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Parse Error: <1 or="">&gt;10, and promoter methylation (PMR&gt;&gt;4) was tightly associated with loss of respective protein expression (P &lt; 10(-16)). In conclusion, sodium bisulfite conversion and quantitative MethyLight assays have good precision and linearity and can be effectively used for high-throughput DNA methylation analysis on paraffin-embedded tissue.</1></div></div></div></div><div class="cc"><div id="ARTICLE:PUBMED:16645207" class="carousel pubmedImagesCarousel" style="height:300px"><div class="controls_menu pubmedImagesCarousel hidden"><button class="btn btn-default pubmedImagesCarousel first" title=""><span class="buttonText"></span></button><button class="btn btn-default pubmedImagesCarousel 1" title=""><span class="buttonText"></span></button><button class="btn btn-default pubmedImagesCarousel 2 last" title=""><span class="buttonText"></span></button><div class="groupSeparator"></div></div><div class="carouselContainer pubmedImagesCarousel" style="width:100%;height:initial"><div class="carouselBtn_left btn btn-text-hover btn-auto-height btn-disable"><i class="icon icon-previous"></i></div><div 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class="subContainer pubmedImagesCarousel 2" style="display:inline-block;width:33.333333333333336%;overflow-y:auto"><div class="imageContainer"><img data-nolayout="true" alt="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867588/bin/zjx0020663900003.jpg" data-src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867588/bin/zjx0020663900003.jpg" src="/images/CircularProgressAnimation.gif"/></div></div></div><div class="carouselBtn_right btn btn-text-hover btn-auto-height"><i class="icon icon-next"></i></div></div><div class="progressIndicator"><div class="indicator active" data-id="0"></div><div class="indicator" data-id="1"></div><div class="indicator" data-id="2"></div></div></div></div></div><div class="section author"><div class="sectionTitle"><div class="leftBorder"></div><span class="titleValue">Authors</span><div class="rightBorder"></div></div><div class="sectionContent"><a href="/us/eng/research/author/shuji_ogino_s" data-id="AUTHOR:PUBMED:FUZZY:LN[OGINO]FN[SHUJI]I[S]" data-type="author" data-text="Shuji Ogino" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[OGINO]FN[SHUJI]I[S]" data-type="author" data-text="Shuji Ogino" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Shuji Ogino</span></a><span>; </span><a href="/us/eng/research/author/takako_kawasaki_t" data-id="AUTHOR:PUBMED:FUZZY:LN[KAWASAKI]FN[TAKAKO]I[T]" data-type="author" data-text="Takako Kawasaki" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[KAWASAKI]FN[TAKAKO]I[T]" data-type="author" data-text="Takako Kawasaki" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Takako Kawasaki</span></a><span>; </span><a href="/us/eng/research/author/mohan_brahmandam_m" data-id="AUTHOR:PUBMED:FUZZY:LN[BRAHMANDAM]FN[MOHAN]I[M]" data-type="author" data-text="Mohan Brahmandam" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[BRAHMANDAM]FN[MOHAN]I[M]" data-type="author" data-text="Mohan Brahmandam" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Mohan Brahmandam</span></a><span>; </span><a href="/us/eng/research/author/mami_cantor_m" data-id="AUTHOR:PUBMED:FUZZY:LN[CANTOR]FN[MAMI]I[M]" data-type="author" data-text="Mami Cantor" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[CANTOR]FN[MAMI]I[M]" data-type="author" data-text="Mami Cantor" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Mami Cantor</span></a><span>; </span><a href="/us/eng/research/author/gregory_j_kirkner_gj" data-id="AUTHOR:PUBMED:FUZZY:LN[KIRKNER]FN[GREGORY_J]I[GJ]" data-type="author" data-text="Gregory J Kirkner" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[KIRKNER]FN[GREGORY_J]I[GJ]" data-type="author" data-text="Gregory J Kirkner" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Gregory J Kirkner</span></a><span>; </span><a href="/us/eng/research/author/donna_spiegelman_d" data-id="AUTHOR:PUBMED:FUZZY:LN[SPIEGELMAN]FN[DONNA]I[D]" data-type="author" data-text="Donna