title: Polymorphisms of MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival.
abstract: OBJECTIVE
  To examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Cases 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America ; Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Williams
authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America ; Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America ; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Allison F
authors.initials: AF
authors.lastname: Vitonis
authors.affiliation: Department of Community & Family Medicine, Department of Pediatrics, Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire, United States of America.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Titus
authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America ; Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Cramer
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000367:Age Factors; D000368:Aged; D018394:CA-125 Antigen / Q000235:genetics*; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D018293:Cystadenoma, Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D018394:CA-125 Antigen; C060192:MUC1 protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; D018396:Mucin-1