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Researchers Update Risk-of-Death Charts
Gastroenterology and Hepatology News Richard Peek and K. Rajender Reddy, Section Editors
though less penetrant genetic predisposition may not only influence colorectal cancer risk but also patient survival. This finding may reflect a distinct underlying molecular and pathogenic mechanism in cancers that develop in the setting of a common (i.e., sporadic) family history,” the researchers write. “Further studies are needed to more fully elucidate potential mechanisms by which a common family history may influence the outcome for patients with colorectal cancer.” In an accompanying editorial, Boris Pasche, MD, PhD, of the Northwestern University Feinberg School of Medicine, Chicago, and Contributing Editor to JAMA, writes:
mong patients with advanced colon cancer receiving treatment that includes chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death, and this risk is reduced further by having an increasing number of affected first-degree relatives, according to a study in the June 4 issue of JAMA. Approximately 16%–20% of patients with colorectal cancer have a first-degree relative with colorectal cancer. Beyond rare but highly penetrant hereditary colorectal cancer syndromes, numerous studies have demonstrated that a history of colorectal cancer in a first-degree relative increases the risk of developing the disease by approximately 2-fold. However, “the influence of family history on cancer recurrence and survival among patients with established colon cancer remains uncertain,” the authors write. Jennifer A. Chan, MD, MPH, of the Dana-Farber Cancer Institute, Boston, and colleagues examined the association of a family history of colorectal cancer with recurrence and survival of 1,087 patients with stage III colon cancer who were receiving supplemental chemotherapy. Patients provided family history information at the beginning of the study, and were followed up until March 2007 for cancer recur-
rence and death (median [midpoint] follow-up, 5.6 years). Among the 1,087 participants, 195 (17.9%) reported a family history of colorectal cancer in ⱖ1 first-degree relatives. The researchers found that a family history of colorectal cancer was associated with a significant reduction in the risk of cancer recurrence or death. Compared with patients without a family history, those with a family history had a 28% lower risk for cancer recurrence or death, which occurred in 57 (29%) of 195 patients with a family history of colorectal cancer compared with 343 (38%) of 892 patients without a family history. Examining just the risk for cancer recurrence, patients with a family history of colorectal cancer had a 26% reduced risk compared with patients without a family history. Cancer recurrence occurred in 27% of patients with a family history of colorectal cancer and 35% of patients without a family history. The reduced risk of death for patients with a family history of colorectal cancer was 25%. The apparent benefit associated with family history was stronger with an increasing number of affected family members. Compared with participants without a family history of colorectal cancer, participants with ⱖ2 affected relatives had a 51% lower risk for cancer recurrence or death. “Beyond rare, well-characterized hereditary colorectal cancer syndromes, our data support the hypothesis that a relatively common
For more details, see “Familial Colorectal Cancer,” JAMA. 2008;299: 2515-2523.
Researchers Update Risk-of-Death Charts esearchers have now updated charts that show an American’s risk of dying from a given cause over the next 10 years, based on age, gender, and smoking status. The charts appeared online June 10 in the Journal of the National Cancer Institute.
To help physicians and patients assess an individual’s risk of dying from 1 condition versus another, Lisa Schwartz, MD, of the Department of Veterans Affairs Medical Center in White River Junction, Vermont, and colleagues at Dartmouth University used the National Center for Health Statistics Multiple Cause
of Death Public Use File for 2004 to generate charts that depict the risk of dying from a given cause within the next 10 years. To generate the updated charts, Schwartz et al modified their previous methodology by including former smokers as a separate category to better account for a person’s smoking status.
For Patients With Colon Cancer, a Family History of Colorectal Cancer is Associated With Reduced Risk of Recurrence and Death
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If these intriguing findings are validated in other studies, family history may well become a new prognostic factor in colorectal cancer. Should this be the case, genomewide association studies and tumor gene expression profiling studies will be warranted to identify germline and tumor-specific genetic features associated with a family history of colorectal cancer and favorable outcome following adjuvant chemotherapy. Over the past 2 decades, some of the first major molecular genetics inroads were achieved through careful study of patients with a strong family history of colorectal cancer. . . . The study by Chan et al suggests that family history of colorectal cancer will lead to the identification of novel genetic features predictive of response to chemotherapy. Familial colorectal cancer may therefore confirm its role as a genetics treasure trove for medical discovery.
