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Panel Calls for Reducing Colorectal Cancer Deaths by Striking Down Barriers to Screening

NIH Newsbot — Thu, 04 Feb 2010 20:31:00 +0000

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Despite evidence and guidelines supporting the value of screening for this disease, rates of screening for colorectal cancer are consistently lower than those for other types of cancer, particularly breast and cervical. Although the screening rates in the target population of adults over age 50, have increased from 20-30 percent in 1997 to nearly 55 percent in 2008 – the rates are still too low. An NIH state-of-the-science panel was convened this week to identify ways to further increase the use and quality of colorectal cancer screening in the United States.

“We recognize that some may find colorectal cancer screening tests to be unpleasant and time-consuming. However, we also know that recommended screening strategies reduce colorectal cancer deaths,” said Dr. Donald Steinwachs, panel chair, and professor and director of the Health Services Research and Development Center at the Johns Hopkins University. “We need to find ways to encourage more people to get these important tests.”

The panel found that the most important factors associated with being screened are having insurance coverage and access to a regular health care provider. Their recommendations highlighted the need to remove out-of-pocket costs for screening tests.

Panel Calls for Reducing Colorectal Cancer Deaths by Striking Down Barriers to Screening originally appeared on Highlight HEALTH.

NIH to Hold Press Telebriefing on February 4 following State-of-the-Science Conference on Colorectal Cancer Screening

NIH Newsbot — Tue, 26 Jan 2010 21:03:00 +0000

Although colorectal cancer is the second leading cause of cancer-related deaths in the United States, screening for this disease is currently underutilized among eligible individuals. An NIH State-of-the-Science Conference on Enhancing Use and Quality of Colorectal Cancer Screening will be held February 2-4, 2010.

NIH to Hold Press Telebriefing on February 4 following State-of-the-Science Conference on Colorectal Cancer Screening originally appeared on Highlight HEALTH.

Detection of Colorectal Cancer Using a Blood-based, Six-Gene Biomarker Set

Walter Jessen — Thu, 29 May 2008 20:13:44 +0000

At the annual meeting of the American Association for Cancer Research (AACR) last month, researchers from GeneNews Corp. reported that the probability of colorectal cancer (CRC) in asymptomatic patients can be accurately stratified by RNA expression profiling of six genes in whole blood [1]. The company focuses on developing blood-based biomarker tests for the early detection of diseases and personalized health management.

Stratification is a statistical method of sampling from a population, whereby members are grouped into subgroups that display a consistent feature. In the current study, the six-gene panel was able to stratify a population with average risk for CRC into three groups:

Increased probability (18% had a 3-fold increased probability of currently having CRC)
Average probability (20% had an average probability of currently having CRC)
Decreased probability (62% had a 4-fold decreased probability of currently having CRC)

The study comes after publication of their approach to detecting blood biomarker sets earlier this year in the journal Clinical Cancer Research [2]. The study evaluated blood RNA samples from an Asian population and identified five genes in patients with CRC that could be differentiated from controls.

photo credit: DimsumDarren

In the study, researchers screened 31 whole blood samples from patients without CRC (n = 15) or patients with CRC (n = 16) by DNA microarray, a technology that enables scientists to examine how active thousands of genes are at a given time. They identified 37 genes unrelated to age or gender that were significantly different between controls and patients with CRC. The 37 genes were then tested with a large training set of 115 samples (57 controls, 58 CRC) using real-time PCR. 17 of the 37 genes were validated as differentially expressed. Five of the 37 validated genes were selected for logistic regression analysis.

Logistic regression is a statistical model used for prediction of the probability of occurrence of an event, using predictor variables that may be either numerical or categorical.

The predictive power of the five genes was then validated with a third independent set of 92 samples (49 controls, 43 CRC). The validation correctly identified 88% of CRC samples and 64% of non-CRC samples.

