Choosing the right adjuvant therapy for stage III-IVA endometrial cancer: A comparative analysis of chemoradiotherapy and chemotherapy.

OBJECTIVE: The optimal adjuvant treatment for patients with locally advanced endometrial cancer (EC) remains debatable. We comparatively analyzed recurrence patterns and survival outcomes in patients with stage III-IVA EC treated with adjuvant chemotherapy (CT) exclusively or combined with radiotherapy (CRT). METHODS: We retrospectively analyzed 184 patients treated for stage III-IVA EC at 2 tertiary institutions between 2010 and 2021. All patients underwent standard primary surgery and received either CT alone (n = 89) or CRT (n = 95) as an adjuvant treatment. We compared the failure patterns, recurrence-free survival (RFS), and overall survival (OS) between the CT and CRT groups. RESULTS: The median follow-up period was 54.8 months. Most patients underwent pelvic (94.6%) or para-aortic (75.5%) lymphadenectomies. The 5-year RFS was 69.2% with CRT versus 56.3% with CT (P = 0.038), and 5-year OS was 86.1% versus 78.9% (P = 0.357). Pelvic and para-aortic recurrence rates were significantly higher in the CT group (pelvic: 29.2%; para-aortic: 20.2%) than in the CRT group (pelvic: 10.5%; para-aortic: 6.3%). The CRT group showed a higher rate of distant recurrence (CRT, 23.2% vs. CT, 14.6%) however, the 5-year cumulative incidence of distant recurrence was not significantly different between the two groups (CRT, 28% vs. CT, 35%). CONCLUSIONS: This study highlights the potential benefits of adjuvant CRT in patients with stage III-IVA EC. The incorporation of molecular classification is necessary to derive optimal personalized adjuvant treatment strategies for this patient population.

Risk of occult atypical hyperplasia or cancer in women with nonatypical endometrial hyperplasia.

AIM: The aim of this study was to identify subsets of patients diagnosed with nonatypical endometrial hyperplasia (NAEH) by endometrial biopsy who had high risk for occult atypical endometrial hyperplasia (AEH) or endometrial cancer (EC). METHODS: We retrospectively reviewed the medical records of 281 patients who underwent hysterectomy within 6 months after a diagnosis of NAEH. We collected data on age, body mass index, menopausal status, tamoxifen use, previous history of NAEH, details of endometrial biopsy (location, curettage vs. pipelle sampling), NAEH subtype (simple vs. complex), interval between endometrial biopsy and hysterectomy, indication of hysterectomy and the presence of occult AEH or EC in hysterectomy specimen. Associations between variables and occult AEH or EC were analyzed. Risk of occult AEH or EC in subsets were calculated and visualized using a heatmap. RESULTS: Among 281 patients, 34 (12.1%) and 9 (3.2%) had occult AEH and EC in hysterectomy specimens, respectively. Using univariate analysis, we found age, menopausal status and subtype were associated with occult AEH or EC. Using multivariate analysis, older age (odds ratio = 1.09, P < 0.01) and complex subtype (odds ratio = 3.34, P < 0.01) were independent risk factors. Patients at an age ≥ 51 years with complex NAEH had about 50% risk of occult AEH or EC. CONCLUSION: Women at an age ≥ 51 years with complex NAEH had high risk for occult AEH or EC and surgical treatment can be considered for these patients.

Real-world effectiveness of bevacizumab based on AURELIA in platinum-resistant recurrent ovarian cancer (REBECA): A Korean Gynecologic Oncology Group study (KGOG 3041).

