Comments on: Gene Polymorphisms in FAS (Rs3740286 and Rs4064) are Involved in Endometriosis Development in Brazilian Women, but not those in CASP8 (rs13416436 and rs2037815)

We thank our colleagues for their correspondence commenting our article published in RBGO, 9 mainly for their valuable comments. The purpose of our manuscript was to investigate the association between caspase-8 ( CASP8 ) (rs13416436 and rs2037815) and Fas cell surface death receptor ( FAS ) (rs3740286 and rs4064) polymorphisms and endometriosis in Brazilian women. In fact, endometriosis is categorized into three types: peritoneal superficial endometriosis (SUP), ovarian endometrioma (OMA) and deeply infiltrating endometriosis (DIE). 10 This classification relates the disease to its pathophysiology and also to the symptoms presented. The information about the three different types of manifestations is not present in the medical records. Therefore, it was not possible to evaluate the association with the studied polymorphisms. We emphasize the rigorous diagnosis used to include cases and controls in our sample. The presence of endometriosis was verified by laparoscopy or laparotomy in both case and control groups. A recent study evaluated the histological and immunohistochemical characterization of the similarity and difference between OMAs and DIE. 11 The many similarities shared indicate that the two conditions may actually share the same pathogenesis/pathophysiology. Their differences, however, suggest that the source of these differences may result from the different lesional microenvironments. 11 The authors suggest that the establishment of a unified histological classification/staging of endometriosis may be within reach. These results reinforce that current clinical practice lacks an adequate definition for endometriosis. 12 According to the American Society for Reproductive Medicine, endometriosis exists in four stages: I (minimal disease), stage II (mild disease), stage III (moderate disease) and stage IV (severe disease). 13 This surgical classification is based on the extent of adhesions and size of the lesions. Comparison between rs3740286 and rs4064 polymorphisms genotypes in the FAS gene and the different stages of endometriosis (I + II vs III + IV) revealed no statistically significant difference (Chi-square test; p  = 0.15 and p  = 0.72, respectively), indicating that these polymorphisms are related to the development of endometriosis independent of the disease stage. Although it is not possible to associate the different phenotypes of endometriosis with the studied polymorphisms, our results highlight the importance of apoptosis genes for susceptibility to endometriosis. Still, they open the way to new studies, which may contribute to elucidate the genesis of endometriosis.

Conflicts of Interest The authors have no conflicts of interest to declare.