gastric cancer had a lower prevalence of colorectal adenoma or cancer than those with gastric adenoma or intestinal type cancer. In gastric cancer patients younger than 50 years, intestinal type histology was significantly associated with colorectal adenoma or cancer (OR = 3.838, 95 % CI = 1.077–13.677).

Conclusions

The colorectal adenoma or cancer risk was significantly increased in patients with gastric adenoma or cancer. Therefore, screening colonoscopy should be considered for gastric adenoma or cancer patients including young patients, in the case of intestinal type gastric cancer.     

Polyp surveillance after surgery for colorectal cancer

Purpose

Although it is known that those patients who have developed colorectal cancer (CRC) are at a higher risk to develop metachronous adenoma or CRC, no study has been performed to analyze the relationship between the risk factors and the time course for the formation of postoperative adenoma using survival analysis.

Methods

One hundred seventy-six patients with CRC, who had received surgical resection, were endoscopically followed-up to detect the development of metachronous adenoma or adenocarcinoama. The association between the risk factors such as age, synchronous adenomas with index CRC or other clinicopathological variables and the formation of postoperative adenoma was assessed using the logrank test and the Cox proportional hazard model.

Results

Age over 60, synchronous lesions at the time of surgery for primary CRCs and presence of diabetes mellitus (DM) as the associated disease were positively related to the formation of postoperative adenoma. Among those patients with the three risk factors, only 27.8% remained adenoma-free during 5?years after operation, whereas in the group without any risk factor, it was 90.4%.

Conclusions

From our data, age over 60, synchronous adenomas or CRCs and DM were the potential risk factors for the postoperative formation of adenoma or CRC, and they should be taken into consideration when defining the appropriate interval of postoperative colonoscopy.     

Sporadic Duodenal Adenoma and Association with Colorectal Neoplasia: A Case–Control Study

Background

Sporadic duodenal adenomas are uncommon. Prior studies show that patients with sporadic duodenal adenoma have increased risk of colorectal neoplasia and should undergo colorectal screening. However, the nature of the risk, location, and type of colorectal neoplasia are not well studied.

Aim

We aimed to identify the risk of colorectal neoplasia in patients who have duodenal adenomas.

Methods

A retrospective case–control study was conducted to identify sporadic duodenal adenoma patients using the databases at one academic center. Colonoscopic findings including histology and location of colorectal cancer neoplasia in sporadic duodenal adenoma patients were compared with a control group of patients without duodenal adenomas who underwent both gastroduodenoscopy and colonoscopy.

Results

Hundred and two patients with sporadic duodenal adenomas or adenocarcinomas were identified. Colonoscopy was performed in 47 patients (46 %), and colorectal neoplasia was present in 22 (46 %). There was a significantly higher rate of colorectal neoplasia in patients with sporadic duodenal adenoma (43 %) compared to the control group (24 %) odds ratio 4.8, 95 % confidence interval (1.7–7.4), but not for advanced colorectal adenoma (9 vs. 26 %, p = 0.17). Case patients had significantly more right-sided lesions than matched controls (p = 0.02).

Limitations

Single-center, retrospective study.

Conclusions

Individuals with sporadic duodenal adenomas have a significantly higher risk of colorectal neoplasia and proximal location of neoplasia. Therefore, these patients should undergo colonoscopy with particular attention to the right colon.     

Prevalence of Colorectal Neoplasia Among Young African Americans and Hispanic Americans

Background

The disproportionately higher incidence of and mortality from colorectal cancer (CRC) among African Americans (AA) led the American College of Gastroenterology to recommend screening starting at age 45 in 2005.

Aim

The purpose of this study was to determine the prevalence of colorectal neoplasia among 40–49-year-old inner city AA and Hispanic Americans (HA).

Methods

We reviewed the medical records of 2,435 inner city AA and HA who underwent colonoscopy regardless of indication and compared the prevalence of colorectal neoplasia between AA and HA patients. We used logistic regression models to calculate odds ratios (OR) and 95 % confidence intervals (CI).

Results

There were 2,163 AAs and 272 HA. There were 57 % women in both groups. A total of 158 (7 %) AA and 9 (3 %) HA (P = 0.014) underwent the procedures for CRC screening. When compared to HAs, AAs had higher prevalence of any polyp (35 vs. 18 %, OR = 2.53; 95 % CI 1.82–3.52). Overall, AA had higher prevalence of colorectal neoplasia (adenoma and cancer) when compared to HAs (16 vs. 10 %; OR = 1.68; 95 % CI 1.10–2.56).

