BMC Med: "It's good to have a few more" evidence +1! 46% lower risk of endometrial cancer!

Endometrial cancer is the sixth most common cancer in women worldwide and its incidence is increasing
worldwide, especially in developing countries.
Many observational studies have shown a relationship
between different factors and EC risk.
In particular, late menarche, early menopause, and the use of some forms of oral contraceptives have been observed to be associated with
a reduced risk of EC.
One possible explanation for these associations is that higher lifetime estrogen exposure increases EC risk
.
This may explain why reproductive duration segments (i.
e.
, late menarche and early menopause) are associated
with EC protection in observational epidemiological studies.

However, it is unclear whether these relationships are causal and whether the risk factors are independent
of each other.
Therefore, this study performed a series of observational analyses to investigate various risk factors and EC risks
in the UK Biobank (UKBB).
In addition, multivariate analyses were performed to elucidate the relationship between the number of live births, age at last live birth, years of ovulation, and other relevant factors such as age at natural menopause, age at menarche, and body mass index (BMI).

Second, Mendelian randomization (MR) is used to assess whether these observed relationships are causal
.
Genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from previous studies of female live births, age at menopause and menarche, and BMI
.
A genome-wide association analysis was performed using UKBB to identify SNPs
associated with years of ovulation, years of contraceptive use, and age at last live birth.

The results showed that in univariate MR analysis, in addition to the known risk factors BMI, age at menarche, and age at menopause, the researchers also found evidence of
a causal effect of live births (inverse variance weighted (IVW) odds ratio (OR): 0.
537, p=0.
006), years of ovulation (IVW OR: 1.
051, p=0.
014) on EC risk.
Based on the close relationship between these factors, the researchers followed up with a multivariate MR (MVMR) analysis
.
The results of MVMR analysis showed that the number of live births was causally related to EC risk (OR: 0.
783, p=0.
036), independent of
BMI, age at menarche, and age at menopause.

Overall, the researchers found evidence that BMI, age at menarche, and number of live births all had independent causal effects
on EC risk.
To our knowledge, this is the first study to report that the number of live births may have a protective effect against EC risk, even after accounting for other risk factors
.
However, this analysis suggests that the causal effect of the number of live births on EC risk may be driven by the age at which women last gave birth, a relationship that requires further study
.
Observational analysis showed that the age of ovulation and contraceptive use had a significant effect on EC risk; However, we were unable to replicate this
in the MR analysis.

Original source:

D'Urso S, Arumugam P, Weider T, Hwang LD, Bond TA, Kemp JP, Warrington NM, Evans DM, O'Mara TA, Moen GH.
Mendelian randomization analysis of factors related to ovulation and reproductive function and endometrial cancer risk.
BMC Med.
2022 Nov 1; 20(1):419.
doi: 10.
1186/s12916-022-02585-w.
PMID: 36320039; PMCID: PMC9623961.