Cancer Risk In Population Research Articles

Impact of Socioeconomic Deprivation on Care Quality and Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer in United States Veterans

Background: Socioeconomic deprivation has been associated with higher lung cancer risk and mortality in non-Veteran populations. However, the impact of socioeconomic deprivation on outcomes for non-small cell lung cancer (NSCLC) in an integrated and equal-access healthcare system, such as the Veterans Health Administration (VHA), remains unclear. Hence, we investigated the impact of area-level socioeconomic deprivation on access to care and postoperative outcomes for early-stage NSCLC in United States Veterans. Methods: We conducted a retrospective cohort study of patients with clinical stage I NSCLC receiving surgical treatment in the VHA between 1 October 2006 and 30 September 2016. A total of 9704 Veterans were included in the study and assigned an area deprivation index (ADI) score, a measure of socioeconomic deprivation incorporating multiple poverty, education, housing, and employment indicators. We used multivariable analyses to evaluate the relationship between ADI and postoperative outcomes as well as adherence to guideline-concordant care quality measures (QMs) for stage I NSCLC in the preoperative (positron emission tomography [PET] imaging, appropriate smoking management, pulmonary function testing [PFT], and timely surgery [≤12 weeks after diagnosis]) and postoperative periods (appropriate surveillance imaging, smoking management, and oncology referral). Results: Compared to Veterans with low socioeconomic deprivation (ADI ≤ 50), those residing in areas with high socioeconomic deprivation (ADI > 75) were less likely to have timely surgery (multivariable-adjusted odds ratio [aOR] 0.832, 95% confidence interval [CI] 0.732–0.945) and receive PET imaging (aOR 0.592, 95% CI 0.502–0.698) and PFT (aOR 0.816, 95% CI 0.694–0.959) prior to surgery. In the postoperative period, Veterans with high socioeconomic deprivation had an increased risk of 30-day readmission (aOR 1.380, 95% CI 1.103–1.726) and decreased odds of meeting all postoperative care QMs (aOR 0.856, 95% CI 0.750–0.978) compared to those with low socioeconomic deprivation. There was no association between ADI and overall survival (adjusted hazard ratio [aHR] 0.984, 95% CI 0.911–1.062) or cumulative incidence of cancer recurrence (aHR 1.047, 95% CI 0.930–1.179). Conclusions: Our results suggest that Veterans with high socioeconomic deprivation have suboptimal adherence to care QMs for stage I NSCLC yet do not have inferior long-term outcomes after curative-intent resection. Collectively, these findings demonstrate the efficacy of an integrated, equal-access healthcare system in mitigating disparities in lung cancer survival that are frequently present in other populations. Future VHA policies should continue to target increasing adherence to QMs and reducing postoperative readmission for socioeconomically disadvantaged Veterans with early-stage NSCLC.

Causal effect of breast cancer on endometrial cancer risk: A two-sample Mendelian randomization study

BackgroundObservational studies have indicated a higher incidence of endometrial cancer in individuals with breast cancer. However, to date, there is a dearth of Mendelian randomization studies that explore the causal relationship between breast cancer and the risk of endometrial cancer. Material and methodsWe conducted Mendelian randomization (MR) to investigate the causal relationship between breast cancer and endometrial cancer risk in European populations. ResultsA total of 112 valid instrumental variables were included in the analysis. Our research has revealed a compelling causal association between genetic predisposition for breast cancer and an augmented likelihood of developing endometrial cancer (Inverse variance weighted (IVW) method, odds ratio (OR) = 1.105, 95 % confidence interval (CI): 1.025 to 1.181, p = 0.003; Weighted median method, OR = 1.109, 95 % CI: 1.020 to 1.205, p = 0.015; Weighted mode method: OR = 1.101, 95 % CI: 1.013 to 1.195, p = 0.025). ConclusionTo our knowledge, this study is the first to report a causal association between breast cancer and endometrial cancer risk. Robust results were obtained through rigorous testing for heterogeneity and pleiotropy. Our findings indicate a causal effect of breast cancer on the risk of endometrial cancer.