Conclusion

We observed a higher frequency of colorectal neoplasia among 40–49-year-old AAs as compared to HAs suggesting an increased susceptibility to CRC risk in this population.     

Prediabetes Is Associated with a High-Risk Colorectal Adenoma

Background

Type 2 diabetes mellitus is associated with an increased risk of colorectal neoplasia. However, association between prediabetes and colorectal adenoma has not been reported.

Aims

The aim of this study was to evaluate the relationship between prediabetes and the presence of colorectal adenomas.

Methods

Consecutive prediabetic subjects who underwent screening colonoscopy were enrolled at Kyung Hee University Hospital in Gangdong, Seoul, Korea, between June 2006 and May 2012. Non-prediabetic subjects were separately pooled from the database of the Center for Health Promotion between January 2012 and May 2012. Prediabetes was defined according to the recommendations of the American Diabetes Association. The prevalence of colorectal adenomas and their characteristics were compared between prediabetic and non-prediabetic groups.

Results

The prevalence of colorectal adenoma was higher in prediabetic subjects than in non-prediabetic subjects (39.6 vs. 30.6 %, respectively, p = 0.019). Prediabetic subjects had more multiple and high-risk adenomas than the control group in non-matched analysis (p = 0.000, respectively). In age-matched analysis, the prevalence of multiple and high-risk adenomas were significantly higher in a prediabetic group than those in a control group (44.4 vs. 28.4 %, p = 0.034; 51.9 vs. 34.6 %, p = 0.026, respectively). Furthermore, prediabetes (odds ratio = 2.198; 95 % confidence interval = 1.042–4.637; p = 0.039) was found to be an independent risk factor for a high-risk adenoma by multivariate analysis.

Conclusions

The prevalence of multiple and high-risk colorectal adenomas is significantly higher in the prediabetic subjects than those in the control group. Furthermore, prediabetes was found to be an independent risk factor for a high-risk colorectal adenoma.     

Associations Between Markers of Colorectal Cancer Stem Cells and Adenomas Among Ethnic Groups

Background and Purposes

Most colorectal tumors develop from adenomatous polyps, which are detected by colonoscopy. African Americans (AAs) have higher incidence of colorectal cancer (CRC) and greater mortality from this disease than Caucasian Americans (CAs). We investigated whether differences in predisposition to CRC and its surrogate (colonic adenomas) between these ethnic groups were related to numbers of cancer stem or stem-like cells (CSCs) in colonocytes.

Methods

We analyzed colonic effluent from 11 AA and 14 CA patients who underwent scheduled colonoscopy examinations at the John D. Dingell Veterans Affairs Medical Center. We determined proportions of cells that expressed the CSC markers CD44 and CD166 by flow cytometry.

Results

The proportion of colonocytes that were CD44⁺CD166^? in effluent from patients with adenomas was significantly greater than from patients without adenomas (P?=?0.01); the proportion of CD44⁺CD166⁺ colonocytes was also greater (P?=?0.07). Effluent from AAs with adenomas had 60?% more CD44⁺166^? colonocytes than from CAs with adenomas. Using cutoff values of 8?% for AAs and 3?% for CAs, the proportion of CD44⁺166^? colonocytes that had positive predictive value for detection of adenomas was 100?% for AAs and CAs, determined by receiver operator characteristic curve analysis.

Conclusion

The proportion of CD44⁺166^? colonocytes in colonic effluent can be used to identify patients with adenoma. AAs with adenomas have a higher proportion of CD44⁺166^? colonocytes than CA. The increased proportion of CSCs in colonic tissue from AA might be associated with the increased incidence of CRC in this population.     

Incidence of diabetes among postmenopausal breast cancer survivors

Aims/hypothesis

Evidence is emerging of an association between breast cancer and diabetes; however, it is uncertain whether diabetes incidence is increased in postmenopausal breast cancer survivors compared with women without breast cancer. The objective of this study was to determine whether postmenopausal women who develop breast cancer have a higher incidence of diabetes than those who do not develop breast cancer.

Methods

We used population-based data from Ontario, Canada to compare the incidence of diabetes among women with breast cancer, aged 55 years or older, from 1996 to 2008, with that of age-matched women without breast cancer. We used Cox proportional hazard models to estimate the effect of breast cancer on the cause-specific hazard of developing diabetes overall and in the subgroup of women who received adjuvant chemotherapy.