In their most recent study, GeneNews examined more samples than previously analyzed, this time in a heterogeneous North American population. Researchers screened a training set of 243 whole blood samples from patients without CRC (n = 127) or patients with CRC (n = 116) by DNA microarray. Six genes whose expression could meaningfully discriminate between the two groups were identified [3]:

Annexin A3 (ANXA3), which plays a role in the regulation of cellular growth and in signal transduction pathways.
C-type lectin domain family 4, member D (CLEC4D), which has diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response.
Lamin B1 (LMNB1), which is thought to be involved in nuclear stability, chromatin structure and gene expression.
Proline rich Gla (G-carboxyglutamic acid) 4 (PRRG4), function unknown.
Vanin 1 (VNN1), involved in the recycling of pantothenic acid (vitamin B5).
Interleukin 2 receptor, beta (IL2RB), which is involved in T cell-mediated immune responses.

The predictive power of the six genes was then validated in a blinded, independent set of 337 samples (171 controls, 166 CRC). The combined training/blind set had an average accuracy of 70.8%. GeneNews has announced plans to develop a laboratory test later this year based on the six-gene panel called ColonSentry [4]. Similar blood screening tests are under investigation by the GeneNews for prostate, breast and ovarian cancer.

Why is this important? Colorectal cancer (CRC) is the third most common cancer in both men and women with an estimated 49,960 deaths expected to occur in 2008, accounting for 9% of all cancer deaths [5]. A simple, noninvasive test that can classify average risk patients into more defined groups would help to assess an individual’s risk for CRC. Since CRC can often be treated if caught early enough, those having an increased probability could be screened more frequently. Screening can result in the detection and removal of colorectal polyps before they become cancerous. Additionally, screening can help to detect CRC that is at an early stage.

Consider these statistics: when CRC is detected early, the 5-year survival rate is 90%. If the cancer has spread locally, the 5-year survival rate decreases to 68%. For patients with advanced CRC that has metastasized, the 5-year survival rate is 10% [5].

The American Cancer Society (ACS) has published guidelines for the early detection of cancer. Beginning at age 50, men and women at average risk for developing CRC should be screened with one of the following tests:

Tests that find polyps and cancer

Flexible sigmoidoscopy every 5 years
Colonoscopy every 10 years
Double contrast barium enema every 5 years
CT colonography (virtual colonoscopy) every 5 years

Tests that mainly find cancer

Fecal occult blood test (FOBT) every year
Fecal immunochemical test (FIT) every year
Stool DNA test (sDNA), interval uncertain

Don’t underestimate the importance of regular cancer screening. One of the reasons for a decline in CRC incidence rates since 1998 is increased surveillance. If you’re at risk, get checked.

References

Stratification of colorectal cancer probability using six genes from whole blood. American Association for Cancer Research (AACR) annual meeting abstract, Clinical Research. 2008 Apr 15.
Han et al. Novel blood-based, five-gene biomarker set for the detection of colorectal cancer. Clin Cancer Res. 2008 Jan 15;14(2):455-60. Epub 2008 Jan 18.
View abstract
Six-Gene Cluster Stratifies Which Patients Most Need Colonoscopy. OncologySTAT. 2008 Apr 29.
GeneNews Reports Positive Results From Validation Study of Colorectal Cancer Biomarkers in Late Breaking Abstract at AACR. Biomarkers form basis of blood-based ColonSentry test. GeneNews Press Release. 2008 Apr 14.
Cancer Facts & Figures 2008. American Cancer Society. Atlanta, Ga. 2008.

Detection of Colorectal Cancer Using a Blood-based, Six-Gene Biomarker Set originally appeared on Highlight HEALTH.

Common Therapy for Prostate Cancer May Promote Metastasis

Walter Jessen — Wed, 14 Nov 2007 15:12:03 +0000

A study published in the journal Cancer Research last month suggests that the principle treatment for advanced prostate cancer may actually encourage prostate cancer cells to metastasize [1]. Researchers at The Johns Hopkins University School of Medicine focused on a gene called Nestin, which encodes an intermediate filament protein. Intermediate filaments are cytoskeletal or scaffolding structures found in cells that, in addition to maintaining cell shape, control a variety of cellular processes including proliferation, migration and survival [2]. Nestin gene expression also distinguishes stem cells from differentiated cells and has been shown to be activated in pediatric brain tumors and rhabdomyosarcomas (cancers that develop from skeletal muscle), central nervous system tumors and gastrointestinal stromal tumors [3-6].

