Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study

Sci Rep. 2024 Oct 12;14(1):23891. doi: 10.1038/s41598-024-75305-4.

Abstract

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies on sex hormones and from the Trøndelag Health Study (HUNT) and large consortia on cancers. There was suggestive evidence of 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio 0.60, 95% confidence interval 0.37-0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry.

Keywords: Colorectal cancer; Estradiol; HUNT; Lung cancer; Mendelian randomization; Sex hormones.

MeSH terms

  • Colorectal Neoplasms* / epidemiology
  • Colorectal Neoplasms* / genetics
  • Female
  • Genome-Wide Association Study*
  • Gonadal Steroid Hormones* / metabolism
  • Humans
  • Lung Neoplasms* / epidemiology
  • Lung Neoplasms* / genetics
  • Mendelian Randomization Analysis*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sex Hormone-Binding Globulin / genetics
  • Sex Hormone-Binding Globulin / metabolism
  • Testosterone / blood
  • White People / genetics

Substances

  • Gonadal Steroid Hormones
  • Sex Hormone-Binding Globulin
  • Testosterone
  • SHBG protein, human