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Background: At present, squamous cell carcinoma accounts for most esophageal cancers in Japan; however, there is concern that the incidence of esophageal adenocarcinoma in Japan is increasing in comparison to Western countries. Akita Prefecture, with a population of 1 million, has the highest rate of esophageal cancer-associated mortality in Japan; the vast majority of these cases are squamous cell carcinoma. The aim of the present study was to investigate the latest trends in the incidence of esophageal adenocarcinoma in Akita Prefecture using a registration system.Methods: We examined the data from a collaborative hospital-based registration system for cancer patients. Eleven of the main hospitals in Akita Prefecture participate in this system, which covers 90% of the cancer cases in the region and which provides near population-based data. Using this registration system, we examined the sequential trends in the percentage of adenocarcinoma cases in relation to total esophageal cancer cases in Akita Prefecture from 2007 to 2014.Results: In 2007-2014, a total of 2527 esophageal cancer patients were registered in the system. Among these, only 43 (1.8%) had adenocarcinoma. However, the number of adenocarcinoma patients gradually increased from 1 case in 2007 to 14 cases in 2014. Consequently, the percentage of adenocarcinoma cases showed a significant increase from 0.66% in the first 4 years of the study period to 2.5% in the latter 4 years of the study period (P < 0.01).Conclusions: The latest hospital-based registration data for 2007-2014 suggest that the incidence of esophageal adenocarcinoma may have begun to increase in Akita Prefecture; this may reflect recent trends in other parts of Japan. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to clarify the efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy with three-field lymph node (LN) dissection for clinical Stage III patients and for clinical Stage IVB patients with supraclavicular LN metastasis as the only distant metastatic factor. We observed that NACRT followed by esophagectomy with three-field lymph node dissection is feasible and offers the potential for long-term survival of these patients. It is also suggested that supraclavicular LNs should be treated as regional LNs at least in patients with upper and middle thoracic esophageal squamous cell carcinoma (ESCC). Background: Neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy is now the standard treatment for patients with resectable advanced thoracic esophageal squamous cell carcinoma (ESCC) worldwide. However, the efficacy of NACRT followed by esophagectomy with three-field lymph node dissection for clinical Stage III patients and for clinical Stage IVB patients with supraclavicular LN metastasis has not yet been determined. Methods: Between 2008 and 2018, 94 ESCC patients diagnosed as clinical Stage III and 18 patients diagnosed as clinical Stage IVB with supraclavicular LN metastasis as the only distant metastatic factor were treated with NACRT followed by esophagectomy with extended lymph node dissection at Akita University Hospital. Long-term survival and the patterns of recurrence in these 112 patients were analyzed. Results: The median follow-up period of censored cases was 60 months. The five-year OS and DSS rates among the clinical Stage III patients were 57.6% and 66.6%, respectively. The five-year OS and DSS rates among the clinical Stage IVB patients were 41.3% and 51.6%, respectively. The most frequent recurrence pattern was distant metastasis (69.2%) in the Stage III patients and LN metastasis (75.0%) in the Stage IVB patients. Conclusion: NACRT followed by esophagectomy with three-field LN dissection is feasible and offers the potential for long-term survival of clinical Stage III ESCC patients and even clinical Stage IVB patients with supraclavicular LN metastasis as the only distant metastatic factor. At least in patients with upper and middle thoracic ESCC, treating supraclavicular LNs as regional LNs seems to be appropriate. [ABSTRACT FROM AUTHOR]