The Prostate and cancer

The prostate is a small, walnut-sized gland that is located beneath the bladder and wrapped around the urethra in men. The urethra is a tube that carries urine from the bladder and semen from the epididymis. A male sex gland, the prostate secretes components of prostatic fluid, which forms part of the semen that carries sperm.

The prostate can be affected by a number of problems, including:

Prostatitis (inflammation of the prostate)
Benign Prostatic Hyperplasa (BPH, an enlarged prostate)
Prostate cancer

Prostate cancer is the most common male neoplasia (meaning abnormal proliferation of cells in a tissue or organ) and is the leading cause of cancer death in American men [7]. It is a heterogeneous disease (meaning that the disease consists of a wide spectrum of presentations with variable response to treatment) ranging from asymptomatic to a rapidly fatal systemic malignancy, and progresses from pre-cancerous lesions, termed prostatic intraepithelial neoplasia (PIN), to invasive adenocarcinoma and ultimately to metastatic disease [8-10].

Androgen is the generic term for a group of steroid hormones, including testosterone, that principally influence the growth and development of the male reproductive system. Androgens affect prostatic epithelial cell differentiation and proliferation. The mainstay of treatment for advanced prostate cancer is androgen deprivation therapy, i.e. surgical or medical castration (meaning the use of surgery or drugs to suppress androgen production). However, despite high initial response rates to androgen deprivation, virtually all men progress to androgen-insensitive or androgen-independent prostate cancer. Thus, while early detection and treatment are generally associated with favorable clinical outcomes, there are presently no curative interventions for patients with advanced disease.

Nestin expression is linked to androgen withdrawal and affects cell migration

In cell lines derived from metastatic prostate cancer, Johns Hopkins researchers found that Nestin gene expression was elevated only in androgen-independent cells. They then examined Nestin gene expression in prostate cancer samples from 254 patients that encompassed the entire clinical spectrum of the disease, from untreated localized tumors to lethal metastatic cases. Increased levels of Nestin gene expression were found exclusively in lethal cases following androgen deprivation therapy. No detectable Nestin was found in prostate cancers that had not been subjected to the therapy. In an androgen-independent cell line derived from metastatic prostate cancer, loss of Nestin expression had no effect on cell viability or growth rate but was shown to greatly reduce cell motility. In a mouse model of human prostate cancer, compared to control tumors, transplanted prostate cancer cells with reduced Nestin expression produced one fourth the number of metastatic deposits and the deposits were dramatically reduced in size. The study thus identifies a specific role for Nestin in cell motility and a novel pathway for prostate cancer metastasis.

In the same issue of Cancer Research, another study in a genetically engineered mouse model of human prostate cancer demonstrated that prolonged exposure of the mice to reduced levels of androgen accelerated prostate tumor development compared to mice exposed to physiologically normal levels of androgen [11]. The mice displayed a molecular profile similar to that of mice with androgen-independent prostate tumors. The finding is significant since the mouse model is based on the loss-of-function of genes known to be relevant for human prostate cancer and is consistent with the conclusions of the first study described above.

Taken together, these results suggest that androgen deprivation therapy encourages prostate cancer cells to accelerate tumor development, making them more likely to spread throughout the body. While these results are too preliminary to alter current clinical practice, the findings warrant further study. Although the effects of androgen deprivation therapy are temporary, it is an effective treatment for slowing prostate tumor growth and can boost the effect of neoadjuvant therapy (e.g. radiation therapy used to shrink a tumor prior to surgical removal).