Association between TERT gene polymorphisms (rs2736100 and rs2736109) and breast cancer risk in the Iranian population: A case-control study

Association between TERT gene polymorphisms (rs2736100 and rs2736109) and breast cancer risk in the Iranian population: A case-control study

Estimation of Environmental Burden of Disease related to Arsenic exposure in European Populations

Abstract Background Arsenic (As) exposure poses significant health risks to exposed populations, with exposure occurring predominantly via diet for the general population as recently referred by the European Food Safety Authority. This study assesses the environmental burden of disease (EBD) for three cancer types related to arsenic, across Europe. Methods A literature review was conducted to 1) identify the dose-response function (DRF) to assess the cancer risk in European populations, and 2) define EBD approaches applicable to the available data. Country-specific data (Belgium, Denmark, Portugal) for EBD calculation (exposure, socioeconomic status, health outcomes) were gathered. Disability-Adjusted Life Years (DALY) estimations were performed by calculating attributable cases (AC). Results Two main references are used for DRF: the United States Food and Drug Administration DRF for assessing bladder and lung cancer risks, and the United States Environmental Protection Agency DRF for skin cancer. Preliminary results for Belgium indicate that inorganic arsenic dietary exposure ranges from 0.084 [0.080 - 0.088] to 0.102 [0.097 - 0.107] µg/kg body weight per day, varying with education level. Stratified estimates suggest that individuals with higher educational attainment (ISCED levels 5 & 6) have a marginally higher average daily intake of arsenic compared to those with lower educational attainment (ISCED levels 0, 1 & 2). DALY attributable to inorganic arsenic exposure follow the same trend as exposure levels, i.e. individuals with a higher education level bear a higher burden of disease than individuals of the low education stratum. This concerns the three studied cancers. Conclusions This study quantifies DALY related to inorganic arsenic from dietary exposure for different European countries. Our findings will contribute to better target public health policies and interventions for arsenic risk mitigation. Key messages • Exposure to inorganic arsenic is confirmed in European countries. • EBD studies guide action priorities to tackle chemical risk factors.

Radon Exposure Is Associated with Breast Cancer Risk: A Long-Term Population-Based Study from Finland

Abstract Background Radon is a common environmental carcinogen. It is not known whether radon exposure and breast cancer risk are associated at the population level. Methods Women continuously living in Finland during the 1987-2016 period were linked to municipality-level indoor radon data annually to estimate their cumulative radon exposure over 30 years. Breast cancer incidence was observed over five years from 2017 onwards. Association between radon exposure and breast cancer incidence was assessed using conditional Cox models adjusted for family history of breast cancer, reproductive history, and socio-demographic covariates. Population attributable fractions (PAF) of breast cancer due to radon exposure were estimated. Robustness analyses were conducted in the population who lived only in houses. Results Among 1,335,947 women, 20,067 breast cancer cases were observed during a median follow-up period of 4.9 years. Among women who were exposed to high levels of radon (>100 Bq/m3), overall breast cancer incidence was 10% higher (Hazard ratio 1·10 [95% CI 1·05-1·16]), duct carcinoma incidence was 6% higher (1·06 [1·00-1·13]), lobular carcinoma incidence was 8% higher (1·08 [0·94-1·23]), and the incidence of other morphological sub-types was 34% higher (1·34 [1·17-1·53]) than among other women. Robust associations with overall breast cancer incidence (1·12 [1·05-1·20]) and the incidence of morphological sub-types in the house sample. Correspondingly, suggestive dose-response associations were observed. Conclusions High radon exposure is associated with elevated breast cancer risk at the population level, and this relationship is independent of well-established risk factors. Key messages • This study investigates the association between long-term radon exposure and breast cancer incidence based on national register data. • High radon exposure is robustly associated with breast cancer risk in general Finnish population.

