Search NASA⌕ Search

SEARCH · Search NASA

Results for “cancer”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Time trend analysis of rare cancer incidence 2011–2018: Nationwide population-based cancer registries in Japan

Rare cancers collectively account for a significant proportion of the overall cancer burden in Japan. We aimed to describe and examine the incidence of each rare cancer and the temporal changes using the internationally agreed rare cancer classification. Cancer cases registered in regional population-based cancer registries from 2011 to 2015 and the National Cancer Registry (NCR) from 2016 to 2018 were classified into 18 families, 68 Tier-1 cancer groupings, and 216 single cancer entities based on the RARECAREnet list. Crude incidence rates and age-standardized incidence rates (ASR) were calculated for Tier-1 and Tier-2 cancers. The annual percent change and the 95% and 99% confidence limits for annual ASR for each of the 68 Tier-1 cancers were estimated using the log-linear regression of the weighted least squares method. The differences in ASRs between 2011 and 2018 were evaluated as an absolute change. A total of 5,640,879 cases were classified into Tier-1 and Tier-2 cancers. The ASRs of 18 out of 52 Tier-1 cancers in the rare cancer families increased, whereas the ASR for epithelial tumors of gallbladder decreased. The ASRs of 6 out of the 16 Tier-1 cancers in the common cancer families increased, whereas those of epithelial tumors of stomach and liver decreased. There was no significant change in the incidence of the other 40 Tier-1 cancers. The incidence of several cancers increased due to the dissemination of diagnostic concepts, improved diagnostic techniques, changes in coding practice, and the initiation of the NCR.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Cancer survival in the United States 2007–2016: Results from the National Program of Cancer Registries

Background Cancer survival has improved for the most common cancers. However, less improvement and lower survival has been observed in some groups perhaps due to differential access to cancer care including prevention, screening, diagnosis, and treatment. Methods To further understand contemporary relative cancer survival (one- and five- year), we used survival data from CDC’s National Program of Cancer Registries (NPCR) for cancers diagnosed during 2007–2016. We examined overall relative cancer survival by sex, race and ethnicity, age, and county-level metropolitan and non-metropolitan status. Relative cancer survival by metropolitan and non-metropolitan status was further examined by sex, race and ethnicity, age, and cancer type. Results Among persons with cancer diagnosed during 2007–2016 the overall one-year and five-year relative survival was 80.6% and 67.4%, respectively. One-year relative survival for persons living in metropolitan counties was 81.1% and 77.8% among persons living in non-metropolitan counties. We found that persons who lived in non-metropolitan counties had lower survival than those who lived in metropolitan counties, and this difference persisted across sex, race and ethnicity, age, and most cancer types. Conclusion Further examination of the differences in cancer survival by cancer type or other characteristics might be helpful for identifying potential interventions, such as programs that target screening and early detection or strategies to improve access to high quality cancer treatment and follow-up care, that could improve long-term outcomes. Impact This analysis provided a high-level overview of contemporary cancer survival in the United States.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Prevalence of Americans reporting a family history of cancer indicative of increased cancer risk: Estimates from the 2015 National Health Interview Survey

The collection and evaluation of family health history in a clinical setting presents an opportunity to discuss cancer risk, tailor cancer screening recommendations, and identify people with an increased risk of carrying a pathogenic variant who may benefit from referral to genetic counseling and testing. National recommendations for breast and colorectal cancer screening indicate that men and women who have a first-degree relative affected with these types of cancers may benefit from talking to a healthcare provider about starting screening at an earlier age and other options for cancer prevention. The prevalence of reporting a first-degree relative who had cancer was assessed among adult respondents of the 2015 National Health Interview Survey who had never had cancer themselves (n = 27,999). We found 35.6% of adults reported having at least one first-degree relative with cancer at any site. Significant differences in reporting a family history of cancer were observed by sex, age, race/ethnicity, educational attainment, and census region. Nearly 5% of women under age 50 and 2.5% of adults under age 50 had at least one first-degree relative with breast cancer or colorectal cancer, respectively. We estimated that 5.8% of women had a family history of breast or ovarian cancer that may indicate increased genetic risk. A third of U.S. adults who have never had cancer report a family history of cancer in a first-degree relative. Furthermore, this finding underscores the importance of using family history to inform discussions about cancer risk and screening options between healthcare providers and their patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Tea consumption and risk of bladder cancer in the Bladder Cancer Epidemiology and Nutritional Determinants (BLEND) Study: Pooled analysis of 12 international cohort studies