Results

Of 24,976 breast cancer survivors and 124,880 controls, 9.7% developed diabetes over a mean follow-up of 5.8 years. The risk of diabetes among breast cancer survivors compared with women without breast cancer began to increase 2 years after diagnosis (HR 1.07 [95% CI, 1.02, 1.12]), and rose to an HR of 1.21 (95% CI, 1.09, 1.35) after 10 years. Among those who received adjuvant chemotherapy (n?=?4,404), risk was highest in the first 2 years after diagnosis (HR 1.24 [95% CI 1.12, 1.38]) and then declined.

Conclusions/interpretation

We found a modest increase in the incidence of diabetes among postmenopausal breast cancer survivors that varied over time. In most women the risk began to increase 2 years after cancer diagnosis but the highest risk was in the first 2 years in those who received adjuvant therapy. Our study suggests that greater diabetes screening and prevention strategies among breast cancer survivors may be warranted.     

Vegetarianism as a Protective Factor for Colorectal Adenoma and Advanced Adenoma in Asians

Background

Although epidemiologic and animal studies suggest a vegetarian diet protects against the development of colorectal cancer, the relationship between vegetarian diet and incidence of colorectal adenoma is not yet conclusive, especially for Asians.

Aim

The purpose of this study was to examine the protective effect of a vegetarian diet against colorectal adenoma and advanced adenoma.

Methods

This cross-sectional study compared the prevalence of colorectal adenoma among Buddhist priests, who are obligatory vegetarians, with that among age and sex-matched controls. All the subjects underwent health checkups in a health-promotion center in Korea.

Result

Colorectal adenoma and advanced adenoma were both more prevalent in the general population group than in the Buddhist priest group (25.2 vs. 17.9 %, 6.7 vs. 2.0 %). However, the prevalence of metabolic syndrome, high body mass index, and waist circumference were higher in the Buddhist priest group. According to univariate analysis, non-vegetarian diet (general population) significantly increased the prevalence of colorectal adenoma and advanced adenoma compared with a vegetarian diet (Buddhist priests) (OR 1.54, 95 % CI 1.08–2.21, P = 0.018; OR 3.60, 95 % CI 1.53–8.48, P = 0.003). In a conditional regression analysis model, non-vegetarian diet was also a significant risk factor for colorectal adenoma and advanced adenoma (OR 1.52, 95 % CI 0.75–2.07, P = 0.043; OR 2.94, CI 0.97–7.18, P = 0.036).

Conclusions

Vegetarianism may be effective in preventing both colorectal adenoma and advanced adenoma in Asians.     

Chronic hepatitis C as a risk factor for colorectal adenoma

Introduction

Over the last decade, epidemiologic studies have determined a relationship between chronic hepatitis C (CHC) and malignancies other than hepatocellular carcinoma (HCC), particularly in gastrointestinal malignancies. This study aims to evaluate the incidence of colorectal adenomas and advanced neoplasia in CHC patients compared to the general population and to evaluate whether CHC infection is an independent risk factor for colorectal adenomas and advanced neoplasia.

Methods

This is a retrospective, case–control study. CHC patients who underwent screening colonoscopy between September 2006 and September 2010 were compared to randomly selected non-hepatitis C controls undergoing screening colonoscopy during the same period. Multivariate analysis was performed taking into account the known risk factors for colorectal adenoma.

Results

Two hundred thirty-three CHC patients and 466 controls that underwent screening colonoscopy were included in the study. CHC patients were younger and more likely to be male, smoker and have HIV infection compared to the control group (p?<?0.05). CHC group had a significantly higher number of patients with adenomas (adenoma detection rate of 37.8 vs. 30.3 %; p?=?0.04) and hyperplastic polyps (p?=?0.01) detected on screening colonoscopy. The total number of adenomas detected was also higher in the CHC group; however, this was not statistically significant (0.69 vs. 0.58 per patient; p?>?0.05). CHC patients were twice more likely to have advanced neoplasia detected compared to non-hepatitis C patients (odds ratio 2.04, 95 % confidence interval?=?1.20–3.49; p?=?0.03). CHC group was also more likely to have adenomas of ≥6 mm (p?=?0.005) and macroadenomas of ≥1 cm (p?=?0.02).