MiR-559 rs58450758 polymorphism is associated with colorectal cancer risk and prognosis in Chinese Han population.

Aim: This research examined the correlation between miR-559 rs58450758 and the clinical pathological characteristics and prognosis of CRC.Materials & methods: RT-qPCR was utilized to assess the miR-559 expression levels. Chi-square test was used to investigate the relationship between miR-559 and clinical features. The association between rs58450758 different genotypes and CRC risk, as well as clinical pathological parameters, was explored, utilizing logistic regression analysis and chi-square tests. The Cox regression model and Kaplan-Meier analysis evaluated overall survival in individuals with CRC.Results: The miR-559 was down-regulated in CRC patients' serum. The expressions of miR-559 were significantly associated with tumor size, differentiation, TNM stage and lymph node metastasis. The rs58450758 TT genotype and T allele carriers were more prevalent among CRC patients. The rs58450758 polymorphism was notably linked to tumor size, differentiation, TNM stage and lymph node metastasis in CRC patients. Furthermore, CC genotype carriers exhibited a longer survival period than CT/TT genotypes within the CRC population.Conclusion: The miR-559 rs58450758 polymorphism exhibits promise as a potential biomarker for prognosticating the outcomes of CRC.

Risk of developing a subsequent primary cancer among adult cancer survivors.

Improvements in cancer control have led to a drastic increase in cancer survivors who may be at an elevated risk of developing subsequent primary cancers (SPC). In this study, we assessed the risk and patterns of SPC development among 196,858 adult cancer survivors in Alberta, Canada. We used data from the Alberta Cancer Registry to identify all first primary cancers occurring between 2004 and 2020. A SPC was considered as the next primary cancer occurring in a different site. We estimated standardized incidence ratios (SIR) for SPC development as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up. The risk of developing a SPC up to fifteen years after an initial cancer was 16.2% for males and 12.2% for females. Overall, both males (SIR=1.50) and females (SIR=1.58) had an increased risk of a SPC. There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors diagnosed between ages 18-39. Screen-detectable cancers including colorectal, lung, cervix, and breast accounted for 46% and 27% of SPCs among females and males. Cancer survivors of nearly every initial site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and highlights the need to investigate optimal strategies for screening the growing population of cancer survivors.

GLP-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data.

Data on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on pancreatic cancer incidence are limited and inconsistent. Here we evaluate the association of GLP-1RAs, alone and in combinations, with incident pancreatic cancer risk in a real-world population, stratified by obesity and smoking status. This retrospective cohort included patients with T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications between January 2013 and March 2019 and had no prior diagnosis of pancreatic cancer. The incident (first-time) diagnosis of pancreatic cancer during a 5-year follow-up was compared between propensity-score matched cohorts of patients prescribed GLP-1RAs vs other non-GLP-1RA anti-diabetes medications. Subgroup analyses were performed in patients stratified by the status of obesity and tobacco use disorder. We also compared GLP-1RA combination therapies with monotherapies. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio (HR) and 95% confidence interval (CI) calculated. The study population comprised 1,636,056 eligible patients including 167,091 prescribed GLP-1RAs and 1,468,965 prescribed other anti-diabetes medications. GLP-1RAs were associated with a significantly decreased risk for pancreatic cancer incidence compared with each of six non-GLP-1RA anti-diabetes medications with HR ranging from 0.42 to 0.82. The reduction was greater in patients with obesity and tobacco use disorder than in those without. GLP-1RA combination therapies were associated with lower pancreatic cancer risk compared with monotherapies. GLP-1RAs were associated with reduced pancreatic cancer incidence in patients with T2DM. Further studies and trials are needed to explore mechanisms and confirm causal effects.

