BACKGROUND:Most relatives of women with ovarian cancer are unaware of their increased risk for cancer and their eligibility for genetic counseling. State cancer registries offer a platform to communicate about inherited risk to this population. METHODS:We conducted a two-arm randomized trial to test a theory-based communication intervention-Your Family Connects (YFC)-compared to the standard Georgia Cancer Registry (GCR) contact. A total of 1,938 eligible ovarian cancer survivors were randomly assigned to either the YFC arm (n = 969) or the Standard Care arm (n = 969). We assessed the number of ovarian cancer survivors and their close relatives who logged on to the study website by arm. RESULTS:Survivor reach was significantly higher in the Standard Care arm than YFC (20.8% vs. 15.2%, respectively; P < 0.001). However, reach to relatives was limited to listed relatives in the YFC arm (n = 20, 13.2%), with little participation from those in the Standard Care arm (n = 1, 0.4%). Pooling across arms, minority race, longer time since diagnosis, and older age were all significantly associated with a decreased likelihood that the survivor accessed the website. CONCLUSIONS:The YFC intervention showed lower effectiveness for engaging survivors but was more effective than Standard Care in engaging at-risk relatives. Other factors (e.g., time since diagnosis) associated with lower reach must be considered in refining future outreach approaches. IMPACT:Partnering with a state cancer registry to foster family communication about inherited cancer risk is feasible but the possibility for broad population reach warrants further testing.
Background: Contribution of dominance effects to cancer heritability is unknown. We leveraged existing genome-wide association data for seven cancers to estimate the contribution of dominance effects to the heritability of individual cancer types.Methods: We estimated the proportion of phenotypic variation caused by dominance genetic effects using genome-wide association data for seven cancers (breast, colorectal, lung, melanoma, nonmelanoma skin, ovarian, and prostate) in a total of 166,772 cases and 284,824 controls.Results: We observed no evidence of a meaningful contribution of dominance effects to cancer heritability. By contrast, additive effects ranged between 0.11 and 0.34.Conclusions: In line with studies of other human traits, the dominance effects of common genetic variants play a minimal role in cancer etiology.Impact: These results support the assumption of an additive inheritance model when conducting cancer association studies with common genetic variants.
BACKGROUND:Long-term energy balance-related factors (i.e., lifestyle and physiologic factors that influence the equilibrium between energy intake and energy expenditure over an extended period) such as body mass index (BMI) are linked to colorectal cancer risk, but their impact on colorectal cancer survival is unclear. We explored associations between these long-term energy balance-related factors and survival and examined potential differences across metabolic Warburg-subtypes. METHODS:Associations between long-term energy balance-related factors and survival in the total series of patients with colorectal cancer (n = 2,347) obtained from the prospective Netherlands Cohort Study, as well as according to Warburg-subtype (Warburg-low: n = 652, Warburg-moderate: n = 802, Warburg-high: n = 797), were investigated using Cox regression analysis. RESULTS:Among the long-term energy balance-related factors studied, only increasing prediagnostic BMI was associated with a borderline significant poorer overall survival in patients with colorectal cancer [HR5kg/m2, 1.07; 95% confidence interval (CI), 0.99-1.15]. Stratified analyses showed that prediagnostic weight gain (HR5kg, 1.04; 95% CI, 0.99-1.09) and potentially increased height (HR5cm, 1.04; 95% CI, 0.98-1.11) were associated with poor overall survival only in patients with Warburg-high colorectal cancer. Increasing prediagnostic BMI was associated with poor survival only in patients with Warburg-moderate colorectal cancer (colorectal cancer-specific: HR5kg/m2, 1.12; 95% CI, 0.96-1.32; overall: HR5kg/m2, 1.20; 95% CI, 1.05-1.36). No consistent patterns were observed across energy restriction proxies. CONCLUSIONS:Maintaining a healthy prediagnostic BMI may be beneficial for colorectal cancer survival. Moreover, associations between prediagnostic BMI, weight change, early-life energy restriction, height, and colorectal cancer survival differed according to Warburg-subtypes. IMPACT:Understanding the biologic pathways involved in associations between energy balance-related factors and colorectal cancer survival could help refine prevention strategies in the future.
