BACKGROUND:Chronic nonurological complications are common among prostate cancer (PCa) survivors; however, their spectrum, magnitude, and genetic contribution remain poorly characterized. METHODS:We evaluated 15 commonly reported nonurological complications and tested their associations with exposure to PCa and disease-specific polygenic risk scores (PRS) in the UK Biobank (UKB; N = 219,133). Analyses were conducted using cause-specific Cox proportional-hazards models within a full-cohort framework with time-updated PCa status, delayed entry at study recruitment, and age as the underlying time scale. RESULTS:After recruitment, incident PCa was diagnosed in 13,780 men, of which 1,656 (12.02%) had metastatic PCa (mPCa). Risks for seven complications were higher among men with PCa, adjusting for genetic background (all p < 0.05), including osteoporosis, venous thromboembolism, depression, and four primary cancers (bladder, kidney, colorectal, and pancreatic). Risks were consistently stronger among men exposed to mPCa than non-mPCa; for example, the hazard ratio (HR) (95% confidence interval) for osteoporosis was 1.88 (1.63-2.18) for any PCa, 4.67 (3.11-7.01) for mPCa, and 1.75 (1.50-2.04) for non-mPCa. Elevated risks for three additional complications (coronary artery disease, type 2 diabetes and chronic obstructive pulmonary disease) were observed only among men with mPCa. The risks for these ten complications were further increased among men with higher disease-specific PRS; for example, the HR for osteoperosis in mPCa patients in the top PRS quartile was 13.57 (8.24-22.34) compared with men without PCa (p < 0.001). CONCLUSION:PCa diagnosis and inherited genetic susceptibility jointly contribute to increased risks of multiple chronic non-urological complications among survivors.

ABSTRACT Background Sleep disturbances are common among cancer survivors and negatively impact quality of life. Regular moderate‐ to high‐intensity physical activity may provide a cost‐effective, low‐risk alternative strategy to improve sleep. Methods Data collected as part of two distinct studies, the Detroit Research On Cancer Survivors (ROCS) cohort and the CrossFit And Physical Activity: A Better Life Experience (CAPABLE) High‐Intensity Interval Training (HIIT) trial, were analyzed to evaluate the association between participation in moderate‐ to high‐intensity physical activity and sleep health. Sleep health was assessed using the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). Results Among Detroit ROCS cohort members who completed the supplemental sleep survey at baseline and/or follow‐up (n = 3022), those meeting 2012 American Cancer Society (ACS) physical activity guidelines reported sleep outcomes compared with inactive participants, including lower ISI scores (4.5 vs. 5.9, p < 0.001), lower ESS scores (5.6 vs. 6.6, p < 0.001), and lower PSQI (6.3 vs. 7.9, p < 0.001). In the CAPABLE trial (n = 73), ISI scores improved from 4.5 at baseline to 3.4 at exit (p < 0.001), while PSQI scores showed more modest improvement (6.1 to 5.4, p = 0.063). ESS scores remained unchanged (5.4 to 5.2, p = 0.708). Conclusions These findings support the role of moderate‐ to high‐intensity physical activity in improving sleep health in a diverse cancer survivor population. Future research should further refine current methodologies to maximize benefit to survivors and implementation science to increase uptake and promote adherence to evidence‐based guidelines.

To describe the incidence and patterns of second primary cancer diagnoses and understand the impact on health-related quality of life (HRQOL). The Detroit Research on Cancer Survivors (ROCS) cohort was initiated to understand the multiplex causes of poor outcomes in Black cancer survivors. The Detroit Genetic Epidemiology of Multiple primary cancerS (GEMS) study examines susceptibility to multiple primary cancers (MPC), leveraging follow-up of Detroit ROCS survivors to identify those diagnosed with MPCs. We compared HRQOL, using the Functional Assessment of Cancer Therapy-General survey, between survivors diagnosed with MPC and a frequency-matched set of survivors diagnosed with a single primary cancer (SPC) and reported HRQOL among MPC survivors before and after their second cancer diagnosis. To date, Detroit GEMS includes 371 Black survivors diagnosed with MPC. The cumulative incidence of MPCs among eligible Detroit ROCS participants was 9.8