Simple Summary: Definitive chemoradiotherapy is a standard treatment for stage IVa esophageal cancer, although it is unclear whether T/N factors affect treatment outcomes and whether we should modify chemoradiotherapy regimens based on T/N factors. This single-center retrospective study aimed to determine whether T/N factors affected progression patterns and overall survival after chemoradiotherapy for stage IVa esophageal squamous cell carcinoma. There were no significant differences between the T/N groups in terms of overall survival, progression-free survival, or progression patterns. Therefore, it may not be useful to modify chemoradiotherapy regimens based on T/N factors for patients with stage IVa squamous cell carcinoma. The differences in prognoses or progression patterns between T4b non-N4 and non-T4b N4 esophageal squamous cell carcinoma post chemoradiotherapy (CRT) is unclear. This study compared the outcomes of CRT for stage IVa esophageal squamous cell carcinoma according to T/N factors. We retrospectively identified 66 patients with stage IVa esophageal squamous cell carcinoma who underwent definitive CRT at our center between January 2009 and March 2013. The treatment outcomes, i.e., progression patterns, prognostic factors, and toxicities based on version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events, were studied. The patients (56 men and 10 women) had a median age of 67 (range: 37–87) years. The T/N classifications were T4b non-N4 (28/66), non-T4b N4 (24/66), and T4b N4 (14/66). Objective response was achieved in 57 patients (86.4%, (95% confidence interval, 74.6–94.1%)). There were no significant differences between the T/N groups in terms of overall survival, progression-free survival, and progression pattern. We found no significant differences in prognoses or progression patterns among patients with T4b non-N4, non-T4b N4, and T4b N4 esophageal squamous cell carcinoma. Thus, it seems impractical to modify CRT regimens based on T/N factors. [ABSTRACT FROM AUTHOR]

Objective: To determine whether esophagectomy provides a survival advantage in octogenarians with resectable thoracic esophageal cancer., Summary Background Data: Elderly patients with thoracic esophageal cancer do not always receive the full standard treatment; however, advanced age alone should not preclude the use of effective treatment that could meaningfully improve survival., Methods: We retrieved the 2008 to 2011 data from the National Database of Hospital-based Cancer Registries from the National Cancer Centerin Japan, divided the patients into a ≥75 group (75-79 years; n = 2935) and a ≥80 group (80 years or older; n = 2131), and then compared the patient backgrounds and survival curves. A multivariable Cox proportional hazards regression model was developed to compare the effects of esophagectomy and chemoradiotherapy in the 2 groups., Results: A significantly greater percentage of patients were treated with esoph-agectomy in the ≥75 group (34.6%) than the ≥80 group (18.4%). Among patients who received esophagectomy, the 3-year survival rate was 51.1% in the ≥ 75 group and 39.0% in the ≥80 group (P < 0.001). However, among patients who received chemoradiotherapy, there was no difference in survival curve between the 2 groups (P = 0.17). Multivariable Cox proportional hazard analysis revealed that esoph-agectomy for clinical Stage ii-iii patients was significantly associated to better survival (adjusted HR: 0.731) (95%CI: 0.645-0.829, P < 0.001) in the ≥75 group but not the ≥ 80 group when compared with chemoradiotherapy., Conclusions: Many octogenarians do not necessarily get a survival benefit from esophagectomy. However, patients should be evaluated based on their overall health before ruling out surgery based on age alone., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Disruption of cancer screening programs and diagnoses of gastrointestinal cancers by the COVID-19 pandemic has been reported; however, little attention has been paid to the situation in depopulated areas with low infection rates. Akita Prefecture is one of the most depopulated areas of Japan and has the lowest COVID-19 infection rate per capita; at the same time, the prefecture has been top-ranked for mortality due to gastrointestinal cancer for years. In this population-based study in Akita Prefecture, we investigated the occurrence of gastrointestinal cancers and the number of cancer screening procedures over the five-year period of 2016-2020, employing a database from the collaborative Akita Prefecture hospital-based registration system of cancers. The occurrence of gastrointestinal cancers, especially esophago-gastric cancers, declined by 11.0% in 2020, when the COVID-19 pandemic affected the overall healthcare system, compared with the average of 2016-2019. Nonetheless, the occurrence of advanced-stage (stage IV) esophago-gastric cancers increased by 7.2% in 2020. The decrease in the gastrointestinal cancer diagnosis rate in 2020 coincided with a 30% decline in the total number of regular population-based screening programs. Under the ongoing COVID-19 pandemic, cancer screening was uniformly suspended throughout Japan. Accordingly, the COVID-19 pandemic has substantially disrupted the cancer screening system, leading to delays in diagnoses of gastrointestinal cancer, even in depopulated areas (Akita Prefecture) of Japan with a low prevalence of infection. Suspension of cancer screening procedures during an infectious disease pandemic should be thoroughly considered for each region based on the cancer incidence and infection status in that area.

