Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies

Liu, Zhiqiang; Zhang, Yingfan; Lagergren, Jesper; Li, Shanshan; Li, Jingru; Zhou, Zhixian; Hu, Zhijian; Xie, Shao-Hua

doi:10.1158/1055-9965.epi-23-0039

Cited by 6 publications

(6 citation statements)

References 72 publications

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“…This disparity might be attributed to the variation in dietary and behavioral habits between genders, such as alcohol consumption and smoking patterns. Additionally, biological factors, especially hormonal differences might play a pivotal role ( 54 ). However, our result contrasts with a prospective cohort involving 579 men and 551 women of older US adults diagnosed with CRC ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Garlic consumption and colorectal cancer risk in US adults: a large prospective cohort study

Jiang,

Chen,

et al. 2023

Front. Nutr.

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ObjectiveTo clarify the inconsistent findings of epidemiological studies on the association between dietary garlic consumption and colorectal cancer (CRC) incidence, by prospectively assessing the association in a large US population.MethodsData of 58,508 participants (aged 55–74) from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were analyzed. Dietary data were collected using a validated questionnaire. Multivariable Cox regression analysis determined hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline regression was used to investigate the non-linear relationship, and subgroup analysis was conducted to examine potential effect modifiers.ResultsDuring a median follow-up of 12.05 years, 782 CRC cases were documented, including 456 proximal colon cancer cases, 322 distal CRC cases, and 4 CRC cases with an unknown site. Moderate dietary garlic consumption was significantly associated with a reduced risk of overall CRC (HRquintile 3vs. 1: 0.70, 95% CI: 0.54 to 0.91, p = 0.007, P for trend: 0.434), exhibiting a U-shaped dose-response pattern, and also with overall CRC in males in the stratified Cox regression model (Model 2: HRquintile 3vs. 1: 0.57, 95% CI: 0.40 to 0.81, p = 0.002), but not in females. The protective association was more pronounced in men, Caucasian, and those with lower alcohol consumption. Notably, these protective effects were observed for overall distal CRC (HRquintile 3vs. 1: 0.62, 95% CI: 0.42 to 0.93, p = 0.021; and HRquintile 4vs. 1: 0.63, 95% CI: 0.43 to 0.92, p = 0.018, P for trend: 0.208); and for distal CRC in males (HRquintile 3vs. 1: 0.40, 95% CI: 0.22 to 0.71, p = 0.002, P for trend: 0.696), but not for proximal CRC.ConclusionModerate consumption of dietary garlic is associated with a decreased CRC risk in the US population, with variations based on CRC anatomic subsites. Further in-depth prospective studies are needed to validate these findings in different populations and to explore subsites-specific associations.

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Section: Discussionmentioning

confidence: 99%

Garlic consumption and colorectal cancer risk in US adults: a large prospective cohort study

Jiang,

Chen,

et al. 2023

Front. Nutr.

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“…Besides prostate cancer, the role of androgens in tumorigenesis is less studied compared to oestrogen. Higher concentrations of testosterone are associated with increased risk of liver cancer, particularly in men, while higher levels of DHEA, the adrenal precursor, are associated with a 53% decrease in risk ( 66 , 81 ). Higher circulating testosterone is associated with a decreased risk of CRC in men, but this is not shown in women ( 81 ).…”

Section: Androgens Ar and Tumour Pathophysiologymentioning

confidence: 99%

“…Higher concentrations of testosterone are associated with increased risk of liver cancer, particularly in men, while higher levels of DHEA, the adrenal precursor, are associated with a 53% decrease in risk ( 66 , 81 ). Higher circulating testosterone is associated with a decreased risk of CRC in men, but this is not shown in women ( 81 ). The association between testosterone and oesophageal cancer is unclear, with varying degrees of significance across studies ( 81 , 82 ).…”

Section: Androgens Ar and Tumour Pathophysiologymentioning

confidence: 99%

“…Higher circulating testosterone is associated with a decreased risk of CRC in men, but this is not shown in women ( 81 ). The association between testosterone and oesophageal cancer is unclear, with varying degrees of significance across studies ( 81 , 82 ). Gastric, pancreatic and bladder cancers are also shown to have no significant association with testosterone levels ( 81 ).…”

Section: Androgens Ar and Tumour Pathophysiologymentioning

confidence: 99%

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Sex differences in cancer and immunotherapy outcomes: the role of androgen receptor

Zhao,

Wang,

Tan

et al. 2024

Front. Immunol.