AbstractBackground:The literature on the association between diabetes severity and cancer risk is limited and inconclusive. The study aimed to evaluate the association between the adapted Diabetes Complications Severity Index (aDCSI) and the duration of type 2 diabetes and cancer risk.Methods:Patients ages 20 years or older with newly diagnosed type 2 diabetes between January 1, 2007, and December 31, 2011, were identified from Taiwan National Health Insurance claims data. Standardized incidence ratios (SIR) were calculated to compare cancer incidence in people with diabetes with that in the general population. Poisson regression was used to examine whether SIRs differed by age, sex, aDSCI, and duration of diabetes.Results:A total of 756,547 patients were included, with a median follow-up of 8.8 years. Excluding the first year after diagnosis, the SIR for overall cancer was 1.18 [95% confidence interval (CI) 1.17–1.19]. Higher aDCSI was associated with increased SIRs for overall [SIR ratio 1.03 (1.02–1.03) per point increase], head and neck (1.03; 1.01–1.04), liver (1.04; 1.03–1.05), pancreas (1.03; 1.00–1.05), kidney (1.13; 1.10–1.15), and leukemia (1.09; 1.06–1.13). There was no association between aDCSI and colorectal, extrahepatic biliary tract, uterus and thyroid cancer, and a negative association with breast cancer (0.97; 0.95–0.98). Type 2 diabetes duration was associated with increased SIRs for overall [1.01 (1.00–1.02) per year increase], head and neck (1.03; 1.01–1.05), and liver cancer (1.04; 1.02–1.05).Conclusions:The heterogeneity in the association between diabetes severity and diabetes-related cancers suggests diverse underlying connections.Impact:Adopting distinct approaches in further research and prevention strategies for different kinds of diabetes-related cancers is important.
BACKGROUND:The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations. METHODS:This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts. RESULTS:Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6-4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2-4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1-3.4); BCS2: 2.5/1,000 (95% CI, 2.4-2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6-6.7); HPV2: 3.9 (95% CI, 1.1-6.6)]. CONCLUSIONS:Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk). IMPACT:These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.
Abstract Background: Lifestyle factors may affect cancer risk. This study aimed to identify whether the American Heart Association ideal cardiovascular health (ICH) score and its individual variables in youth are associated with subsequent cancer incidence. Methods: This study comprised participants of the Cardiovascular Risk in Young Finns Study free of cancer at the analysis baseline in 1986 (n = 1,873). The baseline age was 12 to 24 years, and the follow-up occurred between 1986 and 2018. Results: Among 1,873 participants (mean age 17.3 ± 4.1 years; 53.4% females at baseline), 72 incident cancer cases occurred during the follow-up (mean follow-up time 31.4 ± 3.4 years). Baseline ICH score was not associated with future cancer risk (HR, 0.96; 95% confidence interval, 0.78–1.12 per 1-point increment). Of individual ICH score variables, ideal physical activity (PA) was inversely associated with cancer incidence [age- and sex-adjusted HR, 0.45 (0.23–0.88) per 1-category change (nonideal/ideal)] and remained significant in the multivariable-adjusted model, including body mass index, smoking, diet, and socioeconomic status. A continuous PA index at ages 9 to 24 years and moderate-to-vigorous PA in youth were also related to decreased cancer incidence (P < 0.05). Body mass index, smoking, diet, total cholesterol, glucose, and blood pressure were not related to cancer risk. Of the dietary components, meat consumption was associated with cancer incidence (P = 0.023). Conclusions: These findings indicate that higher PA levels in youth are associated with a reduced subsequent cancer incidence, whereas the American Heart Association’s ICH score in youth does not. Impact: This finding supports efforts to promote a healthy lifestyle and encourages PA during childhood, yielding a subsequent healthier life.
Abstract Second malignant neoplasm (SMN) is one of the most severe long-term risks for childhood cancer survivors (CCS), significantly impacting long-term patient survival. While radiotherapy and chemotherapy are known risk factors, the observed inter-individual variability suggests a genetic component contributing to the risk of SMN. This article aims to conduct a systematic review of genetic factors implicated in the SMN risk among CCS. Searches were performed in PubMed, Scopus, and Web of Sciences. Eighteen studies were included (eleven candidate gene studies, three genome-wide association studies, and four whole exome/genome sequencing studies). The included studies were based on different types of first cancers, investigated any or specific types of SMN, and focused mainly on genes involved in drug metabolism and DNA repair pathways. These differences in study design and methods used to characterize genetic variants limit the scope of the results and highlight the need for further extensive and standardized investigations. However, this review provides a valuable compilation of SMN risk-associated variants and genes, facilitating efficient replication and advancing our understanding of the genetic basis for this major risk for CCS.