Genetic association and computational analysis of MTHFR gene polymorphisms rs1801131 and rs1801133 with breast cancer in the Bangladeshi population

Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating one-carbon metabolism. Polymorphisms within the MTHFR gene have been found to increase the risk of breast cancer in different populations. In this study, we evaluated the association of polymorphisms of the MTHFR gene (rs1801133 and rs1801131) with the risk of breast cancer in the Bangladeshi population. This case‒control study included 202 breast cancer patients and 104 healthy controls. After the organic extraction of DNA, genotyping was performed via the PCR-RFLP method. Sanger sequencing was performed to validate the RFLP data. Statistical analyses were performed to evaluate the associations of the polymorphisms. Different computational tools were used to predict the structural and functional consequences of the SNPs. Our study revealed that the MTHFR gene polymorphism rs1801131 is associated with an increased risk of developing breast cancer (p < 0.001, OR = 3.85, 95% CI = 2.06–7.25 for the AC genotype and p < 0.001, OR = 7.82, 95% CI = 2.69–22.05 for the CC genotype). An association was also observed in the dominant model (AC + CC) (p < 0.001, OR = 4.19, 95% CI = 2.28–7.78). For rs1801131, premenopausal status was significantly associated with breast cancer risk (p < 0.001). For rs1801133, no significant association was found with breast cancer risk (p > 0.05, OR = 1.57, 95% CI = 0.90–2.74 for the CT genotype; p > 0.05, OR = 1.35, 95% CI = 0.36–4.92 for the TT genotype). Computational analyses predicted rs1801131 to be tolerated and rs1801133 to be deleterious. Structural analyses demonstrated no significant changes in protein structure but revealed alterations in neighboring interactions according to both bond distances and angles. In conclusion, rs1801131 but not rs1801133 is significantly associated with breast cancer risk in the Bangladeshi population. Moreover, in silico analyses demonstrated changes in the interaction pattern of polymorphic residues with adjacent amino acids.

Utilization of anal cytology screening among sexual and gender minority populations in Pennsylvania.

Despite the risk of anal cancer in sexual and gender minority populations (SGM), anal cancer screening remains infrequent and inconsistent in these populations. The objective of this analysis was to identify factors associated with anal cancer screenings among sexual and gender minority populations (SGM) using the Andersen's Behavioral Model of Health Services Use. Secondary analyses of two cross-sectional surveys from the 2020 (N=1125) and 2022 (N=630) "Pennsylvania LGBTQ Health Needs Assessment." Multiple logistic regression analyses were used to identify correlates of anal cytology screening. Average age was 37.7 (SD=13.3) and 39.7 (SD=13.6) in 2020 and 2022, respectively. Approximately 16-18% reported living with HIV. A minority of respondents reported past year screening (14.0% 2020 and 13.6% 2022). Enabling and need-based factors consistently associated with screening included STI treatment, living with HIV, PrEP use, and multiple sex partners. Robust factors associated with ever being screened were age and living with HIV. Anal cytology screening is being done in Pennsylvania at a small but not insignificant rate. In accordance with existing guidelines, SGM living with HIV were most likely to be screened, but still at a low rate. Predictive factors associated with screening in this study can inform future interventions to implement guideline-specific anal cancer prevention. Factors that reflect consistent connection to healthcare are associated with increased rates of screening via anal cytology testing, indicating there are opportunities to implement anal cancer screening as part of a larger, more comprehensive SGM-focused care pathway.

Preliminary investigation of MMP8 (rs11225395) and MMP9 (rs3787268) polymorphisms association with breast cancer risk in pashtun women of Pakistan.

