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Volume 7, Issue 1, February 2003 |
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What’s inside . . .
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Message From the Coordinator SIG on the Forefront of Promoting Genetics in Oncology 
Agnes Masny, RN, MPH, MSN, CRNPPhiladelphia, PA ac_masny@fccc.edu The year 2003 holds great promise for cancer care. In April, the sequencing of the human genome will be complete. In addition, April will mark the 50th anniversary of James Watson's and Francis Crick's description of the DNA double helix. With these events, we will move from a “medical era” to the “genomic era.” Genomics is expected to revolutionize the way oncology care is delivered. Although most nurses in the Cancer Genetics SIG work in the area of cancer risk assessment and counseling, we will be on the forefront helping other nurses apply genetics to oncology practice. This coming year, the SIG will work to better our networking and resources. Lisa Aiello, RN, MSN, will continue to work as page administrator for our virtual community site. Please visit the site or send information to Lisa if you want something posted. Marty Weinar, RN, MS, CCRC, is compiling a genetics bibliography to be published in a 2003 issue of the Oncology Nursing Forum. In this newsletter, Jean Jenkins, PhD, RN, FAAN, has provided an update of activities and resources from the NHGRI. We also have contacted the Cancer Genetics SIG from the National Society of Genetic Counselors to create a liaison between our SIGs and to work on a common project. To ready the larger ONS membership for the genomics era, the SIG will mark the 50th anniversary of DNA at Congress with a DNA celebration. This event is still in the planning phase. If you would like to help on any of these projects, please call or e-mail me (see SIG Officers page for contact information). Each of us can help the SIG or other oncology nurses learn more about genetics, no matter how small our attempts. Every effort will keep the SIG vital. |
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Special Interest Group Newsletter February 2003 |
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Message From the Editor SIG Seeks Volunteers for Publication 
Judie Much, RN, MSN, APN-C, AOCN®Ottsville, PA muchjk@umdnj.edu Help! Help! Help! We need you! As this newsletter goes into final production, the realization begins to sink in that this will be our first online edition! We hope you will enjoy the electronic access to the information. We continue to need volunteers to review research articles for the publication, as well as to provide news clips and items of interest to the membership. We are looking for co-editors in various regions. Are you planning to go to Congress this year? Do you have a “hot topic” to submit to the SIG for a Congress session? We hope so, and we encourage you to come prepared to present your ideas at the SIG networking meeting. As we only meet once a year, it is very important to bring ideas with you so that we can make the most of our short time together. We hope you will come and spend time “around the table” and get to know those in your SIG. Look for information in the mail and on the virtual community for specifics about related activities at Congress, including the location and time of the SIG networking meetings. Back to SIG Newsletter front page |
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Special Interest Group Newsletter February 2003 |
News and Updates
Summer Genetics InstituteThe National Institutes of Nursing Research will sponsor the Summer Genetics Institute from June 1-July 25 at the National Institutes of Health. The Institute is designed to provide a foundation in genetics for use in research and clinical practice. The purpose is to develop and expand the research capability among graduate students and faculty in schools of nursing and to develop and expand the basis for clinical practice in genetics among advanced practice nurses. More information, as well as the application process, can be found at http://www.nih.gov/ninr/research/dir/sgi.html, or you can write Summer Genetics Institute, National Institute of Nursing Research, 31 Center Drive, Room 5B-13, Bethesda, MD 20892-2718. SIG Members Edit Genetic Text The new text Genetics in Oncology Practice: Cancer Risk Assessment, edited by our own Amy Strauss Tranin, ARNP, MS, AOCN®, Agnes Masny, RN, MPH, MSN, CRNP, and Jean Jenkins, PhD, RN, FAAN, is now available for purchase through ONS's Publishing Division. The book is a “must have” for anyone practicing in the field, as well as for those who are considering starting a cancer risk assessment clinic. Check ONS Online (www.ons.org) for a 20% discount! SIG Member Joins Staff of NHGRI The National Human Genome Research Institute (NHGRI) has named Jean Jenkins, PhD, RN, FAAN, as senior clinical advisor. Jenkins will continue NHGRI’s mission of educating healthcare professionals and the public about the role of genetic medicine in the clinic, as well as the health and societal implications of the Human Genome Project. Back to SIG Newsletter front page |
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Special Interest Group Newsletter February 2003 |
News From the National Human Genome Research Institute
Jean Jenkins PhD, RN, FAANBethesda, MD Jean.Jenkins@nih.gov There were a lot of 2002 NHGRI activities with potential implications for nurses, and there are several 2003 events that you may want to participate in. You can find out more about each of the topics highlighted below by visiting the newly revamped NHGRI Web site at genome.gov.