Abstract Background: Despite consistent improvements in cancer prevention and care, rural and urban disparities in cancer incidence persist in the United States. Our objective was to further examine rural–urban differences in cancer incidence and trends. Methods: We used the North American Association of Central Cancer Registries dataset to investigate rural–urban differences in 5-year age-adjusted cancer incidence (2015–2019) and trends (2000–2019), also examining differences by region, sex, race/ethnicity, and tumor site. Age-adjusted rates were calculated using SEER∗Stat 8.4.1, and trend analysis was done using Joinpoint, reporting annual percent changes (APC). Results: We observed higher all cancer combined 5-year incidence rates in rural areas (457.6 per 100,000) compared with urban areas (447.9), with the largest rural–urban difference in the South (464.4 vs. 449.3). Rural populations also exhibited higher rates of tobacco-associated, human papillomavirus–associated, and colorectal cancers, including early-onset cancers. Tobacco-associated cancer incidence trends widened between rural and urban from 2000 to 2019, with significant, but varying, decreases in urban areas throughout the study period, whereas significant rural decreases only occurred between 2016 and 2019 (APC = −0.96). Human papillomavirus–associated cancer rates increased in both populations until recently with urban rates plateauing whereas rural rates continued to increase (e.g., APC = 1.56, 2002–2019). Conclusions: Rural populations had higher overall cancer incidence rates and higher rates of cancers with preventive opportunities compared with urban populations. Improvements in these rates were typically slower in rural populations. Impact: Our findings underscore the complex nature of rural–urban disparities, emphasizing the need for targeted interventions and policies to reduce disparities and achieve equitable health outcomes.
Abstract Background: The impact of adverse childhood experiences (ACE, e.g., abuse, neglect, and/or household dysfunction experienced before the age of 18) and resilience on risk for cardiovascular disease (CVD) has not previously been investigated in adult survivors of childhood cancer. Methods: We conducted a nested case–control study among long-term, adult-aged survivors of childhood cancer from the Childhood Cancer Survivor Study. Self-report questionnaires ascertained ACEs and resilience, and scores were compared between cases with serious/life-threatening CVD and controls without CVD matched on demographic and cardiotoxic treatment factors. Results: Among 95 cases and 261 controls, the mean ACE score was 1.4 for both groups; 53.4% of survivors endorsed ≥1 ACE. No association was observed between ACEs or resilience and CVD in adjusted models. Conclusions: ACEs and resilience do not appear to contribute to CVD risk for adult survivors of childhood cancer with cardiotoxic treatment exposures. Impact: Although not associated with CVD in this population, ACEs are associated with serious health issues in other populations. Therefore, future studies could investigate the effects of ACEs on other health outcomes affecting childhood cancer survivors.
Abstract Background: Esophageal adenocarcinoma (EAC) is rising in incidence, and established risk factors do not explain this trend. Esophageal microbiome alterations have been associated with Barrett's esophagus (BE) and dysplasia and EAC. The oral microbiome is tightly linked to the esophageal microbiome; this study aimed to identify salivary microbiome-related factors associated with BE, dysplasia, and EAC. Methods: Clinical data and oral health history were collected from patients with and without BE. The salivary microbiome was characterized, assessing differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features. Microbiome metabolic modeling was used to predict metabolite production. Results: A total of 244 patients (125 non-BE and 119 BE) were analyzed. Patients with high-grade dysplasia (HGD)/EAC had a significantly higher prevalence of tooth loss (P = 0.001). There were significant shifts with increased dysbiosis associated with HGD/EAC, independent of tooth loss, with the largest shifts within the genus Streptococcus. Modeling predicted significant shifts in the microbiome metabolic capacities, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production in HGD/EAC. Conclusions: Marked dysbiosis in the salivary microbiome is associated with HGD and EAC, with notable increases within the genus Streptococcus and accompanying changes in predicted metabolite production. Further work is warranted to identify the biological significance of these alterations and to validate metabolic shifts. Impact: There is an association between oral dysbiosis and HGD/EAC. Further work is needed to establish the diagnostic, predictive, and causal potential of this relationship.
