Subsite-specific incidence rate and stage of disease in colorectal cancer by race, gender, and age group in the United States, 1992-1997.

BACKGROUND: Subsite specific incidence rates of colorectal cancer vary considerably by age, gender, and race. This variation may be related not only to distinctions in exposure to genetic and environment factors but also to current strategies of early detection screening. Patterns of stage of disease in anatomic subsite may reflect the effect of screening. This study used the largest aggregation of cancer incidence data in the U.S. to examine subsite specific incidence rates of colorectal cancer and the relation of stage of disease to anatomic subsites by race, gender, and age group. METHODS: Data on the incidence of invasive colorectal cancer were obtained from 28 population-based central cancer registries. Age-specific and age-adjusted rates and stage distributions were analyzed by subsite, race, and gender. RESULTS: The impact of screening can be observed in the percentage of localized disease, which increased from 31.9% among cancers in the proximal colon to 37.0% in the descending colon to 41.5% in the distal colorectum. Within the same subsite, blacks were less likely than whites to receive a diagnosis of localized disease and more likely to receive a diagnosis of distant disease whereas stage distributions were approximately the same for males and females. Blacks were more likely than whites to receive a diagnosis of proximal colon cancer than distal colorectal cancer. The male-to-female rate ratios progressively increased from the proximal colon to the distal colorectum. The ratios of proximal-to-distal colorectal cancer gradually increased with advancing age. CONCLUSIONS: Differentials in stage of disease by subsites indicate a need for a targeted effort at early detection of cancer in the proximal colon. Risk factors and higher risk populations for colorectal cancers in each subsite need to be studied further to guide actions for improving the efficacy of screening.     

Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology

In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps and a screening test that primarily is effective at early cancer detection. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.     

A fast, cost-efficient and sensitive approach for KRAS mutation detection using multiplexed primer extension with IP/RP-HPLC separation

Mutations in the KRAS gene are very important diagnostic and prognostic markers in cancer. Particularly, KRAS mutations at codons 12 and 13 have a high prognostic value for EGFR-directed antibody therapies. Several methods are available to detect the most common mutations, some of them are commercialized. The most frequently used techniques, allele-specific PCR or direct sequencing, are not standardized and often lack sensitivity to detect low amounts of mutated tumor cells in paraffin-embedded tissue-blocks leading to a high number of false-negatives. Here we present a reliable, fast, cost-effective and sensitive approach for KRAS mutation detection that has a high potential for standardized large scale screening. The method is based on multiplexed primer extension reactions coupled to HPLC separation. The highly sensitive assay gives easily interpretable and reproducible results at affordable costs. We describe the method and an application example for diagnosis in early colorectal cancer screening.     

Multiple serological biomarkers for colorectal cancer detection

The aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumor‐associated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor‐associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme‐linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY‐CO‐16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (≥5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early‐stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer‐associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor‐associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early‐stage patients.     

沈阳市苏家屯地区大肠癌筛查结果分析

[目的]通过大肠癌早诊早治项目,分析沈阳市苏家屯地区居民大肠癌发病情况。[方法]对苏家屯地区40~74岁人群采用问卷调查和粪便潜血实验免疫金标法（FIT）相结合筛出高危人群,对高危人群进行全大肠镜检查。[结果]目标人群40 157人中接受初筛人数为16 893人,顺应率为42.07%。初筛出高危人群3139人,占筛查人数18.58%。进行肠镜检查1655人,顺应率为52.72%。检出进展期腺瘤、大肠癌及类癌共83例。早诊率为95.18%,治疗率为100%。苏家屯地区居民大肠癌检出率为37.35/10万。[结论]苏家屯地区大肠癌检出率略高于我国农村地区平均水平。大肠癌筛查方案适用于城郊地区开展,可提高大肠癌的早诊率,对提高治愈率及延长生存期有重要意义。     

错配修复基因蛋白在结直肠癌诊治中的临床应用

  目的  探讨错配修复基因（mismatch repair gene,MMR）蛋白MLH1、MSH2、MSH6、PMS2在结直肠癌中的表达及在临床中的应用。  方法  选取四川省人民医院2015年1月至2016年9月收治的607例结直肠癌患者,采用免疫组织化学法检测手术标本中MMR蛋白的表达情况,研究其与临床病理学的关系,并评价其在Lynch综合征和散发性结直肠癌筛查中的价值。  结果  607例患者中MMR表达缺失率为35.58%。MMR蛋白表达缺失的阴性组与表达正常的阳性组,在年龄、性别、肿瘤大小、P53、CD34、D2-40的比较,差异均无统计学意义（P>0.05）;两组患者在肿瘤位置、分化程度、TNM分期、淋巴结转移、VEGF、Ki-67的比较,差异均有统计学意义（P < 0.05）。联合检测MLH1、MSH2、PSM2、MSH6蛋白可以作为初步筛选Lynch综合征患者的方法。  结论  对结直肠癌患者的手术标本进行MMR检测,筛查Lynch综合征患者和家族成员,进行管理及干预,可降低部分人群患结直肠癌的风险。      