PURPOSE:Black women with hormone receptor-positive (HR +) breast cancer are twice as likely as White women to have weakly HR + tumors (1-10% positive cells). Patients with weakly HR + tumors are less frequently prescribed ET and have 60% higher mortality than strongly HR + tumors (> 10% positive cells). We evaluated factors associated with ET prescription and self-reported use among Black women with HR + breast cancer. METHODS:Among 922 Detroit ROCS participants, we evaluated associations between demographics, socioeconomic status, and health, tumor, oncologist, and hospital characteristics and ET prescription intent and self-reported ET use. Logistic mixed-effects regression was used to account for oncologist and hospital group effects. RESULTS:Oncologists intended to prescribe ET to 83.4% of participants (n = 769), of which 54.4% (n = 502) reported use. In multivariable models, participants with weakly HR + tumors were 90% less likely to be prescribed ET (OR = 0.10, p < 0.0001). Other significant characteristics of ET prescription included a BMI of 25-29.9 kg/m2 (OR = 0.45, p = 0.0085), HR positivity > 90% vs. 11-90% (OR = 0.37, p = 0.00045), unknown HR percentage (OR = 0.12, p < 0.0001), OncotypeDx testing (OR = 2.65, p < 0.0001), and receiving radiation (OR = 2.20, p = 0.00016). Self-reported ET use was lower among those with lower health literacy (OR = 0.017, p < 0.001), weak HR positivity (OR = 0.46, p = 0.0053), unknown HR percentage (OR = 0.074, p = 0.034), and older age at diagnosis (OR = 0.88, p = 0.002). Increased ET use was associated with an income between $60,000-$79,900 vs. < $20,000 (OR = 1.54, p = 0.035), higher comorbidity count (OR = 1.09, p = 0.0054), distant stage (OR = 2.03, p = 0.029), and surgery (OR = 2.35, p = 0.001). CONCLUSION:Identifying multilevel factors related to ET use may inform strategies to improve ET uptake and survival among Black women with HR + breast cancer.

Importance:Much of the understanding of cancer risk associated with rare pathogenic variants (RPVs) is derived from family-based studies or clinically ascertained samples, which may be limited by ascertainment and selection bias. Objective:To quantify associations between RPVs in previously implicated cancer predisposition genes and single and multiple cancer diagnoses in a large population-based study. Design, Setting, and Participants:In this genetic association study, whole-exome sequencing data were used from the UK Biobank, a UK population-based cohort that enrolled participants aged 40 to 69 years between 2006 and 2010. Participants who were involved in the whole-exome sequencing release of 200 000 genomes in 2020 were included in this study. This analysis included White participants only, as findings in other racial and ethnic groups had small sample sizes. Participants were diagnosed before or after biobank enrollment until March 2024. Exposures:The sequencing data of a set of 96 previously implicated cancer predisposition genes were analyzed and compared using 2 methods. To determine the statistical significance of an association, a robust optimal sequence kernel association test was used, while odds ratios (ORs) and 95% CIs were obtained through Firth logistic regression. Main Outcomes and Measures:The primary study outcome was the diagnosis of 1 of 11 cancers (bladder, breast, central nervous system, colorectal, lung, melanoma, ovary, pancreatic, prostate, renal, thyroid) defined by relevant diagnosis codes in inpatient hospital diagnosis, cancer registry, and/or death registry data. Results:Data from 183 627 participants (101 414 [55.2%] female) were analyzed, including 25 824 participants with at least 1 cancer diagnosis, of whom 23 704 (91.8%) had a single cancer diagnosis and 2130 (8.2%) had 2 or more cancer diagnoses. A total of 157 793 controls had no cancer diagnosis. The median (IQR) age was 62 (56-65) years in participants with at least 1 cancer diagnosis, compared to 57 (50-63) years in those without a cancer diagnosis. Genetic variation in 16 genes was significantly associated with at least 1 cancer of interest (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDKN2A, CHEK2, HOXB13, MITF, MLH1, MSH2, MSH6, NF1, PALB2, RAD51C, and RAD51D). The presence of an RPV in 1 of these 16 genes was associated with increased odds of at least 1 cancer (OR, 1.87; 95% CI, 1.76-1.98) and multiple primary cancers (OR, 2.56; 95% CI, 2.18-2.99). Carrier frequency was 6.28% and 8.36%, respectively. Conclusions and Relevance:This genetic association study demonstrates several established associations between cancer predisposition genes and cancer diagnoses in an unselected population-based study. These results also demonstrate that RPVs in cancer predisposition genes are associated with multiple primary cancer diagnoses, suggesting that multigene panel testing may be warranted in these individuals.