Tea has been shown to be associated with reduced risk of several diseases including cardiovascular diseases, stroke, metabolic syndrome, and obesity. However, the results on the relationship between tea consumption and bladder cancer are conflicting. This research aimed to assess the association between tea consumption and risk of bladder cancer using a pooled analysis of prospective cohort data. Individual data from 532,949 participants in 12 cohort studies, were pooled for analyses. Cox regression models stratified by study centre was used to estimate hazard ratios (HR) and corresponding 95% CIs. Fractional polynomial regression models were used to examine the dose–response relationship. A higher level of tea consumption was associated with lower risk of bladder cancer incidence (compared with no tea consumption: HR = 0.87, 95% C.I. = 0.77–0.98 for low consumption; HR = 0.86, 95% C.I. = 0.77–0.96 for moderate consumption; HR = 0.84, 95% C.I. = 0.75–0.95 for high consumption). When stratified by sex and smoking status, this reduced risk was statistically significant among men and current and former smokers. In addition, dose–response analyses showed a lower bladder cancer risk with increment of 100 ml of tea consumption per day (HR-increment = 0.97; 95% CI = 0.96–0.98). A similar inverse association was found among males, current and former smokers while never smokers and females showed non-significant results, suggesting potential sex-dependent effect. Higher consumption of tea is associated with reduced risk of bladder cancer with potential interaction with sex and smoking status. Further studies are needed to clarify the mechanisms for a protective effect of tea (e.g. inhibition of the survival and proliferation of cancer cells and anti-inflammatory mechanisms) and its interaction with smoking and sex.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Association Between Regional Nodal Irradiation and Breast Cancer Recurrence-Free Interval for Patients With Low-Risk, Node-Positive Breast Cancer

Randomized clinical trials have shown that regional nodal irradiation (RNI) in patients with unselected N1 breast cancer improves breast cancer-specific survival. However, the benefit of RNI in women with biologically low-risk N1 breast cancer is uncertain. We conducted a population-based study to determine whether RNI is associated with improved breast cancer recurrence-free interval (BCRFI) in this population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Describing patterns of familial cancer risk in subfertile men using population pedigree data

