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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EDr. Kenneth Offit, MD, MPH, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA, received the 2013 ASCO-American Cancer Society Award. In his lecture on the use of genetic information as a tool for cancer prevention, Dr. Offit discussed the enormous social, ethical, and legal challenges in the field of oncology, and further highlighted opportunities for change in the practice of medicine.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EExclusive Article - For home page\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EExclusive Article - For home page\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EDr. Kenneth Offit, MD, MPH, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA, received this year\u0027s ASCO-American Cancer Society Award. In his lecture on the use of genetic information as a tool for cancer prevention, Dr. Offit discussed the enormous social, ethical, and legal challenges in the field of oncology, and further highlighted opportunities for change in the practice of medicine.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EOne of Dr. Offit\u0027s most significant contributions to the field was the identification of the BRCA2 mutation (617delT) in Ashkenazi Jewish women affected by breast and ovarian cancers [Neuhausen S et al. \u003Cem\u003ENat Genet\u003C\/em\u003E 1996]. This finding is the single most common genetic mutation associated with a highly penetrant form of cancer. However, the finding applies to women beyond the Ashkenazi population.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EChanges in individual and population behaviors can help reduce\u2014or even prevent\u2014a significant number of cancers. Together, smoking and obesity account for 53% of this potential reduction, while hereditary factors account for only 16% of cancers. Integrating current knowledge about genetic factors into targeted prevention efforts could ultimately reduce the rate of hereditary-related cancers by half.\u003C\/p\u003E\u003Cblockquote id=\u0022disp-quote-1\u0022 class=\u0022disp-quote\u0022\u003E\n         \u003Cp id=\u0022p-5\u0022\u003ESequencing tumors to target therapy will allow focused cancer prevention in families.\u003C\/p\u003E\n      \u003C\/blockquote\u003E\u003Cp id=\u0022p-6\u0022\u003EMuch of our disease knowledge has come from the hereditary history of families. Despite the work of Gregor Mendel, the existence of hereditary cancer was at first considered of little value. Most of Mendel\u0027s genetic work laid in obscurity until the 1930s. In 1971, Henry Lynch was the first to identify a family history of breast and ovarian cancer and advance the idea that cancer arises from gene mutations\u2014lending some credibility to Mendel\u0027s theory.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003E\u201cAll cancer is a genetic disease\u2026.but how much is hereditary?\u201d questioned Dr. Offit. Two studies have reshaped the thinking around this question: the Utah Genealogical \u201cExperiment\u201d and the Scandinavian twin registry. The Utah study tracked the genealogical records of Brigham Young\u0027s 2 million descendents from the time he moved his original 10,000 followers to Salt Lake City, Utah. The Utah Population Database used these data to determine the various genetic relationships among the 2 million individuals, while the Genealogical Index of Familiarity measured the genetic links between cancer cases statewide. The data uncovered unusually high levels of familial clustering of cancer, specifically lymphocytic leukemias, and especially chronic lymphocytic leukemia, lobular breast cancer, early-stage lip cancer, early-stage melanoma, and female lung cancers of alveolar\/adenoma histology [Cannon-Albright LA et al. \u003Cem\u003ECancer Res\u003C\/em\u003E 1994].\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe twin study examined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries to assess the role of inherited genetic factors in the development of malignant diseases. Statistically significant genetic effects were observed for prostate, colorectal, and breast cancer [Lichtenstein P et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2000]. These findings were confirmed using the concept of a \u201cgenometype\u201d in a large number of monozygotic twin pairs. A specific genometype represents the genomes in the population conferring a specific level of genetic risk for a specified disease [Roberts NJ et al. \u003Cem\u003ESci Transl Med\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe discovery of BRCA mutations in ancestral groups may be explained by the Founder Effect. After the Jewish pogroms in Russia, mutations become more concentrated in individuals belonging to groups with marked population decreases. When the group began to repopulate, the mutation spread as a result of low genetic variation.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EThe value of personalized genomics medicine in cancer prevention was first demonstrated in a study of BRCA mutation carriers who underwent a risk-reducing salpingo-oophorectomy (RRSO). The study found that undergoing RRSO can reduce the risk of breast cancer and BRCA-related gynecologic cancer in BRCA carriers [Kauff ND et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2002].\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EAdvances in science and technology are revolutionizing approaches to genetic cancer risk assessment and prevention, but innovation does not come without complications. An example is the \u201cMyriad Case\u201d recently under review by the United States Supreme Court. Myriad Genetics claimed to own the rights to \u003Cem\u003Eany\u003C\/em\u003E test for the presence of the BRCA1 and 2 genes, as well as patents on the methods for interpreting the test results; however, a unanimous ruling by the court in June 2013 bars the patenting of any naturally occurring genes. Evidence-based information regarding the clinical utility of genome testing is needed, along with increased public awareness of the potential dangers associated with premature marketing of first-generation genomic profiles. The continued integration of personalized genomic information into the practice of cancer medicine underscores the need for a multidisciplinary model of genetic cancer risk assessment and management [Weitzel JN et al. \u003Cem\u003ECA Cancer J Clin\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EOne of best examples of consolidation in this area is the Human Genome Project (Genome Wide Association Studies [GWAS]), which has identified 3 billion base pairs or 20,000 genes. The Collaborative Oncological Gene-Environment Study has brought much of the GWAS data together to look at 200,000 single-nucleotide polymorphisms in 200,000 individuals. A number of new variants (mutations) for breast, prostate, ovarian, and other cancers have been identified; however, about one half of the hereditability of cancer remains unexplained. One report suggested that when mathematically pooled, there is only modest improvement in the predicted breast cancer risk. The area under the curve (AUC) for a risk model with age, study, entry year, and four traditional risk factors was 58.0%; with the addition of 10 genetic variants, the AUC was 61.8% (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Wacholder S et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/8\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Discriminatory Accuracy of Breast Cancer SNPs\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1015693761\u0022 data-figure-caption=\u0022Discriminatory Accuracy of Breast Cancer SNPs\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/8\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/8\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/8\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13464\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-13\u0022 class=\u0022first-child\u0022\u003EDiscriminatory Accuracy of Breast Cancer SNPs\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced from Wacholder S et al. Performance of Common Genetic Variants in Breast-Cancer Risk Models. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010;362(11)986\u2013993. Copyright \u00a9 Massachusetts Medical Society.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-14\u0022\u003EWith the advent of germline and tumor sequencing, \u201cright to know\u201d issues will have to be discussed with patients. New technology will often detect mutations that are not under review and that lack effective treatments. Patients may not want to know about these findings, but physicians have a duty to warn patients about incidental findings. Currently, the American College of Medical Genetics guidelines indicate that incidental findings must be disclosed for 24 specific conditions\u201416 of which are cancer syndromes.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003ESequencing tumors to target therapy will mean sequencing inherited genomes to allow targeted prevention in families, and Dr. Offit believes patients must be given the choice to know or not to know.\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/8\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022The editors would like to thank the many members of the American Society of Clinical Oncology presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1015693761\u0022 data-figure-caption=\u0022The editors would like to thank the many members of the American Society of Clinical Oncology presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure2\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/8\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/8\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure2\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/6\/8\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13465\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\n            \u003Cp id=\u0022p-16\u0022 class=\u0022first-child\u0022\u003EThe editors would like to thank the many members of the American Society of Clinical Oncology presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/6\/8.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nznv81\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznv81\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}