PURPOSE Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs). MATERIALS AND METHODS Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database. These P/LP variants were genotyped in a sample of 3,040 lung cancer cases and controls from the Inflammation, Health, Ancestry, and Lung Epidemiology study (NHW: n = 1,915; AA: n = 1,125) and were tested for their association with lung cancer using multivariate logistic regression adjusting for age, sex, pack-years, and race. RESULTS We identified 49 unique rare P/LP variants in 21 genes among 156 carriers. Approximately 5.9% of lung cancer cases and 4.2% of controls carried at least one P/LP variant. P/LP variants in DDR genes were more common in lung cancer cases, particularly those diagnosed with adenocarcinoma (odds ratio [OR], 1.46 [95% CI, 1.00 to 2.14]). MUTYH variants were associated with lung cancer overall (OR, 1.82 [95% CI, 1.10 to 3.12]), with the strongest associations among never smokers (OR, 3.37 [95% CI, 1.08 to 10.26]), and in individuals who do not meet current USPSTF screening criteria (OR, 2.85 [95% CI, 1.20 to 7.53]). CONCLUSION Germline variants in DDR genes appear to be associated with lung cancer, particularly when examined by gene subtype and morphologic subtype. MUTYH , a gene historically associated with colorectal and other GI malignancies, emerged as a candidate gene that should be examined in individuals who do not have a significant smoking history.

736 Background: The OFF State (GDP bound) KRASG 12D inhibitor MRTX1133 is currently being evaluated in pancreatic ductal adenocarcinoma (PDAC) patients. Nevertheless, as with other OFF state KRAS G12C inhibitors sotorasib and adagrasib, the KRAS G12D inhibitor may yield only a modest increase in disease-free survival due to emergence of drug resistance. This underscores the need to identify strategies that can enhance the efficacy of KRAS inhibitors in PDAC. Nuclear protein transport plays an important role in several pro-tumorigenic pathways and has been shown to be a therapeutic vulnerability in KRAS mutant cancers. XPO1 is the major nuclear exporter and plays a pivotal role in shuttling various critical tumor suppressors, genome surveillance proteins, and transcription factors out of the nucleus and is frequently overexpressed in various cancers, including PDAC. In this study, we employed a KRAS G12D inhibitor resistant model and evaluated its sensitivity to nuclear exporter protein inhibitor. Methods: We examined the cytotoxic and molecular effects of KRAS G12D inhibitor MRTX1133 in combination with nuclear transport inhibitor eltanexor in KRAS G12D inhibitor resistant models. The preclinical antitumor efficacy of the combination was evaluated in KRAS G12D mutant PDAC cell derived xenograft (CDX) subcutaneous and orthotopic models. Results: Eltanexor treatment reversed MRTX1133 resistance in vitro yielding suppressed proliferation of KRAS G12D mutant 2D and 3D cultures of PDAC cell lines and patient derived primary tumors cells. High throughput P-kinome analysis showed suppression of a larger repertoire of MAPK substrates in combination treatment compared to single agent group. Eltanexor and MRTX1133 combination led to reduction in protein expression of KRAS downstream effectors and cell cycle markers. Furthermore, a combined administration of eltanexor and MRTX1133 at sub-optimal doses resulted in remarkable tumor growth inhibition in multiple subcutaneous and orthotopic KRAS G12D mutant mice models. Moreover, eltanexor as a maintenance therapy also prevented tumor relapse indicating durability of response in PDAC. Conclusions: This is the first study demonstrating that nuclear transport inhibitors can overcome KRAS G12D inhibitor MRTX1133 resistance in PDAC cells. This study provides a rationale for combining MRTX1133 with eltanexor for the treatment of PDAC patients with KRAS G12D mutant tumors.

