High Prevalence Of Colorectal Cancer Research Articles

KRAS gene mutations in correlation with clinicopathological features of colorectal carcinomas in Indian patient cohort

KRAS gene mutations have been identified as a predictive molecular marker to predict the sensitivity of tumors to anti-EGFR therapeutics. The variability of clinical response to anti-EGFR agents has highlighted the need to select the appropriate patients who can benefit from the treatment. We examined the prevalence of KRAS mutations in 1,323 colorectal cancer patients from different regions of India and its correlation with geographic distribution and clinicopathological characteristics. DNA was extracted from formalin-fixed, paraffin-embedded tissue samples and was amplified by nested polymerase chain reaction at KRAS exon 2 and subjected to nucleotide sequencing using ABI 3100 Genetic Analyzer. The frequency of KRAS mutations was found to be 20.5 % (271/1,323). There was significant association (p < 0.05) between KRAS mutations, age and the tumor differentiation. Statistical analysis revealed significantly higher prevalence of colorectal cancer with mutated KRAS gene in northern regions of the country. No significant association was observed between KRAS mutations and gender (p > 0.05). Our study indicates that KRAS mutations in Indian colorectal cancer patients occur at lower level compared to that of Western population.

Screening Colonoscopy Can Benefit Healthier Elders

Gaithersburg, Md. – The benefits of a transcatheter heart valve outweigh its risks for older patients with severe, symptomatic aortic stenosis who are at a high risk for surgery, voted the majority of an advisory panel to the Food and Drug Administration recently. All panel members also voted that the valve was effective, and 10 of 12 members said that it was safe. The valve entered the U.S. market last November after receiving FDA approval for patients who have severe aortic stenosis and are deemed too sick to undergo surgical heart valve replacement (N. Engl. J. Med. 2010;363:1597-607). On June 12, Edwards Lifescience, the maker of the SAPIEN transcatheter heart valve, said that based on the results of the PARTNER pivotal trial, the valve is also safe and effective in the high-risk cohort. Although FDA officials agreed that the trial met its primary endpoints, they expressed concern with the higher risk of stroke in patients who underwent transcatheter aortic valve replacement (TAVR), compared with those who underwent surgery. They also raised questions about the long-term durability of the device, for which there are no data yet available yet. In his final remarks, Dr. Craig R. Smith, chair of the department of surgery at Columbia University and coprincipal investigator of the PARTNER trial, said that although the risks associated with the procedures must be taken seriously, they should not be an obstacle to the indication’s approval. The main results of the trial showed that all-cause mortality at 30 days favored TAVR at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% and 27%, respectively). The difference at 1 year reached the trial’s prespecified noninferiority margin, yet again, neurologic complications occurred more frequently after TAVR. Surgical valve replacement has evolved over the past 50 years, and although TAVR is radical, it’s the next logical step in that evolution, Dr. Smith told the panel. The results of cohort A of PARTNER, he said, bring the field one step closer to the day that valves can be replaced with no large incisions, no heart-lung machine, and potentially no general anesthesia. The Centers for Medicare & Medicaid Services decided in May that it will cover the procedure in inoperable patients, under certain conditions, including evaluation of the patient by two cardiac surgeons. Dr. Gregory J. Dehmer, professor of medicine at Texas A&M University, said that the field was only at its infancy. Dr. Dehmer disclosed no conflict of interest. Dr. Smith noted that he is an investigator in the PARTNER trial. CfA

Clinical and epidemiological evaluation of patients with colorectal cancer from Rio Grande do Sul

Colorectal cancer has a high incidence in Brazil, with the South and Southeast regions presenting the largest number of cases. OBJECTIVE: Identify the epidemiological characteristics and the regimens used as first-line treatment of patients with colorectal cancer treated at a cancer center in Santa Cruz do Sul (RS, Brazil) from 2006 to 2011. METHODS: The records of 130 patients were retrospectively evaluated. Clinical and epidemiological characteristics, such as age, gender, ethnic group, stage of disease, primary site of disease and first-line treatment, were evaluated. The association of significance was evaluated using the chi-square and Fischer exact tests. The confidence interval used was 95% (p<0.05). RESULTS: The mean age of patients with colorectal cancer in this study was 60.8 years, with higher incidence of the disease in men. At diagnosis, 40% of the patients had advanced disease stage IV. The regimen of 5-fluorouracil/folic acid (68.5%) was used as first-line treatment. CONCLUSION: This study showed high prevalence of colorectal cancer in patients of advanced age with the diagnosis made in the later stage of the disease. This fact demonstrates the importance of prevention campaigns that encourage periodic examinations in patients over 50 years of age.