STUDY QUESTION Can we simultaneously assess risk for multiple cancers to identify familial multicancer patterns in families of azoospermic and severely oligozoospermic men? SUMMARY ANSWER Here, distinct familial cancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in familial cancer risk by both type of subfertility and within subfertility type. WHAT IS KNOWN ALREADY Subfertile men and their relatives show increased risk for certain cancers including testicular, thyroid, and pediatric. STUDY DESIGN, SIZE, DURATION A retrospective cohort of subfertile men (N = 786) was identified and matched to fertile population controls (N = 5674). Family members out to third-degree relatives were identified for both subfertile men and fertile population controls (N = 337 754). The study period was 1966–2017. Individuals were censored at death or loss to follow-up, loss to follow-up occurred if they left Utah during the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS Azoospermic (0 × 10 6 /mL) and severely oligozoospermic (<1.5 × 10 6 /mL) men were identified in the Subfertility Health and Assisted Reproduction and the Environment cohort (SHARE). Subfertile men were age- and sex-matched 5:1 to fertile population controls and family members out to third-degree relatives were identified using the Utah Population Database (UPDB). Cancer diagnoses were identified through the Utah Cancer Registry. Families containing ≥10 members with ≥1 year of follow-up 1966–2017 were included (azoospermic: N = 426 families, 21 361 individuals; oligozoospermic: N = 360 families, 18 818 individuals). Unsupervised clustering based on standardized incidence ratios for 34 cancer phenotypes in the families was used to identify familial multicancer patterns; azoospermia and severe oligospermia families were assessed separately. MAIN RESULTS AND THE ROLE OF CHANCE Compared to control families, significant increases in cancer risks were observed in the azoospermia cohort for five cancer types: bone and joint cancers hazard ratio (HR) = 2.56 (95% CI = 1.48–4.42), soft tissue cancers HR = 1.56 (95% CI = 1.01–2.39), uterine cancers HR = 1.27 (95% CI = 1.03–1.56), Hodgkin lymphomas HR = 1.60 (95% CI = 1.07–2.39), and thyroid cancer HR = 1.54 (95% CI = 1.21–1.97). Among severe oligozoospermia families, increased risk was seen for three cancer types: colon cancer HR = 1.16 (95% CI = 1.01–1.32), bone and joint cancers HR = 2.43 (95% CI = 1.30–4.54), and testis cancer HR = 2.34 (95% CI = 1.60–3.42) along with a significant decrease in esophageal cancer risk HR = 0.39 (95% CI = 0.16–0.97). Thirteen clusters of familial multicancer patterns were identified in families of azoospermic men, 66% of families in the azoospermia cohort showed population-level cancer risks, however, the remaining 12 clusters showed elevated risk for 2-7 cancer types. Several of the clusters with elevated cancer risks also showed increased odds of cancer diagnoses at young ages with six clusters showing increased odds of adolescent and young adult (AYA) diagnosis [odds ratio (OR) = 1.96–2.88] and two clusters showing increased odds of pediatric cancer diagnosis (OR = 3.64–12.63). Within the severe oligozoospermia cohort, 12 distinct familial multicancer clusters were identified. All 12 clusters showed elevated risk for 1–3 cancer types. An increase in odds of cancer diagnoses at young ages was also seen in five of the severe oligozoospermia familial multicancer clusters, three clusters showed increased odds of AYA diagnosis (OR = 2.19–2.78) with an additional two clusters showing increased odds of a pediatric diagnosis (OR = 3.84–9.32). LIMITATIONS, REASONS FOR CAUTION Although this study has many strengths, including population data for family structure, cancer diagnoses and subfertility, there are limitations. First, semen measures are not available for the sample of fertile men. Second, there is no information on medical comorbidities or lifestyle risk factors such as smoking status, BMI, or environmental exposures. Third, all of the subfertile men included in this study were seen at a fertility clinic for evaluation. These men were therefore a subset of the overall population experiencing fertility problems and likely represent those with the socioeconomic means for evaluation by a physician. WIDER IMPLICATIONS OF THE FINDINGS This analysis leveraged unique population-level data resources, SHARE and the UPDB, to describe novel multicancer clusters among the families of azoospermic and severely oligozoospermic men. Distinct overall multicancer risk and familial multicancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in cancer risk by type of subfertility and within subfertility type. Describing families with similar cancer risk patterns provides a new avenue to increase homogeneity for focused gene discovery and environmental risk factor studies. Such discoveries will lead to more accurate risk predictions and improved counseling for patients and their families. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): R01 HD106112). The authors have no conflicts of interest relevant to this work.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Cancer Incidence Trends in Successive Social Generations in the US