PURPOSE: To evaluate the effectiveness of bevacizumab with single-agent chemotherapy for platinum-resistant ovarian cancer in a real-world setting. PATIENTS AND METHODS: We enrolled recurrent platinum-resistant ovarian cancer patients from 27 institutions. All had received bevacizumab with single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin (PLD), topotecan) between 2015 and 2017 for second- or third-line chemotherapy in routine clinical practice. The primary endpoint was progression-free survival (PFS) and safety. Secondary endpoints included the objective response rate (ORR), PFS2, overall survival, duration of chemotherapy, and reasons for discontinuing chemotherapy. RESULTS: Of 391 patients, 259 (66.2%) received bevacizumab with PLD, 94 (24.0%) with topotecan, and 38 (9.7%) with weekly paclitaxel. The median PFS was 6.1 months with all forms of bevacizumab-containing therapy. Although the cohort with weekly paclitaxel had a better PFS than the PLD cohort (P = 0.028), this finding was not found in patients with a previous platinum-free interval of less than three months. The median duration of therapy was five cycles (range, one to 20 cycles), and 29 patients (7.4%) discontinued treatment because of adverse events from bevacizumab-containing regimens. The PLD cohort had fewer grade ≥ 3 adverse events than the other regimens (PLD, 35.8%; weekly paclitaxel, 52.6%; topotecan, 51.1%; P = 0.012), especially events of hematologic toxicities. CONCLUSION: In Korean ovarian cancer patients, the safety and effectiveness of chemotherapy with bevacizumab in a real-world setting was consistent with the results from a randomized controlled study. The effectiveness and toxicity profiles varied among the chemotherapy regimens, and this finding should be considered in practice. CLINICAL TRIALS REGISTRATION: NCT03367182.

Effect of number of retrieved lymph nodes on prognosis in FIGO stage IB-IIA cervical cancer patients treated with primary radical surgery.

AIM: In the treatment of cervical cancer, the extent of lymphadenectomy is a matter of debate. The goal of the current study was to examine the question of whether the number of retrieved lymph nodes (RLN) can influence survival of patients with early stage cervical cancer. METHODS: The medical records of 180 FIGO stage IB-IIA cervical cancer patients treated with primary radical surgery were reviewed. Patients were divided into two groups: those with ≤ 40 RLN and those with > 40 RLN. Patients were also assigned to either the bulky (tumor size > 4 cm) cervical cancer group or the non-bulky (tumor size ≤ 4 cm) cervical cancer group. RESULTS: The number of RLN had a statistically significant effect on both disease-free survival (P = 0.04) and overall survival (P = 0.02) of all patients. Patients with > 40 RLN had better prognoses than those with ≤ 40 RLN. In the bulky cervical cancer group, the number of RLN was an independent prognostic factor. In multivariate analysis for the bulky cervical cancer group, > 40 RLN had a significant positive effect on disease-free survival (adjusted hazard ratio, 0.36; 95% confidence interval, 0.13-0.97) and overall survival (adjusted hazard ratio, 0.23; 95% confidence interval, 0.06-0.90). However, number of RLN was not an independent prognostic factor in the non-bulky cervical cancer group. CONCLUSIONS: A more extensive lymphadenectomy increased the survival of bulky cervical cancer patients. This finding may be helpful in determining surgical extent before surgery for cervical cancer.

Safety of total laparoscopic hysterectomy in patients with prior cesarean section.

AIM: Patients who have undergone a cesarean section (CS) prior to hysterectomy are at a higher perioperative risk of complications. The purpose of this study was to evaluate the safety of total laparoscopic hysterectomy (TLH) in patients with prior CS. METHODS: We enrolled 482 patients treated with TLH. Surgical outcomes including major complications were compared between patients without prior CS (no CS group; n = 324) and patients with prior CS (prior CS group; n = 158). Major complications included vaginal cuff dehiscence, and bowel, bladder, ureter and great vessel injuries. RESULTS: Major complications, uterus weight, hospital day, unscheduled transfusion and conversion to laparotomy did not differ significantly between groups. One bowel injury occurred in the no CS group. Two vaginal cuff dehiscences and one bladder injury occurred in the prior CS group. There were no ureter or great vessel injuries. Operation duration was longer (P = 0.030) in the prior CS group, but only seven minutes longer than the no CS group. The Foley catheter indwelling day was also significantly longer (P < 0.001) in the prior CS group, but did not last one day. The number of prior CS had no effect on the major complication rate. After treatment of major complications, no long-term sequelae were observed. CONCLUSIONS: TLH in patients with a history of CS can be performed safely as such history had no effect on the major complication rate. Complications were rare and were treated successfully.

Comparison of palonosetron, granisetron, and ramosetron for the prevention of postoperative nausea and vomiting after laparoscopic gynecologic surgery: a prospective randomized trial.

