Conditions Associated with Antibodies Against the Tumor-Associated Antigen MUC1 and Their Relationship to Risk for Ovarian Cancer

Abstract

Many cancers, including ovarian, overexpress epithelial mucin (MUC1) and promote anti-MUC1 antibodies that may correlate with more favorable prognosis. By extension, risk for ovarian cancer might be reduced by preexisting MUC1-specific immunity. We measured anti-MUC1 antibodies in 705 control women, identified events predicting antibodies, and estimated ovarian cancer risk by comparing profiles of events generating antibodies in controls with those in 668 ovarian cancer cases. Factors predicting antibodies included oral contraceptive use, breast mastitis, bone fracture or osteoporosis, pelvic surgeries, nonuse of talc in genital hygiene, and to a lesser extent intrauterine device use and current smoking. There was a significant increase in the likelihood of having anti-MUC1 antibodies from 24.2% in women with 0 or 1 condition, to 51.4% in those with five or more conditions. By the same index of events, the risk for ovarian cancer was inversely associated with number of conditions predisposing to anti-MUC1 antibodies. Compared with having experienced 0 or 1 event, the adjusted risk for ovarian cancer decreased progressively with relative risks (

Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF

“…Our results are in accord with a recent report that anti-MUC1 antibodies may be beneficial to the survival of patients with ovarian cancers. 48 In contrast to most reports of DNA vaccines that have documented Th1-biased immune responses, we observed a clear Th2-skewing by the GM-CSF-modified DNA vaccine. We speculated that it might be related to GM-CSF.…”

Association of Single Nucleotide Polymorphisms in Glycosylation Genes with Risk of Epithelial Ovarian Cancer

“…We included a fixed set of nongenetic variables based on the epidemiologic literature linking them with MUC1 antibodies (16,17): BMI, oral contraceptive use, HRT use, menopause status, parity, and smoking. Rather than fitting interactions under all genetic models, this exercise was limited to a dominant genetic effect for all 93 SNPs plus 2 recessive models (based on main effect results).…”

“…Two recent studies provide evidence that links circulating levels of anti-MUC1 antibodies with risk factors for ovarian cancer. The first report (16) observed that oral contraceptive use, breast mastitis, bone fracture or osteoporosis, pelvic surgeries, nonuse of talc in genital hygiene, and (to a lesser extent) current smoking predicted anti-MUC1 antibody levels among 705 women selected as controls for an ovarian cancer study. A second report by the same group (17) on 721 controls found that early age at first birth, menstrual cycles longer than 30 days, and lifetime number of ovulatory cycles were inversely associated with anti-MUC1 antibodies.…”

Healthy individuals have T-cell and antibody responses to the tumor antigen cyclin B1 that when elicited in mice protect from cancer

“…We would like to propose that abnormal expression of self-molecules can occur during nonneoplastic events as well, such as infections and acute and chronic inflammation. We have published that several nonneoplastic events known to affect MUC1-expressing tissues, such as mumps virus infection of MUC1ϩ salivary glands or mastitis affecting MUC1ϩ breast ducts, correlate with the presence of anti-MUC1 antibody in healthy individuals (40). Compelling evidence for a nonneoplastic event eliciting immune responses to self antigens was obtained recently by studying mice recovering from viral infections (41).…”