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Special Interest Group Newsletter February 2003 |
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Review Myriad Genetics Laboratories Gives Report on 10,000 Consecutive Clinical Genetic Tests 
Judie Much, RN, MSN, APN-C, AOCN®muchjk@umdnj.edu Alterations in BRCA1 and BRCA2 originally were found in large families enriched with disease. Clinically, it has been felt for some time that these families are not typical of the majority of families believed to be at risk and who, subsequently, test positive in clinical settings throughout the country. In spite of the fact that testing has been available since 1996, controversy continues to exist regarding the specific features (both family and personal) that should prompt the offering of testing. Some of that controversy involves whether to include ductal carcinoma in situ (DCIS) in the spectrum of consideration when assessing “affected” relatives in a family history and whether male breast cancer is part of the spectrum of disease in either BRCA1 or BRCA2. Also unclear has been the characterization of the spectrum of disease and its prevalence in particular populations, such as African Americans, Ashkenazi Jews, and other ancestries. In an attempt to clarify these issues, Myriad Genetic Laboratories, which has been testing individuals based on their personal and family histories since 1996, looked retrospectively at 10,000 consecutive tests performed by their laboratory (Frank et al., 2002). These were either full sequencing of 17,500 base pairs of the protein-coding and adjacent noncoding regions of the BRCA1 and BRCA2 genes or sequence analysis for the three specific founder mutations prevalent in Ashkenazi Jews. This was an attempt to correlate the presence of mutations with the personal and family histories in order to help clarify the issues mentioned earlier. It is important to note that information regarding family history was not confirmed but was simply a reflection of the information provided on the test request form filled out by the requesting healthcare provider. Individuals were considered to have no history only if the requisition form indicated “none” in the family history section. If there was no information included in the section, the sample was not included in the analysis. Population Ten thousand samples collected consecutively over a three-year period were included. Approximately 7,500 samples were analyzed by full sequencing. Twenty five hundred were analyzed for the three founder mutations in the Ashkenazi Jewish population. Of the 10,000 analyzed, more than 9,000 were women, more than 260 men, and 650 did not specify sex. Median age was 49. Approximately 5,500 individuals had a personal history of breast or ovarian cancer, including 4,679 with breast cancer (76 males), 584 with ovarian cancer, and 240 with both. Of those affected with breast cancer, the median age was 44. The median age in those with ovarian cancer was 53. Ancestry was characterized as “Northern/Western Europe” in 41%, Ashkenazi 30%, no designation 18%, and a small percentage of “others.” Results Results were reported in one of three categories: 1) positive for a deleterious mutation, 2) genetic variant of uncertain significance, or 3) no deleterious mutation detected. More than 1,700 individuals had mutations identified (17.2%), and 11 Ashkenazi Jews had two mutations identified, one in each gene. Mutations occurred in 15.7% of individuals who reported non-Ashkenazi Jewish ancestry and in 20.4% of Ashkenazi Jews. Sixty one percent of the mutations occurred in BRCA1, whereas BRCA2 accounted for 39%. There were 212 deleterious mutations each in BRCA1 and BRCA2. Of those, 60% were frameshift mutations, 25% were nonsense, 9% were missence, and 12.5% occurred in the analyzed regions of the noncoding introns. In individuals who had full sequence testing performed, 13% had variants of uncertain clinical significance, and an additional 6.8% had variants that had at one time been classified as of uncertain significance and had since been reported as polymorphisms. Of the Ashkenazi Jews tested for the founder mutations, 53% had mutations in BRCA1 187delAG, 16% had mutations in BRCA1 5385insC, and 31% had a mutation in BRCA2 6174delT. Of the nearly 5,000 women in the sample with breast cancer, 20% carried deleterious mutations, approximately two-thirds of which were in BRCA1. Median age of diagnosis was 40 for those with BRCA1 mutations and 41 for those with BRCA2 mutations. Of the more than 800 women with ovarian cancer, 34% carried deleterious mutations, with two-thirds presenting in BRCA1. Median age for development of ovarian cancer was 49 and 55 in those with mutations in BRCA1 and BRCA2, respectively. Deleterious mutations were found in approximately 10% of women with no personal history of breast or ovarian cancer. In non-Ashkenazi Jews tested, the highest prevalence of mutations was seen when a proband’s personal and family history included women diagnosed with breast cancer before the age of 50 along with ovarian cancer at any age. Mutations also were prevalent in families without ovarian cancer if there were at least two women with early-age breast cancer. Tables in the body of the paper reveal the earlier the onset of breast cancer, the more likely one is to find a mutation. Most notable was the prevalence rate of mutation in a woman younger than 50 with a personal history of breast cancer and no other family history (9.5%). This same age correlation was not found with ovarian