Variables Affecting CA15.3 Tumor Antigen Expression and Antibodies against It in Female National Health and Nutritional Survey Participants

Author:

Cramer Daniel W.123ORCID,Vitonis Allison F.1ORCID,Fichorova Raina N.24ORCID,Yamamoto Hidemi S.4ORCID,Mudugno Francesmary567ORCID,Finn Olivera J.8ORCID

Affiliation:

1. Department of Obstetrics and Gynecology, Epidemiology Center, Brigham and Women’s Hospital, Boston, Massachusetts. 1

2. Harvard Medical School, Boston, Massachusetts. 2

3. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. 3

4. Genital Tract Biology, Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Boston, Massachusetts. 4

5. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 5

6. Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania. 6

7. Womens Cancer Research Center Magee-Womens Research Institute and Foundation and Hillman Cancer Center, Pittsburgh, Pennsylvania. 7

8. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 8

Abstract

Abstract Background: Cancers of ductal origin often express glycoprotein mucin 1 (MUC1), also known as CA15.3, with higher levels leading to poor prognosis. Conversely, anti-MUC1 antibodies develop in some patients, leading to better prognosis. We sought to identify epidemiologic factors associated with CA15.3 antigen or antibody levels. Methods: Levels of CA15.3 antigen and anti-CA15.3 IgG antibodies were measured in archived sera from 2,302 mostly healthy women from the National Health and Nutritional Survey; and epidemiologic predictors of their levels were examined using multivariate and correlational analyses. Results: Among racial groups, Black women had the highest levels of CA15.3 antigen and lowest levels of antibodies. Increasing body mass index and current smoking were associated with low anti-CA15.3 antibody levels. Low CA15.3 antigen levels were seen in oral contraceptive users and high levels in women who were pregnant or lactating at the time of blood collection, with the latter group also having high antibody levels. Past reproductive events associated with high antigen levels included the following: later age at menarche, having given birth, and history of endometriosis. Lower antigen levels were seen with increasing duration of OC use. Anti-CA15.3 antibody levels decreased with an increasing estimated number of ovulatory years. Conclusions: Key determinants of CA.15.3 antigen or antibody levels include the following: race, body mass index, smoking, later menarche, childbirth, number of ovulatory cycles, and endometriosis. Impact: This study supports the premise that known epidemiologic factors affecting risk for or survival after MUC1-expressing cancers may, at least partially, operate through their association with CA15.3 antigen or antibody levels.

Funder

National Institutes of Health

Publisher

American Association for Cancer Research (AACR)

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