Abstract Background: Health Zone 1 in Jacksonville, Fl contains a large population of underserved residents with limited resources. The high level of poverty, lower educational attainment, increased chronic illness diagnoses, and higher rates of mortality can be attributed to poorer overall health from diseases such as cancer and diabetes when compared to other health zones. Mayo Clinic Comprehensive Cancer Center Community Outreach and Engagement (MCCC COE) partnered with American Legion Post 197 (ALP 197), a veteran led organization, to specifically address the health disparities face by residents of this community. The post is located within Health Zone 1 and has a history of philanthropic contributions, making it a trusted community partner vital to the success of community health initiatives. In November 2022, ALP began instituting twice monthly Lunch & Learn (LL) programs, offering meals/snacks in conjunction with health education. Aims: The aims of LL programs are to increase resident access to: (1) health information, (2) health resources, and (3) clinical trials. Methodology: Using the community based participatory research framework and funded by the Department of Defense, MCCC COE first increased infrastructure of ALP197 by upgrading internet and public connectivity, installation of touch kiosks, mounting digital boards, and health literature (flyers and pamphlets). The LL are where healthcare experts facilitate discussion with participants on various topics, specifically requested by residents. Topics have included SDoH, understanding prescribed medication, the importance of clinical trials, mental health and stress management, stroke prevention, and proton therapy. LL are advertised on radio stations and shared through emails to past participants and other organizations. During LL programs, participants are instructed about and directed to the kiosks, where they may obtain more information on illnesses, access resources, and sign up for clinical trials. Results: To date, LL have been attended by over 50 residents. The efforts at the ALP 197 has led to increased knowledge, access to resources via the kiosks, and an increase in signup for clinical trials. The outcomes of this effort have also resulted in additional partnerships. One such partnership is with LitTV, a black owned and operated TV network that disseminates information locally in Duval County, nationally and internationally. Reach of the activities at the post includes television interviews, and articles, viewed by thousands and disseminated widely discussing our collaboration. Conclusion: The impact of our partnership with ALP 197 to reduce disease burden among in Health Zone 1 is already far reaching. LL continue to increase in monthly participation with new topic requested by residents regularly. Future monitoring of participant knowledge and attitude changes from LL are planned to be studied through pre/post surveys. We have received additional funding from the DOD to expand this initiative to health organizations and to other American Legion Posts in the Duval area. Citation Format: Vinessa Gordon, Shaina Flynn, Jennifer Crook, Arnold Merriweather, Vermelle Smith, Fullwood Marvin, Che Ngufor, Cassandra Small, Folakemi Odedina. Addressing health disparities through lunch and learns in underserved communities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A046.
Prostate cancer is the second most common malignancy in men worldwide. Men of African ancestry (AA) have a higher incidence rate and increased prostate cancer mortality, present with more advanced disease at earlier ages, than men of European ancestry (EA). Aside from socioeconomic factors driving this disparity, genomic factors also greatly contribute to the differences in the incidence and mortality rates. Despite recent advancements in comparisons of genomic alterations, a comprehensive transcriptomic and epigenomic landscape of tumors from AA prostate cancer patients has yet to be developed. Droplet-based single-cell technologies have evolved and now enabled the profiling of transcriptome, epigenome, and chromatin organization from complex tissues at single-cell resolution. To identify cell populations with distinctive molecular features and cell-type specific transcriptional programs and cell states from AA prostate cancer patients, we performed single-cell RNA sequencing for 11 EA and 6 AA prostate cancer patients. By investigating the differentially expressed genes in a cell-type-specific manner between AA and EA patients, we found that endothelial and myeloid cell populations showed significant enrichment of inflammatory pathways in AA patients. In the analysis, we also identified a group of heat shock protein family genes that were upregulated in AA patients in multiple cell types. Then, ligand-receptor interactions between tumor cells and immune microenvironments from AA and EA prostate cancer patients identified significant interactions involving frizzled receptors (FZD) that were enriched in AA patients. Overall, the transcriptomic differences may reveal oncogenic mechanisms in AA prostate cancer patients compared to EA patients. Citation Format: Hanbing Song, Yih-An Chen, William Yue, Hannah N.W. Weinstein, Paul Allegakoen, Heiko Yang, Emory Kim, Julia Pham, Keliana Hui, Matthew R. Cooperberg, Franklin W. Huang. Single-cell RNA sequencing analysis in prostate cancer patients from African ancestry [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C048.