cancer. That is to say that the diagnosis of ovarian cancer alone in these families is sufficient to increase the prevalence rate of mutation status. Age was not a factor. In Ashkenazi individuals, mutation status was correlated with early onset of breast or ovarian cancer as well as younger age of onset of breast cancer in the proband. Ashkenazi Jewish women diagnosed with breast cancer prior to age 50 (12.9%) were found to have mutations even in the absence of a “family history.” Having ovarian cancer raised the proportion to 25.9%, and if one had both breast and ovarian cancer and was Ashkenazi, the prevalence reached 52%. Of the mutations found in Ashkenazi Jews who had full sequencing, 12.6% of these mutations were nonfounder mutations. In those Ashkenazi Jews with a compelling family history of breast cancer prior to age 50 or ovarian cancer at any age, nonfounder mutations were seen in only 4.7% of individuals, as compared with 31.3% of individuals with similar family history who were non-Ashkenazi. Several recurrent missense mutations, thought to be of little clinical consequence, were found in the Ashkenazi population at a prevalence rate of about 5%: BRCA1 variant M10081 and BRCA2 variants P655R and I2285V. In individuals who specified only a single ancestral line, mutations were found in 21% of Ashkenazi Jews, 19% of African Americans, 18% of Latin Americans/Carribeans, 14% of Native Americans, 12% of Asians, and 9% of Near Eastern/Middle Eastern ancestry. In women with DCIS, mutations were found less frequently than in women with invasive cancers: 13% versus 24%, respectively (excluding women also diagnosed with ovarian cancer). Males diagnosed with breast cancer had a prevalence rate of mutation of 28%. These occurred in both BRCA1 and BRCA2. Median age of diagnosis was 52 and 59 for BRCA1 and BRCA2, respectively. Occurrence of the mutations in males was more prevalent when there was a family history of breast or ovarian cancer at any age (36% versus 13%), but this was not statistically significant because of the small numbers in the group. Discussion Prevalence rates found in this study, in which family history was “self report” and not confirmed, were similar to more carefully controlled studies where family history was confirmed. However, it is certainly possible that family history was underreported, as healthcare professionals may pick and choose the information they feel is most relevant to include in the family history section of the requisition form. This is a limitation for interpreting the data. Diagnosis of ovarian cancer is much more critical to mutation status than had been previously thought. Unfortunately, family history of ovarian cancer is less likely to be accurate than is family history of breast cancer. Diagnosis of ovarian cancer after age 50 does not decrease the likelihood that there is a mutation. None of the Ashkenazi individuals with two mutations had deleterious mutations in the same gene. As in most series, those with African American ancestry were underrepresented (1.6% of the total). However, the prevalence of mutation in this population with family history is similar to other non-Ashkenazi Jewish groups. If one uses a cutoff for testing of 10% predicted prevalence of a mutation, non-Ashkenazi Jewish women younger than 50 with breast cancer and no other family history should be considered for testing. Prevalence of mutation status with DCIS needs additional investigation. Mutations in males were equally accounted for by BRCA1 and BRCA2. The data reported likely underestimate the prevalence of mutations in the clinical setting, as the sequence analysis strategy used renders large insertions/deletions invisible. Such rearrangements reportedly account for about 15% of alterations in BRCA1 and BRCA2. In summary, mutation status occurs in individuals with relatively unremarkable family histories. In this study, 36% of non-Ashkenazi Jewish families reported a history of only one first- or second-degree relative with early onset breast or ovarian cancer, and of these individuals, 13% were found to have a mutation. Reference Frank, T.S., Deffenbaugh, A.M., Reid, J.E., Hulick, M., Ward, B.E., Lingenfelter, B., et al. (2002). Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: Analysis of 10,000 individuals. Journal of Clinical Oncology, 20, 1480-1490. Back to SIG Newsletter front page |
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Special Interest Group Newsletter February 2003 |
Cancer Genetics SIG Officers
Know someone who would like to receive a print copy of this newsletter? To print a copy of this newsletter from your home or office computer, click here or on the printer icon located on the SIG Newsletter front page. Print copies of each online SIG newsletter also are available through the ONS National Office. To have a copy mailed to you or another SIG member, contact SIGs Administrative Assistant Carol DeMarco at carol@ons.org or 866-257-4ONS, ext. 6230. The Oncology Nursing Society (ONS) does not assume responsibility for the opinions expressed and information provided by authors or by Special Interest Groups (SIGs). Acceptance of advertising or corporate support does not indicate or imply endorsement of the company or its products by ONS or the SIG. Web sites listed in the SIG newsletters are provided for information only. Hosts are responsible for their own content and availability. Oncology Nursing Society 125 Enterprise Dr. Pittsburgh, PA 15275-1214 412-859-6100 ONS Online: www.ons.org Back to SIG Newsletter front page |