Having more live births lowers endometrial cancer risk
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A greater number of live births causally reduced the risk for endometrial cancer, according to study results published in BMC Medicine.
“It has previously been shown that having gone through a pregnancy and birth is associated with lower risk of endometrial cancer,” Gunn-Helen Moen, PhD, a fellow at the University of Queensland Institute for Molecular Bioscience in Brisbane, Australia, told Healio. “However, it has not been established that this relationship is a cause-and-effect relationship. Further, it has not been shown that the number of live births have a causal effect on decreasing risk of endometrial cancer when taking other risk factors into account, such as age of menarche, age at menopause and BMI. We therefore wanted to use genetics to test if this relationship between number of live birth and decrease risk of endometrial cancer was causal even when accounting for these other known risk factors.”
Moen and colleagues used data from the UK Biobank to conduct Mendelian randomization analyses of the association between endometrial cancer and BMI, ovulatory function, reproductive function and use of oral contraceptive pills.
The researchers identified single nucleotide polymorphisms (SNPs) associated with each phenotype, such as age at menopause and number of live births. The researchers conducted multivariable analyses to determine causal relationships to account for SNPs that were associated with several phenotypes.
Of note, oral contraception was not associated with any genetic loci and was excluded from analyses.
“We would love to work more with the oral contraceptive pill to see if we can get the data needed to properly determine if there is a protective effect of oral contraceptive pill on endometrial cancer,” Moen said.
In univariate analyses, having more live births decreased the risk for endometrial cancer (OR = 0.537; 95% CI, 0.344-0.838), and more years of ovulation increased the risk for endometrial cancer (OR = 1.051; 95% CI, 1.011-1.093).
In multivariable analyses, more live births was independently associated with endometrial cancer risk (OR = 0.783; 95% CI, 0.623-0.985). The association between ovulation duration and endometrial cancer was no longer significant.
Further multivariable analyses of known risk factors for endometrial cancer — BMI, age at menarche and age at menopause — revealed that age at menopause did not have an independent causal effect on endometrial cancer risk, “suggesting that this previously reported relationship could be confounded by BMI or age at menarche,” the researchers wrote.
“There are theories suggesting that pregnancy could be beneficial due to the protective effect of progesterone, which is produced during pregnancy, or because precancerous cells in the endometrium could be removed during the birth. Our results are in line with these theories,” Moen told Healio.
Clinicians should use these findings to help identify women at risk for endometrial cancer, Moen said.