Abstract Background: African American (AA) men are more than twice as likely to die of prostate cancer (PC) compared to non-Hispanic White men in the US. Among AA men, we examined survival after PC diagnosis by neighborhood-level structural racism and whether its effects are mediated by neighborhood socioeconomic status (nSES). Methods: We pooled data for 133,241 AA men diagnosed with PC from 2000-2013 from ten population-based cancer registries across eight states (CA, Detroit, FL, GA, LA, NJ, NY, TX) of the RESPOND Study (Research on Prostate Cancer among African American Men). Residential addresses at PC diagnosis were geocoded and appended to census block-group measures of structural racism (contemporary redlining, racial/ethnic segregation typology, and racial bias in mortgage lending) and nSES, an index comprising measures of income, education, occupation, employment, and housing. We used Cox models and the %mediation SAS macro for causal mediation to assess overall and PC- specific survival according to structural racism and to quantify the extent to which survival differences were mediated by nSES. Models were adjusted for diagnosis year and age, state of residence, and marital status. Results: There were 46,830 deaths overall with 12,272 PC-specific deaths among the study population. Greater mortality risk was observed among AA men residing in neighborhoods in the highest compared to lowest quartile of redlining (total effect) for both overall survival (Hazards ratio [HR]=1.26; 95% CI=1.22, 1.31) and PC-specific survival (HR=1.30; 95% CI=1.21-1.39). Neighborhood SES mediated 59% and 47% of the effect of redlining, resulting in natural direct effects of HR=1.11 (95% CI=1.05, 1.17) and HR=1.16 (95% CI=1.04, 1.29) for overall and PC-specific survival, respectively. Compared to predominantly White neighborhoods, AA men residing in neighborhoods with all other racial/ethnic typologies had greater overall and PC-specific mortality risk, with largest risk for neighborhoods with predominantly AA or mixed with Hispanic and AA residents. Neighborhood SES completely mediated the effect of racial/ethnic typology on survival for all typologies except that of mixed Hispanic and Black residents (37% and 25% mediation by nSES for overall and PC-specific survival, respectively). There was no association between racial bias in mortgage lending and survival. Results from models additionally adjusted for prognosis (Prostate Cancer Cohort Consortium [PC3] classification of aggressive disease) and treatment (receipt of surgery, radiation, chemotherapy, or hormone therapy) were similar. Conclusions: Neighborhood SES explains substantial portions of the impact of redlining and racial/ethnic typology on overall and PC-specific survival among AA men across eight states in the US. Remaining survival differences for the most redlined neighborhoods and neighborhoods with a mix of Hispanic and Black residents independent of nSES suggest alternative pathways for the impact of neighborhood structural racism on mortality risk for AA men with PC. Citation Format: Mindy C. DeRouen, Meera Sangaramoorthy, Katherine Lin, Annie Vu, Dan Meltzer, Pushkar Inamdar, Yuhong Zhou, Kevin Ward, Xiao-Cheng Wu, Antoinette Stroup, Jennifer Beebe-Dimmer, Anshu Shrestha, Aaron P. Thrift, Margaret Gates-Kuliszewski, Peter Kanetsky, Tamara Lotan, Anthony Colombo, David Conti, Christopher Haiman, Ann Hamilton, Kirsten Beyer, Joseph Gibbons, Iona Cheng, Salma Shariff-Marco, Scarlett Gomez. Assessing the impact of neighborhood structural racism on survival for African American men with prostate cancer; a population-based cancer registry study across eight US states [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A041.

