TY - JOUR
T1 - A Prospective Evaluation of Endogenous Sex Hormone Levels and Colorectal Cancer Risk in Postmenopausal Women
AU - Murphy, Neil
AU - Strickler, Howard D.
AU - Stanczyk, Frank Z.
AU - Xue, Xiaonan
AU - Wassertheil-Smoller, Sylvia
AU - Rohan, Thomas E.
AU - Ho, Gloria Y.F.
AU - Anderson, Garnet L.
AU - Potter, John D.
AU - Gunter, Marc J.
N1 - Publisher Copyright:
© 2015 The Author.
PY - 2015/10
Y1 - 2015/10
N2 - Background: Postmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain. Methods: The relation of colorectal cancer risk with circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone and sex hormone-binding globulin (SHBG) was determined in a nested case-control study of 1203 postmenopausal women (401 case patients and 802 age and race/ethnicity-matched control patients) enrolled in the Women's Health Initiative Clinical Trial (WHI-CT) who were not assigned to the estrogen-alone or combined estrogen plus progestin intervention groups. We used multivariable-adjusted conditional logistic regression models that included established colorectal cancer risk factors. All statistical tests were two-sided. Results: Comparing extreme quartiles, estrone (odds ratio [OR]q4-q1 = 0.44, 95% confidence interval [CI] = 0.28 to 0.68, P trend =. 001), free estradiol (ORq4-q1 = 0.43, 95% CI = 0.27 to 0.69, P trend ≤. 0001), and total estradiol (ORq4-q1 = 0.58, 95% CI = 0.38 to 0.90, P trend =. 08) were inversely associated with colorectal cancer risk. SHBG levels were positively associated with colorectal cancer development (OR[q4-q1] = 2.30, 95% CI = 1.51 to 3.51, P trend ≤. 0001); this association strengthened after further adjustment for estradiol and estrone (ORq4-q1 = 2.50, 95% CI = 1.59 to 3.92, P trend <. 0001). Progesterone was not associated with colorectal cancer risk. Conclusion: Endogenous estrogen levels were inversely, and SHBG levels positively, associated with colorectal cancer risk, even after control for several colorectal cancer risk factors. These results suggest that endogenous estrogens may confer protection against colorectal tumorigenesis among postmenopausal women.
AB - Background: Postmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain. Methods: The relation of colorectal cancer risk with circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone and sex hormone-binding globulin (SHBG) was determined in a nested case-control study of 1203 postmenopausal women (401 case patients and 802 age and race/ethnicity-matched control patients) enrolled in the Women's Health Initiative Clinical Trial (WHI-CT) who were not assigned to the estrogen-alone or combined estrogen plus progestin intervention groups. We used multivariable-adjusted conditional logistic regression models that included established colorectal cancer risk factors. All statistical tests were two-sided. Results: Comparing extreme quartiles, estrone (odds ratio [OR]q4-q1 = 0.44, 95% confidence interval [CI] = 0.28 to 0.68, P trend =. 001), free estradiol (ORq4-q1 = 0.43, 95% CI = 0.27 to 0.69, P trend ≤. 0001), and total estradiol (ORq4-q1 = 0.58, 95% CI = 0.38 to 0.90, P trend =. 08) were inversely associated with colorectal cancer risk. SHBG levels were positively associated with colorectal cancer development (OR[q4-q1] = 2.30, 95% CI = 1.51 to 3.51, P trend ≤. 0001); this association strengthened after further adjustment for estradiol and estrone (ORq4-q1 = 2.50, 95% CI = 1.59 to 3.92, P trend <. 0001). Progesterone was not associated with colorectal cancer risk. Conclusion: Endogenous estrogen levels were inversely, and SHBG levels positively, associated with colorectal cancer risk, even after control for several colorectal cancer risk factors. These results suggest that endogenous estrogens may confer protection against colorectal tumorigenesis among postmenopausal women.
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U2 - 10.1093/jnci/djv210
DO - 10.1093/jnci/djv210
M3 - Article
C2 - 26232761
AN - SCOPUS:84944681655
SN - 0027-8874
VL - 107
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 10
M1 - djv210
ER -