Spiegelman" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[SPIEGELMAN]FN[DONNA]I[D]" data-type="author" data-text="Donna Spiegelman" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Donna Spiegelman</span></a><span class="showMoreItems">+5 authors</span></div></div><div class="section relationsCount"><div class="sectionTitle"><div class="leftBorder"></div><span class="titleValue">Related with</span><div class="rightBorder"></div></div><div class="sectionContent"><a href="/us/eng/research/pubmed/Precision_and_performance_characteristics_of_bisulfite_conversion_and_real_time_PCR_MethyLight_for_quantitative_DNA_methylation_analysis_16645207?as=pubmed_citation" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount pubmed_citation-border-bottom-color" data-type="pubmed_citation" data-parent_id="ARTICLE:PUBMED:16645207" data-parent_type="pubmed" data-parent_text="Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis."><i class="icon icon-pubmed_citation pubmed-text-color"></i><span class="itemName pubmed-text-color">Citations</span><span>(176)</span></a><a href="/us/eng/research/pubmed/Precision_and_performance_characteristics_of_bisulfite_conversion_and_real_time_PCR_MethyLight_for_quantitative_DNA_methylation_analysis_16645207?as=pubmed_reference" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount pubmed_reference-border-bottom-color" data-type="pubmed_reference" data-parent_id="ARTICLE:PUBMED:16645207" data-parent_type="pubmed" data-parent_text="Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis."><i class="icon icon-pubmed_reference pubmed-text-color"></i><span class="itemName pubmed-text-color">References</span><span>(42)</span></a><a href="/us/eng/research/pubmed/Precision_and_performance_characteristics_of_bisulfite_conversion_and_real_time_PCR_MethyLight_for_quantitative_DNA_methylation_analysis_16645207?as=disease" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount disease-border-bottom-color" data-type="disease" data-parent_id="ARTICLE:PUBMED:16645207" data-parent_type="pubmed" data-parent_text="Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis."><i class="icon icon-disease disease-text-color"></i><span class="itemName disease-text-color">Diseases</span><span>(1)</span></a><a href="/us/eng/research/pubmed/Precision_and_performance_characteristics_of_bisulfite_conversion_and_real_time_PCR_MethyLight_for_quantitative_DNA_methylation_analysis_16645207?as=chemical" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount chemical-border-bottom-color" data-type="chemical" data-parent_id="ARTICLE:PUBMED:16645207" data-parent_type="pubmed" data-parent_text="Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis."><i class="icon icon-chemical chemical-text-color"></i><span class="itemName chemical-text-color">Chemicals</span><span>(7)</span></a><a href="/us/eng/research/pubmed/Precision_and_performance_characteristics_of_bisulfite_conversion_and_real_time_PCR_MethyLight_for_quantitative_DNA_methylation_analysis_16645207?as=organism" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount organism-border-bottom-color" data-type="organism" data-parent_id="ARTICLE:PUBMED:16645207" data-parent_type="pubmed" data-parent_text="Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis."><i class="icon icon-organism organism-text-color"></i><span class="itemName organism-text-color">Organisms</span><span>(1)</span></a><a href="/us/eng/research/pubmed/Precision_and_performance_characteristics_of_bisulfite_conversion_and_real_time_PCR_MethyLight_for_quantitative_DNA_methylation_analysis_16645207?as=process" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount process-border-bottom-color" data-type="process" data-parent_id="ARTICLE:PUBMED:16645207" data-parent_type="pubmed" data-parent_text="Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis."><i class="icon icon-process process-text-color"></i><span class="itemName process-text-color">Processes</span><span>(4)</span></a><a href="/us/eng/research/pubmed/Precision_and_performance_characteristics_of_bisulfite_conversion_and_real_time_PCR_MethyLight_for_quantitative_DNA_methylation_analysis_16645207?as=author" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount author-border-bottom-color" data-type="author" data-parent_id="ARTICLE:PUBMED:16645207" data-parent_type="pubmed" data-parent_text="Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis."