Reproductive and Hormonal Risk Factors for Antinuclear Antibodies (ANA) in a Representative Sample of U.S. Women

Overview

Journal Cancer Epidemiol Biomarkers Prev

Specialties Biochemistry
Oncology
Public Health

Date 2014 Aug 3

PMID 25086100

Citations 22

Authors

Christine G Parks

Frederick W Miller

Minoru Satoh

Edward K L Chan

Zhanna Andrushchenko

Linda S Birnbaum

Todd A Jusko

Grace E Kissling

Mehul D Patel

Kathryn M Rose

Clarice Weinberg

Darryl C Zeldin

Dale P Sandler

Affiliations

Soon will be listed here.

Abstract

Background: Autoantibodies are of growing interest in cancer research as potential biomarkers; yet, the determinants of autoimmunity are not well understood. Antinuclear antibodies (ANA) are common in the general population and are more prevalent in women and older adults. Here, we examined the relationship of ANA with reproductive and hormonal factors in a representative sample of U.S. women.

Methods: We analyzed data on reproductive history and exogenous hormone use in relation to serum ANA in 2,037 females ages 12 years and older from the National Health and Nutrition Examination Survey (NHANES; 1999-2004). Estimated ANA prevalences were adjusted for sampling weights. Prevalence ORs (POR) and 95% confidence intervals (CI) were adjusted for age, race, and poverty-income ratio, and models were stratified by menopause status.

Results: In premenopausal women ages 20 years and older, ANA prevalence was associated with parity (P < 0.001; parous vs. nulliparous POR = 2.0; 95% CI, 1.2-3.4), but in parous women, ANA did not vary by number of births, age at first birth, years since last birth, or breastfeeding. In postmenopausal women, ANA prevalence was associated with an older age at menarche (P = 0.019; age 16-20 vs. 10-12 years POR = 3.0; 95% CI, 1.6-5.9), but not with parity. Oral contraceptives and estrogen therapy were not associated with a higher ANA prevalence.

Conclusions: Childbearing (having had one or more births) may explain age-associated elevations in ANA prevalence seen in premenopausal women.

Impact: These findings highlight the importance of considering reproductive history in studies of autoimmunity and cancer in women.

Citing Articles

Genetic Analysis of Asymptomatic Antinuclear Antibody Production.

Hocaolu M, Casares-Marfil D, Sawalha A Arthritis Rheumatol. 2024; 77(3):356-361.

PMID: 39420706 PMC: 11865687. DOI: 10.1002/art.43032.

Longitudinal antinuclear antibody titers in systemic lupus erythematosus and other rheumatic diseases.

Littlejohn E, Kong L, Wang L, Somers E Front Med (Lausanne). 2024; 11:1441221.

PMID: 39281812 PMC: 11393736. DOI: 10.3389/fmed.2024.1441221.

Tumor-Associated and Systemic Autoimmunity in Pre-Clinical Breast Cancer among Post-Menopausal Women.

Parks C, Wilson L, Capello M, Deane K, Hanash S Biomolecules. 2023; 13(11).

PMID: 38002248 PMC: 10669589. DOI: 10.3390/biom13111566.

Anti-dense fine speckled 70 (DFS70) autoantibodies: correlates and increasing prevalence in the United States.

Dinse G, Zheng B, Co C, Parks C, Weinberg C, Miller F Front Immunol. 2023; 14:1186439.

PMID: 37426660 PMC: 10326272. DOI: 10.3389/fimmu.2023.1186439.

Metal mixture exposures and multiplexed autoantibody screening in Navajo communities exposed to uranium mine wastes.

Erdei E, Shuey C, Miller C, Hoover J, Cajero M, Lewis J J Transl Autoimmun. 2023; 6:100201.

PMID: 37169001 PMC: 10165442. DOI: 10.1016/j.jtauto.2023.100201.

References

Fugazzola L, Cirello V, Beck-Peccoz P . Fetal microchimerism as an explanation of disease. Nat Rev Endocrinol. 2010; 7(2):89-97. DOI: 10.1038/nrendo.2010.216. View

Hanash S, Baik C, Kallioniemi O . Emerging molecular biomarkers--blood-based strategies to detect and monitor cancer. Nat Rev Clin Oncol. 2011; 8(3):142-50. DOI: 10.1038/nrclinonc.2010.220. View

DAloisio A, DeRoo L, Baird D, Weinberg C, Sandler D . Prenatal and infant exposures and age at menarche. Epidemiology. 2013; 24(2):277-84. PMC: 3563843. DOI: 10.1097/EDE.0b013e31828062b7. View

