Association between mucin polymorphisms and epithelial ovarian cancer survival, New England-based ovarian cancer case-control study, 2003–2008.

<p>Modeled with Cox proportional hazard ratios; “–” frequencies for this SNP were too low to compute co-dominant/recessive models.</p>a<p>Adjusted for age, study center, and race.</p>b<p>Adjusted for age, study center, race, stage (I-IV) and histologic subtype (non-serous, serous).</p

Geometric mean levels of preoperative serum CA125 levels among women with ovarian cancer by MUC16 gene polymorphisms, New England-based ovarian case-control study, 2003–2008.

<p>Abbreviations: GM = Geometric mean.</p>a<p>modeled with general linear regression; adjusted for age, study center, race and time between CA125 to diagnosis (≤30days, >30days, missing).</p

Kaplan–Meier estimates of survival according to rs12984471 genotype among women with epithelial ovarian cancer, New-England based case control study, 2003–2008.

<p><b>A</b>. All women <b>B</b>. Postmenopausal women age 65 and older.</p

Polymorphisms of <i>MUC16</i> (CA125) and <i>MUC1</i> (CA15.3) in Relation to Ovarian Cancer Risk and Survival

<div><p>Objective</p><p>To examine single nucleotide polymorphism (SNPs) in <i>MUC16</i> (CA125) and <i>MUC1</i> (CA15.3) in relation to ovarian cancer risk and survival.</p><p>Methods</p><p>We genotyped germline variants of <i>MUC16</i> (rs2547065, rs1559168, rs12984471, rs2121133) and <i>MUC1</i> (rs2070803, rs4072037, rs1045253) using samples collected from 758 ovarian cancer cases and 788 controls enrolled in the New England Case-Control Study between 2003 and 2008. We calculated age-adjusted odds ratios (OR) and 95% confidence intervals (CIs) for disease risk using unconditional and polytomous logistic regression and hazard ratios (HR) for survival using Cox proportional hazard ratios. In a subset of cases, we compared log-normalized CA125 values by genotype using generalized linear models.</p><p>Results</p><p>Cases homozygous for the variant allele of <i>MUC16</i> SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For <i>MUC1</i> SNP, rs4072037, women homozygous for the G variant had a non-significantly decreased risk for serous invasive types but elevated risk for serous borderline tumors, mucinous borderline and invasive tumors, and endometrioid tumors. Women with the variant allele of <i>MUC16</i> SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset.</p><p>Conclusion</p><p>This targeted screen of seven polymorphisms of <i>MUC16</i> and <i>MUC1</i> genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of <i>MUC16</i> rs12984471 on survival and <i>MUC1</i> rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted.</p></div

Descriptive characteristics of ovarian cancer cases and controls, New England-based ovarian cancer case-control study 2003–2008.

<p>Cases and controls are frequency matched by age.</p>a<p>Includes ovarian and early onset (before age 50) breast cancers.</p>b<p>p value from chi square or t-test.</p

Association between mucin polymorphisms and risk of epithelial ovarian cancer, New England-based ovarian cancer case-control study, 2003–2008.

a<p>OR (95%CI) modeled with unconditional logistic regression; adjusted for age, study center, and race (white, non-white).</p>b<p>OR (95%CI) modeled with polytomous logistic regression adjusted for age, study center, and race.</p>c<p>p-values for heterogeneity (het) are computed with likelihood ratio tests comparing a model that allows the estimate of the association to vary by histologic type (serous borderline, serous invasive, mucinous, endometrioid, clear cell, undifferentiated) to a model that restricts to one estimate of the association for all histologic types.</p>d<p>p_het for co-dominant model.</p>e<p>p_het for per allele model.</p>f<p>p_het for recessive model.</p

Top SNPs associated with SER EOC across racial groups.

<p>¹ MAF, minor allele and its frequency</p><p>² p-value <0.05 are in bold</p><p>³ Odds ratio, 95% confidence interval</p><p>Top SNPs associated with SER EOC across racial groups.</p

The most significant SNPs in the transport pathway genes and risk of EOC by histology, invasiveness, and race/ethnicity¹.

<p>¹ INV: all invasive EOC combined; LMP: low malignant potential / borderline tumors; SER: serous; CC: clear cell; End: endometrioid; Muc: mucinous. Statistically significant associations are indicated in bold (P<0.05). Data format is the following: OR (95% CI); p-value; FDR q-value (white-European women). Only significant FDRs (q<0.2) are shown (<i>HEPH</i>: INV and SER<i>; UGT1A</i>: End).</p><p>The most significant SNPs in the transport pathway genes and risk of EOC by histology, invasiveness, and race/ethnicity<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128106#t001fn001" target="_blank">¹</a>.</p

Association of rs2256787 in the <i>ARHGEF10L</i> gene with invasive endometrioid EOC risk by study site and combined.

<p>Squares represent the estimated per-allele odds ratio (OR) and are proportional to sample size for each study; lines indicate its 95% confidence interval (CI); source indicates contributing study;[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0197561#pone.0197561.ref011" target="_blank">11</a>] MAF, control minor allele frequency; PVal, per-allele p-value adjusted for age, site, and principal components to account for residual differences in European ancestry.</p

Association of variants in small GTPase genes with epithelial ovarian cancer risk (p-value<10⁻⁴) and functional annotation.

<p>Association of variants in small GTPase genes with epithelial ovarian cancer risk (p-value<10⁻⁴) and functional annotation.</p