><i class="icon icon-author author-text-color"></i><span class="itemName author-text-color">Authors</span><span>(11)</span></a><a href="/us/eng/research/pubmed/Precision_and_performance_characteristics_of_bisulfite_conversion_and_real_time_PCR_MethyLight_for_quantitative_DNA_methylation_analysis_16645207?as=affiliate" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount affiliate-border-bottom-color" data-type="affiliate" data-parent_id="ARTICLE:PUBMED:16645207" data-parent_type="pubmed" data-parent_text="Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis."><i class="icon icon-affiliate affiliate-text-color"></i><span class="itemName affiliate-text-color">Affiliates</span><span>(2)</span></a></div></div></div></div><div data-id="ARTICLE:PUBMED:21642682" data-type="pubmed" data-layout-mode="listMode" itemscope="" itemType="http://schema.org/ScholarlyArticle" class="searchCard pubmed" style="width:auto"><div class="cardTitle pubmed-bkgr-color pubmed-border-color" data-draggable="" data-draggabledeny="" data-dragablemode="copy" data-dragabledata="_id=ARTICLE:PUBMED:21642682;text=Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.;type=pubmed" data-dragselector=".searchCard[data-id=&quot;ARTICLE:PUBMED:21642682&quot;]"><a class="itemHiddenLink" href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682"></a><i class="icon icon-pubmed"></i><div itemscope="" itemType="http://schema.org/ScholarlyArticle" data-layout-mode="listMode" class="titleText">Publication</div><div class="dragDropIndicator"><span></span></div></div><div itemscope="" itemType="http://schema.org/ScholarlyArticle" data-layout-mode="listMode" class="cardBody"><div class="itemTitle"><div class="textBlock name pubmed-text-color"><a data-tooltip="shift_quick_info" data-showinfo="true" data-id="ARTICLE:PUBMED:21642682" data-type="pubmed" data-text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome." class="textBlock name pubmed-text-color" itemProp="headline" data-dragdropselectabletext="" href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682">Cancer risks associated with germline mutations in <em>MLH1</em>, MSH2, and MSH6 genes in Lynch syndrome.</a><i data-tooltip="quick_info" data-showinfo="true" data-id="ARTICLE:PUBMED:21642682" data-type="pubmed" data-text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome." class="icon icon-right"></i></div><div class="advanceControls"><div class="translationControl"><div class="selectControl translate"><i class="icon icon-translate"></i><select class="select translate withIcon" name="" data-tooltip="research.card_section.translate_tooltip"><option selected="" value="">Translate</option><option value="ky">Kyrgyz</option><option value="af">Afrikaans</option><option value="am">Amharic</option><option value="ar">Arabic</option><option value="hy">Armenian</option><option value="az">Azerbaijani</option><option value="eu">Basque</option><option value="be">Belarusian</option><option value="bn">Bengali</option><option value="bs">Bosnian</option><option value="bg">Български</option><option value="ca">Catalan</option><option value="ceb">Cebuano</option><option value="zh-CN">中文(简体)</option><option value="zh-TW">中文(繁體)</option><option value="co">Corsican</option><option value="cs">Czech</option><option value="da">Danish</option><option value="nl">Dutch</option><option value="en">English</option><option value="eo">Esperanto</option><option value="et">Estonian</option><option value="fi">Finnish</option><option value="fr">Français</option><option value="ka">Georgian</option><option value="de">Deutsch</option><option value="el">Greek</option><option value="ht">Haitian Creole</option><option value="hi">Hindi</option><option 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value="ru">Russian</option><option value="sm">Samoan</option><option value="sr">Serbian</option><option value="si">Sinhala</option><option value="sk">Slovak</option><option