GASTROENTEROLOGY 2008;135:335–337
Gastroenterology and Hepatology News continued
For all ages, men have a higher risk of death from all causes combined, relative to women. For both men and women, smoking increases the risk of death by nearly the same magnitude as adding 5–10 years to a person’s age. For men who have never smoked, the risk of dying from heart disease at any age exceeds the risk of dying from lung, colon, and prostate cancer combined. For men who currently smoke, the risk of dying from lung cancer is greater than the risk of dying from heart disease after age 60, and it is 10-fold higher than the chance of dying from prostate and colon cancer combined. For women who have never smoked, the chances of dying from heart disease and breast cancer are similar until age 60, after which heart disease incurs a higher risk of death. For women who currently smoke, the chances of dying from lung cancer or heart disease are greater than the chance of dying from breast cancer after age 40.
“The risk charts provide two basic elements that people need if they are to make sense of the health threats they face: the magnitude of the risk and some context,” the authors write. “We hope that the availability of these simple charts will facilitate physician–patient discussion about disease risk and help people understand where to focus risk reduction efforts.” The charts are posted electronically as 10 Supplementary Figures in a variety of formats (as presented in the paper, as separate charts for each smoking category, and as single-page charts presenting all the data in 1 place for men and women), the authors note. “We encourage physicians (and others) to post the charts in clinic offices or distribute them to patients for easy reference when decisions (such as cancer screening) are being made,” the authors write. In an accompanying editorial, Michael Thun, MD, of the American
Cancer Society in Atlanta and colleagues discuss the value of these charts and ways that physicians can best utilize them. For example, just posting the charts in the waiting room of a physician’s office may not be as effective as incorporating them into an interactive format of some kind. “The risk estimates provided by [Schwartz and colleagues] bring us a step closer to the goal of communicating effectively about risk in the context of routine medical care. The next steps could involve collaboration with other risk communication researchers to personalize this information and deliver it in ways that maximize its impact on health behaviors,” the editorial concludes. For further information, see “The Risk of Death by Age, Sex, and Smoking Status in the United States: Putting Health Risks in Context.” J Natl Cancer Inst June 10, 2008 (online edition).
Three Sequencing Companies Join the 1000 Genomes Project
Organizations that have already committed major support to the project are: the Beijing Genomics Institute, Shenzhen, China; the Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK; and the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health. The NHGRI-supported work is being done by the institute’s Large-Scale Sequencing Network, which includes the Human Genome Sequencing Center at Baylor College of Medicine, Houston; the Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and the Washington University Genome Sequencing Center at Washington University School of Medicine, St. Louis, Missouri. “The additional sequencing capacity and expertise provided by the three companies in the pilot phase
will enable us to explore the human genome with even greater depth and speed than we had originally envisioned, and will help us to optimize the design of the full study to follow,” said Richard Durbin, PhD, of the Wellcome Trust Sanger Institute, who co-chairs the consortium. The 1000 Genomes Project builds on the International HapMap Project, which produced a comprehensive catalog of human genetic variation organized into haplotype neighborhoods. The HapMap catalog laid the foundation for the recent explosion of genome-wide association studies that have identified ⬎130 genetic variants linked to a wide range of common diseases, including type 2 diabetes, coronary artery disease, prostate and breast cancers, rheumatoid arthritis, inflammatory bowel disease, and a number of mental illnesses.