Cancer surveillance series: interpreting trends in prostate cancer--part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates.

BACKGROUND: The prostate-specific antigen test was approved by the U.S. Food and Drug Administration in 1986 to monitor the disease status in patients with prostate cancer and, in 1994, to aid in prostate cancer detection. However, after 1986, the test was performed on many men who had not been previously diagnosed with prostate cancer, apparently resulting in the diagnosis of a substantial number of early tumors. Our purpose is to provide insight into the effect of screening on prostate cancer rates. Detailed data are presented for whites because the size of the population allows for calculating statistically reliable rates; however, similar overall trends are seen for African-Americans and other races. METHODS: Prostate cancer incidence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and mortality data from the National Center for Health Statistics were analyzed. RESULTS/CONCLUSIONS: The following findings are consistent with a screening effect: 1) the recent decrease since 1991 in the incidence of distant stage disease, after not having been perturbed by screening; 2) the decline in the incidence of earlier stage disease beginning the following year (i.e., 1992); 3) the recent increases and decreases in prostate cancer incidence and mortality by age that appear to indicate a calendar period effect; and 4) trends in the incidence of distant stage disease by tumor grade and trends in the survival of patients with distant stage disease by calendar year that provide suggestive evidence of the tendency of screening to detect slower growing tumors. IMPLICATIONS: The decline in the incidence of distant stage disease holds the promise that testing for prostate-specific antigen may lead to a sustained decline in prostate cancer mortality. However, population data are complex, and it is difficult to confidently attribute relatively small changes in mortality to any one cause.     

嘉善县人群普查检出的21例结直肠癌临床病理分析

我们首次采用数学模式调查表、反向被动血凝法和纤维乙状结肠镜程序方案,在嘉善县进行结直肠癌普查,共查出结直肠癌21例。与同期在医院诊治的结直肠癌进行比较。结果发现,普查组在肿瘤大小、大体类型、组织学类型、浸润深度和 Dukes 分期均显著地不同于临床组(P<0.05,或 P<0.01)。普查组中肿瘤≤2 cm者达28.6%,高分化管状腺癌占57.1%,Dukes A 期占47.6%;而临床组绝大多数肿瘤>2 cm 者占96%,中分化管状腺癌占50.7%,Dukes A 期仅占14.7%。提示在结直肠癌高发地区实施上述普查方案,有可能发现更多的体积小,分化程度高,侵袭局限的早期癌。     

Co-expression of stem cell genes CD133 and CD44 in colorectal cancers with early liver metastasis

PurposeTo investigate the expression status and clinical implications of stem cell genes CD133 and CD44 in the colorectal cancers with early liver metastasis.Materials and methodsThe differential genes of early liver metastases in colorectal cancer were detected by RT² Profiler? PCR Array. The expression and the relationship of stem cell gene CD133 and CD44 were analyzed by immunofluorescent tests.ResultsCD133 and CD44 were significantly higher co-expressed in colorectal cancer with early liver metastases compared to those without early liver metastases, and the content of CD133 and CD44 proteins decreased following growth of the transplanted tumors. Of the 80 cases without early liver metastases, 12 were observed CD133 and CD44 proteins co-expression, while 36 of the 40 cases with early liver metastases were found CD133 and CD44 proteins co-expression (15% vs. 90%, P < 0.05). Survival analysis revealed CD133 and CD44 proteins co-expression was associated with poorest prognosis (57.14% vs. 87.41%, X² = 48.49, P = 0.001). After Cox regression, age, Duck’s stage, lymph node metastasis, and CD133 and CD44 proteins co-expression were shown to be the independent prognostic factors of colorectal cancers.ConclusionsCD133 and CD44 proteins were highly co-expressed in colorectal cancer with early liver metastases, and may be a potential biomarker for the early liver metastases.     