value="sl">Slovenian</option><option value="so">Somali</option><option value="es">Spanish</option><option value="sw">Swahili</option><option value="sv">Swedish</option><option value="tg">Tajik</option><option value="ta">Tamil</option><option value="th">Thai</option><option value="tr">Turkish</option><option value="uk">Ukrainian</option><option value="ur">Urdu</option><option value="uz">Uzbek</option><option value="vi">Vietnamese</option><option value="xh">Xhosa</option><option value="zu">Zulu</option></select></div></div></div></div><div class="textBlock journal"><span class="textLabel journal">Journal: </span><span>JAMA</span><div class="createDate">June/9/2011<meta itemProp="datePublished" content="2011-06-09T21:00:00.000Z"/></div></div><div class="descriptionContainer"><div class="section"><div class="sectionTitle"><div class="leftBorder"></div><span class="titleValue">Abstract</span><div class="rightBorder"></div></div><div class="sectionContent"><div data-id="ARTICLE:PUBMED:21642682description" class="description dotted" itemProp="description" data-before="..." data-before-open="Hide" data-dragdropselectabletext="true"><div>BACKGROUND</div><div>Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome.</div><div>OBJECTIVE</div><div>To estimate the age-specific cumulative risks of developing various tumors using a large series of families with mutations of the <em>MLH1</em>, MSH2, and MSH6 genes.</div><div>METHODS</div><div>Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with <em>MLH1</em>; 256 with MSH2; and 33 with MSH6) were analyzed.</div><div>METHODS</div><div>Age-specific cumulative cancer risks estimated using the genotype restricted likelihood (GRL) method accounting for ascertainment bias.</div><div>RESULTS</div><div>Significant differences in estimated cumulative cancer risk were found between the 3 mutated genes (P = .01). The estimated cumulative risks of colorectal cancer by age 70 years were 41% (95% confidence intervals [CI], 25%-70%) for <em>MLH1</em> mutation carriers, 48% (95% CI, 30%-77%) for MSH2, and 12% (95% CI, 8%-22%) for MSH6. For endometrial cancer, corresponding risks were 54% (95% CI, 20%-80%), 21% (95% CI, 8%-77%), and 16% (95% CI, 8%-32%). For ovarian cancer, they were 20% (95% CI, 1%-65%), 24% (95% CI, 3%-52%), and 1% (95% CI, 0%-3%). The estimated cumulative risks by age 40 years did not exceed 2% (95% CI, 0%-7%) for endometrial cancer nor 1% (95% CI, 0%-3%) for ovarian cancer, irrespective of the gene. The estimated lifetime risks for other tumor types did not exceed 3% with any of the gene mutations.</div><div>CONCLUSIONS</div><div>MSH6 mutations are associated with markedly lower cancer risks than <em>MLH1</em> or MSH2 mutations. Lifetime ovarian and endometrial cancer risks associated with <em>MLH1</em> or MSH2 mutations were high but do not increase appreciably until after the age of 40 years.</div></div></div></div></div><div class="section author"><div class="sectionTitle"><div class="leftBorder"></div><span class="titleValue">Authors</span><div class="rightBorder"></div></div><div class="sectionContent"><a href="/us/eng/research/author/valerie_bonadona_v" data-id="AUTHOR:PUBMED:FUZZY:LN[BONADONA]FN[VALÉRIE]I[V]" data-type="author" data-text="Valérie Bonadona" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[BONADONA]FN[VALÉRIE]I[V]" data-type="author" data-text="Valérie Bonadona" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Valérie Bonadona</span></a><span>; </span><a href="/us/eng/research/author/bernard_bonaiti_b" data-id="AUTHOR:PUBMED:FUZZY:LN[BONAÏTI]FN[BERNARD]I[B]" data-type="author" data-text="Bernard Bonaïti" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[BONAÏTI]FN[BERNARD]I[B]" data-type="author" data-text="Bernard Bonaïti" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Bernard Bonaïti</span></a><span>; </span><a href="/us/eng/research/author/sylviane_olschwang_s" data-id="AUTHOR:PUBMED:FUZZY:LN[OLSCHWANG]FN[SYLVIANE]I[S]" data-type="author" data-text="Sylviane Olschwang" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[OLSCHWANG]FN[SYLVIANE]I[S]" data-type="author" data-text="Sylviane