Association Between Thyroid Disorders and Colorectal Cancer Risk in Adult Patients in Taiwan

L'Heureux, Abby; Wieland, Daniel R.; Weng, Chien‐Huan; Chen, Yi-Huei; Lin, Ching‐Heng; Lin, Tseng‐Hsi; Weng, Chien‐Hsiang

doi:10.1001/jamanetworkopen.2019.3755

Cited by 30 publications

(22 citation statements)

References 49 publications

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“…The association between thyroid hormone and cancers has been investigated in many in vivo and in vitro studies, as early as 1896 when Beaston published on using thyroid extract to treat metastatic breast cancer in the Lancet (4,9,19,25,26). Specific alterations of thyroid hormone receptors (TRs) have been found in many different types of cancers, including breast cancer, and there are associations between TR expression and oncogene regulation (4,5,27,28).…”

Section: Discussionmentioning

confidence: 99%

Breast Cancer Risk in Postmenopausal Women with Medical History of Thyroid Disorder in the Women's Health Initiative

Weng

Okawa

Roberts

et al. 2020

Thyroid

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Background: The association between thyroid disorders and breast cancer remains controversial, in part, due to small cohort sizes and inconsistent findings. We investigated this association in postmenopausal women to determine whether hyper-or hypothyroidism is associated with the risk of developing breast cancer and to determine whether menopausal hormone therapy (MHT) further modifies the risk. Methods: We conducted a prospective cohort study of multiethnic U.S. postmenopausal women aged 50 to 79 years enrolled in both clinical trial and observational study arms between 1993 and 1998 and followed up through February 28, 2017. Development of invasive breast cancer after enrollment was recorded and a history of hyper-or hypothyroidism before the diagnosis of breast cancer was identified. The effect modification by MHT in both study arms was analyzed. All statistical tests were two sided. Results: Among a total of 134,122 women who were included in our study, 8137 participants developed invasive breast cancer during the follow-up period. There was a significant inverse association of invasive breast cancer among women with a history of hypothyroidism (hazard ratio [HR] 0.91, confidence interval [95% CI] 0.86-0.97) and among women who had taken levothyroxine [HR 0.89, 95% CI 0.82-0.96]. Evaluating effect modification by MHT use, the inverse association between hypothyroidism treated with thyroid replacement medications and breast cancer risk was strongest in non-MHT users [HR 0.80, 95% CI 0.69-0.93]. The results did not significantly differ by race/ethnicity. Although a history of hyperthyroidism was associated with an increased risk of invasive breast cancer [HR 1.11, 95% CI 0.91-1.35], this finding did not reach statistical significance. We did not see significant differences in the breast cancer Surveillance, Epidemiology, and End Results stages, histologic types, morphologic grades, or receptor status (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2) according to thyroid disorder status. Conclusions: Compared with women with no history of thyroid disorder, hypothyroidism was associated with a lower risk of breast cancer. This was mainly seen among those who received thyroid replacement therapy and had never used MHT. Among the treatment options for hypothyroidism, levothyroxine had the strongest inverse association with breast cancer risk.

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Section: Discussionmentioning

confidence: 99%

Breast Cancer Risk in Postmenopausal Women with Medical History of Thyroid Disorder in the Women's Health Initiative

Weng

Okawa

Roberts

et al. 2020

Thyroid

Self Cite

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“…Figure 6b illustrates the heatmap showing differences in expression levels of these biomarkers among the four CMS subtypes. As a result, we found that several statistically significant terms showed demonstrably closed relationships between COADREAD versus type I diabetes mellitus (hsa04940, adjusted P-value = 0.04, Supplementary Table S11) [24], versus autoimmune thyroid disease (hsa05320, adjusted P-value = 0.04, Supplementary Table S11) [25, 26], and versus Inflammatory bowel disease (hsa05321, adjusted P-value = 0.04, Supplementary Table S11) [27].…”

