Abstract

ObjectiveTo examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival.MethodsWe genotyped germline variants of MUC16 (rs2547065, rs1559168, rs12984471, rs2121133) and MUC1 (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.ResultsCases homozygous for the variant allele of MUC16 SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For MUC1 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 MUC16 SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset.ConclusionThis targeted screen of seven polymorphisms of MUC16 and MUC1 genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of MUC16 rs12984471 on survival and MUC1 rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted.

Highlights

  • The tethered human mucins (MUC) are a family of large, heavily glycosylated transmembrane proteins that have a diverse range of functions [1]

  • Our study population consisted primarily of Caucasian women (.95%) and white ethnicity was more common among controls

  • In general the minor allele frequencies (MAF) we found for our controls were comparable to that of the Caucasian European (CEU) HapMap populations

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Summary

Introduction

The tethered human mucins (MUC) are a family of large, heavily glycosylated transmembrane proteins that have a diverse range of functions [1]. CA125, or MUC16, is the largest glycoprotein of the mucin family, and is normally expressed in the epithelial lining of various tissues, especially that of the female reproductive tract [1]. CA15.3, or MUC1, is expressed in the epithelial lining of various tissues, exhibiting strong expression in the mammary gland and the female reproductive tract during pregnancy and lactation. CA15.3 is over-expressed in a wide variety of cancers, including breast and ovarian [1,4]. These two mucins are best known as tumor markers, evidence suggests that they may play a role in cancer metastasis, tumor growth and survival, inhibition of immune response, and prognosis [1,5,6]

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