BACKGROUND: Selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are reported to have potent antiemetic effects for postoperative nausea and vomiting (PONV). The purpose of this study was to prospectively evaluate the efficacy of palonosetron, granisetron, and ramosetron for the prevention of PONV in patients undergoing laparoscopic gynecologic surgery. METHODS: In this prospective, randomized observational study, 105 healthy female patients who were undergoing laparocopic hystectomy under general anaesthesia were enrolled (clinical trial number: NCT01752374, www.clinicaltrials.gov ). Patients were divided into three groups: the palonostron (0.075 mg i.v.; n = 35), the granisetron group (3 mg i.v.; n = 35), and the ramosetron group (0.3 mg i.v.; n = 35). The treatments were given before the end of surgery. The incidence of PONV, severity of nausea/vomiting, and the use of rescue antiemetic requirements during the first 48 h after surgery were evaluated. RESULTS: The overall incidence of PONV was 33.3 % for this series. The number of complete responders at 48 h after the surgery was 21 (60.0 %) for palonosetron, 24 (68.6 %) for granisetron, and 26 (71.4 %) for ramosetron, representing no statistical difference (P = 0.086). CONCLUSIONS: There were no significant differences in the overall incidence of postoperative nausea and vomiting and complete responders for palonosetron, granisetron and ramosetron group. CLINICAL TRIAL NUMBER: NCT01752374 , www.clinicaltrials.gov .

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Management of the elderly patient with gynecologic cancer: report of the 2011 workshop in geriatric gynecologic oncology.

Reflecting the worldwide aging trend and close association of aging with cancer, geriatric oncology is now growing beyond its pioneer years. Nevertheless, geriatric oncology in the gynecologic field is in the beginning stage; indeed, there is no geriatric specialist who is trained in this particular field of gynecologic oncology. Therefore, we held the first workshop in geriatric gynecologic oncology. In this review, we summarize what we discussed at the workshop and provide evidence-based recommendations for the diagnosis and treatment of gynecologic cancer in elderly individuals.

Is tumor size the limiting factor in a laparoscopic management for large ovarian cysts?

PURPOSE: To assess the feasibility and short-term surgical outcome of laparoscopic surgery among women with large ovarian cysts. METHODS: We retrospectively evaluated consecutive 81 patients who received laparoscopic management for ovarian cysts with diameter ≥ 10 cm and without radiologic features suggestive of malignancy, from March 2008 to September 2011. RESULTS: Laparoscopic surgery was successful in 77 (95.1 %) of the total patients. The mean (range) operative time, estimated blood loss (EBL) and hospital stay were 107.6 (55-250 min), 226.9 (10-1300 mL) and 6.1 (4-15 days), respectively. The surgical procedures performed included salpingooophorectomy (SO) (n = 44), ovarian cystectomy (OC) (n = 22), adhesiolysis (n = 1), salpingectomy (n = 2) and total laparoscopic hysterectomy (TLH) with SO (n = 8). Conversion to laparotomy occurred with four patients. One patient had postoperative bleeding and one had minor complications associated with wound oozing at the umbilical port site. Histopathological examination revealed benign tumors in 76 patients (93.8 %), borderline ovarian tumor in three patients (3.7 %) and invasive epithelial ovarian cancer in two patients (2.5 %). Clinicopathological variables according to tumor size were not statistically different. Complications did not appear in any patients during the follow-up period. CONCLUSION: With proper patient selection, laparoscopy is a feasible and safe treatment for women with large ovarian cysts and tumor size did not have effect on laparoscopic management. However, surgeons should carefully consider the potential risk of malignancy in such patients.

Informed consent forms for gynecologic cancer surgery: recommendations from the Korean Society of Gynecologic Oncology.

The sociomedical environment is changing. In the traditional physician-patient relationship, the physician was authoritative and the patient was obedient. The contractual relationship featured patient consent to the physician's decision. Today, the physician must explain fully the planned medical treatment, and any alternative, to the patient, who has the right to choose her treatment after considering the benefits and side-effects. The Korean Society of Gynecologic Oncology thus decided to standardize the surgical consent forms to meet the legal requirements of modern medicine, improve patient understanding of the surgical details, and protect medical staff from legal disputes. To determine the format and content, subcommittees for each cancer type collected and reviewed all relevant articles and the current consent forms of domestic medical institutions. After several meetings, 16 basic items to be included for each type of gynecologic cancer were selected. Also, to help patients understand the surgical details, figures were included. The revised forms were legally reviewed in terms of the appropriateness of the format and content. We also developed English versions to provide adequate information for foreign patients. We hope that these efforts will promote trust between patients and physicians, and contribute to effective treatment by laying a foundation of mutual respect.