References

Kleeberger et al. Roles for the Stem Cell-Associated Intermediate Filament Nestin in Prostate Cancer Migration and Metastasis. Cancer Res. 2007 Oct 1;67(19):9199-206.
View abstract
Coulombe and Wong. Cytoplasmic intermediate filaments revealed as dynamic and multipurpose scaffolds. Nat Cell Biol. 2004 Aug;6(8):699-706.
View abstract
Almqvist et al. Immunohistochemical detection of nestin in pediatric brain tumors. J Histochem Cytochem. 2002 Feb;50(2):147-58.
View abstract
Kobayashi et al. Pediatric rhabdomyosarcomas express the intermediate filament nestin. Pediatr Res. 1998 Mar;43(3):386-92.
View abstract
Dahlstrand et al. Expression of the class VI intermediate filament nestin in human central nervous system tumors. Cancer Res. 1992 Oct 1;52(19):5334-41.
View abstract
Tsujimura et al. Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal. Am J Pathol. 2001 Mar;158(3):817-23.
View abstract
Cancer Facts & Figures 2007. American Cancer Society. Atlanta, Ga. 2007.
DeMarzo et al. Pathological and molecular aspects of prostate cancer. Lancet. 2003 Mar 15;361(9361):955-64.
View abstract
Isaacs et al. Focus on prostate cancer. Cancer Cell. 2002 Aug;2(2):113-6.
View abstract
Nelson and Montgomery. Unconventional therapy for prostate cancer: good, bad or questionable? Nat Rev Cancer. 2003 Nov;3(11):845-58.
View abstract
Banach-Petrosky et al. Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice. Cancer Res. 2007 Oct 1;67(19):9089-96.
View abstract

Common Therapy for Prostate Cancer May Promote Metastasis originally appeared on Highlight HEALTH.

March is National Colorectal Cancer Awareness Month

Walter Jessen — Thu, 08 Mar 2007 06:38:19 +0000

The goal of the annual National Colorectal Cancer Awareness Month is to make people aware of colorectal cancer and to encourage people to learn more about how to reduce their risk of colorectal cancer (CRC) through regular screening and a healthy lifestyle. The results of the National Health Interview Survey (NHIS) administered to 32,374 adults 18 years of age or older in 2000 showed that colorectal cancer screening is underused [1]. Just over 60% of adults had ever had colorectal cancer testing. Only 44% of men and 37% of women greater than 75 years of age were current for testing. Colorectal cancer screening is very important. If colorectal cancer is allowed to metastasize (meaning to spread to other parts of the body), the 5-year survival rate is less than 10%. However, if colorectal cancer is found early, the 5-year survival rate is greater than 90% [2].

Colorectal cancer can be prevented. Colorectal cancer starts in the digestive system and begins as a polyp. Polyps are small growths of tissue that start in the lining and grow in to the center of the colon or rectum. A specific type of polyp, an adenoma, can become cancerous. Screening for colorectal cancer can identify polyps and they can be removed to prevent cancer from ever occurring. Starting at age 50, men and women who are at average risk for colorectal cancer should get screened. Men and women who have a higher risk of the disease may need to be tested earlier and should talk to their health care professional about when. Colorectal cancer incidence rates are also increasing among people younger that 50 years of age. Indeed, colorectal cancer is ranked among the top 10 cancers occurring in males and females aged 20-49 years regardless of race [3]. No matter what your age, know the risk factors, the symptoms and your family history.

Not counting skin cancers, colorectal cancer is the third most common cancer in the U.S. [4]. However, death due to colorectal cancer is declining. Much of the credit for a decrease in the death rate from colorectal cancer in 2004 has been attributed to screening exams and the early detection of polyps that can be removed before they become cancerous.

The exact cause of most colorectal cancers is unknown. However, there are a number of risk factors.

Age: The chance of having colorectal cancer increases after age 50. However, colorectal cancer incidence rates are increasing among persons younger than 50 years of age [3].

Prior occurrence of colorectal cancer: The likelihood of having colorectal cancer is increased if you have a previous history of colorectal cancer.

Prior history of polyps: Specific types of polyps increase the risk of colorectal cancer.

History of bowel disease: Ulcerative colitis and Crohn’s disease, diseases that involve inflammation of the colon over a long period of time, increase the risk of colon cancer.

Family history of colorectal cancer: Risk of colorectal cancer is increased if you have relatives that have had this cancer. Twenty percent of individuals diagnosed with colorectal cancer have a first- or second-degree relative with the disease.

Genetic factors: Familial adenomatous polyposis (FAP) is an inherited condition in which numerous polyps form in the large intestine. Malignant transformation occurs 100% of the time if left untreated.