Factors and trends in cancer screening in the United States from 2004 to 2010.

1565 Background: Understanding the prevalence of cancer screening in the US and the factors associated with its accessibility is important for public health promotion. Methods: The 2004 and 2010 Behavioral Risk Factor Surveillance Systems were used to ascertain cancer screening rates among populations indicated for each test by age, gender, and the American Cancer Society recommendation for cancer screenings [fecal occult blood test (FOBT) or endoscopy for colorectal cancer (CRC) screening, digital rectal examination (DRE) or prostate specific antigen (PSA) for prostate cancer screening, clinical breast examination (CBE) or mammogram for breast cancer screening, and Papanicolaou (Pap) test for cervical cancer screening]. Results: Over this period, CRC and breast cancer screening rates significantly increased (15.9%, 13.9%) while prostate and cervical cancer screening rates significantly decreased (1.2%, 5.2%). Race/ethnicity might be an influence in CRC and cervical cancer screening accessibility. Prostate cancer screening accessibility might be influenced by education and income. The older-aged populations (70-79, &gt;79) had high prevalence of CRC, prostate and breast cancer screenings even though there is insufficient evidence for the benefits and harms of screenings in the older-aged group. Conclusions: The disparities in age, race/ethnicity, health insurance, education, employment, and income for the accession to cancer screening of the US population have decreased since 2004. The trajectory of increasing rates of CRC and breast cancer screenings should be maintained. To reverse the trend, the causes of the decreased rate of cervical cancer screening and the high rates of screenings in older-aged populations should, however, be further explored. [Table: see text]

Abstract 2714: Colorectal Cancer in young (&amp;lt;50 years old) African Americans, Could race be a risk factor? A 20 years experience in an inner city teaching hospital

Abstract BACKGROUND: Colorectal cancer (CRC) is the third most common cancer, and survival in African Americans (AAs) is worse than Caucasians. Some studies suggest that the incidence of CRC is higher in AA patients below the age of 50 when compared to Caucasians. This study aims to confirm the higher prevalence of CRC in an AA population less than 50, and its implications to the screening guidelines. METHOD: In a retrospective study demographic data, indication and outcome of colonoscopy, and biopsy data were collected at Howard University Hospital (HUH) over a period of 21 years (1989-2008). All of the study patients were (AA), and cases were classified either symptomatic average risk (91%); or high risk (family history, IBD) (9%). Distribution of variables was studied by median (inter-quartile range) or number (%). RESULTS: Seventy five CRC cases younger than 50 years old were recorded from 1989 to 2008 at HUH. Median age (inter-quartile range) of these patients were 43 (40-46) years and 35 (47%) were female. Among them 55 (73%) were adenocarcinoma and 43 (57%) were located at left colon. In the same period a total of 671 CRC was recorded in HUH. We compared this data with 4591 CRC cases who were registered at District of Colombia (DC) from 1996 to 2007. While in HUH 11% of all CRC cases were under 50, this ratio for DC area was 9% (P=0.1). Among HUH patients 4%, 16% and 80% were 20-29, 30-39 and 40-49 years old, respectively. In DC area these ratios were 3%, 26% and 70% (P = 0.2). Among HUH tumors with available data 49%, 40%, 11% were local, regional, distant and unknown extension, while these proportions in DC area were 40%, 37%, 23% (P=0.018), respectively. CONCLUSION: Our data showed a high burden of colorectal CRC in young AAs (&amp;lt;50). CRC rate of 80% (60/75) was seen for the age group of 40-49, which indicates cancer in AAs may starts at younger age than predicted (&amp;lt;45). The American College of Gastroenterology recommends to start screening of AAs at age of 45, but this may not cover many high risk people who are younger than 45. Further study is needed on AAs to confirm these findings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2714.