Informed consent forms for gynecologic cancer surgery: recommendations from the Korean Society of Gynecologic Oncology.

The sociomedical environment is changing. In the traditional physician-patient relationship, the physician was authoritative and the patient was obedient. The contractual relationship featured patient consent to the physician's decision. Today, the physician must explain fully the planned medical treatment, and any alternative, to the patient, who has the right to choose her treatment after considering the benefits and side-effects. The Korean Society of Gynecologic Oncology (KSGO) thus decided to standardize the surgical consent forms to meet the legal requirements of modern medicine, improve patient understanding of the surgical details, and protect medical staff from legal disputes. To determine the format and content, subcommittees for each cancer type collected and reviewed all relevant articles and the current consent forms of domestic medical institutions. After several meetings, 16 basic items to be included for each type of gynecologic cancer were selected. Also, to help patients understand the surgical details, figures were included. The revised forms were legally reviewed in terms of the appropriateness of the format and content. We also developed English versions to provide adequate information for foreign patients. We hope that these efforts will promote trust between patients and physicians, and contribute to effective treatment by laying a foundation of mutual respect.

Elevated platelet lymphocyte ratio is a poor prognostic factor in advanced epithelial ovarian cancer.

The platelet lymphocyte ratio (PLR) is an important prognostic biomarker in various cancers. The current retrospective study was undertaken to determine the association between PLR and prognosis of advanced epithelial ovarian cancer. We determined the optimal cutoff values of PLR for predicting survival outcomes using the receiver operating characteristic curve analysis. Based on the PLR cutoff values, patients were divided into two groups: <226 and ≥226. Univariate analysis revealed a greater risk of death in the PLR ≥ 226 group than the PLR < 226 group (HR (hazard ratio), 2.7; 95 % CI (confidence interval), 1.3-5.4; P = 0.006). In multivariate analysis, PLR (HR, 1.9; 95 % CI, 1.1-3.6; P = 0.047) significantly affected the overall survival. Our data indicates that PLR can be used as an independent significant prognostic factor in advanced epithelial ovarian cancer.

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women.

The purpose of the study was to investigate the association between cervical cancer risk and single-nucleotide polymorphisms (SNPs) in three one-carbon metabolism genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) in Korean women. Twelve SNPs were identified in MTHFR, MTR, and MTRR in the 927 case-control samples, which included 165 cervical intraepithelial neoplasia 1 (CIN1), 167 cervical intraepithelial neoplasia 2 and 3 (CIN2/3), 155 cervical cancer patients, and 440 normal controls. The frequencies of the genotypes and haplotypes were assessed in the controls, CINs, and cervical cancers. Individual carriers of the variant allele C of MTHFR A1298C (rs1801131) had a 0.64-fold [95% confidence interval (CI): 0.42-0.98] decreased risk for CIN2/3 compared with common homozygotes. However, no significant association was found between most other variants and cervical cancer risk. The results also identified an increased CIN1 risk in carriers with at least one copy of haplotype 3 in the MTHFR gene (odds ratio, 1.88; 95% CI: 1.03-3.42). In conclusion, there was no significant association between most SNPs in MTHFR, MTR, or MTRR and the risk of CIN and cervical cancer in Korean women. In addition, there was no significant association of MTHFR haplotypes with risk of CIN2/3 and cervical cancer.

Ovarian malignant melanoma without evidence of teratoma.

A 46-year-old woman with ovarian malignant melanoma had advanced intraperitoneal metastasis, retroperitoneal and inguinal lymph node metastases. Extensive debulking surgery was performed and chemotherapy was given. Microscopically, no evidence of other accompanying tumor, such as teratoma was noted. Detailed examination of the patient failed to identify any evidence of another primary melanoma site. It is assumed that spontaneous regression of the primary lesion occurred. Despite the surgery and chemotherapy, the patient died within 2 months of diagnosis. Considering this case, it is assumed that the combination of surgical debulking and chemotherapy are not always beneficial in ovarian malignant melanoma and the prognosis of ovarian malignant melanoma is very poor.