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Across the wide range of clinical conditions, there exists a sex imbalance where biological females are more prone to autoimmune diseases and males to some cancers. These discrepancies are the combinatory consequence of lifestyle and environmental factors such as smoking, alcohol consumption, obesity, and oncogenic viruses, as well as other intrinsic biological traits including sex chromosomes and sex hormones. While the emergence of immuno-oncology (I/O) has revolutionised cancer care, the efficacy across multiple cancers may be limited because of a complex, dynamic interplay between the tumour and its microenvironment (TME). Indeed, sex and gender can also influence the varying effectiveness of I/O. Androgen receptor (AR) plays an important role in tumorigenesis and in shaping the TME. Here, we lay out the epidemiological context of sex disparity in cancer and then review the current literature on how AR signalling contributes to such observation via altered tumour development and immunology. We offer insights into AR-mediated immunosuppressive mechanisms, with the hope of translating preclinical and clinical evidence in gender oncology into improved outcomes in personalised, I/O-based cancer care.

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“…In a reanalysis of nine prospective studies, it was found that the levels of testosterone examined were significantly associated with an increased risk of breast cancer [ 7 ]. Conversely, another systematic review and meta-analysis of prospective studies suggested that circulating levels of SHBG and testosterone may affect the risk of gastric, liver, and colorectal cancer, but not in women [ 8 ]. Additionally, a prospective cohort study indicated that a doubling in female testosterone levels was associated with multifactorially adjusted hazard ratios of 2.21 (1.39–3.51; P = 0.001) for bladder cancer and 2.11 (1.09–2.32; P = 0.04) for liver cancer.…”

Section: Introductionmentioning

confidence: 99%

Association between testosterone and cancers risk in women: a two-sample Mendelian randomization study

Li,

Wang,

Hua

et al. 2023

Discov Onc

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Objective Previous observational studies have explored the correlation between testosterone and cancer risk. However, the causal association between testosterone and various cancer types in women remains inconclusive. The objective of this Mendelian randomization study is to evaluate the causal links between total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in females. Methods Initially, a rigorous quality control process was employed to identify suitable instrumental single nucleotide polymorphisms (SNPs) associated with the exposure under investigation that exhibited a significant association. The genetic causal relationship between female testosterone levels and the risk of developing cancers was examined through a two-sample Mendelian randomization. Various analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were applied in the investigation. Key findings were primarily based on the results obtained via IVW (random effects), and sensitivity analyses were conducted to assess the reliability of the obtained results. Furthermore, maximum likelihood, penalized weighted median, and IVW (fixed effects) methods were utilized to further validate the robustness of the results. Results Based on the results of IVW analysis, our study indicated a positive causal relationship between BT and breast cancer (OR = 1.1407, 95%CI: 1.0627–1.2244, P = 0.0015) and endometrial cancer (OR = 1.4610, 95%CI: 1.2695–1.6813, P = 1.22E-06). Moreover, our findings also showed a positive causal association between TT and breast cancer (OR = 1.1764, 95%CI: 1.0846–1.2761, P = 0.0005), cervical cancer(OR = 1.0020, 95%CI: 1.0007–1.0032, P = 0.0077), and endometrial cancer(OR = 1.4124, 95%CI: 1.2083–1.6511, P = 0.0001). Additionally, our results demonstrated a negative causal relationship between BT and ovarian cancer (OR = 0.8649, 95%CI: 0.7750–0.9653, P = 0.0320). However, no causal relationship was found between BT, TT and other types of cancer (corrected P > 0.05). Conclusions This study elucidates the role of testosterone on the development of breast cancer, endometrial cancer, ovarian cancer, and cervical cancer. It also hints at a potential but fragile link between testosterone and bladder cancer, as well as thyroid cancer. Nonetheless, it's worth noting that no statistically significant relationship between testosterone and various other types of cancer in females was identified.

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Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies

Cited by 6 publications

References 72 publications

Garlic consumption and colorectal cancer risk in US adults: a large prospective cohort study

Garlic consumption and colorectal cancer risk in US adults: a large prospective cohort study

Sex differences in cancer and immunotherapy outcomes: the role of androgen receptor

Association between testosterone and cancers risk in women: a two-sample Mendelian randomization study

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