Preliminary testing for endometriosis and gene polymorphisms



We read your review on the relation between endometriosis and ovarian cancer [1]. Endometriosis is characterized by inflammation and invasion of endometrial cells into other tissues and organs. It is a serious condition associated with complications such as infertility, dysmenorrhea, and dyspareunia in females of reproductive age, and the pathophysiology of the disease occurrence and progression is unclear. An evaluation for endometriosis should be considered for adolescent female patients with chronic pelvic pain because early diagnosis and management are important to maintain quality of life and reduce the need for extensive surgical management [2].

Your review is highly informative for gynecologists to follow up patients with endometriosis and investigate the condition. We believe that it is important for gynecologists to know that ovarian cancer is associated with endometriosis. However, identification of a biomarker of the relation between endometriosis and ovarian cancer is needed. Single-nucleotide polymorphisms are currently under investigation in terms of the prediction and prevention of many diseases. Endometriosis is known to be an estrogen-dependent disease. Single-nucleotide polymorphisms of the CYP17 GG and GA genotype, which is related to steroidogenic genes, are significantly increased in infertile females with endometriosis [3].

We have reviewed the estrogen receptor (ER) gene polymorphisms associated with endometriosis [4]. Polymorphism in PvuII of ERα is associated with an increased tendency for endometriosis in Europe, and polymorphism in XbaI of ERα is associated with a risk of occurrence in both Asia and Europe [4]. We also investigated the relation between MUC4 and endometriosis. Epithelial surfaces secrete mucous components composed of mucin-glycosylated proteins. The MUC series has been investigated with other mucous secretory-related cancer markers. MUC1 is overexpressed in ovarian tumors and is present in endometriotic lesions [5]. We preliminarily studied associations between patients with two types of functional cysts and two patients with endometriosis in the ER and MUC4 genes by PCR, restriction fragment length polymorphism, or DNA sequencing. The clinical characteristics of the two patients with functional cysts and two patients with endometriosis are shown in Table 1, which shows that patients with endometriosis had four mutant haplotypes in MUC4 (rs882605, intron 22 + 66, intron 23 + 45, and intron 23 + 47) and a double-mutant haplotype in ESR1 PvuII and ESR1 XbaI (figure available on request). We also found that MUC4 (introns 23 + 45 and introns 23 + 47), ESR PvuII, and XbaI may be associated with endometriosis. However, small case reports cannot confirm the effect of polymorphisms on the relation between endometriosis and functional cysts. We plan to investigate the effect of ESR and MUC4 (introns 23 + 45 and introns 23 + 47) on the relation between endometriosis and functional cysts. One report showed that the MUC4 polymorphism was related to endometriosis and infertility in a Taiwanese population [6]. No other reports have described endometriosis in association with polymorphisms of both the MUC4 and ER genes. We believe that a study of concurrent MUC4 and ERα polymorphisms would provide useful information for the diagnosis and prevention of recurrence of endometriosis.

Table 1. Genotypes and clinical characteristics of the ESR1, ESR2, and MUC4 genes in controls and endometriosis patients
No.Clinical characteristicsGenotypes of the ESR1, ESR2, and MUC4 genes
AgeWeightHeightBody mass indexRecurrenceStageaESR1 PvuIIESR1 XbaIESR2 RsaIESR2 AluIMUC4 rs882605, T > G, Phe300ValMUC4 Intron 22 + 66, C > GMUC4 Intron 23 + 45, G > TMUC4 Intron 23 + 47, C > T
  1. C, control; E, endometriosis; ESR, estrogen receptor; MUC, mucin.

  2. Wild (wild-type), Hetero (hetero-type), and Homo (homo-type) polymorphisms from genotyping.

  3. a

    Stage: revised American Society for Reproductive Medicine classification (rASRM).