Section: Resultsmentioning

confidence: 99%

A biphasic Deep Semi-supervised framework for Suptype Classification and biomarker discovery

Le¹,

Nguyen²,

Nguyen³

et al. 2022

Preprint

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To take full advantage of the unprecedented development of -omics technologies and generate further biological insights into human disease, it is a pressing need to develop novel computational methods for integrative analysis of multi-omics data. Here we proposed a biphasic Deep Semi-supervised multi-omics integration framework for Subtype Classification and biomarker discovery, DeepSSC. In phase 1, each denoising autoencoder was used to extract a compact representation for each -omics data, and then they were concatenated and put into a feed-forward neural network for subtype classification. In phase 2, our Biomarker Gene Identification procedure leveraged that neural network classifier to render subtype-specific important biomarkers. We also validated our given results on independent dataset. We demonstrated that DeepSSC exhibited better performance over other state-of-the-art techniques concerning classification tasks. As a result, DeepSSC successfully detected well-known biomarkers and hinted at novel candidates from different -omics data types related to the investigated biomedical problems.

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“…( 12) Interestingly, in a subgroup analysis for use of levothyroxine by patients with hypothyroidism, the association between hypothyroidism and a lower risk of CRC was no longer observed (adjusted OR 0.93 [0.66-1.30]). (12) In general, evidence linking CRC onset and levothyroxine intake remains controversial as distinct studies find varying results of the use of levothyroxine and the risk of CRC.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies found evidence for a protective effect of levothyroxine, while others found no association. (10)(11)(12)(13) Furthermore, some of these 6 studies are limited by including a relatively small number of patients, relying on self-reported information, and lacking details on the dose and duration of levothyroxine use as well as tumour location and staging.…”

Section: Introductionmentioning

confidence: 99%

Levothyroxine use and the risk of colorectal cancer: a large population-based case–control study

Kuiper

Fenneman

Spek

et al. 2022

Endocrine Connections

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Objective: Whether an association between oral levothyroxine use, leading to supraphysiological exposure of the colon to thyroid hormones, and risk of colorectal cancer exists in humans is unclear. We therefore aimed to assess whether the use of levothyroxine is associated with a reduced risk of colorectal cancer in a linked cohort of pharmacy and cancer data. Design: Population-based matched case-control study. Methods: A total of 28,121 patients diagnosed with colorectal cancer between 1998-2014 were matched to 106,086 controls. Multivariable logistic regression was used to estimate the association between levothyroxine use and occurrence of colorectal cancer, adjusted for potential confounders. Results were stratified by gender, age, tumour subtype and staging as well as treatment duration and dosing. Results: A total of 1066 colorectal cancer patients (4%) and 4024 (4%) controls had used levothyroxine at any point before index date (adjusted odds ratio 0.95 [0.88-1.01]). Long-term use of levothyroxine was seen in 323 (30%) colorectal cancer patients and 1111 (28%) controls (adjusted odds ratio 1.00 [0.88-1.13]). Stratification by tumour subsite showed a borderline significant risk reduction of rectal cancer, while this was not seen for proximal colon cancer or distal colon cancer. There was no relationship with treatment duration or with levothyroxine dose. Conclusions: In this study, no reduced risk of colorectal cancer was seen in levothyroxine users. When stratifying by tumour subsite, a borderline significant risk reduction of rectal cancer was found and may warrant further research.

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Association Between Thyroid Disorders and Colorectal Cancer Risk in Adult Patients in Taiwan

Cited by 30 publications

References 49 publications

Breast Cancer Risk in Postmenopausal Women with Medical History of Thyroid Disorder in the Women's Health Initiative

Breast Cancer Risk in Postmenopausal Women with Medical History of Thyroid Disorder in the Women's Health Initiative

A biphasic Deep Semi-supervised framework for Suptype Classification and biomarker discovery

Levothyroxine use and the risk of colorectal cancer: a large population-based case–control study

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