TY - JOUR
T1 - Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes and tumor location
AU - Labadie, Julia D.
AU - Harrison, Tabitha A.
AU - Banbury, Barbara
AU - Amtay, Efrat L.
AU - Bernd, Sonja
AU - Brenner, Hermann
AU - Buchanan, Daniel D.
AU - Campbell, Peter T.
AU - Cao, Yin
AU - Chan, Andrew T.
AU - Chang-Claude, Jenny
AU - Englishc, Dallas
AU - Figueiredo, Jane C.
AU - Gallingerc, Steven J.
AU - Gilesc, Graham G.
AU - Gunter, Marc J.
AU - Hoffmeisterc, Michael
AU - Hsu, Li
AU - Jenkins, Mark A.
AU - Lin, Yi
AU - Milnec, Roger L.
AU - Moreno, Victor
AU - Murphyc, Neil
AU - Ogino, Shuji
AU - Phipps, Amanda I.
AU - Sakoda, Lori C.
AU - Slattery, Martha L.
AU - Southey, Melissa C.
AU - Sun, Wei
AU - Thibodeau, Stephen N.
AU - Van Guelpen, Bethany
AU - Zaidi, Syed H.
AU - Peters, Ulrike
AU - Newcomb, Polly A.
N1 - Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: Adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2- sided. Results: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors. Conclusions: We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.
AB - Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: Adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2- sided. Results: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors. Conclusions: We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.
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U2 - 10.1093/JNCICS/PKAA042
DO - 10.1093/JNCICS/PKAA042
M3 - Article
AN - SCOPUS:85100740939
SN - 2515-5091
VL - 4
JO - JNCI Cancer Spectrum
JF - JNCI Cancer Spectrum
IS - 5
M1 - pkaa042
ER -