BACKGROUND:Acute lymphoblastic leukemia (ALL) accounts for 80% of all leukemias diagnosed in children. Although ALL age patterns are consistent across racial/ethnic groups, their incidence and mortality rates are highly variable. We assessed the age-standardized ALL incidence and mortality rates of Puerto Rican Hispanic (PRH) children and compared them with those of US mainland Hispanics (USH), non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), and Non-Hispanic Asian or Pacific Islanders (NHAPI). METHODS:Differences between racial/ethnic groups were assessed by estimating the standardized rate ratio (SRR) for 2010 to 2014. Secondary data analyses of the Puerto Rico Central Cancer Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) databases were performed for the 2001 to 2016 period. RESULTS:PRH children had 31% lower incidence rates than USH, but 86% higher incidence rates than NHB. In addition, the incidence trends of ALL increased significantly from 2001 to 2016 among PRH and USH, with 5% and 0.9% per year, respectively. Moreover, PRH have a lower 5-year overall survival (81.7%) when compared with other racial/ethnic groups. CONCLUSIONS:PRH children were found to have disparities in ALL incidence and mortality rates compared with other racial/ethnic groups in the US. Additional research is warranted to identify the genetic and environmental risk factors that may be associated with the disparities observed. IMPACT:This is the first study reporting the incidence and mortality rates of childhood ALL for PRH and making comparisons with other racial/ethnic groups in the US. See related commentary by Mejía-Aranguré and Núñez-Enríquez, p. 999.
Purpose: Although breast cancer (BrCa) disparities by age of onset, subtype and mortality are well recognized between Black and White women, the underlying causes remain unknown. We were interested in the impact of methylation on racial disparities, BrCa subtypes and social vulnerability index (SVI). Methods: A whole-genome methylation array was used with DNA extracted from blood samples from women diagnosed with BrCa. After quality control, 158 BrCa patients were included. The biological age and epigenetic age acceleration, defined as the residual from regressing chronological and biological age, were computed using Horvath and GrimAge clocks. The association with aging for the independent factors of self-reported race, BrCa molecular subtypes (ER and HER2), and SVI were evaluated with Mann-Whitney tests and linear regression models. Statistical significance was defined as a P value <0.05. Results: Nearly one-third of our sample were self-reported Black women (28.8%) and the overall mean age at diagnosis was 57.8 years ±11.6. The proportion of women diagnosed with ER− and HER2+ BrCa was 43.6% (N = 68) and 14.7% (N = 23), respectively. Overall, the mean age acceleration is estimated as 2.41 years greater for Black women compared to White women by the GrimAge clock (P = 0.005), and 0.87 years for the Horvath clock (P = 0.52). Among ER- BrCa subtypes, Black women had an average biological age of 1.68 years greater than White women (P = 0.24). Similarly, among HER2+ BrCa, the biological age for Black women was 2.62 years older than White women (P = 0.14). In addition, the SVI median stratified analysis identified a 1.24-year increased age difference for Black women compared to White women in the upper SVI. In the lower SVI stratified analysis, the biological age for Black women was 0.67 years younger than White women. Conclusions: Our analysis identified statistically significant epigenetic age acceleration differences between self-reported Black and White BrCa patients. Both stratified analyses by BrCa subtype and SVI yielded biological age differences by self-reported race, however, directional effects differed based on strata. Although our sample size is limited, our stratified analysis revealed novel research directions to better understand racial disparities in BrCa.
Abstract Background: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by self-identified race may contribute to poorer HGSC survival among Black versus White individuals. Methods: We included newly generated RNA sequencing data from Black and White individuals and array-based genotyping data from four existing studies of White and Japanese individuals. We used K-means clustering, a method with no predefined number of clusters or dataset-specific features, to assign subtypes. Cluster- and dataset-specific gene expression patterns were summarized by moderated t-scores. We compared cluster-specific gene expression patterns across datasets by calculating the correlation between the summarized vectors of moderated t-scores. After mapping to The Cancer Genome Atlas–derived HGSC subtypes, we used Cox proportional hazards models to estimate subtype-specific survival by dataset. Results: Cluster-specific gene expression was similar across gene expression platforms and racial groups. Comparing the Black population with the White and Japanese populations, the immunoreactive subtype was more common (39% vs. 23%–28%) and the differentiated subtype was less common (7% vs. 22%–31%). Patterns of subtype-specific survival were similar between the Black and White populations with RNA sequencing data; compared with mesenchymal cases, the risk of death was similar for proliferative and differentiated cases and suggestively lower for immunoreactive cases [Black population HR = 0.79 (0.55, 1.13); White population HR = 0.86 (0.62, 1.19)]. Conclusions: Although the prevalence of HGSC subtypes varied by race, subtype-specific survival was similar. Impact: HGSC subtypes can be consistently assigned across platforms and self-identified racial groups.