Race: African Americans have the highest rate of colorectal cancer and the highest death rate from colorectal cancer of all racial groups in the United States. The reason for this is not known.

Diet: A diet high in saturated fat can increase the risk of colorectal cancer. Consumption of red meats [4] and processed meats [6] can also increase colorectal cancer risk.

Lack of exercise: According to the American Cancer Society (ACS), regular physical activity reduces the risk of colorectal cancer as well as breast and possibly other cancers, and also reduces the risk of cardiovascular disease and diabetes.

Overweight: Being overweight at diagnosis is associated with an increased risk for recurrence of and death from colon cancer [7].

Smoking: Recent studies suggest that tobacco use, particularly recent use, increases risk for both adenomatous and hyperplastic polyps, precursors of colorectal cancer [8].

Heavy alcohol use: High alcohol intake is significantly associated with increased risk of colon and rectal cancer [9].

Diabetes: People with diabetes have an increased risk of colon and rectal cancer [10].

Many of these risk factors can be avoided by choosing healthy lifestyle alternatives to reduce your risks for developing cancer. Additionally, a number of studies have suggested that folate, beta-carotene, vitamin C and vitamin B6 have a protective effect against colorectal cancer [11-13]. Other studies have suggested protective roles for calcium and vitamin D against colorectal cancer [14-15].

During National Colorectal Awareness Month, experts recommend remembering these important points:

Colorectal cancer can be prevented.
Screening for colorectal cancer can identify polyps that can be removed to prevent cancer from ever developing.
You should begin colorectal cancer screening at age 50 unless you have an increased risk for the disease.
Colorectal cancer is treatable.
Know the risk factors, symptoms and your family history of colorectal cancer.
Talk with your health professional about colorectal cancer and your own risk for the disease.

References

Peterson et al. Colorectal Cancer Screening among Men And Women in The United States. J Womens Health (Larchmt). 2007 Jan-Feb;16(1):57-65.
View abstract
Dashwood RH. Early detection and prevention of colorectal cancer (review). Oncol Rep. 1999 Mar-Apr;6(2):277-81.
View abstract
Fairley et al. Colorectal cancer in U.S. adults younger than 50 years of age, 1998-2001. Cancer. 2006 Sep 1;107(5 Suppl):1153-61.
View abstract
Cancer Facts & Figures 2007. Leading Sites of New Cancer Cases and Deaths””2007 Estimates. American Cancer Society. Atlanta, Ga. 2007.
English et al. Red meat, chicken, and fish consumption and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1509-14.
View abstract
Ward et al. Processed meat intake, CYP2A6 activity, and risk of colorectal adenoma. Carcinogenesis. 2007 Feb 2; [Epub ahead of print].
View abstract
Dignam et al. Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. J Natl Cancer Inst. 2006 Nov 15;98(22):1647-54.
View abstract
Ji et al. Tobacco smoking and colorectal hyperplastic and adenomatous polyps. Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):897-901.
View abstract
Moskal et al. Alcohol intake and colorectal cancer risk: a dose-response meta-analysis of published cohort studies. Int J Cancer. 2007 Feb 1;120(3):664-71.
View abstract
Larsson et al. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst. 2005 Nov 16;97(22):1679-87.
View abstract
Kune and Watson. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer. 2006;56(1):11-21.
View abstract
Senesse et al. Tobacco use and associations of beta-carotene and vitamin intakes with colorectal adenoma risk. J Nutr. 2005 Oct;135(10):2468-72.
View abstract
Kato et al. Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study. Br J Cancer. 1999 Apr;79(11-12):1917-22.
View abstract
Gorham et al. Optimal vitamin d status for colorectal cancer prevention a quantitative meta analysis. Am J Prev Med. 2007 Mar;32(3):210-6.
View abstract
Park et al. Calcium and Vitamin D Intake and Risk of Colorectal Cancer: The Multiethnic Cohort Study. Am J Epidemiol. 2007 Jan 10; [Epub ahead of print].
View abstract

March is National Colorectal Cancer Awareness Month originally appeared on Highlight HEALTH.