10556 Background: Sleep disturbances are particularly prevalent among cancer survivors, likely attributed in part to anxiety over prognosis, treatment, and associated financial concerns. We know little about prevalence, patterns and predictors of poor sleep health in African American (AA) cancer survivors. Sleep problems may contribute in part to the observed disparities in outcomes in this high-risk population and represents a modifiable target to improve quality of life and longer-term health problems. Methods: The Detroit Research on Cancer Survivors (ROCS) study is a large cohort of AA cancer survivors diagnosed with female breast, prostate, colorectal, endometrial, lung or any other early onset cancer on or after 01/01/2013 in Metropolitan Detroit. We have enrolled 5,073 survivors into the study, each completing a baseline survey with annual follow-up to update medical history, health related quality of life (QoL), and other prognostic factors. In 2021, a supplemental sleep survey was administered to all eligible survivors. The current investigation analyzes sleep, QoL (measured using the Functional Assessment of Cancer Therapy - General (FACT-G) survey), and relevant health behavior data from 716 survivors who completed the sleep survey. Sleep health was measured using the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). Block regression was used to estimate the contribution of clustered factors to QoL. Five blocks were evaluated: sleep health, demographics, cancer characteristics, comorbidities, and health behaviors. Results: Nearly 60% of AA cancer survivors in the study reported symptoms indicative of poor sleep quality (PSQI score 6-21) with 17% reporting excessive daytime sleepiness (ESS score 11-24) and 11% reporting moderate to severe insomnia (ISI score ≥ 15). Sleep disturbances and poor quality of sleep were associated with clinically meaningful declines in QoL, where survivors with ISI scores in the clinical range reported adjusted FACT-G scores 19 points lower than those with ISI score below the clinical range (95% CI -14.7, -22.6). Sleep health accounted for the largest proportion of variability in FACT-G scores (R 2 = 0.28) and accounted for an additional 19% of the variance over and above the other 4 blocks. Finally, AA survivors reporting regular physical activity also reported better sleep quality in all 3 sleep scales (p < 0.001). Conclusions: A substantial proportion of AA cancer survivors reported poor sleep quality which impacted their QoL. Understanding the determinants of sleep health in this population will lead to the development of interventions aimed at improving quality of life and downstream health consequences in AA cancer survivors.

10604 Background: It has been estimated that up to 40% of prostate cancer may be attributed to inherited genetic susceptibility, yet very few variants have been consistently associated with risk and/or adverse outcomes after diagnosis. Moreover, because prostate cancer survival is generally good, risk of developing a second primary cancer (SPC) is an important concern. Identifying men at greater genetic risk of developing an SPC will lead to improved post-diagnostic cancer surveillance practices and lifestyle behavior modifications. Methods: The current investigation leverages genetic and phenotypical data from the UK Biobank (UKB) to examine inherited genetic factors, including rare pathogenic mutations (RPMs) and polygenic risk scores (PRS) with prostate cancer risk and SPC. The individual and joint contribution of (RPM in 26 cancer susceptibility genes and trans-ethnic PRS previously derived for 11 different cancer sites with both risk of prostate cancer and also SPCs among men diagnosed after primary prostate cancer. Cox regression models were used to estimate Hazard Ratio (HR) for prostate cancer, adjusted for age and ancestry. Cumulative incidence of SPC by person-year among prostate cancer patients was estimated from the age of diagnosis and compared with that in men without cancer. Results: Among 228,472 men in the UKB, 17,547 were diagnosed with prostate cancer. RPMs in five genes ( ATM, BRCA2, CHEK2, HOXB13 and PTEN) were significantly associated with prostate cancer risk. The rate of prostate cancer among RPM carriers was 15.59% compared with 7.72% in non-carriers (HR=2.26, 95% CI=1.97-2.59). The top decile of PRSProstate was associated with a 9.99-fold increase in risk of prostate cancer (95% CI=9.08-11). Having a diagnosis of prostate cancer had a significantly increased risk for two SPCs (bladder and kidney) and reduced risk for lung cancer, p<0.001. Those that developed SPC of bladder cancer had significantly higher PRSBladder, p=5.91E-06. The number of RPM carriers (n=77) among SPC bladder cancers was prohibitively small to precisely estimate risk. Conclusions: In this large population-based cohort, both RPMs in largely DNA damage repair genes and PRS contribute to risk of prostate cancer and PRS with second primary bladder cancer among men with prostate cancer. These data both contribute to our understanding of the genetic susceptibility to prostate cancer and reinforce the need for refinement of genetic screening panels.

