Association between haplogroup and CRC risk in European Americans.

<p>^Haplogroup estimation was based on HaploGrep (version 2.0) using PhyloTree 16.</p><p>*Log additive model was adjusted for age, sex and global ancestry PC1 to PC5.</p><p>Association between haplogroup and CRC risk in European Americans.</p

Association between mitochondrial genome, pathways, genes and CRC risk in European Americans.

<p>#Association tests were adjusted for age, sex and global ancestry PC1-PC5</p><p>* False Discovery Rate test</p><p>Association between mitochondrial genome, pathways, genes and CRC risk in European Americans.</p

Pleiotropy of Cancer Susceptibility Variants on the Risk of Non-Hodgkin Lymphoma: The PAGE Consortium

<div><p>Background</p><p>Risk of non-Hodgkin lymphoma (NHL) is higher among individuals with a family history or a prior diagnosis of other cancers. Genome-wide association studies (GWAS) have suggested that some genetic susceptibility variants are associated with multiple complex traits (pleiotropy).</p><p>Objective</p><p>We investigated whether common risk variants identified in cancer GWAS may also increase the risk of developing NHL as the first primary cancer.</p><p>Methods</p><p>As part of the Population Architecture using Genomics and Epidemiology (PAGE) consortium, 113 cancer risk variants were analyzed in 1,441 NHL cases and 24,183 controls from three studies (BioVU, Multiethnic Cohort Study, Women's Health Initiative) for their association with the risk of overall NHL and common subtypes [diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL)] using an additive genetic model adjusted for age, sex and ethnicity. Study-specific results for each variant were meta-analyzed across studies.</p><p>Results</p><p>The analysis of NHL subtype-specific GWAS SNPs and overall NHL suggested a shared genetic susceptibility between FL and DLBCL, particularly involving variants in the major histocompatibility complex region (rs6457327 in 6p21.33: FL OR = 1.29, <i>p</i> = 0.013; DLBCL OR = 1.23, <i>p</i> = 0.013; NHL OR = 1.22, <i>p</i> = 5.9×E-05). In the pleiotropy analysis, six risk variants for other cancers were associated with NHL risk, including variants for lung (rs401681 in <i>TERT</i>: OR per C allele = 0.89, <i>p</i> = 3.7×E-03; rs4975616 in <i>TERT</i>: OR per A allele = 0.90, <i>p</i> = 0.01; rs3131379 in <i>MSH5</i>: OR per T allele = 1.16, <i>p</i> = 0.03), prostate (rs7679673 in <i>TET2</i>: OR per C allele = 0.89, <i>p</i> = 5.7×E-03; rs10993994 in <i>MSMB</i>: OR per T allele = 1.09, <i>p</i> = 0.04), and breast (rs3817198 in <i>LSP1</i>: OR per C allele = 1.12, <i>p</i> = 0.01) cancers, but none of these associations remained significant after multiple test correction.</p><p>Conclusion</p><p>This study does not support strong pleiotropic effects of non-NHL cancer risk variants in NHL etiology; however, larger studies are warranted.</p></div

Characteristics of non-Hodgkin lymphoma (NHL) cases and controls in the PAGE studies.

<p>* Any prior cancer cases were excluded from the NHL cases and controls for the current analysis, based on self-report (BioVU, MEC, WHI), the SEER registry linkage (BioVU, MEC), and medical record reviews (BioVU, WHI).</p><p>Abbreviations: BioVU (the biorepository of the Vanderbilt University), MEC (the Multiethnic Cohort Study), WHI (the Women's Health Initiative); CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma), DLBCL (diffuse large B-cell lymphoma), FL (follicular lymphoma), SEER (Surveillance, Epidemiology and End Results).</p

Pleiotropic association of selected cancer susceptibility variants with the risk of overall non-Hodgkin lymphoma (NHL).

<p>* ORs and 95% CIs in individual studies were estimated in unconditional logistic regression models that were adjusted for age, sex (in BioVU and MEC) and ethnicity (ancestry informative markers). Summary ORs and 95% CIs were estimated in a meta-analysis of fixed-effects models.</p>†<p>The Bonferroni corrected <i>p-value</i> for 53 SNPs/tests is 4.4E-04.</p><p>Abbreviations: <i>p</i>-het. (<i>P</i>-values for heterogeneity across studies measured in Cochran's Q statistic); BioVU (the biorepository of the Vanderbilt University), MEC (the Multiethnic Cohort Study), WHI (the Women's Health Initiative).</p

Associations between a risk score (RS) for 53 GWAS-identified cancer risk variants and the overall and subtype-specific risks of NHL.

<p>* ORs and 95% CIs in individual studies were estimated per risk allele in unconditional logistic regression models that were adjusted for age, sex (in BioVU and MEC) and ethnicity. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in a meta-analysis of fixed effects models.</p><p>Abbreviations: <i>p-het</i>. (<i>p-values</i> for heterogeneity across studies measured in Cochran's Q statistic); BioVU (the biorepository of Vanderbilt University), MEC (the Multiethnic Cohort Study), WHI (the Women's Health Initiative).</p

Forest plots for the association between a published follicular lymphoma risk variant (rs6457327) and the risk of follicular lymphoma or overall non-Hodgkin lymphoma (NHL) in the Multiethnic Cohort (MEC) and the Women's Health Initiative (WHI) in the PAGE consortium.

<p>(a) follicular lymphoma, (b) overall NHL, and (c) overall NHL among whites only.</p