Molecular markers for human colon cancer in stool and blood identified by RT-PCR

There is a need for sensitive and specific diagnostic and prognostic molecular markers which can monitor early patterns of gene expression in non-invasive exfoliated colonocytes shed in the stool, and aggression in carcinoma cells in blood of resected colorectal cancer patients. RNA-based detection methods are more comprehensive than either DNA- or protein-based methods. By routinely and systematically being able to perform quantitative gene expression studies on non-invasive samples using carefully selected tumor-specific colon cancer genes, we can quantitatively and accurately monitor changes at various stages in the neoplastic process, allowing for surgical and/or other therapies, and thus, decrease mortality from colorectal cancer.     

Colorectal cancer screening: Systematic review of screen-related morbidity and mortality

BackgroundImplementation of mass colorectal cancer screening, using faecal occult blood test or colonoscopy, is recommended by the European Union in order to increase cancer-specific survival by diagnosing disease in an earlier stage. Post-colonoscopy complications have been addressed by previous systematic reviews, but morbidity of colorectal cancer screening on multiple levels has never been evaluated before.AimTo evaluate potential harm as a result of mass colorectal cancer screening in terms of complications after colonoscopy, morbidity and mortality following surgery, psychological distress and inappropriate use of the screening test.MethodsA systematic review of all literature on morbidity and mortality attributed to colorectal cancer screening, using faecal occult blood test or colonoscopy, from each databases’ inception to August 2016 was performed. A meta-analysis was conducted to examine the pooled incidence of major complications of colonoscopy (major bleedings and perforations).ResultsSixty studies were included. Five out of seven included prospective studies on psychological morbidity reported an association between participation in a colorectal screening program and psychological distress. Serious morbidity from colonoscopy in asymptomatic patients included major bleedings (0.8/1000 procedures, 95% CI 0.18–1.63) and perforations (0.07/1000 procedures, 95% CI 0.006–0.17).ConclusionsParticipation in a colorectal cancer screening program is associated with psychological distress and can cause serious adverse events. Nevertheless, the short duration of psychological impact as well as the low colonoscopy complication rate seems reassuring. Because of limited literature on harms other than perforation and bleeding, future research on this topic is greatly needed to contribute to future screening recommendations.     

BAGE hypomethylation, a new epigenetic biomarker for colon cancer detection.

Early detection of colorectal cancer is a decisive step in the successful and complete cure of the disease. Epigenetic markers, in particular, those based on aberrant DNA methylation, can be used to diagnose cancer. B melanoma antigens (BAGE) are a family of genes and truncated genes located in the heterochromatic regions of several human chromosomes. Our previous work showed that BAGE loci (i.e., genes and truncated genes) were hypermethylated in normal tissues and hypomethylated in 98% of human cancers. In the present study, we analyzed DNA methylation of the BAGE loci in 54 colon cancers and in neighboring histopathologic normal tissue samples. Using a combined bisulfite restriction assay, we showed that BAGE loci were hypomethylated in 81% of carcinoma samples. Colon cancer could be diagnosed with 94% specificity, 83% sensitivity, and 89% accuracy. No correlation was found between DNA methylation of BAGE loci and age, gender of patients, nor with the tumor stage or site. Based on the hypothesis that during neoplastic transformation, hypomethylation occurs in juxtacentromeric CpG islands, we suggest that other genes located in the heterochromatic compartment should be tested. These new markers enrich the list of currently studied epigenetic alterations in colon cancer and could be associated with hypermethylation markers to develop reliable diagnostic tests.     

结直肠癌淋巴结中黏蛋白1的表达和临床意义

目的研究结直肠癌区域淋巴结中黏蛋白1（MUC1）的表达，以寻找1种检测结直肠癌淋巴结微转移的可靠指标。方法采用免疫组织化学Elivision法，对69例结直肠癌457枚区域淋巴结中MUC1的表达进行检测和分析。结果常规病理学检查无转移的结直肠癌淋巴结，其MUC1的阳性表达率（淋巴结微转移率）为18．6％（61／328），DukesA、B和C期淋巴结微转移率分别是4．7％（3／64）、16．8％（28／167）和30．9％（30／97）。DukesA、B和C期转移淋巴结的检出率分别是4．7％（3／64）、16．8％（28／167）和70．4％（159／226）。免疫组织化学方法对结直肠癌转移淋巴结的检出率显著高于常规病理检查（P〈0．05），淋巴结微转移率和转移淋巴结的检出率随Dukes期别上升呈显著递增（P〈0．05）。1例DukesA期患者，9例B期患者因免疫组织化学检测到微转移，分期从DukesA或B期上调至C期。结论MUC1在结直肠癌区域淋巴结中有表达，是检测淋巴结微转移可靠指标。检测淋巴结中MUC1的表达可更准确的对结直肠癌进行临床分期。     