Advances in cancer screening and treatment have improved survival after a diagnosis of cancer. As the number of cancer survivors as well as their overall life-expectancy increases, investigations of health-related quality of life (HRQOL) are critical in understanding the factors that promote the optimal experience over the course of survivorship. However, there is a dearth of information on determinants of HRQOL for African American cancer survivors as the vast majority of cohorts have been conducted predominantly among non-Hispanic Whites. In this review, we provide a review of the literature related to HRQOL in cancer survivors including those in African Americans. We then present a summary of published work from the Detroit Research on Cancer Survivors (ROCS) cohort, a population-based cohort of more than 5000 African American cancer survivors. Overall, Detroit ROCS has markedly advanced our understanding of the unique factors contributing to poorer HRQOL among African Americans with cancer. This work and future studies will help inform potential interventions to improve the long-term health of this patient population.

PURPOSE:People with cancer commonly rely on loved ones as informal caregivers during and after treatment. Costs related to caregiving and their association with caregiver financial burden are not well understood. METHODS:Results include data from 964 caregivers of African American cancer survivors in the Detroit Research on Cancer Survivors (ROCS) cohort. Caregiving costs include those related to medications, logistics (e.g., transportation), and medical bills. Financial burden measures included caregiver financial resources, strain, and difficulty paying caregiving costs. Prevalence ratios (PR) and 95% confidence intervals (CI) of associations between costs and high financial burden were calculated using modified Poisson models controlling for caregiver characteristics. RESULTS:Caregivers included spouses (36%), non-married partners (8%), family members (48%), and friends (9%). Nearly two-thirds (64%) of caregivers reported costs related to caregiving. Logistical costs were the most common (58%), followed by medication costs (35%) and medical bills (17%). High financial hardship was reported by 38% of caregivers. Prevalence of high financial hardship was 52% (95% CI: 24%, 86%) higher among caregivers who reported any versus no caregiver costs. Associations between caregiver costs and high financial burden were evident for costs related to medications (PR: 1.33, 95% CI: 1.12, 1.58), logistics (PR: 1.57, 95% CI: 1.29, 1.92), and medical bills (PR: 1.57, 95% CI: 1.28, 1.92). CONCLUSIONS:Most caregivers experienced costs related to caregiving, and these costs were associated with higher prevalence of high caregiver financial burden. IMPLICATIONS FOR CANCER SURVIVORS:Informal caregivers experience financial hardship related to cancer along with cancer survivors.

Background Social risks are common among cancer survivors who have the fewest financial resources; however, little is known about how prevalence differs by age at diagnosis, despite younger survivors' relatively low incomes and wealth. Methods The authors used data from 3703 participants in the Detroit Research on Cancer Survivors (ROCS) cohort of Black cancer survivors. Participants self-reported several forms of social risks, including food insecurity, housing instability, utility shut-offs, not getting care because of cost or lack of transportation, and feeling unsafe in their home neighborhood. Modified Poisson models were used to estimate prevalence ratios and 95% confidence intervals (CIs) of social risks by age at diagnosis, controlling for demographic, socioeconomic, and cancer-related factors. Results Overall, 35% of participants reported at least one social risk, and 17% reported two or more risks. Social risk prevalence was highest among young adults aged 20-39 years (47%) followed by those aged 40-54 years (43%), 55-64 years (38%), and 65 years and older (24%; p for trend < .001). Compared with survivors who were aged 65 years and older at diagnosis, adjusted prevalence ratios for any social risk were 1.75 (95% CI, 1.42-2.16) for survivors aged 20-39 years, 1.76 (95% CI, 1.52-2.03) for survivors aged 40-54 years, and 1.41 (95% CI, 1.23-1.60) for survivors aged 55-64 years at diagnosis. Similar associations were observed for individual social risks and experiencing two or more risks. Conclusions In this population of Black cancer survivors, social risks were inversely associated with age at diagnosis. Diagnosis in young adulthood and middle age should be considered a risk factor for social risks and should be prioritized in work to reduce the financial effects of cancer on financially vulnerable cancer survivors.