Limitations

Limitations include the single-center, retrospective design of the study.

Conclusions

Our study is the first to demonstrate a significantly higher rate of adenomas, advanced neoplasia, and hyperplastic polyps in CHC patients compared to the general population. On multivariate analysis, CHC infection was found to be an independent risk factor for colorectal adenoma, particularly advanced neoplasia. Larger prospective studies are needed to strengthen our findings which may have implications for colorectal cancer screening.     

SEL1L, an UPR Response Protein, a Potential Marker of Colonic Cell Transformation

Background

SEL1L gene product is implicated in the endoplasmic reticulum (ER)-associated protein degradation and Unfolded Protein Response pathways. This gene and associated miRNAs have been indicated as predictive and prognostic markers of pancreatic cancer.

Aim

Explore the role of SEL1L in colorectal cancer (CRC) progression.

Methods

SEL1L expression was analysed immunohistochemically in 153 adenomas and 71 CRCs from African American and North Italian patients. The distribution of stained cells was determined by computing median and inter quartile range. The receiver operating characteristics plot was used as discriminate power of SEL1L expression, CRC diagnosis and the effects on patient survival.

Results

SEL1L was low in normal mucosa and confined to few scattered cells at the base crypt of the villi and in the foveolar glandular compartment. The highest levels were in Paneth cells within the lysosomes. The enterocytic progenitor cells and mature enterocytes showed less cytoplasmic staining. In CRCs, SEL1L expression significantly correlated with the progression from adenoma to carcinoma (P?=?0.0001) being stronger in well-to-moderately differentiated cancers. No correlation was found with other clinicopathological characteristics or ethnicity.

Conclusions

SEL1L expression is a potential CRC tissue biomarker since its expression is significantly higher in adenoma cells with respect to normal mucosa. The levels of expression decrease sensibly in undifferentiated CRC cancers. Interestingly, Paneth cells contain high levels of SEL1L protein that could indicate pre-neoplastic mucosa undergoing neoplastic transformation. Since SEL1L’s major function lies within ER stress and active ERAD response, it may identify CRCs with differentiated secretory phenotype and acute cellular stress.     

ß-catenin, Cox-2 and p53 immunostaining in colorectal adenomas to predict recurrence after endoscopic polypectomy

Background

Endoscopic polypectomy significantly reduces the incidence of colorectal cancer, but recurrence rates are high, especially for adenomas with advanced histology. The present guidelines recommend re-colonoscopy 3 to 5 years later. Due to limited resources, more precise predictions of adenoma recurrence are required.

Design

Lesions from 109 patients with colorectal adenomas recruited into a randomized, placebo-controlled chemoprevention trial with mesalazine were included. Formalin-fixed paraffin-embedded tissue sections were stained for ß-catenin, cyclooxygenase-2 (Cox-2), and p53 and scored. Adenoma recurrence rates were recorded after 3 years and associated with clinical and immunohistochemical parameters by contingency table analysis.

Results

After 3 years, adenomas recurred in 51.4 % of patients. Out of 109 adenomas, 95 met at least one criterion of advanced adenoma (size >1 cm, villous histology, high-grade intraepithelial neoplasia). There was no influence of age, sex, size or villous histology on adenoma reappearance, whilst the number of adenomas at baseline was positively associated with recurrence (p?=?0.003). In contrast, ß-catenin nuclear localisation, Cox-2 expression and p53 nuclear expression were significantly associated with adenoma recurrence after 3 years (ß-catenin: p?=?0.002; Cox-2: p?=?0.001; p53: p?=?0.001). Combining these three markers led to a negative predictive value of 88.5 % and a sensitivity of 94.6 %. (OR?=?13.54)

Conclusions

Scoring each single parameter and, more strongly, the combination of all three parameters of the expression of ß-catenin, Cox-2 and p53 in colorectal adenoma tissue may be a useful negative predictor for adenoma recurrence in patients with advanced colorectal adenomas.     

Body Mass Index, Age, and Gender Affect Prep Quality, Sedation Use, and Procedure Time During Screening Colonoscopy

Background

Body mass index (BMI), age, and gender influence colorectal cancer (CRC) and adenoma risk. Their effects on colonoscopy characteristics are unclear, but might inform the screening approach in patient subgroups.

Aims

The aims of this study were to assess the effect of BMI, age, and gender on prep quality, amount of sedation, procedure time, and adenoma prevalence for screening colonoscopy.

