Does ESR2 rs3020450 Polymorphism Increase Risk of Ovarian Cancer?

ESR2 rs3020450 polymorphism was linked to ovarian cancer risk at a population level, while high ESR2 expression levels were associated with long survival in ovarian cancer patients, according to results of a study published in Gene.

“Multiple signaling pathways can be mediated via the interaction of estrogen and its receptors, and single nucleotide polymorphisms of genes that are related to hormone signaling and/or metabolism are possible elements affecting cancer susceptibility,” wrote authors, led by Yajing Feng, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.  “Epidemiological and laboratorial studies have shown that tumorigenesis and progression of gastric cancer, thyroid cancer, ovarian cancer, and lung cancer are associated with ERα and ERβ.”

 “Studies have demonstrated that the shielding effect of estrogen could impede the incidence of cancer, which was also confirmed by the correlation between high ESR2 expression and long survival data in 829 ovarian cancer samples,” the authors continued.

On the basis of meta-analysis, the correlation between ESR2 rs3020450 polymorphism and cancer susceptibility was estimated. Additionally, a case-control design was used to confirm this result in ovarian cancer. The epidemiological effect of ESR2 rs3020450 polymorphism was analyzed using attributable risk percentage (ARP) and population attributable risk percentage (PARP).

The pooled analysis demonstrated no significant association between the ESR2 rs3020450 polymorphism and cancer susceptibility. Per the stratified analysis by cancer types, a significantly reduced risk was discovered in ovarian cancer (AG vs GG: OR=0.73; 95% CI, 0.53–0.97, P=0.03). Results of an unconditional logistic regression results per a case-control study in ovarian cancer showed significant differences in all comparisons

On the basis of meta-analysis and case-control pooled results, respectively, ARP and PARP were determined in allele (21.95% and 7.97%), heterozygote (36.99% and 12.11%), and dominant models (36.84% and 12.97%) of the rs3020450 polymorphism in ovarian cancer. The levels of expression of ESR2 in normal tissues was higher vs cancer tissues (OV, median, 4.7:0.21). Furthermore, significant correlations were noted between high ESR2 expression levels and long OS (HR=0.80; 95% CI, 0.70–0.92, P=0.002), as well as PFS (HR=0.767; 95% Cl, 0.67–0.88, P < 0.001).

In an exclusive interview with Cancer Network, Cesar M. Castro, MD, a medical oncologist at Massachusetts General Hospital Cancer Center in Boston, noted the future implications of the study.

“The study addresses the ‘nature/nurture’ interplay between inherent patient-level genetics and the environmental factors leading to potential cancers,” he said. “The study highlights the need to study populations historically peripheral to genomic-based testing of cancers. Validating or disproving prior genomic findings in such populations would provide the additional clarity needed for precision oncology.

However, he noted the study has some shortcomings.

"The study lacks actionable findings in its current iteration," he said. "But certainly paves the way for larger, prospective testing of ESR2 polymorphisms across subsets of the Chinese population. If validated, this biomarker could influence who receives chemotherapy in borderline cases where it is not so clear cut. Or in scenarios where two-drug chemotherapy regimens has questionable tolerability, the biomarker could justify who receives the two drugs rather than single agents as a function of prognosis-in Chinese populations. Achieving success here would motivate further inquiries across other marginalized populations.”