AbstractBackground: Acidic urine pH is associated with rapid hydrolysis of N-glucuronide conjugates of aromatic amines into metabolites that may undergo metabolism in the bladder lumen to form mutagenic DNA adducts. We previously reported that consistently acidic urine was associated with increased bladder cancer risk in a hospital-based case–control study in Spain. Here, we conducted a separate study in northern New England to replicate these findings. Methods: In a large, population-based case–control study conducted in Maine, New Hampshire, and Vermont, we examined bladder cancer risk in relation to consistent urine pH, measured twice daily by participants over 4 consecutive days using dipsticks. In parallel, we collected spot urine samples and conducted laboratory measurements of urinary acidity using a pH meter. Unconditional logistic regression was used to estimate associations, adjusting for age, gender, race, Hispanic status, and state. Analyses were further stratified by smoking status. Results: Among 616 urothelial carcinoma cases and 897 controls, urine pH consistently ≤ 6.0 was associated with increased bladder cancer risk (OR = 1.27; 95% confidence interval, 1.02–1.57), with the effect limited to ever-smokers. These findings were supported by analyses of a spot urine, with statistically significant exposure–response relationships for bladder cancer risk overall (Ptrend = 5.1×10−3) and among ever-smokers (Ptrend = 1.2×10−3). Conclusions: Consistent with a previous study in Spain, our findings suggest that acidic urine pH is associated with increased bladder cancer risk. Impact: Our findings align with experimental results showing that acidic urine pH, which is partly modifiable by lifestyle factors, is linked to hydrolysis of acid-labile conjugates of carcinogenic aromatic amines.
AbstractBackground: One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus, we assessed its relationship with ovarian cancer risk. Methods: In prospectively collected samples, we evaluated the association of kidney function markers and C-reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, >3.0 mg/L). Results: Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006–2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: HR, 1.00; 95% confidence intervals, 0.83–1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33, 0.11–0.98) and clear cell (4.74, 1.39–16.16) tumors. Poor kidney function was associated with a nonsignificant increase in ovarian cancer risk among women with CRP>3.0 mg/L (e.g., uric acid Q4 vs. Q1; 1.23, 0.81–1.86), but not CRP≤3.0 mg/L (0.83, 0.66–1.05). Other associations did not vary across CRP categories. Conclusions: Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions. Impact: This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk.
Purpose: To evaluate whether residential proximity to air emissions of correlated industrial carcinogens, both singly and in combination, are associated with breast cancer incidence. Methods: Using the US Environmental Protection Agency's Toxics Release Inventory, we estimated the 10-year annual average air releases of 26 known or probable carcinogens within 3, 5, and 10 km of Sister Study participants' baseline residences (n = 50,343, 2003–2009). We used Cox proportional hazards regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between ambient concentrations of each individual compound and incident breast cancer. To assess mixtures, we applied an exposure continuum mapping (ECM) framework to identify latent mixture profiles via a self-organizing map and assessed whether these profiles were related to incident breast cancer by estimating a joint exposure-response function with generalized additive models. Results: During follow-up (mean = 11.6 years), 4,282 breast cancer cases were identified. The exposure prevalence for compounds emitted within 3-km of participants' residences varied from <1%–15%. For individual compounds, HRs for the association between quantiles of emission levels and breast cancer were largely null, except for cadmium, vinyl chloride and asbestos (e.g., asbestos 3-km HR>median vs. no exposure = 2.61, 95% CI: 1.37–5.09). Our application of ECM identified 49 profiles that explained 79% of the variance in emission patterns observed within 3-km of participant residences. Profiles revealed that relatively high levels of exposure to several compounds were rare (<1%) and most participants resided in locations defined by low emissions patterns. Estimation of a joint exposure-response surface indicated that breast cancer was not significantly related to changing patterns of the composition of emission mixtures (P = 0.31). Conclusions: Preliminary results suggest that breast cancer incidence may be related to emissions of certain individual industrial carcinogens, particularly asbestos. Examination of complex exposure scenarios revealed that high simultaneous exposure to many compounds was rare, and that our identified latent patterns of these emissions were not associated with breast cancer.
