Men with increased sex hormone-binding globulin (SHBG) have a corresponding increased risk of gastric cancer but decreased risk of colorectal cancer, while higher free testosterone may be protective against esophageal squamous cell carcinoma and colorectal cancer in women, according to the results of a study in The American Journal of Gastroenterology.

The study, conducted by a team of UK and US researchers, was an analysis of patient data from the UK Biobank. A total of 220,150 men and 147,180 women from this cohort were included in this analysis. The researchers collected data on sex hormone concentrations and cancer incidence over a 10-year follow-up period via cancer registry linkages.

The investigators evaluated 333 cases of esophageal adenocarcinoma in men and 43 cases in women. Esophageal squamous cell carcinoma was recorded in 57 men and 51 women, and gastric cancer was recorded in 256 men and 77 women. Additionally, colorectal cancer was found in 1892 men and 976 women.

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The researchers found a higher risk of gastric cancer with higher SHBG in men (Q4 vs Q1: hazard ratio [HR], 1.43; 95% CI, 0.95-2.17; Ptrend =.01). An inverse association between free testosterone and esophageal squamous cell carcinoma was noted in women (Q4 vs Q1: HR, 0.32; 95% CI, 0.110.98; Ptrend =.05).

Higher SHBG was associated with a significantly reduced risk of colorectal cancer in men (Q4 vs Q1: HR, 0.89; 95% CI, 0.77–1.03; Ptrend =.04), while higher free testosterone was associated with a reduced risk of colorectal cancer in women (Q4 vs Q1: HR, 0.80; 95% CI, 0.66-0.97; Ptrend =.01).

The researchers of this study indicated they could not rule out possible residual confounding factors in their research, including diabetes duration, colonoscopy, and number of pack years of smoking.

Additional prospective studies, particularly among women, are required to verify these novel findings to determine the utility of sex hormone modulation in the prevention of gastrointestinal cancers.


McMenamin ÚC, Liu P, Kunzmann AT, et al. Circulating sex hormones are associated with gastric and colorectal cancers but not esophageal adenocarcinoma in the UK Biobank. Published online November 4, 2020. Am J Gastroenterol. doi:10.14309/ajg.0000000000001045

This article originally appeared on Gastroenterology Advisor