10505 Background: Much of our understanding of cancer risk attributable to rare pathogenic variants (RPV) is derived from family-based and case-only cohort studies, which may be limited by ascertainment bias. We sought to identify associations between RPVs and cancer diagnoses in a large population-based study. Methods: We conducted a case-control study using the UK Biobank. We performed gene-based aggregate testing to examine the relationship between RPVs (defined as pathogenic or likely pathogenic variants) in 96 genes implicated in cancer risk and the diagnosis of 11 common cancers using the combined optimal unified sequence kernel association test (SKAT-O). Odds ratios (OR) and 95% confidence intervals (CI) were then calculated using Firth logistic regression. Results were adjusted for age, sex and genetic ancestry. Bonferroni-adjusted p-values were used to determine statistical significance. Variant pathogenicity was determined by American College of Medical Genetics criteria. Results: We identified 24 genes in which RPVs were statistically significantly associated with at least one of 11 common cancers among 183,626 individuals. The presence of an RPV in one of these 24 genes was associated with increased odds of one cancer (OR 1.8; 95% CI: 1.7-2.0), and multiple cancers (OR 2.5; 95% CI: 2.2-2.9). Conclusions: This large population-based study identified 24 established cancer risk genes in which RPVs were associated with common cancers. We identified both known and novel associations between cancer and RPVs. Some associations—i.e. renal/pancreas and MEN1—may be due to ascertainment and/or misclassification bias. We also show that individuals with RPVs in cancer risk genes not only have higher odds of one cancer diagnosis, but also multiple cancers.[Table: see text]

Purpose: Given the well-documented benefits of regular exercise to cancer survivors, current American Cancer Society guidelines recommend that patients engage in a minimum of 150 min per week of moderate-to-vigorous physical activity with a minimum of two days of strength training. However, few survivors meet this goal, particularly among minorities.Methods: The CAPABLE study is a single-arm, pilot exercise intervention that introduced 48 cancer survivors to a high intensity interval and strength training program three days a week for 12 weeks. We evaluated the impact of this unique training method on bodyweight, % body fat, serum markers correlated with an adverse cardiometabolic profile and health-related quality of life (HRQoL). Measures were summarized at baseline and program exit. Paired t-tests were used to assess change in each of these measures over time.Results: We observed losses in weight, body mass index, and % body fat, and glycosylated hemoglobin (HbA1c) levels over 12-weeks. There were also clinically meaningful improvements in reported overall HRQoL (FACTG total change +9.5 (95% CI, 4.6, 14.4)) and in each one of the individual domains (physical, social, emotional, and functional well-being).Conclusions: We observed meaningful improvements in body composition, HbA1c and quality of life over 12 weeks among cancer survivors participating in a high-intensity interval training program. Future work will include a control arm for comparison and address barriers to participation and adherence which will be important in using this intervention and others like it to improve outcomes and reduce cancer health disparities.

