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

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.

Clinical Significance of Serum HE4, CA125, CA724, and CA19-9 in Patients With Endometrial Cancer

“…The serum CA125 was considered to be the most effective tumor marker for EC but have poor diagnostic sensitivity. [10][11][12] Besides CA125, EC also could be diagnosed by elevated levels of HE4, CA724, and CA19-9, each with their own unique advantages. [13][14][15] In our test, we detected serum level of HE4, CA125, CA724, and CA19-9 in 105 patients with EC; the results showed that the level of tumor markers was obviously higher in the EC group than that in the healthy controls.…”

The effect of CA125 on metastasis of ovarian cancer: old marker new function

“…Many reports have focused on the diagnostic value of CA125 in ovarian cancer, and have advocated for increased use of serum CA125 in primary care as means of increasing detection of ovarian cancer [ 3 , 4 ]. CA125 is member of the tethered human mucus (MUC) family of large, heavily glycosylated transmembrane proteins that have a diverse range of functions [ 5 ]. The extracellular region of MUC16, which is over-expressed in epithelial ovarian carcinoma, is cleaved from the cell surface and circulates in the blood.…”

Common Genetic Variants of PSCA, MUC1 and PLCE1 Genes are not Associated with Colorectal Cancer

“…A recent large metaanalysis study of 6,580 gastric cancer cases and 10,324 controls including both Asian and European populations showed that G allele of rs4072037 polymorphism was associated with decreased risk of gastric cancer (OR = 0.72) (Zheng et al, 2013). Recent publications showed that genetic variation of MUC1 may be associated with ovarian cancer (Williams et al, 2014) and esophageal cancer (Palmer et al, 2012). In the only case-control study including CRC patients (Li et al, 2012c) rs4072037 showed a marginal association in Chinese population (OR 0.69,P=0.06).…”