Importance: The incidence of some cancers in the US is increasing in younger age groups, but underlying trends in cancer patterns by birth year remain unclear. Objective: To estimate cancer incidence trends in successive social generations. Design, Setting, and Participants: In this cohort study, incident invasive cancers were ascertained from the Surveillance, Epidemiology, and End Results (SEER) program’s 13-registry database (November 2020 submission, accessed August 14, 2023). Invasive cancers diagnosed at ages 35 to 84 years during 1992 to 2018 within 152 strata were defined by cancer site, sex, and race and ethnicity. Exposure: Invasive cancer. Main Outcome and Measures: Stratum-specific semiparametric age-period-cohort (SAGE) models were fitted and incidence per 100 000 person-years at the reference age of 60 years was calculated for single-year birth cohorts from 1908 through 1983 (fitted cohort patterns [FCPs]). The FCPs and FCP incidence rate ratios (IRRs) were compared by site for Generation X (born between 1965 and 1980) and Baby Boomers (born between 1946 and 1964). Results: A total of 3.8 million individuals with invasive cancer (51.0% male; 8.6% Asian or Pacific Islander, 9.5% Hispanic, 10.4% non-Hispanic Black, and 71.5% non-Hispanic White) were included in the analysis. In Generation X vs Baby Boomers, FCP IRRs among women increased significantly for thyroid (2.76; 95% CI, 2.41-3.15), kidney (1.99; 95% CI, 1.70-2.32), rectal (1.84; 95% CI, 1.52-2.22), corpus uterine (1.75; 95% CI, 1.40-2.18), colon (1.56; 95% CI, 1.27-1.92), and pancreatic (1.39; 95% CI, 1.07-1.80) cancers; non-Hodgkins lymphoma (1.40; 95% CI, 1.08-1.82); and leukemia (1.27; 95% CI, 1.03-1.58). Among men, IRRs increased for thyroid (2.16; 95% CI, 1.87-2.50), kidney (2.14; 95% CI, 1.86-2.46), rectal (1.80; 95% CI, 1.52-2.12), colon (1.60; 95% CI, 1.32-1.94), and prostate (1.25; 95% CI, 1.03-1.52) cancers and leukemia (1.34; 95% CI, 1.08-1.66). Lung (IRR, 0.60; 95% CI, 0.50-0.72) and cervical (IRR, 0.71; 95% CI, 0.57-0.89) cancer incidence decreased among women, and lung (IRR, 0.51; 95% CI, 0.43-0.60), liver (IRR, 0.76; 95% CI, 0.63-0.91), and gallbladder (IRR, 0.85; 95% CI, 0.72-1.00) cancer and non-Hodgkins lymphoma (IRR, 0.75; 95% CI, 0.61-0.93) incidence decreased among men. For all cancers combined, FCPs were higher in Generation X than for Baby Boomers because gaining cancers numerically overtook falling cancers in all groups except Asian or Pacific Islander men. Conclusions and Relevance: In this model-based cohort analysis of incident invasive cancer in the general population, decreases in lung and cervical cancers in Generation X may be offset by gains at other sites. Generation X may be experiencing larger per-capita increases in the incidence of leading cancers than any prior generation born in 1908 through 1964. On current trajectories, cancer incidence could remain high for decades.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

COVID-19 Outcomes by Cancer Status, Site, Treatment, and Vaccination

Background: Studies have shown an increased risk of severe SARS-CoV-2–related (COVID-19) disease outcome and mortality for patients with cancer, but it is not well understood whether associations vary by cancer site, cancer treatment, and vaccination status. Methods: Using electronic health record data from an academic medical center, we identified a retrospective cohort of 260,757 individuals tested for or diagnosed with COVID-19 from March 10, 2020, to August 1, 2022. Of these, 52,019 tested positive for COVID-19 of whom 13,752 had a cancer diagnosis. We conducted Firth-corrected logistic regression to assess the association between cancer status, site, treatment, vaccination, and four COVID-19 outcomes: hospitalization, intensive care unit admission, mortality, and a composite “severe COVID” outcome. Results: Cancer diagnosis was significantly associated with higher rates of severe COVID, hospitalization, and mortality. These associations were driven by patients whose most recent initial cancer diagnosis was within the past 3 years. Chemotherapy receipt, colorectal cancer, hematologic malignancies, kidney cancer, and lung cancer were significantly associated with higher rates of worse COVID-19 outcomes. Vaccinations were significantly associated with lower rates of worse COVID-19 outcomes regardless of cancer status. Conclusions: Patients with colorectal cancer, hematologic malignancies, kidney cancer, or lung cancer or who receive chemotherapy for treatment should be cautious because of their increased risk of worse COVID-19 outcomes, even after vaccination. Impact: Additional COVID-19 precautions are warranted for people with certain cancer types and treatments. Further, significant benefit from vaccination is noted for both cancer and cancer-free patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

Comparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer. We analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases. From multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH 1Gy ) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH 1Gy = 0.038 (95 % CI: –0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH 1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH 1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001. There is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors. A direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

YAP1 Dysfunction Promotes Molecular Properties Linked to Breast Cancer Susceptibility