Olschwang" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Sylviane Olschwang</span></a><span>; </span><a href="/us/eng/research/author/sophie_grandjouan_s" data-id="AUTHOR:PUBMED:FUZZY:LN[GRANDJOUAN]FN[SOPHIE]I[S]" data-type="author" data-text="Sophie Grandjouan" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[GRANDJOUAN]FN[SOPHIE]I[S]" data-type="author" data-text="Sophie Grandjouan" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Sophie Grandjouan</span></a><span>; </span><a href="/us/eng/research/author/laetitia_huiart_l" data-id="AUTHOR:PUBMED:FUZZY:LN[HUIART]FN[LAETITIA]I[L]" data-type="author" data-text="Laetitia Huiart" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[HUIART]FN[LAETITIA]I[L]" data-type="author" data-text="Laetitia Huiart" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Laetitia Huiart</span></a><span>; </span><a href="/us/eng/research/author/michel_longy_m" data-id="AUTHOR:PUBMED:FUZZY:LN[LONGY]FN[MICHEL]I[M]" data-type="author" data-text="Michel Longy" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[LONGY]FN[MICHEL]I[M]" data-type="author" data-text="Michel Longy" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">Michel Longy</span></a><span class="showMoreItems">+21 authors</span></div></div><div class="section relationsCount"><div class="sectionTitle"><div class="leftBorder"></div><span class="titleValue">Related with</span><div class="rightBorder"></div></div><div class="sectionContent"><a href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682?as=pubmed_citation" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount pubmed_citation-border-bottom-color" data-type="pubmed_citation" data-parent_id="ARTICLE:PUBMED:21642682" data-parent_type="pubmed" data-parent_text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome."><i class="icon icon-pubmed_citation pubmed-text-color"></i><span class="itemName pubmed-text-color">Citations</span><span>(164)</span></a><a href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682?as=disease" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount disease-border-bottom-color" data-type="disease" data-parent_id="ARTICLE:PUBMED:21642682" data-parent_type="pubmed" data-parent_text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome."><i class="icon icon-disease disease-text-color"></i><span class="itemName disease-text-color">Diseases</span><span>(4)</span></a><a href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682?as=condition" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount condition-border-bottom-color" data-type="condition" data-parent_id="ARTICLE:PUBMED:21642682" data-parent_type="pubmed" data-parent_text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome."><i class="icon icon-condition condition-text-color"></i><span class="itemName condition-text-color">Conditions</span><span>(1)</span></a><a href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682?as=chemical" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount chemical-border-bottom-color" data-type="chemical" data-parent_id="ARTICLE:PUBMED:21642682" data-parent_type="pubmed" data-parent_text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome."><i class="icon icon-chemical chemical-text-color"></i><span class="itemName chemical-text-color">Chemicals</span><span>(5)</span></a><a href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682?as=gene" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount gene-border-bottom-color" data-type="gene" data-parent_id="ARTICLE:PUBMED:21642682" data-parent_type="pubmed" data-parent_text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome."><i class="icon icon-gene gene-text-color"></i><span class="itemName gene-text-color">Genes</span><span>(3)</span></a><a href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682?as=organism" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount organism-border-bottom-color" data-type="organism" data-parent_id="ARTICLE:PUBMED:21642682" data-parent_type="pubmed" data-parent_text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome."