Prospective case-control study of serum mullerian inhibiting substance and breast cancer risk.
BACKGROUND
Müllerian inhibiting substance (MIS) is a member of the transforming growth factor beta family of growth and differentiation factors that inhibits elongation and branching of mammary ducts and has been shown to inhibit mammary tumor growth in vitro and in animal models. The objective of this study was to determine whether serum MIS levels are associated with breast cancer risk.


METHODS
We conducted a prospective case-control study of 309 participants who were registered in the Columbia, Missouri Serum Bank. Each of 105 in situ or invasive breast cancer case patients with prediagnostic serum collected before menopause was matched to two control subjects by age, date, menstrual cycle day, and time of day of blood collection. MIS was measured in serum by using an enzyme-linked immunosorbent assay, and estradiol and testosterone concentrations were quantified by using specific radioimmunoassays. Data were analyzed using conditional logistic regression. All tests of statistical significance were two-sided.


RESULTS
The relative odds ratio of breast cancer for women in increasing MIS quartiles were 1, 2.8 (95% confidence interval [CI] = 1.0 to 7.4), 5.9 (95% CI = 2.4 to 14.6), and 9.8 (95% CI = 3.3 to 28.9, P(trend) < .001). The association of MIS with breast cancer was weaker in women who were not taking oral contraceptives at the time of blood collection, but adjustment for estradiol and testosterone levels did not materially alter results for these women. The association of MIS with breast cancer did not vary by age at blood collection but was stronger among women who were diagnosed with breast cancer at an older age than among those who were diagnosed at a younger age.


CONCLUSIONS
MIS may be a novel biomarker of increased breast cancer risk. Additional research including confirmatory epidemiological studies and mechanistic studies is needed.
Dorgan
Joanne F
JF
Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA. joanne.dorgan@fccc.edu
Stanczyk
Frank Z
FZ
Egleston
Brian L
BL
Kahle
Lisa L
LL
Shaw
Christiana M
CM
Spittle
Cynthia S
CS
Godwin
Andrew K
AK
Brinton
Louise A
LA
D000328:Adult; D000367:Age Factors; D054304:Anti-Mullerian Hormone / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001771:Blood Banks; D001943:Breast Neoplasms / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D008923:Missouri; D016017:Odds Ratio; D017697:Premenopause; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
D014408:Biomarkers, Tumor; D054304:Anti-Mullerian Hormone