YAP1 is a cotranscription factor that promotes malignant and stem cell properties in cancer. We previously found that YAP1 dysregulation is associated with aging in human mammary epithelia. With increased age, YAP1 expression changes in luminal epithelial cells, the prospective breast cancer cell of origin. Because age is a significant risk factor for breast cancer, we tested whether YAP1 dysregulation acted early in cancer progression by conferring cellular states associated with increased cancer susceptibility. In this study, we find that with increased age and genetic risk for developing cancer, human breast tissues showed significantly increased YAP1 expression, and cultured primary human mammary epithelial cells (HMEC) showed significantly increased expression of both YAP1 and its transcriptional targets. Increased YAP1 expression in cultured HMEC induced gene expression changes associated with increased cancer susceptibility, such as genes associated with stem cell states, increased telomerase activity, breast cancer progression, and increased age and genetic breast cancer risk. Furthermore, overexpression of YAP1 in post-stasis HMEC—finite lifespan cells that have bypassed a retinoblastoma-mediated senescence barrier—promoted properties related to increased growth potential. We found that YAP1 dysregulation in finite epithelial cells allows for access to gene programs and functions that are typically thought to be restricted to stem cells. We hypothesize that YAP1 acts early in breast cancer progression, long before the development of a tumor, to impose cancer-susceptible molecular states.

YAP1↗
DOE OSTI2022

Comparison of All Solid Cancer Mortality and Incidence Dose-Response in the Life Span Study of Atomic Bomb Survivors, 1958–2009

Recent analysis of all solid cancer incidence (1958–2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950–2003) was also observed in the 0–2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose response analyses for all solid cancer mortality and incidence applying similar methods (1958–2009 follow-up, DS02R1 doses, including subjects notin-city (NIC) at the time of the bombing) and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates over entire Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before Jan 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose response exhibited a borderline significant upward curvature among males (P=0.062) and significant upward curvature among females (P=0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P=0.001) but not among females (P=0.624). The sex difference in magnitude of dose response curvature was statistically significant for cancer incidence (P=0.017) but not for cancer mortality (P=0.781). The results of analyses in the 0–2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958–1987 vs 1988–2009) and age at exposure (0–19 vs 20–83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0–19 year old male survivors in both calendar periods and among 0–19 year old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; it appears to depend on composition of case series and age at exposure or time. Further follow-up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose response curvature among young survivors and unveil the contributing factors and sites.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2026

Significance and challenges in dissecting cancer-bacteriome interactions

Cancer is the leading cause of death around the world. While some types of cancer have become manageable due to advancements in medicine, most cancers still lack available cures and treatments. Recent studies have shown that changes in the human microbiome, especially in the bacteriome, are associated with some cancers. Certain bacterial strains have been reported to promote the initiation and progression of cancer in humans. Other studies have used sequencing to observe changes in the bacteriome of healthy and cancer patients. However, studies that investigate the interactions between cancer cells and the complex bacteriome as a whole remain scarce. This is due to the absence of experimental methods to study the interactions between cancer cells and complex bacterial populations, which has delayed the progress in identifying cancer-causing and cancer-inhibiting bacteria, and in understanding the bacterial interactions and their influence on host cells. Here, we review approaches to studying cancer cell interactions with complex bacteriomes and suggest possible routes to overcome this problem, highlighting the need for interdisciplinary studies that may help advance this field. We speculate that a good understanding of cancer-bacteriome interactions may open the door to new lines of holistic bacteriotherapy for cancer that is otherwise unavailable.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

The association between neighborhood obesogenic factors and prostate cancer risk and mortality: the Southern Community Cohort Study