Single Nucleotide polymorphisms (SNPs) in MMP8 and MMP9 have been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check MMP8 (rs11225395) and MMP9 (rs3787268) polymorphism with breast cancer risk in the selected population. This study, consisting of 300 breast cancer patients and 168 gender and age-matched healthy controls was subjected to confirm MMP8 and MMP9 polymorphisms. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using the T-ARMS-PCR protocol. Based on our study results, significant associations were observed between the MMP8 rs11225395 risk allele (G) and increased breast cancer risk, with the G allele frequency higher in patients (65%) compared to controls (51%) (OR = 1.752, 95% CI = 1.423-3.662, p = 0.002). Genotypes GG (OR = 4.218, p = 0.005) and AG (OR = 7.286, p = 0.0001) of MMP8 rs11225395 were also significantly associated with elevated breast cancer risk. Similarly, MMP9 rs3787268 exhibited a higher frequency of the risk allele (A) in breast cancer cases (81%) compared to controls (41%), correlating strongly with increased risk (OR = 6.320, p = 0.0001). Genotypes AA (OR = 14.500, p = 0.0001) and AG (OR = 2.429, p = 0.077) of MMP9 rs3787268 containing the risk allele showed significant associations with heightened breast cancer risk. Subgroup analyses based on age, disease progression, tumor size, and grade revealed noteworthy associations for both MMP8 rs11225395 and MMP9 rs3787268. MMP8 rs11225395 genotypes displayed significant correlations with age (p = 0.066), disease progression (p = 0.0001), larger tumor size (p = 0.005), and higher tumor grade (p = 0.006). Similarly, MMP9 rs3787268 genotypes were significantly associated with age (p = 0.001), disease progression (p = 0.010), larger tumor size (p = 0.018), and higher tumor grade (p = 0.037). Logistic regression analyses further underscored these genetic variants' potential role as biomarkers in breast cancer, particularly in relation to specific hormone receptor statuses such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) positivity. The results revealed significant associations between the mutant alleles and genotypes of MMP8 (rs11225395) and MMP9 (rs3787268) with increased breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.

Trigeminal neuralgia and risk of cancer: A population-based cohort study.

Evidence of an association between trigeminal neuralgia (TN) and subsequent cancer risk remains sparse. The present study aimed to examine the association between TN and cancer risk in the Danish population. A nationwide population-based cohort study using hospital diagnoses collected routinely and prospectively from Danish population-based registries in 1994-2022. We identified 7846 individuals with a first-time diagnosis of TN. Within one year of diagnosis, we observed 193 cancer cases (standardized incidence rate (SIR) = 2.45, 95% confidence interval (CI) = 2.11-2.82). Absolute risk (AR) for all cancers within one year of TN diagnosis was 2.5% (95% CI = 2.2-2.9). Cancers of the head, neck and nervous system were most strongly associated with TN (AR 0.9% (95% CI = 0.7-1.1); SIR = 13.5 (95% CI = 10.5-17.0)) and the risk was persistently elevated one year after TN diagnosis. We observed 827 cancer diagnoses beyond one year after TN diagnosis, where smoking related cancers were associated with elevated cancer risk (SIR 1.13 = (95% CI = 0.98-1.29)). TN was associated with an elevated risk of cancers of the head, neck and nervous system including site-specific cancers in the area. Our results suggest the potential importance of smoking related tumors in TN, either as a symptom, cause or shared risk factor.

Implementation of the updated Sydney system biopsy protocol improves the diagnostic yield of gastric preneoplastic conditions: Results from a real-world study

BackgroundThe updated Sydney system biopsy protocol (USSBP) standardizes the sampling of gastric biopsies for the detection of preneoplastic conditions (e.g., gastric intestinal metaplasia [GIM]), but the real-world diagnostic yield is not well-described. AimTo determine whether regular application of USSBP is associated with higher detection of chronic atrophic gastritis (CAG), GIM and autoimmune gastritis (AIG). MethodsWe performed a real-world retrospective study at an academic urban tertiary hospital in Chile. We manually reviewed medical records from consecutive patients undergoing esophagogastroduodenoscopy (EGD) from January to December 2017. Seven endoscopists who performed EGDs were categorized into two groups (USSBP ‘regular’ and USSBP ‘infrequent’) based on USSBP adherence, using minimum 20% adherence as the prespecified threshold. Multivariable logistic regression models were used to estimate the odds ratios (aOR) and 95% confidence intervals (CI) for the association between endoscopist groups and the likelihood of diagnosing CAG, GIM or AIG. Results1206 patients were included in the study (mean age: 58.5; 65.3% female). The USSBP regular group demonstrated a higher likelihood of detecting CAG (20% vs. 5.3%; aOR 4.03, 95%CI: 2.69–6.03), GIM (12.2% vs. 3.4%; aOR 3.91, 95%CI: 2.39–6.42) and AIG (2.9% vs. 0.8%; aOR 6.52, 95%CI: 1.87–22.74) compared to infrequent group. Detection of advanced-stage CAG (Operative Link for Gastritis Assessment stage III/IV) was significantly higher in the USSBP regular vs. infrequent group (aOR 5.84, 95%CI: 2.23–15.31). ConclusionsRoutine adherence to USSBP increases the detection rates of preneoplastic conditions, including CAG, GIM and AIG. Standardized implementation of USSBP should be considered in high gastric cancer risk populations.