Methods

We conducted a review of 773 eligible colonoscopies performed for average-risk CRC screening. We performed multivariable regression analyses to assess the outcomes of prep quality, amount of fentanyl and midazolam used, procedure time, and the adenoma prevalence rate (APR).

Results

Obese patients were less likely (p = 0.01) to have a good or excellent prep, had similar procedure times, and received similar amounts of fentanyl and midazolam. Increasing age had no effect on prep quality or procedure time, but was associated with decreased fentanyl and midazolam (both p ≤ 0.001). Women had similar prep quality, longer procedure times (increased by 2.8 ± 0.7 min, p < 0.001) for colonoscopies in which no polyps were detected, and received more fentanyl and midazolam (both p = 0.01). Increasing BMI, increasing age, and male gender were associated with an increased APR. The APR for women aged 50–59 with a normal BMI was 17.9 %.

Conclusions

Normal-weight females, particularly those under age 60, have the lowest APR but have longer procedure times and require higher amounts of sedation. Screening options other than colonoscopy might be well-suited to this population.     

Changes of the Intestinal Microbiota, Short Chain Fatty Acids, and Fecal pH in Patients with Colorectal Cancer

Background

New molecular biology-based methods of bacterial identification are expected to help elucidate the relationship between colorectal cancer (CRC) and intestinal microbiota. Although there is increasing evidence revealing the potential role of microbiota in CRC, it remains unclear whether microbial dysbiosis is the cause or the result of CRC onset.

Aim

We investigated the changes of intestinal environments in CRC or adenoma.

Methods

We analyzed 13 groups of microbiota, 8 types of organic acids, and pH in feces obtained from the following 3 groups: individuals with CRC, adenoma, and non-adenoma. Ninety-three patients with CRC and 49 healthy individuals (22 with adenoma and 27 without adenoma) were enrolled.

Results

The counts of total bacteria (10.3 ± 0.7 vs. 10.8 ± 0.3 log₁₀ cells/g of feces; p < 0.001), 5 groups of obligate anaerobe, and 2 groups of facultative anaerobes were significantly lower in the CRC group than in the healthy individuals. While the concentrations of short chain fatty acids (SCFAs) were significantly decreased in the CRC group, the pH was increased in the CRC group (7.4 ± 0.8 vs. 6.9 ± 0.6; p < 0.001). Comparison among the CRC, adenoma, and non-adenoma groups revealed that fecal SCFAs and pH in the adenoma group were intermediate to the CRC group and the non-adenoma group. Within the CRC group, no differences in microbiota or organic acids were observed among Dukes stages.

Conclusions

CRC patients showed significant differences in the intestinal environment, including alterations of microbiota, decreased SCFAs, and elevated pH. These changes are not a result of CRC progression but are involved in CRC onset.     

Quality colonoscopy and risk of interval cancer in Lynch syndrome

Purpose

Despite colonoscopic surveillance, Lynch syndrome patients develop colorectal cancer (CRC). Identification of modifiable factors has the potential to improve outcome of surveillance. The aims of this study were to determine (1) characteristics of patients with CRC, (2) endoscopic and histological features of these cancers, and (3) quality of the previous colonoscopy.

Methods

Approximately 2,200 medical reports from proven and obligate mutation carriers identified at the Dutch Lynch Syndrome Registry and two large hospitals were retrospectively analyzed for the presence of an interval cancer defined as CRC diagnosed within 24 months of previous colonoscopy.

Results

Thirty-one interval cancers were detected in 29 patients (median age of 52 [range 35–73]), after a median time of 17 months. All were MLH1 or MSH2 mutation carriers, and 39 % had a previous CRC. In patients without previous surgery for CRC, 84 % was proximally located. Of all interval cancers, 77 % were at local stage (T1–3N0Mx). In three patients (9 %) with an incomplete previous colonoscopy, CRC was located in the unexamined colon. In six of the nine patients with an adenoma during previous colonoscopy, the cancer was detected in the same colonic segment as the previously removed adenoma.

Conclusions

Interval cancers were detected in MLH1 and MSH2 mutation carriers, especially in those with a history of previous CRC and between 40 and 60 years. Interval cancer could be related to incompleteness of previous endoscopy and possibly residual adenomatous tissue. Further reduction of the interval cancer risk may be achieved by optimizing endoscopy quality and individualization of surveillance guidelines.     