L
eaders of the 1000 Genomes Project announced on June 11 that 3 firms that have pioneered development of new sequencing technologies have joined the international effort to build the most detailed map to date of human genetic variation as a tool for medical research. The new participants are: 454 Life Sciences, a Roche company, Branford, Connecticut; Applied Biosystems, an Applera Corp. business, Foster City, California; and Illumina Inc, San Diego. The 1000 Genomes Project, which was announced in January 2008, is an international research consortium that is creating a new map of the human genome that will provide a view of biomedically relevant DNA variations at a resolution unmatched by current resources. 336
though less penetrant genetic predisposition may not only influence colorectal cancer risk but also patient survival. This finding may reflect a distinct underlying molecular and pathogenic mechanism in cancers that develop in the setting of a common (i.e., sporadic) family history,” the researchers write. “Further studies are needed to more fully elucidate potential mechanisms by which a common family history may influence the outcome for patients with colorectal cancer.” In an accompanying editorial, Boris Pasche, MD, PhD, of the Northwestern University Feinberg School of Medicine, Chicago, and Contributing Editor to JAMA, writes:
mong patients with advanced colon cancer receiving treatment that includes chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death, and this risk is reduced further by having an increasing number of affected first-degree relatives, according to a study in the June 4 issue of JAMA. Approximately 16%–20% of patients with colorectal cancer have a first-degree relative with colorectal cancer. Beyond rare but highly penetrant hereditary colorectal cancer syndromes, numerous studies have demonstrated that a history of colorectal cancer in a first-degree relative increases the risk of developing the disease by approximately 2-fold. However, “the influence of family history on cancer recurrence and survival among patients with established colon cancer remains uncertain,” the authors write. Jennifer A. Chan, MD, MPH, of the Dana-Farber Cancer Institute, Boston, and colleagues examined the association of a family history of colorectal cancer with recurrence and survival of 1,087 patients with stage III colon cancer who were receiving supplemental chemotherapy. Patients provided family history information at the beginning of the study, and were followed up until March 2007 for cancer recur-
rence and death (median [midpoint] follow-up, 5.6 years). Among the 1,087 participants, 195 (17.9%) reported a family history of colorectal cancer in ⱖ1 first-degree relatives. The researchers found that a family history of colorectal cancer was associated with a significant reduction in the risk of cancer recurrence or death. Compared with patients without a family history, those with a family history had a 28% lower risk for cancer recurrence or death, which occurred in 57 (29%) of 195 patients with a family history of colorectal cancer compared with 343 (38%) of 892 patients without a family history. Examining just the risk for cancer recurrence, patients with a family history of colorectal cancer had a 26% reduced risk compared with patients without a family history. Cancer recurrence occurred in 27% of patients with a family history of colorectal cancer and 35% of patients without a family history. The reduced risk of death for patients with a family history of colorectal cancer was 25%. The apparent benefit associated with family history was stronger with an increasing number of affected family members. Compared with participants without a family history of colorectal cancer, participants with ⱖ2 affected relatives had a 51% lower risk for cancer recurrence or death. “Beyond rare, well-characterized hereditary colorectal cancer syndromes, our data support the hypothesis that a relatively common
For more details, see “Familial Colorectal Cancer,” JAMA. 2008;299: 2515-2523.
Researchers Update Risk-of-Death Charts esearchers have now updated charts that show an American’s risk of dying from a given cause over the next 10 years, based on age, gender, and smoking status. The charts appeared online June 10 in the Journal of the National Cancer Institute.
To help physicians and patients assess an individual’s risk of dying from 1 condition versus another, Lisa Schwartz, MD, of the Department of Veterans Affairs Medical Center in White River Junction, Vermont, and colleagues at Dartmouth University used the National Center for Health Statistics Multiple Cause
of Death Public Use File for 2004 to generate charts that depict the risk of dying from a given cause within the next 10 years. To generate the updated charts, Schwartz et al modified their previous methodology by including former smokers as a separate category to better account for a person’s smoking status.
For Patients With Colon Cancer, a Family History of Colorectal Cancer is Associated With Reduced Risk of Recurrence and Death
A
R
If these intriguing findings are validated in other studies, family history may well become a new prognostic factor in colorectal cancer. Should this be the case, genomewide association studies and tumor gene expression profiling studies will be warranted to identify germline and tumor-specific genetic features associated with a family history of colorectal cancer and favorable outcome following adjuvant chemotherapy. Over the past 2 decades, some of the first major molecular genetics inroads were achieved through careful study of patients with a strong family history of colorectal cancer. . . . The study by Chan et al suggests that family history of colorectal cancer will lead to the identification of novel genetic features predictive of response to chemotherapy. Familial colorectal cancer may therefore confirm its role as a genetics treasure trove for medical discovery.