To address the major issue of regional disparity in the treatment for elderly cancer patients in an aging society, we compared the treatment strategies used for elderly patients with thoracic esophageal cancer and their survival outcomes in metropolitan areas and other regions. Using the national database of hospital-based cancer registries in 2008-2011, patients aged 75 years or older who had been diagnosed with thoracic esophageal cancer were enrolled. We divided the patients into two groups: those treated in metropolitan areas (Tokyo, Kanagawa, Osaka, Aichi, Saitama, and Chiba prefectures) with populations of 6 million or more and those treated in other areas (the other 41 prefectures). Compared were patient backgrounds, treatment strategies, and survival curves at each cancer stage. In total, 1236 (24%) patients from metropolitan areas and 3830 (76%) patients from nonmetropolitan areas were enrolled. Patients in metropolitan areas were treated at more advanced stages. There was also a difference in treatment strategy. The 3-year survival rate among cStage I patients was better in metropolitan areas (71.6% vs. 63.7%), and this finding mainly reflected the survival difference between patients treated with radiotherapy alone. For cStage II-IV patients, there were no differences. Multivariable Cox proportional hazard analysis including interaction terms between treatment areas, cStage, and the first-line treatments revealed that treatments in the metropolitan areas were significantly associated with better survival among patients treated with radiotherapy alone for cStage I cancer. Treatment strategies for elderly patients with thoracic esophageal cancer and its survival outcomes differed between metropolitan areas and other regions., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The efficacy and safety of nivolumab versus chemotherapy was evaluated in the Japanese subpopulation from the overall intent-to-treat (ITT) population of the ATTRACTION-3 trial conducted in patients with advanced esophageal squamous cell carcinoma (ESCC) as second-line treatment., Methods: Data from Japanese patients enrolled in the multicenter, randomized, open-label, phase 3 ATTRACTION-3 trial were analyzed. The primary endpoint was overall survival (OS). Secondary endpoints included duration of response (DOR), objective response rate (ORR), disease control rate (DCR), and safety. Exploratory subgroup analyses evaluated the association between OS and stratification factors/baseline variables., Results: Overall, 274 (nivolumab, 136; chemotherapy, 138) of the 419 patients in ATTRACTION-3 were enrolled from Japan: response-evaluable population (107; 108) and safety population (135; 138). OS tended to be longer in the nivolumab group versus the chemotherapy group (median: 13.4 months vs. 9.4 months; HR, 0.77; 95% CI 0.59-1.01). Median DOR was longer in the nivolumab group (7.6 months) versus the chemotherapy group (3.6 months). ORRs were similar between the nivolumab [22.4% of patients (24/107)] and chemotherapy groups [22.2% (24/108); odds ratio, 0.98; 95% CI 0.52-1.87]. DCR was lower in the nivolumab group [41.1% (44/107)] versus the chemotherapy group [66.7% (72/108)]. OS in the exploratory analysis consistently favored the nivolumab group versus the chemotherapy group. Overall, nivolumab demonstrated favorable efficacy and safety versus chemotherapy in the Japanese subpopulation, and the trend was similar to that observed in the overall ATTRACTION-3 ITT population., Conclusion: Nivolumab represents a new standard second-line treatment option for Japanese patients with advanced ESCC.