Anatomic distribution of cancers and colorectal adenomas according to age and sex and relationship between proximal and distal neoplasms in an i-FOBT-positive average-risk Italian screening cohort

Background and aims

Subsite-specific incidence rates of colorectal cancer (CRC) and adenomas may vary considerably by race, sex and age as well as due to different screening strategies. We assessed variations in the anatomical distribution of adenomas according to age and sex in an average-risk screening cohort testing positive at immunological faecal occult blood test (i-FOBT) in northern Italy.

Methods

Data from 2,281 consecutive asymptomatic i-FOBT-positive subjects ageing 50–70 years undergone colonoscopy were reviewed. Size, number, macroscopic and histological features of all adenomas found as well as their proximal or distal location in relation to the splenic flexure were examined. Odds ratios (OR) of proximal neoplasms, according to the presence of distal neoplasms and other selected covariates were assessed by multiple logistic regression analysis.

Results

A total of 2,599 neoplasms were found in 1,396 patients. Of these, 116 (5 %) were colorectal cancers, diagnosed in 106 patients. Out of 2,483 adenomas found, 1,564 (63 %) were sessile, 795 (32 %) were peduncolated and 124 (5 %) were flat-type; 54 % of all adenomas were tubular, 36 % were tubulovillous or villous, and 10 % were serrated adenomas. The majority of neoplasms (66 %) were located in the distal colon. Tumour subsite distribution was consistent in both sexes, whereas significant proximal migration of neoplasms occurred in the older age cohort. Indeed, the rate of proximal neoplasms in patients aged ≥60 years was 37 % as compared with 29 % in those ageing 50–59 years. Male gender (OR 1.84), age of 60 years or older (OR 1.44), having a family history of colorectal neoplasms (OR 1.47) and presence of at least 1 distal advanced adenoma (OR 1.63) were all significant predictors of advanced proximal neoplasms.

Conclusions

A left to right shift of colorectal adenomas with increasing age is evident in northern Italian asymptomatic i-FOBT-positive population. Advanced proximal neoplasms are not uncommon in subjects with or without distal adenomas, especially after 60 years of age. This should be carefully considered when implementing public screening strategies for CRC since the use of flexible sigmoidoscopy as a screening tool, particularly in older age groups, appears to be less effective.     

Excess weight among colorectal cancer survivors: target for intervention

Background

Healthy lifestyle might improve outcome among colorectal cancer (CRC) survivors. In this study we investigated the proportion of survivors who meet recommended lifestyle and weight guidelines and compared this to the general population. Factors that predict current behaviour were also assessed.

Method

A random sample of CRC survivors diagnosed between 1998 and 2007 were surveyed. Percentages of current smokers, alcohol consumers, excess weight and clustering of these variables were calculated. Using logistic regression we assessed demographical and clinical factors that predict current lifestyle and excess weight.

Results

We included 1349 (74% response rate) survivors in this study of whom only 8 and 16% of male and female survivors met the recommended lifestyle and body weight. Among male survivors up to 10% had at least two unhealthy lifestyle factors and among women, up to 19%. The proportion of smokers and those who had ever consumed alcohol was lower compared to the general population (13 vs. 31%, 82 vs. 86% respectively), but excess weight (BMI at least 25?kg/m²) was more prevalent among survivors (69 vs. 53% respectively). Having received chemotherapy was significantly associated with being overweight (adjusted odd ratio 1.5, 95% confidence interval 1.05–2.3). Younger patients, male gender and survivors of lower socioeconomic status were more likely to show non-compliance to healthy lifestyle recommendations.

Conclusion

The observed clustering of unhealthy lifestyle warrants interventions targeting multiple behaviours simultaneously. Reducing excess weight should be one of the most important targets of interventions, particularly for males, those who had chemotherapy and survivors of lower socioeconomic status.     

Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer

Purpose

The purpose of present study was to investigate the methylation status of the promoter region in five genes (mothers against decapentaplegic homolog 4, fragile histidine triad protein, death-associated protein kinase 1, adenomatous polyposis coli (APC), and E-cadherin), which are known to be involved in the pathogenesis of colorectal cancer (CRC) and its clinicopathological significance.

Methods

The study subjects were 60 CRC patients, 40 patients with adenomatous colorectal polyp and 60 healthy control individuals. We further enrolled a total of 16 patients (two patients with Crohn’s disease, two patients with ulcerative colitis, one patient with serrated adenoma, and 11 patients with colorectal cancer). The methylation states of the five genes were determined in peripheral blood plasma using methylation-specific polymerase chain reaction single-strand conformation polymorphism analysis.