Effect of delayed palliative chemotherapy on survival of patients with recurrent ovarian cancer.

For patients with recurrent ovarian cancer, the goals of chemotherapy include palliation of disease-related symptoms with minimum treatment-related side effects. However, there is currently a paucity of data regarding the initiation of palliative chemotherapy. This study aimed to compare the differences in survival rates and toxicities between patients with recurrent ovarian cancer who started palliative chemotherapy immediately versus those who received delayed chemotherapy. Through a retrospective chart review, patients who received more than three lines of chemotherapy were included. Based on the timing of third-line chemotherapy initiation, the patients were divided into two groups: delayed (DTG) and immediate (ITG) treatment groups. The chi-square test or Fisher's exact tests, and t-test or Mann-Whitney U test were used for comparing variables, as appropriate. The Kaplan-Meier method was used for survival analysis. P-value of <0.05 was considered significant. Although there was no statistically significant difference, the total number of regimens and cycles was lower in the DTG than in the ITG. No differences in toxicities and survival rates were observed between the two groups. Overall, survival and toxicity did not differ significantly between the two groups. In a palliative care setting, our findings suggest that delaying the treatment had no adverse effect on survival. Despite the lack of evidence of a survival benefit with aggressive treatment, patients chose to continue chemotherapy. Because recurrent ovarian cancer is a complex condition, patients require sufficient explanation and time to fully understand the costs and benefits related to aggressive chemotherapy.

Feasibility and efficacy of gonadotropin-releasing hormone agonists for the prevention of chemotherapy-induced ovarian insufficiency in patients with malignant ovarian germ cell tumours (KGOG 3048R).

BACKGROUND: This study assessed the effects of gonadotropin-releasing hormone agonists (GnRHa) on the prevention of chemotherapy-induced ovarian insufficiency among young patients with malignant ovarian germ cell tumour (MOGCT) receiving chemotherapy. METHODS: This multicentre, retrospective study was conducted at 15 sites affiliated with the Korean Gynecologic Oncology Group and enrolled 354 patients between January 1995 and September 2018. Among them, 227 patients were included in this study and divided into two groups according to the use of GnRHa during chemotherapy (GnRHa versus no GnRHa groups). The primary objective was to compare the rates of menstrual resumption between the two groups. We also assessed the clinical determinants affecting menstrual resumption among the study groups. RESULTS: There were no significant differences between the GnRHa (n = 63) and no GnRHa (n = 164) groups regarding age at diagnosis, parity, ethnicity, age at menarche, body mass index, International Federation of Gynecology and Obstetrics stage, mode of surgery and surgery type. The rate of menstrual resumption after chemotherapy was 100% (63 of 63) in the GnRHa group and 90.9% (149 of 164) in the no GnRHa group (p = 0.013). The mean periods from last chemotherapy to menstrual resumption were 7.4 and 7.3 months in the GnRHa and no GnRHa groups, respectively. GnRHa co-administration during chemotherapy reduced the likelihood of amenorrhoea after chemotherapy, although statistical significance was not confirmed in the univariate analysis (odds ratio: 0.276; 95% confidence interval, 0.004-1.317; p = 0.077). CONCLUSION: Temporary ovarian suppression with GnRHa during chemotherapy does not significantly increase the chances of menstrual resumption in young patients with MOGCT.

The risk of lymph node metastasis based on myometrial invasion and tumor grade in endometrioid uterine cancers: a multicenter, retrospective Korean study.