><i class="icon icon-organism organism-text-color"></i><span class="itemName organism-text-color">Organisms</span><span>(1)</span></a><a href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682?as=process" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount process-border-bottom-color" data-type="process" data-parent_id="ARTICLE:PUBMED:21642682" data-parent_type="pubmed" data-parent_text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome."><i class="icon icon-process process-text-color"></i><span class="itemName process-text-color">Processes</span><span>(2)</span></a><a href="/us/eng/research/pubmed/Cancer_risks_associated_with_germline_mutations_in_MLH1_MSH2_and_MSH6_genes_in_Lynch_syndrome_21642682?as=author" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount author-border-bottom-color" data-type="author" data-parent_id="ARTICLE:PUBMED:21642682" data-parent_type="pubmed" data-parent_text="Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome."><i class="icon icon-author author-text-color"></i><span class="itemName author-text-color">Authors</span><span>(27)</span></a></div></div></div></div><div data-id="ARTICLE:PUBMED:11325821" data-type="pubmed" data-layout-mode="listMode" itemscope="" itemType="http://schema.org/ScholarlyArticle" class="searchCard pubmed" style="width:auto"><div class="cardTitle pubmed-bkgr-color pubmed-border-color" data-draggable="" data-draggabledeny="" data-dragablemode="copy" data-dragabledata="_id=ARTICLE:PUBMED:11325821;text=Accelerated age-related CpG island methylation in ulcerative colitis.;type=pubmed" data-dragselector=".searchCard[data-id=&quot;ARTICLE:PUBMED:11325821&quot;]"><a class="itemHiddenLink" href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821"></a><i class="icon icon-pubmed"></i><div itemscope="" itemType="http://schema.org/ScholarlyArticle" data-layout-mode="listMode" class="titleText">Publication</div><div class="dragDropIndicator"><span></span></div></div><div itemscope="" itemType="http://schema.org/ScholarlyArticle" data-layout-mode="listMode" class="cardBody"><div class="itemTitle"><div class="textBlock name pubmed-text-color"><a data-tooltip="shift_quick_info" data-showinfo="true" data-id="ARTICLE:PUBMED:11325821" data-type="pubmed" data-text="Accelerated age-related CpG island methylation in ulcerative colitis." class="textBlock name pubmed-text-color" itemProp="headline" data-dragdropselectabletext="" href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821">Accelerated age-related CpG island methylation in ulcerative colitis.</a><i data-tooltip="quick_info" data-showinfo="true" data-id="ARTICLE:PUBMED:11325821" data-type="pubmed" data-text="Accelerated age-related CpG island methylation in ulcerative colitis." class="icon icon-right"></i></div><div class="advanceControls"><div class="translationControl"><div class="selectControl translate"><i class="icon icon-translate"></i><select class="select translate withIcon" name="" data-tooltip="research.card_section.translate_tooltip"><option selected="" value="">Translate</option><option value="ky">Kyrgyz</option><option value="af">Afrikaans</option><option value="am">Amharic</option><option value="ar">Arabic</option><option value="hy">Armenian</option><option value="az">Azerbaijani</option><option value="eu">Basque</option><option value="be">Belarusian</option><option value="bn">Bengali</option><option value="bs">Bosnian</option><option value="bg">Български</option><option value="ca">Catalan</option><option value="ceb">Cebuano</option><option value="zh-CN">中文(简体)</option><option value="zh-TW">中文(繁體)</option><option value="co">Corsican</option><option value="cs">Czech</option><option value="da">Danish</option><option value="nl">Dutch</option><option value="en">English</option><option 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value="mn">Mongolian</option><option value="my">Myanmar (Burmese)</option><option value="ne">Nepali</option><option value="no">Norwegian</option><option value="ps">Pashto</option><option value="fa">Persian</option><option value="pl">Polish</option><option value="pt">Portuguese</option><option value="ro">Romanian</option><option value="ru">Russian</option><option value="sm">Samoan</option><option value="sr">Serbian</option><option