1558P Independent validation of the Breast Cancer Risk Assessment Tool (Gail model) for predicting breast cancer risk in Egyptian population

1558P Independent validation of the Breast Cancer Risk Assessment Tool (Gail model) for predicting breast cancer risk in Egyptian population

Cadmium Exposure and Risk of Pancreatic Cancer: A Protocol of Systematic Review and Meta-analysis

Background: Pancreatic cancer is a devastating disease with a poor prognosis, and its etiology involves a complex interplay of genetic, environmental, and lifestyle factors. Among environmental factors, cadmium, a toxic heavy metal, has been implicated in carcinogenesis and is found in various industrial processes, tobacco smoke, and certain foods. Previous studies examining the association between cadmium exposure and pancreatic cancer risk have reported inconsistent findings, necessitating a systematic review and meta-analysis to clarify this relationship. Methods: A systematic search was conducted following PRISMA guidelines to identify relevant studies from electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, Scopus, and Google Scholar. Eligible studies included observational designs (cohort, case-control, cross-sectional) that investigated the association between cadmium exposure and pancreatic cancer risk in human populations. Data extraction, risk of bias assessment, and meta-analysis were conducted using established protocols. Subgroup analyses were performed based on study characteristics and exposure assessment methods. Results: The systematic review and meta-analysis included a comprehensive assessment of the existing literature on cadmium exposure and pancreatic cancer risk. Pooled analysis of eligible studies revealed a potential association between cadmium exposure and an increased risk of pancreatic cancer. However, the magnitude and consistency of this association varied across studies, highlighting the complexity of environmental exposures and their impact on cancer risk. Subgroup analyses and sensitivity analyses were conducted to explore sources of heterogeneity and assess the robustness of the results. Conclusion: This systematic review and meta-analysis contribute to the current understanding of the relationship between cadmium exposure and pancreatic cancer risk. While the findings suggest a potential association, further research is needed to elucidate the underlying mechanisms and clarify the role of cadmium in pancreatic carcinogenesis. These results underscore the importance of environmental risk factors in cancer development and highlight the need for public health interventions aimed at reducing cadmium exposure and improving cancer prevention strategies.

Breast, Colorectal, and Prostate Cancer Incidence among Filipino Americans by Generational Status in the Multiethnic Cohort Study.

Filipino Americans constitute 12% and 4% of the respective populations of Hawaii and California, with a large proportion of immigrants experiencing increasing cancer rates. This study investigated the incidence of colorectal, breast, and prostate cancers by generational status in the Multiethnic Cohort. We analyzed 10,495 Filipino Multiethnic Cohort first-, second-, and third-generation participants, in which 26.8% were of mixed race and ethnicity. Linkage to statewide cancer registries identified 375 breast, 249 colorectal, and 436 prostate cancer incident cases. Cox models were used to calculate HRs and 95% confidence intervals (CI) for the association between generational status and cancer incidence. Models were adjusted for age at cohort entry and cancer-specific covariates that were chosen based on stepwise regression. Compared with the first generation, colorectal cancer showed a significantly higher incidence in the second and third generations with respective HRs of 1.43 (95% CI, 1.04, 1.98) and 1.76 (95% CI, 1.29, 2.38). This association was attenuated after adjustment for relevant covariates. Breast cancer incidence was elevated in the third versus first generation (HR = 1.29; 95% CI, 1.01, 1.63) even in the fully adjusted model, whereas little difference was observed for prostate cancer. In this prospective study, we found differences in incidence by generational status, specifically colorectal cancer among men and female breast cancer. Understanding behavioral changes due to acculturation is warranted to mitigate cancer risks in migrant populations.

