Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Cancer. A Population-Based Study

Hyde, Zoë; Flicker, Leon; McCaul, Kieran; Almeida, Osvaldo P.; Hankey, Graeme J.; Chubb, S. A. Paul; Yeap, Bu B.

doi:10.1158/1055-9965.epi-12-0129

Cited by 77 publications

(58 citation statements)

References 55 publications

(47 reference statements)

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“…Testosterone levels in the lowest quartile at baseline was significantly associated with the subsequent development of MetS and diabetes in one study (Laaksonen et al, 2004), but not with the development of T2DM in another study (Chen et al, 2006). Higher TT was associated with incident lung but not prostate or colorectal cancer (Hyde et al, 2012a).…”

Section: Morbiditymentioning

confidence: 90%

“…Morbidity was examined in nine studies (Laaksonen et al, 2004;Muller et al, 2004;Chen et al, 2006;Fink et al, 2006;Vikan et al, 2009;Yeap et al, 2009;Corona et al, 2010;Yilmaz et al, 2011;Hyde et al, 2012a) and included CVD events, rapid bone loss, T2DM, MetS and cancer, and was studied in population-based studies and disease-specific studies. Low T at baseline was significantly related to subsequent CVD morbidity in three (Muller et al, 2004;Yeap et al, 2009;Yilmaz et al, 2011) of five (Muller et al, 2004;Vikan et al, 2009;Yeap et al, 2009;Corona et al, 2010;Yilmaz et al, 2011) studies and to subsequent rapid bone loss (Fink et al, 2006) in one study.…”

Section: Morbiditymentioning

confidence: 99%

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Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men

et al. 2014

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SUMMARYThe objective of this review was to summarize the literature on the risk factors, comorbidities, and consequences of male hypogonadism, which is defined as a syndrome complex that includes biochemical confirmation of low testosterone (T) and the consistent symptoms and signs associated with low T. A systematic literature search was performed in PubMed/MEDLINE, EMBASE, Cochrane Library for articles published in the last 10 years on risk factors, comorbidities, and consequences of male hypogonadism. Of the 53 relevant studies identified, nine examined potential risk factors, 14 examined potential comorbidities, and 30 examined potential consequences of male hypogonadism. Based on studies conducted in Asia, Australia, Europe, and North & South America, the important factors that predicted and correlated with hypogonadism were advanced age, obesity, a diagnosis of metabolic syndrome (MetS), and a poor general health status. Diabetes mellitus was correlated with hypogonadism in most studies, but was not established as a risk factor. Although diseases, such as coronary heart disease, hypertension, stroke, and peripheral arterial disease did not predict hypogonadism, they did correlate with incident low T. The data reviewed on potential consequences suggest that low T levels may be linked to earlier all-cause and cardiovascular related mortality among men. This literature review suggests that men with certain factors, such as advanced age, obesity, MetS, and poor general health, are more likely to have and develop hypogonadism. Low levels of T may have important long-term negative health consequences.

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Section: Morbiditymentioning

confidence: 90%

Section: Morbiditymentioning

confidence: 99%

Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men

et al. 2014

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“…Moreover, the mitochondrial defects that we observed in the rank mutant lung tumors were present in both genders, and we observed apparently similar induction of PGC1β in male and female pneumocytes, although we cannot exclude subtle differences between the genders. Whether male sex hormones also affect lung cancer via RANKL/ RANK, which are also regulated by testosterone (Hyde et al 2012), needs to be determined. It would be also interesting to test in future experiments using different lung cancer models whether RANK might affect regional and cell type-specific differences in lung tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer

Sigl

Wimmer

et al. 2017

Genes Dev.

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Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer.

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“…Both male and female hormones are products of oxidative metabolism of cholesterol and their biosynthetic pathways are closely interrelated (15). Testosterone is the most important androgen and plays key roles in health and well-being in both males and females (16). Likewise, estradiol and progesterone are female hormones and essential for a variety of physiological processes in both males and females (17).…”

Section: Discussionmentioning

confidence: 99%

Decreased levels of circulating sex hormones as a biomarker of lung cancer in male patients with solitary pulmonary nodules

Gu¹,

Wen²,

Xu³

et al. 2014

Afr H. Sci.

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Associations between Testosterone Levels and Incident Prostate, Lung, and Colorectal Cancer. A Population-Based Study

Cited by 77 publications

References 55 publications

Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men

Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer

Decreased levels of circulating sex hormones as a biomarker of lung cancer in male patients with solitary pulmonary nodules

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