Cancer screening in the United States, 2009: A review of current American Cancer Society guidelines and issues in cancer screening

Each year, the American Cancer Society (ACS) publishes a report summarizing its recommendations for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In 2008, the ACS, the American Gastroenterological Association, the American College of Gastroenterology, the Society for Gastrointestinal Endoscopy, and the American College of Radiology issued a joint update of guidelines for colorectal cancer screening in average‐risk adults. In this issue, the current ACS guidelines and recent issues are summarized, updates of testing guidelines for early prostate cancer detection and colorectal cancer screening by the United States Preventive Services Task Force are discussed, and the most recent data from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System and the National Health Interview Survey pertaining to participation rates in cancer screening are described. CA Cancer J Clin 2009;59:27–41. © 2009 American Cancer Society.     

Identification of GABRA1 and LAMA2 as new DNA methylation markers in colorectal cancer

Aberrant methylation of CpG islands in the promoter region of genes is a common epigenetic phenomenon found in early cancers. Therefore conducting genome-scale methylation studies will enhance our understanding of the epigenetic etiology behind carcinogenesis by providing reliable biomarkers for early detection of cancer. To discover novel hypermethylated genes in colorectal cancer by genome-wide search, we first defined a subset of genes epigenetically reactivated in colon cancer cells after treatment with a demethylating agent. Next, we identified another subset of genes with relatively down-regulated expression patterns in colorectal primary tumors when compared with normal appearing-adjacent regions. Among 29?genes obtained by cross-comparison of the two gene-sets, we subsequently selected, through stepwise subtraction processes, two novel genes, GABRA1 and LAMA2, as methylation targets in colorectal cancer. For clinical validation pyrosequencing was used to assess methylation in 134 matched tissue samples from CRC patients. Aberrant methylation at target CpG sites in GABRA1 and LAMA2 was observed with high frequency in tumor tissues (92.5% and 80.6%, respectively), while less frequently in matched tumor-adjacent normal tissues (33.6% for GABRA1 and 13.4% for LAMA2). Methylation levels in primary tumors were not significantly correlated with clinico-pathological features including age, sex, survival and TNM stage. Additionally, we found that ectopic overexpression of GABRA1 in colon cancer cell lines resulted in strong inhibition of cell growth. These results suggest that two novel hypermethylated genes in colorectal cancer, GABRA1 and LAMA2, may have roles in colorectal tumorigenesis and could be potential biomarkers for the screening and the detection of colorectal cancer in clinical practice.     

High-Resolution Melting Assay (HRMA) is a Simple and Sensitive Stool-Based DNA Test for the Detection of Mutations in Colorectal Neoplasms

BackgroundStool-based DNA testing for colorectal cancer is becoming a favored alternative to existing DNA screening tests. However, current methods of analysis often become more complicated and costly with increased sensitivity. The high-resolution melting assay (HRMA) is a simple and rapid mutation scanning method with low cost and superb accuracy. In this study, we verified the accuracy of HRMA for screening KRAS/TP53 mutations in stool-isolated DNA from patients with colorectal cancer.Materials and MethodsComparing to direct DNA sequencing, the accuracy of HRMA was verified by detecting KRAS/TP53 mutations in 2 independent stages. In study stage I, both tissue and stool samples from colorectal neoplasm patients were analyzed. In study stage II, stool samples from patients with colorectal neoplasms, and normal controls in clinical screening settings were examined.ResultsIn study stage I, the HRMA identified 14 of 17 target mutations (82.4%) in stools from cancer patients, and 4 of 5 (80.0%) target mutations in stools from advanced adenoma patients. The mutation detection rate in fecal samples (45.0%; 18/40) and referred tissue samples (55.0%; 22/40) was highly consistent (κ = 0.79). The HRMA detected 1% mutant DNA in a background of wild type DNA. In study stage II, the HRMA assay detected 58.8% (20/34) mutations in tumor samples, 41.5% (17/41) in advanced adenomas samples, and 3.33% (2/60) in age-matched normal control samples. The results from HRMA and DNA sequencing revealed 100% sensitivity and specificity in both tissue and stool samples.ConclusionHRMA is a simple, reliable, and sensitive method for detecting DNA mutations in the stool samples from patients with colorectal neoplasms.