A Literature Review and Pooled Case Analysis of Cardiofaciocutaneous Syndrome to Estimate Cancer Risk.

Cardiofaciocutaneous syndrome (CFC) is a rare disorder with multiple congenital anomalies including macrocephaly, failure to thrive, and neurocognitive delay. CFC is part "RASopathy" syndromes caused by pathogenic germline variants in BRAF, KRAS, MAP2K1, and MAP2K2. To estimate cancer risk in CFC we conducted a systematic review using case reports and series. We reviewed articles and abstracted CFC cases to form a retrospective cohort based on PRISMA guidelines. Genotype-pphenotype (cancer) correlations, standardized incidence ratios (SIR), cumulative incidence and cause-specific hazard rates for cancer and cancer-free in CFC were calculated. This study includes 198 publications reporting 690 patients. Only 1.6% (11) had cancer, including acute lymphoblastic leukemia (ALL). Six cancer patients harbored pathogenic variants within BRAF, MAP2K1 , and MAP2K2 . Cumulative incidence by age 10 was 5% for cancer or cancer-free death. Hazard Ratio (death) was 1-2% until age 3 and declined thereafter. Significant SIRs were found for all sites (SIR=4.96) and ALL (SIR=24.23). This is the largest investigation of cancer in CFC to date. Cancer risk in the CFC population is elevated but appears limited to earlier childhood. Modest case and cancer numbers could pose limitations to accurately assess cancer risk in CFC and more studies are needed. The review was registered using PROSPERO under the identification tag CRD42023405823 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=405823 ).

Hepatitis B virus infection and the risk of gynecologic cancers: a systematic review and meta-analysis

ObjectivesThe relationship between hepatitis B virus (HBV) infection and gynecologic cancers is controversial. We aimed to evaluate the risk of gynecologic cancers associated with HBV infection using a meta-analysis.MethodsTwo independent reviewers identified publications in the PubMed, Embase and Cochrane Library databases that reported an association between HBV and the risk of gynecologic malignancy from inception to December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included articles. Pooled odds ratios (ORs) and 95% corresponding confidence intervals (CIs) were calculated using a fixed effects model or random effects model.ResultsWe collected data from 7 studies that met the inclusion criteria, including 2 cohort studies and 5 case-control studies. HBV was significantly associated with the risk of cervical cancer in the general population (OR 1.22, 95% CI 1.09–1.38, P = 0.001), although the same trend was not found in endometrial cancer (OR 1.30, 95% CI 0.95–1.77, P = 0.105) and ovarian cancer (OR 1.03, 95% CI 0.79–1.35, P = 0.813). Subgroup analysis showed that HBV infection was positively associated with the risk of cervical cancer (OR 1.27, 95% CI 1.13–1.44, P = 0.000) in case-control studies. Asian women infected with HBV have a significantly increased risk of cervical cancer (OR 1.24, 95% CI 1.10–1.40, P = 0.001) and endometrial cancer (OR 1.46, 95% CI 1.07–1.99, P = 0.018). Hospital-based studies were found to be associated with an increased risk of cervical cancer (OR 1.30, 95% CI 1.14–1.47, P = 0.000) and endometrial cancer (OR 1.61, 95% CI 1.04–2.49, P = 0.032). The results of Begg’s and Egger’s tests showed no publication bias.ConclusionsThis meta-analysis shows a positive association between HBV infection and cervical cancer. HBV is positively correlated with the risk of cervical cancer and endometrial cancer in Asian women and hospital-based populations. More multicenter prospective studies are required to confirm the findings.

