Anti-MUC1 antibodies and ovarian cancer risk: prospective data from the Nurses' Health Studies.
BACKGROUND
The surface epithelial glycoprotein MUC1 becomes overexpressed and hypoglycosylated in adenocarcinomas; similar changes occur during nonmalignant inflammatory events. Antibodies developed against tumor-like MUC1 in response to such events could be one way through which ovarian cancer risk factors operate.


METHODS
We evaluated the association between anti-MUC1 antibodies and risk of ovarian cancer in a prospective nested case-control study in the Nurses' Health Studies. We used an ELISA to measure plasma anti-MUC1 antibodies in 117 ovarian cancer cases collected at least 3 years before diagnosis and 339 matched controls.


RESULTS
In controls, younger women (P-trend = 0.03), those with a tubal ligation (P = 0.03), and those with fewer ovulatory cycles (P-trend = 0.04) had higher antibody levels. In cases, women with late-stage disease (P = 0.04) and those whose specimen was >11 years remote from diagnosis (P = 0.01) had higher antibody levels. Overall, increasing anti-MUC1 antibody levels were associated with a nonsignificant trend for lower risk for ovarian cancer, but there was highly significant heterogeneity by age (P-heterogeneity = 0.005). In women <64 years, the antibody level in quartiles 2 to 4 versus quartile 1 were associated with reduced risk (relative risk = 0.53; 95% confidence interval, 0.31-0.93; P-trend = 0.03), whereas in women > or = 64 years, the corresponding relative risk was 2.11 (95% confidence interval, 0.73-6.04); P-trend = 0.05).


CONCLUSIONS
Anti-MUC1 antibodies evaluated several years before diagnosis may be associated with lower risk of subsequent ovarian cancer in women <64 years old at assessment.


CONCLUSIONS
Key elements of an "immune model" to explain ovarian cancer risk factors are confirmed and should be evaluated in larger prospective studies.
Pinheiro
Simone P
SP
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Hankinson
Susan E
SE
Tworoger
Shelley S
SS
Rosner
Bernard A
BA
McKolanis
John R
JR
Finn
Olivera J
OJ
Cramer
Daniel W
DW
D000328:Adult; D000912:Antibodies, Neoplasm / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires
D000912:Antibodies, Neoplasm; D018396:Mucin-1