value="si">Sinhala</option><option value="sk">Slovak</option><option value="sl">Slovenian</option><option value="so">Somali</option><option value="es">Spanish</option><option value="sw">Swahili</option><option value="sv">Swedish</option><option value="tg">Tajik</option><option value="ta">Tamil</option><option value="th">Thai</option><option value="tr">Turkish</option><option value="uk">Ukrainian</option><option value="ur">Urdu</option><option value="uz">Uzbek</option><option value="vi">Vietnamese</option><option value="xh">Xhosa</option><option value="zu">Zulu</option></select></div></div></div></div><div class="textBlock journal"><span class="textLabel journal">Journal: </span><span>Cancer research</span><div class="createDate">May/20/2001<meta itemProp="datePublished" content="2001-05-20T21:00:00.000Z"/></div></div><div class="descriptionContainer"><div class="section"><div class="sectionTitle"><div class="leftBorder"></div><span class="titleValue">Abstract</span><div class="rightBorder"></div></div><div class="sectionContent"><div data-id="ARTICLE:PUBMED:11325821description" class="description dotted" itemProp="description" data-before="..." data-before-open="Hide" data-dragdropselectabletext="true"><div>CpG island hypermethylation is a mechanism of gene silencing that can be usurped by neoplastic cells to inactivate undesirable genes. In the colon, hypermethylation often starts in normal mucosa as a function of age and is markedly increased in cancer. To test the hypothesis that subjects at increased risk of colon cancer have higher levels of methylation in their nonneoplastic mucosa, we studied methylation patterns of five genes in the normal and dysplastic mucosa of patients with ulcerative colitis (UC), a condition associated with a marked increased risk of colon cancer. One gene (<em>Mlh1</em>) was unmethylated in all tissues examined. All four remaining genes had low but detectable levels of methylation in the epithelium of UC patients without evidence of dysplasia, and this methylation was not different from non-UC controls. By contrast, all four genes were highly methylated in dysplastic epithelium from high-grade dysplasia (HGD)/cancer patients with UC; methylation in HGD versus controls averaged 40.0% versus 7.4% (P = 0.00003) for ER, 44.0% versus 3.0% (P &lt; 0.00003) for MYOD, 9.4% versus 2.4% (P = 0.03) for p16 exon 1, and 57.5% versus 30.6% (P = 0.01) for CSPG2. Importantly, three of the four genes were also highly methylated in the normal appearing (nondysplastic) epithelium from these same HGD/cancer patients, indicating that methylation precedes dysplasia and is widespread in these patients. Compared with controls, methylation averaged 20.1% versus 7.2% (P = 0.07) for ER, 18.4% versus 3.0% (P &lt; 0.008) for MYOD, and 7.9% versus 2.4% (P = 0.007) for p16 exon 1. These results are consistent with the hypothesis that age-related methylation marks (and may lead to) the field defect that reflects acquired predisposition to colorectal neoplasia. Furthermore, the data suggest that chronic inflammation is associated with high levels of methylation, perhaps as a result of increased cell turnover, and that UC can be viewed as resulting in premature aging of colorectal epithelial cells.</div></div></div></div></div><div class="section author"><div class="sectionTitle"><div class="leftBorder"></div><span class="titleValue">Authors</span><div class="rightBorder"></div></div><div class="sectionContent"><a href="/us/eng/research/author/j_p_issa_jp" data-id="AUTHOR:PUBMED:FUZZY:LN[ISSA]FN[J_P]I[JP]" data-type="author" data-text="J P Issa" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[ISSA]FN[J_P]I[JP]" data-type="author" data-text="J P Issa" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">J P Issa</span></a><span>; </span><a href="/us/eng/research/author/n_ahuja_n" data-id="AUTHOR:PUBMED:FUZZY:LN[AHUJA]FN[N]I[N]" data-type="author" data-text="N Ahuja" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[AHUJA]FN[N]I[N]" data-type="author" data-text="N Ahuja" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">N Ahuja</span></a><span>; </span><a