Postgraduate Medical Journal

CD47 as a biomarker for ovarian cancer: prospects and challenges

Abstract Ovarian cancer is one of the deadliest malignant tumors in the female reproductive system. Currently, an efficient approach for the early detection and reliable prognosis assessment of ovarian cancer remains unavailable, which is still a difficult problem worthy of study. In recent years, cluster of differentiation 47 (CD47) has attracted attention in tumor biology, it provides new possibilities for solving ovarian cancer problems. Although CD47 still has many challenges in clinical practice, such as standardization of detection methods and joint application strategies with other biomarkers, it still shows its potential as a biomarker. This article reviews some serum biomarkers in ovarian cancer, the biological characteristics of CD47, prospects and challenges faced as a biomarker in ovarian cancer, aiming to provide a comprehensive analysis of CD47 application in ovarian cancer.

Long-term trends analysis of the incidence and mortality in patients with ovarian cancer: a large sample study based on SEER database

Abstract Background To analyze long-term trends of the incidence and mortality of ovarian cancer in the United States. Methods Patients diagnosed with ovarian cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2017. Joinpoint regression analysis was used to analyze the incidence and mortality trend, and the changes were reported as average annual percentage change (AAPC) with a 95% confidence interval (CI). Kaplan–Meier survival curve and Cox regression analyses were utilized for survival analysis. Results A total of 74 682 patients were included, among whom 49 491 (66.27%) died and 44 487 (59.57%) died from ovarian cancer. The mean age was 61.95 ± 15.23 years. The incidence of ovarian cancer showed a decreased trend from 2000 to 2017 with an AAPC of −1.9 (95%CI: −2.0, −1.7). Both the overall mortality and cancer-specific mortality for ovarian cancer decreased from 2000 to 2017, with AAPCs of −5.0 (95%CI: −5.7, −4.2) and −4.6 (95%CI: −5.4, −3.8), respectively. There was a significant decrease in the incidence and mortality of patients with the distant SEER stage, histological subtypes of serous and malignant Brenner carcinoma, and grades II and III from 2000 to 2017. Older age, Black race, histological subtypes of carcinosarcoma, higher tumor grade, and radiotherapy were associated with poorer overall survival and cancer-specific survival, whereas higher income, histological subtype of endometrioid, and surgery were associated with better survival. Conclusion This study provided evidence of a statistically significant decrease in the incidence and mortality of ovarian cancer from 2000 to 2017. Key message What is already known on this topic?  Ovarian cancer is one of the most common tumors in women, with high morbidity and mortality. However, trends in long-term morbidity and mortality of patients with ovarian cancer have not been reported. What this study adds  Overall incidence and mortality for ovarian cancer showed a decreased trend from 2000 to 2017, and trends in incidence and mortality varied by stage, histological subtype, and tumor grade. Factors associated with overall survival and cancer-specific survival also differ. How this study might affect research, practice, or police  This study provides evidence of long-term trends in ovarian cancer incidence and mortality from 2000 to 2017.

Causal association between telomere length and female cancers: a two-sample Mendelian randomization study

Abstract Purpose To explore the causal associations between genetically predicted telomere length and gynecologic and breast cancers. Methods This Mendelian randomization study used data from genome-wide association studies on telomere length and breast (BC), cervical cancer, endometrial (EC), and ovarian (OC) cancers. The primary analysis was performed using the inverse variance weighted (IVW) method, with confirmation using the weighted median, weighted mode, and MR-Egger methods. Heterogeneity was detected using Cochran’s Q-test, horizontal pleiotropy using MR-Egger regression, outliers using MR-PRESSO, and discordant single-nucleotide polymorphisms using the leave-one-out method. Results The genetic prediction results indicated causal associations between the risk of telomere length and EC [IVW; OR = 1.29, 95% confidence interval (95%CI): 1.05–1.59, P = .02], leukocyte telomere length and EC (IVW; OR = 1.23, 95%CI: 1.01–1.51, P = .04), telomere length and OC (IVW; OR = 1.27, 95%CI: 1.01–1.60, P = .04), telomere length and BC (IVW; OR = 1.12, 95%CI: 1.01–1.23, P = .03), and leukocyte telomere length and BC (IVW; OR = 1.12, 95%CI: 1.02–1.24, P = .02). Cochran’s Q-test revealed heterogeneity for telomere length and BC (P < .001), leukocyte telomere length and BC (P < .001), and B-cell telomere length and BC (P = .012). The MR-Egger regression results suggest that the analyses of telomere length and BC (P = .014) and leukocyte telomere length and BC (P = .044) were influenced by horizontal pleiotropy. The MR-PRESSO analysis indicated the presence of outliers in the analyses of telomere length and BC and leukocyte telomere length and breast cancer. After removing the outliers, the statistical significance remained. Conclusion This MR study suggests a causal association between telomere length and BC, EC, and OC, warranting additional study. Key message What is already known on this topic?  Previous research has indicated an association between telomere length and the risk of various cancers, including breast and gynecologic cancers. However, the causal relationship remained unclear, necessitating further exploration to establish whether telomere length could be a modifiable risk factor for these cancers. What this study adds?  This study provides robust evidence of a causal relationship between genetically predicted telomere length and an increased risk of breast cancer, endometrial cancer, and ovarian cancer, with specific odds ratios indicating a significant association. It highlights that both leukocyte and overall telomere length are important factors in cancer risk. How this study might affect research, practice, or policy?  The findings could inform future research into telomere length as a biomarker for cancer risk, promote investigations into telomere-targeting interventions, and influence guidelines on screening and preventive strategies for at-risk populations based on genetic predispositions.