BACKGROUND: Knowledge of the risk factors for lymph node metastasis (LNM) is necessary to treat patients with endometrioid uterine cancer to optimize and further individualize treatment. This study was designed to determine the risk of LNM based on myometrial invasion and tumor grade in endometrioid uterine cancer. METHODS: The authors retrospectively reviewed the medical records and pathological findings of 834 patients who underwent surgical staging, including pelvic lymphadenectomy with or without para-aortic lymphadenectomy, for endometrioid uterine cancer from 2002 to 2008 in Korea. RESULTS: Of the 834 patients with endometrioid uterine cancer, 107 (12.8%) patients had LNM. Sixty-one (57%) patients had only pelvic LNM, 39 (36.4%) had pelvic and para-aortic LNM, and 7 (6.6%) had isolated para-aortic LNM. Tumor grade, myometrial invasion, tumor diameter, cervical extension, lymphovascular space invasion, and adnexal involvement were found to be significant predictors of LNM. Of 215 patients with no myometrial invasion and tumor grade I/II, only 1 (0.47%) had LNM. However, in other patients, the risk of LNM was significant and at least > 3.5%. Furthermore, the risk of LNM was found to be well correlated with increases in myometrial invasion and tumor grade based on subgroup analyses, when patients with no myometrial invasion and tumor grade I/II were used as a reference group (p < 0.0001). CONCLUSIONS: Patients with endometrioid uterine cancers with no myometrial invasion and tumor grade I/II might have minimal risk of LNM, whereas others might require complete pelvic and para-aortic lymphadenectomy for surgical staging.

Functional polymorphism in manganese superoxide dismutase and antioxidant status: their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer.

OBJECTIVE: Manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, plays a key role in protecting cells from oxidative stress. Furthermore, the MnSOD rs4880 polymorphism is associated with enzyme activity. The authors evaluated the interaction between MnSOD genotypes and cervical carcinogenesis risk and the modulating effects of serum antioxidant nutrient status (beta-carotene, lycopene, zeaxanthin/lutein, retinol, alpha-tocopherol and gamma-tocopherol). METHODS: Cases and controls for this study were recruited between June 2006 and July 2007 (263 controls, 84 cervical intraepithelial neoplasia (CIN), 94 CIN 2/3, and 99 cases of cervical cancer). The MnSOD polymorphism at rs4880T/C was examined using SNaPshot assays. Serum antioxidant vitamin concentrations were measured by reverse-phase gradient high-pressure liquid chromatography. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated after adjusting for age, menopause, parity, oral contraceptive use, smoking and alcohol consumption. RESULTS: No association was found between the MnSOD rs4880 polymorphism and cervical cancer. However, genotypes significantly modified the risk of cervical cancer in association with the serum statuses of micronutrients (P(interaction)<0.05 for beta-carotene, lycopene, zeaxanthin/lutein, alpha-tocopherol, and gamma-tocopherol). Decreased CIN1 risk in association with the MnSOD rs4880 variant genotype was also observed particularly for subjects with higher beta-carotene and gamma-tocopherol levels. Similar results were observed for lycopene and alpha-tocopherol in relation to the risk of CIN2/3. CONCLUSION: Our findings suggest that a higher antioxidant micronutrients status may decrease the risk of CIN and cervical cancer and modify the effect of the MnSOD polymorphism on disease risk.

Relationship of serum antioxidant micronutrients and sociodemographic factors to cervical neoplasia: a case-control study.

BACKGROUND: Although there have been some epidemiological studies on the effects of diet and nutritional status on cervical carcinogenesis, evidence for a protective effect of antioxidant micronutrients against cervical neoplasia is insufficient. The relationship between serum antioxidant micronutrients and sociodemographic factors and the risk of cervical neoplasia was investigated in this multi-center, case-control study. METHODS: The study population included women with histopathological diagnosis of cervical intraepithelial neoplasia (CIN) 1 (n=147), CIN 2/3 (n=177), cervical cancer (n=160), and a control group (n=378). Epidemiological data were collected and the serum concentrations of beta-carotene, lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma-tocopherol were measured using reverse-phase, gradient high-pressure liquid chromatography. RESULTS: Cervical cancer was found to be associated with older age, increased body mass index, and lower socioeconomic status as measured by education level and income. The mean serum concentrations of beta-carotene, lycopene, zeaxanthin plus lutein, retinol, alpha-tocopherol, and gamma-tocopherol of cervical cancer patients were significantly lower than those of control subjects. Odds ratio adjusted for age, smoking status, alcohol consumption, and human papillomavirus infection status revealed a significant gradient of decreasing risk of CIN 1, CIN 2/3, and cervical cancer with increasing serum concentrations of most antioxidant micronutrients. CONCLUSIONS: The results of this study show an inverse association between serum antioxidant micronutrient concentrations and the risk of cervical neoplasia. These results suggest that antioxidant micronutrients play a role in the prevention of cervical carcinogenesis.