Jorgensen K, Pedersen B, Nielsen N, Jacobsen S, Frisch M . Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort. J Autoimmun. 2011; 38(2-3):J81-7. DOI: 10.1016/j.jaut.2011.06.004. View

Simard J, Karlson E, Costenbader K, Hernan M, Stampfer M, Liang M . Perinatal factors and adult-onset lupus. Arthritis Rheum. 2008; 59(8):1155-61. PMC: 2748190. DOI: 10.1002/art.23930. View

Quintero O, Amador-Patarroyo M, Montoya-Ortiz G, Rojas-Villarraga A, Anaya J . Autoimmune disease and gender: plausible mechanisms for the female predominance of autoimmunity. J Autoimmun. 2011; 38(2-3):J109-19. DOI: 10.1016/j.jaut.2011.10.003. View

Hooper B, Whittingham S, Mathews J, Mackay I, CURNOW D . Autoimmunity in a rural community. Clin Exp Immunol. 1972; 12(1):79-87. PMC: 1553644. View

Borchers A, Naguwa S, Keen C, Gershwin M . The implications of autoimmunity and pregnancy. J Autoimmun. 2009; 34(3):J287-99. DOI: 10.1016/j.jaut.2009.11.015. View

Boynton-Jarrett R, Harville E . A prospective study of childhood social hardships and age at menarche. Ann Epidemiol. 2012; 22(10):731-7. PMC: 3469794. DOI: 10.1016/j.annepidem.2012.08.005. View

10.

Pennell L, Galligan C, Fish E . Sex affects immunity. J Autoimmun. 2012; 38(2-3):J282-91. DOI: 10.1016/j.jaut.2011.11.013. View

11.

Brix T, Kyvik K, Hegedus L . Validity of self-reported hyperthyroidism and hypothyroidism: comparison of self-reported questionnaire data with medical record review. Thyroid. 2001; 11(8):769-73. DOI: 10.1089/10507250152484619. View

12.

Rockhill B, Colditz G, Rosner B . Bias in breast cancer analyses due to error in age at menopause. Am J Epidemiol. 2000; 151(4):404-8. DOI: 10.1093/oxfordjournals.aje.a010220. View

13.

Laustrup H, Heegaard N, Voss A, Green A, Lillevang S, Junker P . Autoantibodies and self-reported health complaints in relatives of systemic lupus erythematosus patients: a community based approach. Lupus. 2004; 13(10):792-9. DOI: 10.1191/0961203304lu2015oa. View

14.

Njemini R, Meyers I, Demanet C, Smitz J, Sosso M, Mets T . The prevalence of autoantibodies in an elderly sub-Saharan African population. Clin Exp Immunol. 2002; 127(1):99-106. PMC: 1906275. DOI: 10.1046/j.1365-2249.2002.01713.x. View

15.

Chao T, Ladd J, Qiu J, Johnson M, Israel R, Chin A . Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy. Proteomics Clin Appl. 2013; 7(5-6):327-36. PMC: 4681300. DOI: 10.1002/prca.201200058. View

16.

Satoh M, Chan E, Ho L, Rose K, Parks C, Cohn R . Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum. 2012; 64(7):2319-27. PMC: 3330150. DOI: 10.1002/art.34380. View

17.

Vella L, Yu M, Fuhrmann S, El-Amine M, Epperson D, Finn O . Healthy individuals have T-cell and antibody responses to the tumor antigen cyclin B1 that when elicited in mice protect from cancer. Proc Natl Acad Sci U S A. 2009; 106(33):14010-5. PMC: 2720407. DOI: 10.1073/pnas.0903225106. View

18.

Bellinger D, Lubahn C, Lorton D . Maternal and early life stress effects on immune function: relevance to immunotoxicology. J Immunotoxicol. 2009; 5(4):419-44. DOI: 10.1080/15476910802483415. View

19.

Gammill H, Guthrie K, Aydelotte T, Adams Waldorf K, Nelson J . Effect of parity on fetal and maternal microchimerism: interaction of grafts within a host?. Blood. 2010; 116(15):2706-12. PMC: 2974583. DOI: 10.1182/blood-2010-02-270942. View

20.

Mariz H, Sato E, Barbosa S, Rodrigues S, Dellavance A, Andrade L . Pattern on the antinuclear antibody-HEp-2 test is a critical parameter for discriminating antinuclear antibody-positive healthy individuals and patients with autoimmune rheumatic diseases. Arthritis Rheum. 2010; 63(1):191-200. DOI: 10.1002/art.30084. View