href="/us/eng/research/author/m_toyota_m" data-id="AUTHOR:PUBMED:FUZZY:LN[TOYOTA]FN[M]I[M]" data-type="author" data-text="M Toyota" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[TOYOTA]FN[M]I[M]" data-type="author" data-text="M Toyota" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">M Toyota</span></a><span>; </span><a href="/us/eng/research/author/m_p_bronner_mp" data-id="AUTHOR:PUBMED:FUZZY:LN[BRONNER]FN[M_P]I[MP]" data-type="author" data-text="M P Bronner" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[BRONNER]FN[M_P]I[MP]" data-type="author" data-text="M P Bronner" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">M P Bronner</span></a><span>; </span><a href="/us/eng/research/author/t_a_brentnall_ta" data-id="AUTHOR:PUBMED:FUZZY:LN[BRENTNALL]FN[T_A]I[TA]" data-type="author" data-text="T A Brentnall" data-tooltip="shift_quick_info" data-showinfo="true"><span data-id="AUTHOR:PUBMED:FUZZY:LN[BRENTNALL]FN[T_A]I[TA]" data-type="author" data-text="T A Brentnall" data-tooltip="shift_quick_info" class="authorName author-text-color" itemProp="author">T A Brentnall</span></a></div></div><div class="section relationsCount"><div class="sectionTitle"><div class="leftBorder"></div><span class="titleValue">Related with</span><div class="rightBorder"></div></div><div class="sectionContent"><a href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821?as=pubmed_citation" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount 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href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821?as=chemical" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount chemical-border-bottom-color" data-type="chemical" data-parent_id="ARTICLE:PUBMED:11325821" data-parent_type="pubmed" data-parent_text="Accelerated age-related CpG island methylation in ulcerative colitis."><i class="icon icon-chemical chemical-text-color"></i><span class="itemName chemical-text-color">Chemicals</span><span>(10)</span></a><a href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821?as=organism" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount organism-border-bottom-color" data-type="organism" data-parent_id="ARTICLE:PUBMED:11325821" data-parent_type="pubmed" data-parent_text="Accelerated age-related CpG island methylation in ulcerative colitis."><i class="icon icon-organism organism-text-color"></i><span class="itemName organism-text-color">Organisms</span><span>(1)</span></a><a href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821?as=process" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount process-border-bottom-color" data-type="process" data-parent_id="ARTICLE:PUBMED:11325821" data-parent_type="pubmed" data-parent_text="Accelerated age-related CpG island methylation in ulcerative colitis."><i class="icon icon-process process-text-color"></i><span class="itemName process-text-color">Processes</span><span>(3)</span></a><a href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821?as=anatomy" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount anatomy-border-bottom-color" data-type="anatomy" data-parent_id="ARTICLE:PUBMED:11325821" data-parent_type="pubmed" data-parent_text="Accelerated age-related CpG island methylation in ulcerative colitis."><i class="icon icon-anatomy anatomy-text-color"></i><span class="itemName anatomy-text-color">Anatomy</span><span>(1)</span></a><a href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821?as=author" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount author-border-bottom-color" data-type="author" data-parent_id="ARTICLE:PUBMED:11325821" data-parent_type="pubmed" data-parent_text="Accelerated age-related CpG island methylation in ulcerative colitis."><i class="icon icon-author author-text-color"></i><span class="itemName author-text-color">Authors</span><span>(5)</span></a><a href="/us/eng/research/pubmed/Accelerated_age_related_CpG_island_methylation_in_ulcerative_colitis_11325821?as=affiliate" data-tooltip="shift_quick_info" data-showchildrenlist="true" class="relationCount affiliate-border-bottom-color" data-type="affiliate" 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