The incidence of anastomotic leakage after esophagectomy remains around 10%. It was previously reported that PDSII rapidly loses tensile strength at pH 1.0 and pH 8.5. By contrast, LACLON degradation is reportedly insensitive to pH. We therefore compared LACLON with PDSII for esophago-gastric conduit, layer-to-layer, handsewn anastomosis. Between January 2016 and January 2020, 90 patients who received posterior mediastinal gastric conduit reconstruction with layer-to-layer handsewn anastomosis (51 using PDSII and 39 using LACLON) at Akita University Hospital were enrolled. The incidence of anastomotic leakage was significantly lower in the LACLON (2.6%, 1/39 patients) than PDSII group (15.7%, 8/51 patients) (p = 0.0268). Multivariable logistic analysis showed the risk of anastomotic leakage was significantly greater with PDSII than LACLON (odds ratio 11.01; 95% CI 1.326-277.64; p = 0.024). The percentages of time the pH was higher than 8 on the gastric conduit side of the anastomosis were 3.1%, 5.7%, 20.9% and 80.5%, respectively, in the four most recent patients. The present study showed that pH at the anastomosis soon after esophagectomy tends to be alkaline rather than acidic, which raises the possibility that this alkalinity facilitates the deterioration of surgical sutures including PDSII.

Background: It will be important for the Japan Esophageal Society (JES) to show an evident advantage of its institution certification system. To achieve this essential task, we used nationally acquired big data to re-analyze 5-year survival information., Methods: In 2008-2009, there were 4897 thoracic esophageal cancer patients who underwent esophagectomy and were registered in the National Database of Hospital-based Cancer Registries. We divided these patients into two groups, those who underwent surgery at an Authorized Institute for Board Certified Esophageal Surgeons (AIBCES) or a Non-AIBCES. We then compared the patient backgrounds and 5-year survival rates between these two groups, with and without propensity score matching., Results: There were 3080 (63%) patients who underwent esophagectomy at an AIBCES and 1817 (37%) who underwent surgery at a Non-AIBCES. Comparison of the Kaplan-Meier survival curves using log-rank tests indicated a significant difference between the AIBCES and Non-AIBCES groups at all cStages (cStages I-IV). Multivariable Cox proportional hazard analysis stratified by clinical stage and adjuvant treatment revealed that AIBCES vs. Non-AIBCES is a significant independent factor (adjusted HR 0.78) for survival. After propensity score matching ensuring the backgrounds of the two groups being equivalent, there were significant differences in the 5-year survival rates for patients with cStages I-III disease between the AIBCES and Non-AIBCES groups., Conclusions: There is a survival advantage to undergoing esophagectomy at an AIBCES. The institute certification system from the JES will contribute to the future establishment of a more appropriate surgery delivery system for thoracic esophageal cancer.

Background: In 2009, the Japan Esophageal Society (JES) established a system for certification of qualified surgeons as "Board Certified Esophageal Surgeons" (BCESs) or institutes as "Authorized Institutes for Board Certified Esophageal Surgeons" (AIBCESs). We examined the short-term outcomes after esophagectomy, taking into consideration the certifications statuses of the institutes and surgeons., Methods: This study investigated patients who underwent esophagectomy for thoracic esophageal cancer and who were registered in the Japanese National Clinical Database (NCD) between 2015 and 2017. Using hierarchical multivariable logistic regression analysis adjusted for patient-level risk factors, we determined whether the institute's or surgeon's certification status had greater influence on surgery-related mortality or postoperative complications., Results: Enrolled were 16,752 patients operated on at 854 institutes by 1879 surgeons. There were significant differences in the backgrounds and incidences of postoperative complications and surgery-related mortality rates between the 11,162 patients treated at AIBCESs and the 5590 treated at Non-AIBCESs (surgery-related mortality rates: 1.6% vs 2.8%). There were also differences between the 6854 patients operated on by a BCES and the 9898 treated by a Non-BCES (1.7% vs 2.2%). Hierarchical logistic regression analysis revealed that surgery-related mortality was significantly lower among patients treated at AIBCESs. The institute's certification had greater influence on short-term surgical outcomes than the operating surgeon's certification., Conclusions: The certification system for surgeons and institutes established by the JES appears to be appropriate, as indicated by the improved surgery-related mortality rate. It also appears that the JES certification system contributes to a more appropriate medical delivery system for thoracic esophageal cancer in Japan.