GASTROENTEROLOGY 2008;135:335–337
Gastroenterology and Hepatology News continued
For all ages, men have a higher risk of death from all causes combined, relative to women. For both men and women, smoking increases the risk of death by nearly the same magnitude as adding 5–10 years to a person’s age. For men who have never smoked, the risk of dying from heart disease at any age exceeds the risk of dying from lung, colon, and prostate cancer combined. For men who currently smoke, the risk of dying from lung cancer is greater than the risk of dying from heart disease after age 60, and it is 10-fold higher than the chance of dying from prostate and colon cancer combined. For women who have never smoked, the chances of dying from heart disease and breast cancer are similar until age 60, after which heart disease incurs a higher risk of death. For women who currently smoke, the chances of dying from lung cancer or heart disease are greater than the chance of dying from breast cancer after age 40.
“The risk charts provide two basic elements that people need if they are to make sense of the health threats they face: the magnitude of the risk and some context,” the authors write. “We hope that the availability of these simple charts will facilitate physician–patient discussion about disease risk and help people understand where to focus risk reduction efforts.” The charts are posted electronically as 10 Supplementary Figures in a variety of formats (as presented in the paper, as separate charts for each smoking category, and as single-page charts presenting all the data in 1 place for men and women), the authors note. “We encourage physicians (and others) to post the charts in clinic offices or distribute them to patients for easy reference when decisions (such as cancer screening) are being made,” the authors write. In an accompanying editorial, Michael Thun, MD, of the American
Cancer Society in Atlanta and colleagues discuss the value of these charts and ways that physicians can best utilize them. For example, just posting the charts in the waiting room of a physician’s office may not be as effective as incorporating them into an interactive format of some kind. “The risk estimates provided by [Schwartz and colleagues] bring us a step closer to the goal of communicating effectively about risk in the context of routine medical care. The next steps could involve collaboration with other risk communication researchers to personalize this information and deliver it in ways that maximize its impact on health behaviors,” the editorial concludes. For further information, see “The Risk of Death by Age, Sex, and Smoking Status in the United States: Putting Health Risks in Context.” J Natl Cancer Inst June 10, 2008 (online edition).
Three Sequencing Companies Join the 1000 Genomes Project
Organizations that have already committed major support to the project are: the Beijing Genomics Institute, Shenzhen, China; the Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK; and the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health. The NHGRI-supported work is being done by the institute’s Large-Scale Sequencing Network, which includes the Human Genome Sequencing Center at Baylor College of Medicine, Houston; the Broad Institute of MIT and Harvard, Cambridge, Massachusetts; and the Washington University Genome Sequencing Center at Washington University School of Medicine, St. Louis, Missouri. “The additional sequencing capacity and expertise provided by the three companies in the pilot phase
will enable us to explore the human genome with even greater depth and speed than we had originally envisioned, and will help us to optimize the design of the full study to follow,” said Richard Durbin, PhD, of the Wellcome Trust Sanger Institute, who co-chairs the consortium. The 1000 Genomes Project builds on the International HapMap Project, which produced a comprehensive catalog of human genetic variation organized into haplotype neighborhoods. The HapMap catalog laid the foundation for the recent explosion of genome-wide association studies that have identified ⬎130 genetic variants linked to a wide range of common diseases, including type 2 diabetes, coronary artery disease, prostate and breast cancers, rheumatoid arthritis, inflammatory bowel disease, and a number of mental illnesses.
L
eaders of the 1000 Genomes Project announced on June 11 that 3 firms that have pioneered development of new sequencing technologies have joined the international effort to build the most detailed map to date of human genetic variation as a tool for medical research. The new participants are: 454 Life Sciences, a Roche company, Branford, Connecticut; Applied Biosystems, an Applera Corp. business, Foster City, California; and Illumina Inc, San Diego. The 1000 Genomes Project, which was announced in January 2008, is an international research consortium that is creating a new map of the human genome that will provide a view of biomedically relevant DNA variations at a resolution unmatched by current resources. 336