Background: Prostate cancer is one of the leading causes of cancer-related mortality among men in the United States. We examined the role of neighborhood obesogenic attributes on prostate cancer risk and mortality in the Southern Community Cohort Study (SCCS). Methods: From the total of 34,166 SCCS male participants, 28,356 were included in the analysis. We assessed the relationship between neighborhood obesogenic factors [neighborhood socioeconomic status (nSES) and neighborhood obesogenic environment indices including the restaurant environment index, the retail food environment index, parks, recreational facilities, and businesses] and prostate cancer risk and mortality by controlling for individual-level factors using a multivariable Cox proportional hazards model. We further stratified prostate cancer risk analysis by race and body mass index (BMI). Results: Median follow-up time was 133 months [interquartile range (IQR): 103, 152], and the mean age was 51.62 (SD: ± 8.42) years. There were 1,524 (5.37%) prostate cancer diagnoses and 98 (6.43%) prostate cancer deaths during follow-up. Compared to participants residing in the wealthiest quintile, those residing in the poorest quintile had a higher risk of prostate cancer (aHR = 1.32, 95% CI 1.12–1.57, p = 0.001), particularly among non-obese men with a BMI < 30 (aHR = 1.46, 95% CI 1.07–1.98, p = 0.016). The restaurant environment index was associated with a higher prostate cancer risk in overweight (BMI ≥ 25) White men (aHR = 3.37, 95% CI 1.04–10.94, p = 0.043, quintile 1 vs. None). Obese Black individuals without any neighborhood recreational facilities had a 42% higher risk (aHR = 1.42, 95% CI 1.04–1.94, p = 0.026) compared to those with any access. Compared to residents in the wealthiest quintile and most walkable area, those residing within the poorest quintile (aHR = 3.43, 95% CI 1.54–7.64, p = 0.003) or the least walkable area (aHR = 3.45, 95% CI 1.22–9.78, p = 0.020) had a higher risk of prostate cancer death. Conclusion: Living in a lower-nSES area was associated with a higher prostate cancer risk, particularly among Black men. Restaurant and retail food environment indices were also associated with a higher prostate cancer risk, with stronger associations within overweight White individuals. Finally, residing in a low-SES neighborhood or the least walkable areas were associated with a higher risk of prostate cancer mortality.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Identifying intragenic functional modules of genomic variations associated with cancer phenotypes by learning representation of association networks

Background Genome-wide Association Studies (GWAS) aims to uncover the link between genomic variation and phenotype. They have been actively applied in cancer biology to investigate associations between variations and cancer phenotypes, such as susceptibility to certain types of cancer and predisposed responsiveness to specific treatments. Since GWAS primarily focuses on finding associations between individual genomic variations and cancer phenotypes, there are limitations in understanding the mechanisms by which cancer phenotypes are cooperatively affected by more than one genomic variation. Results This paper proposes a network representation learning approach to learn associations among genomic variations using a prostate cancer cohort. The learned associations are encoded into representations that can be used to identify functional modules of genomic variations within genes associated with early- and late-onset prostate cancer. The proposed method was applied to a prostate cancer cohort provided by the Veterans Administration’s Million Veteran Program to identify candidates for functional modules associated with early-onset prostate cancer. The cohort included 33,159 prostate cancer patients, 3181 early-onset patients, and 29,978 late-onset patients. The reproducibility of the proposed approach clearly showed that the proposed approach can improve the model performance in terms of robustness. Conclusions To our knowledge, this is the first attempt to use a network representation learning approach to learn associations among genomic variations within genes. Associations learned in this way can lead to an understanding of the underlying mechanisms of how genomic variations cooperatively affect each cancer phenotype. This method can reveal unknown knowledge in the field of cancer biology and can be utilized to design more advanced cancer-targeted therapies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Advances in statistical methods for cancer surveillance research: an age-period-cohort perspective

