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Updated: Jul 20, 2026
Establishment of an Experimental Mouse Model of Endometrioma to Study its Related Infertility
Published on: April 5, 2024
KRAS variation and risk of endometriosis
Zhen Zhen Zhao1, Dale R Nyholt, Lien Le
1Molecular Epidemiology Laboratory and Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Abstract:
Endometriosis is a common gynaecological disease with symptoms of pelvic pain and infertility which affects 7-10% of women in their reproductive years. Activation of an oncogenic allele of Kirsten rat sarcoma viral oncogene homologue (KRAS) in the reproductive tract of mice resulted in the development of endometriosis. We hypothesized that variation in KRAS may influence risk of endometriosis in humans. Thirty tagSNPs spanning a region of 60.7 kb across the KRAS locus were genotyped using iPLEX chemistry on a MALDI-TOF MassARRAY platform in 959 endometriosis cases and 959 unrelated controls, and data were analysed for association with endometriosis. Genotypes were obtained for most individuals with a mean completion rate of 99.1%. We identified six haplotype blocks across the KRAS locus in our sample. There were no significant differences between cases and controls in the frequencies of individual single-nucleotide polymorphisms (SNPs) or haplotypes. We also developed a rapid method to screen for 11 common KRAS and BRAF mutations on the Sequenom MassARRAY system. The assay detected all mutations previously identified by direct sequencing in a panel of positive controls. No germline variants for KRAS or BRAF were detected. Our results demonstrate that any risk of endometriosis in women because of common variation in KRAS must be very small.
Insights
Genetic variations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) do not appear to significantly increase endometriosis risk in women. This study found no association between KRAS gene variations and the common gynecological disease.
Area of Science:
- Reproductive Medicine
- Human Genetics
- Oncology
Background:
- Endometriosis is a prevalent gynecological condition affecting 7-10% of women, characterized by pelvic pain and infertility.
- Studies in mice demonstrated that activating an oncogenic Kirsten rat sarcoma viral oncogene homologue (KRAS) allele can induce endometriosis.
- This suggests a potential role for KRAS in the development of endometriosis in humans.
Purpose of the Study:
- To investigate the hypothesis that variations in the KRAS gene influence the risk of developing endometriosis in humans.
- To analyze the association between common KRAS genetic variations and endometriosis susceptibility.
Main Methods:
- Genotyped thirty single-nucleotide polymorphisms (SNPs) across the KRAS locus in 959 endometriosis cases and 959 controls using MALDI-TOF MassARRAY.
- Analyzed data for associations between individual SNPs, six identified haplotype blocks, and endometriosis risk.
- Developed and validated a rapid assay for screening common KRAS and BRAF mutations.
Main Results:
- No significant differences were observed in the frequencies of individual KRAS SNPs or haplotypes between endometriosis cases and controls.
- The developed assay successfully detected known KRAS and BRAF mutations, but no relevant germline variants were found in the study population.
- The study indicates that common variations in KRAS do not confer a substantial risk for endometriosis.
Conclusions:
- Common variations within the KRAS gene locus are unlikely to be a significant risk factor for endometriosis in the studied population.
- Further research may be needed to explore other genetic factors or rarer mutations in KRAS or related pathways.
- The findings suggest that the role of KRAS in human endometriosis may be minimal, despite evidence from mouse models.
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