Higher levels of certain sex hormones are associated with an increased risk of some gastrointestinal cancers, according to research published in Cancer Epidemiology, Biomarkers, and Prevention.
Researchers found that higher levels of sex hormone-binding globulin (SHBG) were associated with an increased risk of gastric cancer and liver cancer. Higher levels of testosterone were associated with an increased risk of liver cancer as well. However, neither SHBG nor testosterone were associated with esophageal cancer, pancreatic cancer, or colorectal cancer.
To uncover these findings, researchers conducted a meta-analysis of 29 prospective cohort, nested case-control, and case-cohort studies. The studies were conducted in the United States, Europe, Asia, and Australia.
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In 5 studies, researchers examined associations between esophageal cancer and circulating levels of 6 sex hormones (testosterone, free testosterone, androstenedione, estradiol, testosterone/estradiol ratio, and SHBG). There were no associations between levels of these hormones and the overall risk of esophageal cancer.
Another 5 studies were designed to uncover associations between gastric cancer and levels of 6 sex hormones (testosterone, free testosterone, androstenedione, estrone, estradiol, and SHBG). There were no associations between levels of 5 hormones and the overall risk of gastric cancer.
However, higher levels of SHBG were associated with an increased risk of gastric cancer (odds ratio [OR], 1.35; 95% CI, 1.06-1.72). In subgroup analyses, this increased risk was seen in:
- Men (OR, 1.43; 95% CI, 1.10-1.85)
- Asian populations (OR, 1.71; 95% CI, 1.01-2.90)
- Studies with a follow-up of 10 years or more (OR, 1.71; 95% CI, 1.01-2.90).
There were 11 studies in which researchers examined associations between liver cancer and levels of 5 sex hormones (testosterone, free testosterone, estradiol, testosterone/estradiol ratio, and SHBG). Higher levels of SHBG were associated with an increased risk of liver cancer (OR, 2.07; 95% CI, 1.40-3.06). In subgroup analyses, this increased risk was seen in:
- Postmenopausal women (OR, 1.58; 95% CI, 1.09-2.29)
- Patients with hepatocellular carcinoma (OR, 2.92; 95% CI, 1.19-7.14)
- Studies with a follow-up of less than 10 years (OR, 2.20; 95% CI, 1.34-3.63).
Higher levels of testosterone were associated with an increased risk of liver cancer as well (OR, 2.10; 95% CI, 1.48-2.96). In subgroup analyses, this increased risk was seen in:
- Men (OR, 2.63; 95% CI, 1.65-4.18)
- Asian populations (OR, 3.27; 95% CI, 1.57-6.83)
- Patients with hepatitis B surface antigen (OR, 3.90; 95% CI, 1.43-10.64)
- Those with hepatocellular carcinoma (OR, 2.72; 95% CI, 1.52-4.87)
- Studies with follow-up of less than 10 years (OR, 2.55; 95% CI, 1.60-4.08).
There were 3 studies designed to assess the association between pancreatic cancer and levels of 5 sex hormones (testosterone, free testosterone, estradiol, free estradiol, and SHBG). Analyses revealed an association between free estradiol levels and a decreased risk of pancreatic cancer (OR, 0.68; 95% CI, 0.49-0.93) but no associations with the other hormones.
There were 15 studies in which researchers assessed associations between colorectal cancer and levels of 12 sex hormones (testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dihydrotestosterone, estrone, estradiol, free estradiol, estradiol/testosterone ratio, luteinizing hormone, progesterone, and SHBG). Analyses revealed no association between these hormones and the overall risk of colorectal cancer.
The researchers noted that more prospective studies are needed to further clarify associations between circulating sex hormone levels and the risk of gastrointestinal cancers.
Reference
Liu Z, Zhang Y, Lagergren J, et al. Circulating sex hormone levels and risk of gastrointestinal cancer: Systematic review and meta-analysis of prospective studies. Cancer Epidemiol Biomarkers Prev. Published online April 27, 2023. doi:10.1158/1055-9965.EPI-23-0039