Background: Analysis of Lexis diagrams (population-based cancer incidence and mortality rates indexed by age group and calendar period) requires specialized statistical methods. However, existing methods have limitations that can now be overcome using new approaches. Methods: We assembled a “toolbox” of novel methods to identify trends and patterns by age group, calendar period, and birth cohort. We evaluated operating characteristics across 152 cancer incidence Lexis diagrams compiled from United States (US) Surveillance, Epidemiology and End Results Program data for 21 leading cancers in men and women in four race and ethnicity groups (the “cancer incidence panel”). Results: Nonparametric singular values adaptive kernel filtration (SIFT) decreased the estimated root mean squared error by 90% across the cancer incidence panel. A novel method for semi-parametric age-period-cohort analysis (SAGE) provided optimally smoothed estimates of age-period-cohort (APC) estimable functions and stabilized estimates of lack-of-fit (LOF). SAGE identified statistically significant birth cohort effects across the entire cancer panel; LOF had little impact. As illustrated for colon cancer, newly developed methods for comparative age-period-cohort analysis can elucidate cancer heterogeneity that would otherwise be difficult or impossible to discern using standard methods. Conclusions: Cancer surveillance researchers can now identify fine-scale temporal signals with unprecedented accuracy and elucidate cancer heterogeneity with unprecedented specificity. Birth cohort effects are ubiquitous modulators of cancer incidence in the US. The novel methods described here can advance cancer surveillance research.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Utility of Physiologically Based Pharmacokinetic Modeling to Investigate the Impact of Physiological Changes of Pregnancy and Cancer on Oncology Drug Pharmacokinetics

The treatment of cancer during pregnancy remains challenging with knowledge gaps in drug dosage, safety, and efficacy due to the under-representation of this population in clinical trials. Our aim was to investigate physiological changes reported in both pregnancy and cancer populations into a PBPK modeling framework that allows for a more accurate estimation of PK changes in pregnant patients with cancer. Methods: Paclitaxel and docetaxel were selected to validate a population model using clinical data from pregnant patients with cancer. The validated population model was subsequently used to predict the PK of acalabrutinib in pregnant patients with cancer. Results: The Simcyp pregnancy population model reasonably predicted the PK of docetaxel in pregnant patients with cancer, while a modified model that included a 2.5-fold increase in CYP2C8 abundance, consistent with the increased expression during pregnancy, was needed to reasonably predict the PK of paclitaxel in pregnant patients with cancer. Changes in protein binding levels of patients with cancer had a minimal impact on the predicted clearance of paclitaxel and docetaxel. PBPK modeling predicted approximately 60% lower AUC and Cmax for acalabrutinib in pregnant versus non-pregnant patients with cancer. Conclusions: Our results suggest that PBPK modeling is a promising approach to investigate the effects of pregnancy and cancer on the PK of oncology drugs and potentially inform dosing for pregnant patients with cancer. Further evaluation and refinement of the population model are needed for pregnant patients with cancer with additional compounds and clinical PK data.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Social Disparities of Pain and Pain Intensity Among Women Diagnosed With Early Stage Breast Cancer

Background: Breast cancer is one of the most commonly diagnosed cancers among women in the United States and pain is the most common side effect of breast cancer and its treatment. Yet, the relationships between social determinants of pain and pain experience/intensity remain under-investigated. We examined the associations between social determinants of pain both at the individual level and the neighborhood level to understand how social conditions are associated with pain perception among early stage breast cancer patients. Methods: We conducted integrated statistical analysis of 1,191 women with early stage breast cancer treated at a large cancer center in Memphis, Tennessee. Combining electronic health records, patient-reported data and census data regarding residential address at the time of first diagnosis, we evaluated the relationships between social determinants and pain perception. Pain responses were self-reported by a patient as a numerical rating scale score at the patient’s initial diagnosis and follow-up clinical visits. We implemented two sets of statistical analyses of the zero-inflated Poisson model and estimated the associations between neighborhood poverty prevalence and breast cancer pain intensity. After adjustment for demographic characteristics, cancer stage, and chemotherapy, pain perception was significantly associated with poverty and blight level of the neighborhood. Results: Among women living in the highest-poverty areas, the odds of reporting pain were 2.48 times higher than those in the lowest-poverty area. Women living in the highest-blight area had 5.43 times higher odds of reporting pain than those in the lowest-blight area. Neighborhood-level social determinants were significantly associated with pain intensity among women diagnosed with early-stage breast cancer. Conclusions: Distressed neighborhood conditions are significantly associated with higher pain perception. Breast cancer patients living in socio-economically disadvantaged neighborhoods and in poor environmental conditions reported higher pain severity compared to patients from less distressed neighborhoods. Therefore, post-diagnosis pain treatment design needs to be tailored to the social determinants of the breast cancer patients.

60 APPLIED LIFE SCIENCES↗