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Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location.

ABSTRACT: 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; P het =.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; P het =.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.

SUBMITTER: Labadie JD

PROVIDER: S-EPMC7477374 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location.

Labadie Julia D JD Harrison Tabitha A TA Banbury Barbara B Amtay Efrat L EL Bernd Sonja S Brenner Hermann H Buchanan Daniel D DD Campbell Peter T PT Cao Yin Y Chan Andrew T AT Chang-Claude Jenny J English Dallas D Figueiredo Jane C JC Gallinger Steven J SJ Giles Graham G GG Gunter Marc J MJ Hoffmeister Michael M Hsu Li L Jenkins Mark A MA Lin Yi Y Milne Roger L RL Moreno Victor V Murphy Neil N Ogino Shuji S Phipps Amanda I AI Sakoda Lori C LC Slattery Martha L ML Southey Melissa C MC Sun Wei W Thibodeau Stephen N SN Van Guelpen Bethany B Zaidi Syed H SH Peters Ulrike U Newcomb Polly A PA

JNCI cancer spectrum 20200519 5

<h4>Background</h4>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.<h4>Methods</h4>We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, <i>BRAF</i> and <i>KRAS</i> mutations, pathway: adenoma-carcinoma, alternate, se ...[more]

PMID: 32923935

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Dataset Information

Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location.

Publications

Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location.

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