Results

This study showed the most sensitive epigenetic markers, E-cadherin (60 %), followed by APC (57 %), for detecting CRC. E-cadherin and APC had similar specificities and amplified 84 and 86 %, respectively, of CRC patients compared to non-CRC patients. Additionally, APC was the only marker to be significantly increased (OR?=?6.67, 95 % CI?=?1.19–23.4, P?=?0.045) and the most sensitive (57 %) and specific (89 %) marker in stage I CRC. Though we have not examined the paired cancer tissues and plasma, there was relatively high concordant rate (60–80 %) in our limited number of colorectal cancer patients.

Conclusions

Five genes, promoter methylation, in plasma were statistically significant risk factors in CRC patients. In this study, E-cad and APC genes may be particularly useful epigenetic biomarkers in plasma for the detection of CRC. Additionally, APC may able to identify early potential CRC.     

A pilot study comparing protein expression in different segments of the normal colon and rectum and in normal colon versus adenoma in patients with Lynch syndrome

Purpose

Lynch syndrome (LS) is a common inherited predisposition to colorectal cancer (CRC). In LS patients, CRC is predominantly located in the right colon, as opposed to sporadic CRC, which usually affects the left colon or rectum. Previous studies have demonstrated a clear distinction in gene expression between sporadic CRC and normal colon at different locations in the colorectum. However, little is known about LS gene expression profiles in different areas of the colorectum. Here, we compared the protein expression profiles for normal colorectal samples among different locations as well as between adenomas and matched normal tissue in LS.

Methods

Protein from 33 tissue samples (27 normal tissues and 6 adenomas) from 9 patients with LS was extracted for reverse-phase protein array (RPPA) analysis. The antibody panel used for RPPA included 109 key proteins involved in various cancer-related pathways. Cluster 3.0 was used for unsupervised and supervised clustering analysis.

Results

IGF1R and COL6A1 were expressed significantly differently between the normal right and normal left colon (q < 0.05); FN1, COL6A1, and IGF1R were expressed significantly differently between the normal right colon and normal rectum (q < 0.05). In the adenomas and matched normal tissue, PEA-15 was the only protein with significantly different expression (q < 0.05).

Conclusion

We found differences in protein expression between normal tissues from the right colon, left colon, and rectum as well as between adenomas and matched normal tissue. However, those differences should be further confirmed in a larger sample size.     

Changing Epidemiology of Colorectal Cancer Makes Screening Sigmoidoscopy Less Useful for Identifying Carriers of Colorectal Neoplasms

Background

There is renewed interest in flexible sigmoidoscopy (FS) colorectal cancer (CRC) screening following trials showing significantly reduced CRC incidence and mortality.

Aims

To evaluate the potential usefulness of FS screening in our population.

Methods

We examined rectosigmoid (RS) cancer epidemiology in our Jewish population using Israel National Cancer Registry data, computed by CRC site, age groups, and gender. We also reviewed endoscopy-screening publications for prevalence of RS and proximal advanced adenomas (AAP) and having both or either.

Results

During 1980–2008, there were 64,559 CRCs registered; 31.6 % were RS cancer which has now decreased to 29 % of men’s and 26 % of women’s CRC (both P < 0.01). In <50 year olds, RS cancer occurred in 42 % of males’ and 35 % of females’ CRC, and in the last 2 decades this ratio is unchanged. In 50–74 year olds, RS cancer decreased to stable levels of 32 % of males’ and 29 % females’ CRC (both P < 0.01). In ≥75 year olds, RS cancer progressively decreased to 24 % of males’ and 22 % females’ CRC (both P < 0.001). From endoscopy screening reports in 40–79 year olds, RS AAPs occurred in 2.0–5.8 %, being least in women, most in men, and not increased with aging. Some 50–57 % of screenees had both RS and proximal AAPs, least when aged 40–49 years at 25 %, women were 35 %, and with aging 40 %, but most in men at 70 %.

Conclusions

With the changing CRC epidemiology, having fewer RS neoplasms but more proximal cancer, the effectiveness of FS screening for identifying significant neoplasms decreases with screenees’ age and especially in females. These make FS screening less suitable for our aging and increasingly female population.