Background: Since 2013, The Japan Esophageal Society has been certifying "Authorized Institute for Board Certified Esophageal Surgeon (AIBCES)" to contribute to improving national medical care by enhancing the professional knowledge and skills of esophageal surgeons. However, the appropriateness on this certification system has not yet been verified. Our aim was to assess the appropriateness of the institute certification system for esophageal surgeries used by the medical society., Methods: Using data from the National Database of Hospital-based Cancer Registries, we analyzed the 5-year overall survival rates among 2135 patients with thoracic esophageal cancer who underwent an esophagectomy at 53 AIBCES or 141 non-AIBCES., Results: There were 1343 (63%) patients who underwent surgery at an AIBCES and 792 (37%) who underwent surgery at a non-AIBCES. Registered patients were followed up for a median of 53 (range 1-88) months. Over the followed-up period examined, 670 (50%) patients treated at an AIBCES died and 455 (57%) treated at a non-AIBCES died. Comparison of the Kaplan-Meier survival curves indicated that patients with cStage II or cStage III disease treated at an AIBCES had significantly better 5-year survival rates than those treated at a non-AIBCES (55.4% vs. 44.9% and 38.0% vs. 30.3%, respectively). Univariate and multivariate analyses stratified based on stages and adjuvant therapies revealed that institute certification (AIBCES vs. non-AIBCES) is a significant independent factor for 5-year survival., Conclusions: The institute certification system used by the Japan Esophageal Society may be appropriate, as indicated by improved 5-year survival outcomes. The institute certification system has the potential to contribute to a more appropriate medical delivery system in the future.

Aim: We investigated the safety of adding Japanese-style extended 3-field lymphadenectomy in patients treated with neoadjuvant chemoradiotherapy (NACRT) for thoracic esophageal squamous cell carcinoma (TESCC). Furthermore, the efficacy of NACRT, as shown by the pathological and metabolic responses were determined., Patients and Methods: One hundred consecutive patients with cStage II-IV TESSC were enrolled. We analyzed the adverse events related to NACRT and surgical complications following surgery. Pathological responses to NACRT and the association between pCR and [ 18 F]-fluorodeoxyglucose positron-emission tomography (FDG-PET) evaluation were investigated., Results: Adding Japanese-style extended 3-field lymph node dissection after NACRT did not increase serious surgical complications. Seventy-four percent of patients experienced grade 2-3 pathological response, with 25% achieving pCR. There was a significant relationship between the change from positive to negative findings on FDG-PET/CT and pCR., Conclusion: Transthoracic esophagectomy with Japanese-style extended 3-field lymph node dissection after NACRT is a safe and powerful treatment., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

C-reactive protein (CRP) is one of the acute-phase proteins produced predominantly by hepatocytes in response to inflammation, and it has been widely reported that CRP genetic polymorphism is a risk factor for cardiovascular disease and ischemic stroke. In addition, we previously showed that the CRP 1846T/T genotype is related to lymph node metastasis in patients with esophageal cancer. In the present study, we investigated the correlation between CRP 1846C>T polymorphism and the clinicopathological characteristics of non-small cell lung cancer (NSCLC). The study participants were 146 Japanese patients who underwent curative surgery for NSCLC. DNA was extracted from tumor samples, and CRP1846C>T polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then correlated genotype with known clinicopathological factors. Five-year overall survival among patients with the CRP 1846T/T genotype was significantly lower than among those with the 1846C/C or C/T genotype (p = 0.002, p = 0.001; log-rank test). Multivariate Cox proportional hazard analysis revealed age, sex, pathological stage III, and 1846T/T (hazard ratio, 1.76; 95% confidence interval, 1.003-3.16; p = 0.049) to be independent factors affecting 5-year overall survival. These findings suggest the CRP 1846T/T genotype is an independent predictor of a poor prognosis in patients with NSCLC.

