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Female Reproductive Traits and Late-Life Hormone-Sensitive Cancer Risk: A Mendelian Randomization Study.

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Summary
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Higher anti-Müllerian hormone (AMH) levels increase endometrial cancer risk but lower breast cancer risk. Later menopause age elevates risks for breast, ovarian, and endometrial cancers, highlighting key reproductive trait links to hormone-sensitive cancers.

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Area of Science:

  • Reproductive endocrinology
  • Oncology
  • Genetic epidemiology

Background:

  • Ovarian reserve and reproductive traits are vital for female fertility.
  • The causal links between ovarian reserve, reproductive traits, and hormone-sensitive cancers require further elucidation.

Purpose of the Study:

  • To investigate the potential causal effects of reproductive traits on hormone-sensitive cancers using Mendelian randomization.
  • To explore the mediating roles of reproductive traits in the relationship between ovarian reserve and hormone-sensitive cancers.

Main Methods:

  • Two-sample Mendelian randomization (MR) analyses were employed.
  • Multivariable MR was utilized to assess mediation effects.
  • Genetic variants associated with anti-Müllerian hormone (AMH), age at menarche, age at natural menopause, and nulliparity were used as instrumental variables.

Main Results:

  • Increased anti-Müllerian hormone (AMH) levels were associated with higher endometrial cancer risk (OR=1.27) and lower breast cancer risk (OR=0.80).
  • Later age at natural menopause correlated with increased risks of breast (OR=1.04), ovarian (OR=1.03), and endometrial cancers (OR=1.07).
  • Nulliparity was linked to an increased risk of breast cancer (OR=1.07).
  • Later age at natural menopause partially mediated the effect of AMH on endometrial cancer risk (2.67%) and age at menarche on endometrial cancer risk (4.71%).

Conclusions:

  • Anti-Müllerian hormone (AMH) may serve as a significant biological marker for endometrial and breast cancer risk.
  • Age at natural menopause is a critical factor influencing the risk of multiple hormone-sensitive cancers.
  • These findings enhance the understanding of the underlying mechanisms of hormone-sensitive cancers.