Supplementary Table 1. Summary of Study Design and Case/Control Definitions for participating studies. Supplementary Table 2. Distribution of the incident index and second cancer site among incident multiple primary cancer cases, stratified by study and cancer latency. Supplemental Table 3. Detailed distribution of incident index and second cancer site among incident multiple primary cancer cases for WHI study. Supplemental Table 4. Detailed distribution of incident index and second cancer site among incident multiple primary cancer cases for MEC study. Supplemental Table 5. Frequency and cancer site of IMPC cases with 3 or more cancers. Supplementary Table 6. Meta-analysis of the non-significant associations (p{greater than or equal to}0.05) between 178 risk variants for other cancers and incident multiple primary cancer risk. Supplementary Table 7. Ten SNPsa associated with other cancers and multiple primary cancer risk by race/ethnicityb

BackgroundThe use of electronic cigarettes (e-cigarettes) is increasing rapidly in the United States, although the negative health outcomes associated with these products are still unknown. Emerging research has examined the use of e-cigarettes in the cancer survivor population as a whole, yet none has focused on e-cigarette use in the African American (AA) cancer survivor population. MethodsThe authors used data from the Detroit Research on Cancer Survivors cohort study, comprised of AA adult cancer survivors. Logistic regression models were used to evaluate factors potentially associated with e-cigarette ever use and current use. ResultsOf 4443 cancer survivors who completed a baseline interview, 8.3% (n = 370) reported ever using e-cigarettes, and 16.5% (n = 61) of those reporting ever use also reported current use of e-cigarettes. Ever users and current users were on average younger than those who did not use e-cigarettes (57.5 vs. 61.2 years; p < .001). Current cigarette smokers were >20 times more likely (odds ratio, 20.75; 95% confidence interval, 12.84-33.55) and former smokers were almost 10 times more likely (odds ratio, 9.50; 95% confidence interval, 6.03-14.97) to have ever used e-cigarettes than never-smokers. Preliminary data suggested that ever use of e-cigarettes is associated with later stage at diagnosis for breast and colorectal cancers. ConclusionsAs the use of e-cigarettes increases in the general population, it is important to continue to monitor their use in cancer survivors and to gain more insight as it pertains to the AA cancer survivor population. Elucidation of the factors associated with e-cigarette use in this population may help inform comprehensive cancer survivorship recommendations and interventions.

BACKGROUND:Published studies have demonstrated inconclusive relationships between serum lipid levels and mortality after cancer. METHODS:The primary objective was to evaluate the relationship between fasting lipid levels and mortality after cancer. Data were obtained on baseline lipids and outcomes after cancer from 1263 postmenopausal women diagnosed with 13 obesity-related cancers who were part of the Women's Health Initiative (WHI) lipid biomarkers cohort. Obesity-related cancers included incident invasive cancers of the breast, colorectum, endometrium, esophagus (adenocarcinoma), kidney, liver, gallbladder, pancreas, ovaries, small intestine, thyroid, stomach, as well as multiple myeloma. Baseline lipid measurements included high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-HDL-cholesterol. Outcomes were all cause, cancer-specific, and CVD mortality. Multivariable Cox proportional hazards models were used to measure associations between lipid levels and mortality (all cause, cancer, and CVD) after a cancer diagnosis, with lipids analyzed as continuous variables. RESULTS:Among women with obesity-related cancer, there were 707 deaths, of which 379 (54%) were due to cancer and 113 (16%) were due to CVD. Mean time from blood draw to cancer diagnosis was 5.1 years (range: 0.05-10 years). LDL-C values above the 95th percentile were associated with higher risk of all-cause mortality (p < 0.001), and cancer-specific mortality (p < 0.001), but not mortality due to CVD. Non-HDL-C values above the 65th percentile were associated with higher risk of all-cause mortality (p = 0.01) and mortality due to CVD (p = 0.003), but not cancer-specific mortality (p = 0.37). HDL-C values above the 95th percentile were associated with lower all-cause mortality (p = 0.002), and above the 65th percentile with lower cancer-specific mortality (p = 0.003), but no significant relationship with mortality due to CVD was observed. CONCLUSIONS:The relationship between pre-diagnosis fasting lipid levels and mortality after cancer diagnosis is complex. These results suggest that improved lipid control through lifestyle and anti-lipid medications could have a meaningful impact on outcomes after cancer.