Objective: To investigate whether somatic mutations in cell cycle checkpoint genes, TP53 and p21, are involved in the development of ovarian cancer with or without BRCA1 germline mutation., Methods: We analyzed somatic genetic alterations of TP53 and p21 in 46 ovarian cancer patients with BRCA1 germline mutations and 93 sporadic patients, using direct sequencing for the entire coding sequences in TP53 and p21., Results: TP53 somatic mutations were detected in 25 of the 46 BRCA1 cases and 40 of the 93 sporadic cases (54.3% vs. 43.0%). In contrast, p21 somatic mutations were detected in 1 of the 46 BRCA1 cases and 2 of the 93 sporadic cases (2.2% vs. 2.2%). TP53 mutations in sporadic cases more frequently occurred in exons 6-11 than those in cases with germline BRCA1 mutations (84.4% vs. 56.3%: P = 0.013). The proportion of sporadic cases with TP53 mutations in non-serous tumors (e.g. endometrioid, clear cell, or mucinous) was significantly lower than that in serous tumors (18.5% vs. 53.0%: P = 0.0038). However, there was no significant difference between the proportion of BRCA1 cases with TP53 mutation in non-serous and in serous tumors (37.5% vs. 57.9%)., Conclusions: Our results suggest that somatic mutation of TP53 plays less of a role in the carcinogenesis of sporadic non-serous tumors than in that of sporadic serous tumors or BRCA1-related tumors. Furthermore, p21 somatic mutation appears to be less involved in the development of ovarian cancer than TP53 somatic mutation.

Background: The aim of the present study was to determine the major causes of death among esophageal cancer patients whose lymph nodes did not show metastasis at the time they received esophagectomy, and to consider strategies for improving survival rates among these patients., Study Design: Between 1989 and 1999, 93 of our patients who underwent curative esophagectomy with extended lymph node dissection for thoracic squamous cell esophageal cancer showed no lymph node metastasis. We followed up these node-negative patients for as long as 10 years and determined the major causes of death., Results: Sixty-three patients were still alive after esophagectomy, although 30 had died. Six patients died within 3 years after esophagectomy as a direct result of recurrence of their esophageal cancer; 13 died as a result of a second (extraesophageal) malignancy. Within the first 3 years, the major causes of death were recurrence (35%) and the second malignancy (35%); thereafter, the major cause was only the second malignancy (54%). There was no difference in the survival rates among patients with earlier, synchronous, or subsequent malignancies. Univariate and multivariate analyses of the 10-year survival showed the independent prognostic factors to be recurrence of esophageal cancer and development of a second malignancy, which respectively increased the risk of death 6.4 and 2.7 times., Conclusions: The major cause of reduced survival among thoracic squamous esophageal cancer patients, whose lymph nodes did not show metastasis, was a second malignancy. New strategies aimed at preventing or treating synchronous and subsequent malignancies could prolong the survival of these patients.

Objective: Endometriosis is an immune-related, chronic inflammatory disease with polygenic predisposition. Cell adhesion molecules are expressed in endometriotic lesions, and in cells and tissues that are involved in the development and progression of the disease. In this study, we investigated the possible association between endometriosis and the G241R and K469E polymorphisms in the intercellular adhesion molecule-1 (ICAM-1) gene in a Japanese population., Methods: We compared the distribution of the G241R and K469E polymorphisms in the ICAM-1 gene in 126 endometriosis patients and 172 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in a Japanese population., Results: There were no significant differences between the cases and controls in the allele frequencies or genotype distributions of either the G241R or K469E polymorphisms in the ICAM-1 gene. The endometriosis patients were divided into a subgroup of women with severe disease only. However, no significant differences were observed in the allele frequencies and genotype distributions of the ICAM-1 K469E polymorphisms between this subgroup and the controls. In contrast, only one in 169 controls was heterozygous (G/A genotype), and the A allele in the G241R polymorphism was not found in any of the 126 endometriosis patients., Conclusion: Our findings suggest that the G241R and K469E polymorphisms in the ICAM-1 gene are unlikely to be associated with an increased risk of endometriosis in the Japanese population.

