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Endometrial cancer risk is lower for women who have given birth

The more children a woman gives birth to, the fewer chances she has to get endometrial cancer – study findings

Sad statistics – industrialization has reduced the number of children in the family. Every year, many developed countries report falling or negative population growth due to the rapid decline in the number of children born each year. At the same time, a group of researchers from the University of Bristol, the University of Oslo and the University of Queensland found that carrying a child protects the lining of the uterus from endometrial cancer (EC).

Scientists reported this in the journal BMC Medicine on November 1, 2022.

About endometrial cancer

Endometrial cancer ranks sixth in the world among cases of female oncology and is a deadly disease. Women in low-income countries are most at risk, with hundreds of thousands of lives lost to this type of cancer every year.

Рак ендометрію endometrial cancer рак эндометрия
Cancer cells in the uterine mucosa

Previous studies confirmed: the development of endometrial malignancies is influenced by processes related to the reproductive function of women. Namely, ovulation and pregnancy. So, scientists considered the hormonal nature of EC, since in women who used only estrogen during the menopausal transition, the risk of endometrial cancer increased. At the same time, in women who also took progesterone as part of Hormone Replacement Therapy (HRT), these risks were reduced.

Plus, combined oral contraceptives (COCs), containing estrogen and progesterone (the pregnancy hormone), have been shown to reduce the likelihood of EC. And this protective feature increases over time. Moreover, pregnancy that ended in abortion or miscarriage provides even greater protection against endometrial cancer than COCs.

In particular, late menarche, early menopause, and the use of some forms of oral contraceptives are observationally associated with decreased risk of EC… One potential explanation for these associations is that higher lifetime estrogen exposure causally increases EC risk. This could explain why a short reproductive span (i.e., late menarche and early menopause) is associated with protection against EC in observational epidemiological studies.

Authors of the study in BMC Medicine

Another risk factor for endometrial cancer is an excessive Body Mass Index (BMI). This factor is most important for menopausal women and is also associated with hormonal changes.

The purpose of the study

So, scientists decided to investigate how the reproductive period, the number of babies born and the age of the last birth, correlate with the risk of endometrial cancer. And if a link is found, to determine whether it is causal.

Methods

The researchers used data from the UK Biobank (UKBB), which has information on more than 270,000 women. Only white European women were included in the study.

The scientists conducted multivariate analyses to find out the association between the number of live births, age at last birth, years of ovulation and other related aspects like age at natural menopause, age at menarche and BMI.

Genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from previous studies of a woman’s number of live births, age at menopause and menarche, and BMI. We conducted a genome-wide association analysis using the UKBB to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

Authors of the study in BMC Medicine

The scientists also used the Mendelian randomization (MR) method to assess the potential for causality. Here, genetic variants determine the causal relationship between exposure and outcome.

Findings of the study on endometrial cancer

The results included hundreds of genetic variants. Still, the analysis demonstrated that the risk of endometrial cancer is inversely proportional to the number of live births. Women who had given birth to three children had half the risk of developing EC than those who had not. Women with a longer reproductive period had a higher risk of endometrial cancer.

Incomplete pregnancies, i.e. miscarriages or abortions, also reduce the risk of EC, but less compared to full-term pregnancies.

To our knowledge, this is the first study to report that number of live births may have a protective effect on the risk of EC, even when accounting for other risk factors. However, our analyses suggest that the causal effect of the number of live births on EC risk may be driven through the age when a woman last gave birth, and this relationship should be further investigated. Our observational analyses suggested strong effects for years of ovulating and contraceptive pill use on EC risk; however, we were not able to replicate that in the MR analysis.

Authors of the study in BMC Medicine

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