M1033 Colorectal Neoplasia in Young African Americans, Could Race Be a Risk Factor? a 40 Years Experience in An Inner City Teaching Hospital

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer, and survival in African Americans (AAs) is worse than Caucasians. Some studies suggest that the incidence of CRC is higher in AA patients below the age of 50 when compared to Caucasians. This study aims to confirm the higher prevalence of CRC in an AA population within the age groups of 40-49, and its implications to the screening guidelines. METHOD: In a retrospective study demographic data, indication and outcome of colonoscopy, and biopsy data were collected at Howard University Hospital over a period of 38 years (1970-2007). All of the study patients were (AA), and cases were classified either symptomatic average risk, 692 (91%); or high risk (family history, IBD), 69 (9%). Distribution of variables were studied by mean (standard deviation) or number (%) . RESULTS: A total of 8851 patients who had colonoscopy were analyzed. Female comprise 56%, and the mean (SD) for age was 60.3 (14.9). Out of the total, 965 (11%) were in the age group of 40-49, of which 409 (42%) had adenoma, and 45 (4.8%) had CRC. The location of 86% of the 409 adenomas were obtained. Two-hundred six (59%) adenomas were on the left side, and 144 (41%) were right sided. The histology of the adenomas included, 264 tubular adenomas (64.5%), 83 hyperplastic lesions (0.3%), 44 villous adenomas (10.8%), and 18 other histology (4.4%). When patients from age 40-44 (378) were compared for the prevalence of adenoma and CRC to those age 45-49 (587), the 40-44 age group had 148 (39.2%) adenomas and 18 (4.8%) CRC, vs. the 45-49 age group had 349 (59.4%) adenomas and 28.1(4.8%) CRC. Twenty four (68.5%) cancers were on the left side, and 11(31.5%) were right sided. Females had higher CRC rates 27 (61%), compared to males 18(39%). CONCLUSION: Our data showed a very high burden of colorectal adenoma and CRC in young AAs (<45). CRC rate of (4.8%) was seen for both the age group of 40-44, and 45-49, which indicates cancer in AAs may starts at younger age than predicted (<45). The American College of Gastroenterology recommends to start screening of AAs at age of 45, but this may not cover many high risk people who are younger than 45. Further study is needed on AAs to confirm these findings.

M1036 Real World Clinical Outcomes Observed After Adoption of CTC in a Gastroenterology Practice Setting

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer, and survival in African Americans (AAs) is worse than Caucasians. Some studies suggest that the incidence of CRC is higher in AA patients below the age of 50 when compared to Caucasians. This study aims to confirm the higher prevalence of CRC in an AA population within the age groups of 40-49, and its implications to the screening guidelines. METHOD: In a retrospective study demographic data, indication and outcome of colonoscopy, and biopsy data were collected at Howard University Hospital over a period of 38 years (1970-2007). All of the study patients were (AA), and cases were classified either symptomatic average risk, 692 (91%); or high risk (family history, IBD), 69 (9%). Distribution of variables were studied by mean (standard deviation) or number (%) . RESULTS: A total of 8851 patients who had colonoscopy were analyzed. Female comprise 56%, and the mean (SD) for age was 60.3 (14.9). Out of the total, 965 (11%) were in the age group of 40-49, of which 409 (42%) had adenoma, and 45 (4.8%) had CRC. The location of 86% of the 409 adenomas were obtained. Two-hundred six (59%) adenomas were on the left side, and 144 (41%) were right sided. The histology of the adenomas included, 264 tubular adenomas (64.5%), 83 hyperplastic lesions (0.3%), 44 villous adenomas (10.8%), and 18 other histology (4.4%). When patients from age 40-44 (378) were compared for the prevalence of adenoma and CRC to those age 45-49 (587), the 40-44 age group had 148 (39.2%) adenomas and 18 (4.8%) CRC, vs. the 45-49 age group had 349 (59.4%) adenomas and 28.1(4.8%) CRC. Twenty four (68.5%) cancers were on the left side, and 11(31.5%) were right sided. Females had higher CRC rates 27 (61%), compared to males 18(39%). CONCLUSION: Our data showed a very high burden of colorectal adenoma and CRC in young AAs (<45). CRC rate of (4.8%) was seen for both the age group of 40-44, and 45-49, which indicates cancer in AAs may starts at younger age than predicted (<45). The American College of Gastroenterology recommends to start screening of AAs at age of 45, but this may not cover many high risk people who are younger than 45. Further study is needed on AAs to confirm these findings.