Objective: We investigated the association between endometriosis and polymorphisms in the N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2) genes in a Japanese population, having previously demonstrated a positive association with NAT2 polymorphisms in a UK population., Methods: Genotyping for NAT1 alleles *3, *4, *10, and *11, and NAT2 alleles *4, *5A, *5B, *5C, *6A, and *7B was performed using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and allele-specific PCR (AS-PCR) analysis in 145 ethnically Japanese, endometriosis patients and 182 controls. The NAT1 and NAT2 allele and genotype frequencies were compared in cases and controls using the Fisher exact test., Results: No significant differences between cases and controls were observed in the frequencies of the NAT1 and NAT2 alleles (P = .13; P = .91) and genotypes (P = .24; P = .79), and the NAT2 acetylation phenotypes (P = .46). Dividing the cases into a subgroup, consisting of women with severe disease only (n = 80), had no effect on the results., Conclusion: The distribution of NAT1 and NAT2 allele and genotype frequencies were not significantly different between Japanese cases and controls. Our findings suggest that polymorphisms in NAT1 and NAT2 are unlikely to be associated with an increased risk of endometriosis in the Japanese population.

Endometriosis is a complex trait, which means that multiple susceptibility genes interact with one another and the environment to produce the phenotype. One of the genes previously implicated in the disease is CYP17; this encodes the enzyme P450c17alpha, which plays a vital role in steroid biosynthesis in the ovary. The presence of a single nucleotide polymorphism (T-->C) in the 5'-promoter region of the gene creates a new recognition site for the restriction enzyme MspA1 producing a mutant allele (A2), which affects circulating estrogen levels. In this study, we compared the frequency of the CYP17 MspA1 polymorphism in two different ethnic populations. DNA was obtained from (1) 94 women with revised American Fertility Society (rAFS) stage III-IV endometriosis and 97 male blood donors in the UK, and (2) 130 women with rAFS stage III-IV endometriosis and 179 female newborn infants in Japan. No significant differences in allele or genotype frequencies were seen in either population. The genotype distribution in the UK population was 33/94 [35.1%] (cases) and 39/97 [40.2%] (controls) for A1A1 (homozygous wild-type); 43/94 [45.7%] (cases) and 44/97 [45.4%] (controls) for A1A2; and 18/94 [19.1%] (cases) and 14/97 [14.4%] (controls) for A2A2. The genotype distribution in the Japanese population was 31/130 [23.9%] (cases) and 57/179 [31.8%] (controls) for A1A1; 73/130 [56.2%] (cases) and 89/179 [49.7%] (controls) for A1A2; and 26/130 [20.0%] (cases) and 33/179 [18.4%] (controls) for A2A2. The CYP17 MspA1 polymorphism is probably not associated with endometriosis in either the UK or the Japanese population.

Background: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional proinflammatory cytokine, associated with various inflammatory and autoimmune diseases. Elevated TNF-alpha levels in peritoneal fluid have been reported in women with endometriosis, suggesting that TNF-alpha may be involved in the development of endometriosis. In this study, we investigated the possible association between endometriosis and the TNF-alpha gene promoter polymorphisms -238G/A, -308G/A, -857C/T, -863C/A and -1031T/C in a Japanese population., Methods: We compared the distribution of the -238G/A, -308G/A, -857C/T, -863C/A and -1031T/C polymorphisms in the promoter region of TNF-alpha in 130 endometriosis cases and 185 controls using PCR-RFLP analysis., Results: The allele frequencies of -238A, -308A, -857T, -863A and -1031C in controls were 2.0%, 1.3%, 19.4%, 17.0% and 18.6%, and in the cases 1.1%, 0.3%, 19.6%, 18.6% and 13.6%, respectively. No significant differences in frequencies were found between the crude endometriosis cases and controls. However, when the endometriosis group was divided into a subgroup of women with stage IV disease only, the frequency of the -1031C allele was significantly lower in this subgroup than controls., Conclusions: The variability of the -1031T/C polymorphism of the TNF-alpha gene may be associated with susceptibility to (AUTHOR: as meant?) endometriosis.