Krukenberg tumour

Pregnancy among thyroid cancer survivors: do thyroidectomy and radioactive iodine matter?

Abstract Background Thyroid cancer primarily affects young women and raises concerns about future fertility due to treatments of thyroidectomy and radioactive iodine (RAI) therapy. This study investigated the effects of these treatments on pregnancy probability in young female patients post-diagnosis. Methods A nationwide, population-based study using data from Taiwan’s National Health Insurance Research Database (2000–2017) examined pregnancy likelihood in women ≤45 years with thyroid cancer. The effects of thyroidectomy and RAI therapy on pregnancy were analyzed using logistic regression and Cox proportional-hazards models. Results In a cohort of 10 937 patients with thyroid cancer, 7022 (64.2%) underwent total thyroidectomy, with 718 receiving RAI treatment. The type of thyroidectomy and RAI treatment, even at doses exceeding 120 millicuries, did not reduce the likelihood of pregnancy. Age was identified as the most critical factor influencing pregnancy; women aged >30 years had a significantly lower likelihood of becoming pregnant than younger women did. Other factors associated with a reduced likelihood of pregnancy included comorbidity with diabetes (HR = 0.65, P = .002) and higher socioeconomic status (HR = 0.69, P = .085). Conclusions Thyroidectomy and RAI therapy do not diminish pregnancy probability in young women with thyroid cancer. Age remains a crucial factor, with younger women more likely to conceive. These findings are critical for fertility counseling and treatment planning. Key message What is already known on this subjec?  Thyroid cancer primarily affects young women, and its standard treatments, including thyroidectomy and radioactive iodine (RAI) therapy, have raised concerns about their potential impact on fertility. Previous studies have shown that RAI treatment may temporarily affect ovarian function but typically does not have a significant long-term effect on fertility. What this study adds?  This nationwide population-based study found that neither total nor partial thyroidectomy, nor RAI treatment, adversely affects the likelihood of pregnancy in young women with thyroid cancer. Age was identified as the most significant factor influencing pregnancy, with younger women having a higher probability of becoming pregnant after treatment. How this study might affect research, practice, or policy?  Clinicians should recognize that age, rather than the type of thyroidectomy or RAI treatment, is the most critical factor influencing fertility in young women with thyroid cancer. This insight can guide personalized fertility counseling and treatment planning to optimize outcomes.

Genetic predisposition to female infertility in relation to epithelial ovarian and endometrial cancers

AbstractBackgroundThe associations between female infertility and epithelial ovarian cancer (EOC) or endometrial cancer (EC) have been reported in observational studies, but its causal relationship remains unknown. We intended to assess the causal effect of female infertility on EOCs and ECs using a two-sample Mendelian Randomization (MR) approach.MethodsLarge pooled genome-wide association study (GWAS) datasets for female infertility (6481 cases and 68 969 controls), EOC (25 509 cases and 40 941 controls), and EC (12 906 cases and 108 979 controls) were derived from public GWAS databases and published studies. The Inverse Variance Weighted method, Weighted Median method, MR-Egger regression, and MR-Pleiotropy Residual Sum and Outlier test were adopted for MR analyses.ResultsOur results suggested that genetically predicted infertility was positively associated with the risk of EOC (OR = 1.117, 95% CI = 1.003–1.245, P = .045), but did not find a causal relationship between infertility and EC (OR = 1.081, 95% CI = 0.954–1.224, P = .223). As to the reverse direction, our study did not obtain evidence from genetics that EOCs (OR = 0.974, 95% CI = 0.825–1.150, P = .755) and ECs (OR = 1.039, 95% CI = 0.917–1.177, P = .548) were associated with an increased risk of infertility.ConclusionsThis large MR analysis supported a causal association between female infertility and increased risk of EOCs, but did not find a causal relationship between infertility and ECs.

Health outcomes of age at menarche in European women: a two-sample Mendelian randomization study

Abstract Background Observational studies have shown an association between age at menarche (AAM) and the risk of gynecological diseases. However, the causality cannot be determined due to residual confounding. Methods We conducted a Mendelian randomization (MR) study to evaluate the causal effect of AAM on several gynecological diseases, including endometriosis, female infertility, pre-eclampsia or eclampsia, uterine fibroids, breast cancer, ovarian cancer, and endometrial cancer. Single nucleotide polymorphisms were used as genetic instruments. The inverse variance weighted method was used as the primary approach and several other MR models were conducted for comparison. Cochran’s Q test, Egger’s intercept test, and leave-one-out analysis were conducted for sensitivity analysis. Radial MR analysis was conducted when detecting the existence of heterogeneity. Results After Bonferroni correction and thorough sensitivity analysis, we observed a robust causal effect of AAM on endometrial cancer (odds ratio: 0.80; 95% confidence interval: 0.72–0.89; P = 4.61 × 10−5) and breast cancer (odds ratio: 0.94; 95% confidence interval: 0.90–0.98; P = .003). Sensitivity analysis found little evidence of horizontal pleiotropy. The inverse variance weighted method also detected weak evidence of associations of AAM with endometriosis and pre-eclampsia or eclampsia. Conclusions This MR study demonstrated a causal effect of AAM on gynecological diseases, especially for breast cancer and endometrial cancer, which indicates AAM might be a promising index to use for disease screening and prevention in clinical practice. Key messages What is already known on this topic – Observational studies have reported associations between age at menarche (AAM) and a variety of gynecological diseases but the causality has not been determined. What this study adds – This Mendelian randomization study demonstrated that AAM causally affects the risk of breast cancer and endometrial cancer. How this study might affect research, practice, or policy – The findings of our study imply that AAM could be a candidate marker for early screening of populations at higher risk of breast cancer and endometrial cancer.