Phenotype Comparison of MLH1 and MSH2 Mutation Carriers in a Cohort of 1,914 Individuals Undergoing Clinical Genetic Testing in the United States

Lynch syndrome is caused by germ-line mismatch repair gene mutations. We examined the phenotypic differences between MLH1 and MSH2 gene mutation carriers and whether mutation type (point versus large rearrangement) affected phenotypic expression. This is a cross-sectional prevalence study of 1,914 unrelated probands undergoing clinical genetic testing for MLH1 and MSH2 mutations at a commercial laboratory. Fifteen percent (285 of 1,914) of subjects had pathogenic mutations (112 MLH1, 173 MSH2). MLH1 carriers had a higher prevalence of colorectal cancer (79% versus 69%, P = 0.08) and younger mean age at diagnosis (42.2 versus 44.8 years, P = 0.03) than MSH2 carriers. Forty-one percent of female carriers had endometrial cancer and prevalence was similar in both groups. Other cancers were more frequent in MSH2 carriers (24% versus 9%, P = 0.001) and their families (P < 0.001). Multivariable analyses confirmed these associations. Of the 1,016 subjects who underwent Southern blot analysis, 42 had large rearrangements (7 MLH1, 35 MSH2). There were no phenotypic differences between carriers with large rearrangements and point mutations. In this large study of mismatch repair gene mutation carriers from the United States, MLH1 carriers had more colorectal cancer than MSH2 carriers whereas endometrial cancer prevalence was similar. Large genomic rearrangements were more frequent in the MSH2 gene. MSH2 carriers and their relatives have more extracolonic nonendometrial Lynch syndrome-associated cancers and may benefit from additional screening.

Association Between Serum Insulin Levels and Prevalent Colorectal Neoplasia in a Japanese Population

Background: Colorectal cancer (CRC) is one of the leading causes of cancer death in Japan. Previously we reported that patients with acromegaly had higher prevalence of CRC as well as hyperplastic polyps (HPPs). Since elevated insulin levels may promote proliferation of sporadic colorectal epithelium through insulin like growth factor-1 mediated mechanisms, similar to acromegaly, we hypothesized that hyperinsulinemia may promote colorectal tumorigenesis. We showed preliminary data of association between insulin resistance syndrome and increased prevalence of HPPs, which tend to associate with serrated adenoma and advanced adenomas. However, the specific relationship between serum insulin levels and HPPs has not yet been shown. Aim: To determine if serum insulin levels are associated with the prevalence of solitary HPPs, adenomas, and advanced adenomas in our hospital-based patient population. Methods: We used data from 193 consecutive patients 1) who underwent colonoscopy in our hospital and 2) provided informed consent to measure serum insulin levels. Fasting serum levels of insulin (INS) and the information of lifestyle were obtained prior to colonoscopy. Based on histological diagnosis, the prevalence of solitary HPPs, adenomas, and advanced adenomas (size of >10mm, villous component (+), or severe dysplasia) were determined in total, right, and left colon segments and assessed for association with INS. We used chi-square tests as well as multiple logistic regression to adjust for age, gender, and smoking status. Results: There were significant associations between INS levels and the prevalence of adenomas (p<0.05) as well as advanced adenomas (p<0.005). The prevalence of each lesion for INS levels of <5 mU/ml, 5-10 mU/ml, 10-15 mU/ml, and >15 mU/ml were: adenoma (32%, 42%, 50%, 73%) and advanced adenomas (8%, 6%, 25%, 36%). The adjusted odds ratios of each lesion for 5 mU/ml of increase in INS (OR (95%CI)) were: adenomas (1.6 (1.1, 2.5)) and advanced adenomas (2.2 (1.4, 3.9)). The prevalence of solitary HPPs was not significantly associated with INS overall, but there was significant association between INS and right colon HPPs (p<0.05, OR=1.4(1.0, 2.2)). Conclusion: Hyperinsulinemia may promote colorectal tumorigenesis; In the right colon, this condition may be associated with solitary HPPs, which have uncertain malignant potential.

The role of CD8(+) T cells in immune responses to colorectal cancer.

Cytotoxic T lymphocytes (CTL) are essential effectors of the cell-mediated immune response. The ability of CTL to specifically recognise and lyse malignant cells expressing the relevant surface antigens under optimal in vitro conditions justifies attempts to boost their number and activity through various forms of immunotherapy. Considering the high prevalence of colorectal cancer and poor survival rates for patients with advanced-stage disease, the development of new protocols based on CTL stimulation represents a genuine and promising treatment option. Significant advances in recombinant DNA technology and molecular biology have led to the identification of a number of tumour-associated antigens (TAA). These have served as vaccine constituents and/or stimuli for obtaining CTL used for adoptive immunotherapy after in vitro stimulation and expansion. The present review describes the properties and functions of CTL as effectors of the immune response against tumours, and summarises the known TAA recognised by CTL and the current status of CTL-related immunotherapeutic interventions in colorectal cancer patients.