Exploring the relationship between gut microbiota and breast cancer risk in European and East Asian populations using Mendelian randomization

BackgroundSeveral studies have explored the potential link between gut microbiota and breast cancer; nevertheless, the causal relationship between gut microbiota and breast cancer remains unclear.MethodsWe utilized summary statistics from genome-wide association studies (GWAS) of the gut microbiome from the MiBioGen project with summary data from GWAS on breast cancer from the FinnGen consortium and the IEU database, with the IEU data sourced from the Biobank Japan. Preliminary statistical analyses were conducted using inverse variance weighting (IVW), supplemented by various sensitivity analysis methods, including MR-Egger regression, weighted median, weighted mode, simple median, and simple mode, to ensure the robustness of our findings. Heterogeneity and pleiotropy were assessed to avoid misleading conclusions caused by unconsidered confounders or non-specific effects of genetic variants, ensuring that the results reflect a genuine causal relationship.ResultsIn European populations, four types of gut microbiota were associated with breast cancer. The genus Erysipelatoclostridium was positively associated with the risk of breast cancer, with an odds ratio (OR) of 1.21 (95% confidence interval [CI] 1.083–1.358), false discovery rate (FDR) = 0.0039. The class Coriobacteriia, order Coriobacteriales, and family Coriobacteriaceae, which belong to the same phylogenetic system, showed a consistent inversely association with breast cancer risk, with an OR of 0.757 (95% CI 0.616–0.930), FDR = 0.0281. In East Asian populations, three types of gut microbiota were related to breast cancer. The Eubacterium ruminantium group was positively associated with breast cancer risk, with an OR of 1.259 (95% CI 1.056–1.499), FDR = 0.0497. The families Porphyromonadaceae and Ruminococcaceae were inversely associated with breast cancer risk, with ORs of 0.304 (95% CI 0.155–0.596), FDR = 0.0005, and 0.674 (95% CI 0.508–0.895), FDR = 0.03173, respectively. However, these two taxa had limited instrumental variables, restricting the statistical power and potentially affecting the interpretation of the results.ConclusionThis MR analysis demonstrated a probable causal link between specific gut microbiota and breast cancer. This study, through Mendelian randomization analysis comparing European and East Asian populations, reveals that gut microbiota may influence breast cancer risk differently across populations, providing potential directions for developing targeted prevention and treatment methods.

Food biodiversity and gastrointestinal cancer risk in nine European countries: Analysis within a prospective cohort study

BackgroundFood biodiversity in human diets has potential co-benefits for both public health and sustainable food systems. However, current evidence on the potential relationship between food biodiversity and cancer risk, and particularly gastrointestinal cancers typically related to diet, remains limited. This study evaluated how dietary species richness (DSR) was associated with gastrointestinal cancer risk in a pan-European population. MethodsAssociations between DSR and subsequent gastrointestinal cancer risk were examined among 450,111 adults enrolled in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC, initiated in 1992), free of cancer at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires. DSR of an individual’s yearly diet was calculated based on the absolute number of unique biological species in each food and drink item. Associations between DSR and cancer risk were assessed by multivariable Cox proportional hazards regression models. FindingsDuring a median follow-up time of 14.1 years (SD=3.9), 10,705 participants were diagnosed with gastrointestinal cancer. Hazard ratios (HRs) and 95 % confidence intervals (CIs) comparing overall gastrointestinal cancer risk in the highest versus lowest quintiles of DSR indicated inverse associations in multivariable-adjusted models [HR (95 % CI): 0.77 (0.69–0.87); P-value < 0·0001] (Table 2). Specifically, inverse associations were observed between DSR and oesophageal squamous cell carcinoma, proximal colon, colorectal, and liver cancer risk (p-trend<0.05 for all cancer types). InterpretationGreater food biodiversity in the diet may lower the risk of certain gastrointestinal cancers. Further research is needed to replicate these novel findings and to understand potential mechanisms.