Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes

Background: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health. Results: The discovery study population was derived from three Women’s Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm β value, the risk of incident CHD increased by 9% in one site and decreased by 6–10% in two sites over 25 years. Conclusions: Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health

Renal cell carcinoma health disparities in stage and mortality among american indians/alaska natives and hispanic americans: Comparison of national cancer database and arizona cancer registry data

Renal cell carcinoma (RCC) is one of the top 10 cancers in the United States. This study assessed RCC health disparities in American Indians/Alaska Natives (AIs/ANs) and Hispanic Americans (HAs) focusing on advanced-stage and mortality. RCC patients’ data were obtained from the National Cancer Database (NCDB) and Arizona Cancer Registry (ACR). Logistic and Cox regression analyses were performed to ascertain the effect of race/ethnicity on stage and mortality, adjusting for neighborhood socioeconomic factors, rural/urban residence pattern, and other factors. In both data sets, AIs/ANs had significantly increased odds of advanced-stage RCC in the unadjusted model, but not in adjusted models. Mexican Americans had higher odds of advanced-stage compared to non-Hispanic Whites in NCDB (OR 1.22, 95% CI: 1.11–1.35) and ACR (OR 2.02, 95% CI: 1.58–2.58), even after adjusting for neighborhood characteristics. AIs/ANs did not show increased mortality risk in NCDB after adjusting for neighborhood characteristics, while the association remained significant in ACR (HR 1.33, 95% CI: 1.03–1.72). The great risk of all-cause and RCC-specific mortality was observed in U.S.-born Mexican Americans in Arizona (HR 3.21, 95% CI: 2.61–3.98 and sub-distribution HR 2.79, 95% CI: 2.05–3.81). RCC disparities in AIs/ANs is partially explained by neighborhood factors, but not in HAs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Renal Cell Carcinoma Surgical Treatment Disparities in American Indian/Alaska Natives and Hispanic Americans in Arizona

American Indians/Alaska Natives (AI/AN) and Hispanic Americans (HA) have higher kidney cancer incidence and mortality rates compared to non-Hispanic Whites (NHW). Herein, we describe the disparity in renal cell carcinoma (RCC) surgical treatment for AI/AN and HA and the potential association with mortality in Arizona. A total of 5111 stage I RCC cases diagnosed between 2007 and 2016 from the Arizona Cancer Registry were included. Statistical analyses were performed to test the association of race/ethnicity with surgical treatment pattern and overall mortality, adjusting for patients’ demographic, healthcare access, and socioeconomic factors. AI/AN were diagnosed 6 years younger than NHW and were more likely to receive radical rather than partial nephrectomy (OR 1.49 95% CI: 1.07–2.07) compared to NHW. Mexican Americans had increased odds of not undergoing surgical treatment (OR 1.66, 95% CI: 1.08–2.53). Analysis showed that not undergoing surgical treatment and undergoing radical nephrectomy were statistically significantly associated with higher overall mortality (HR 1.82 95% CI: 1.21–2.76 and HR 1.59 95% CI: 1.30–1.95 respectively). Mexican Americans, particularly U.S.-born Mexican Americans, had an increased risk for overall mortality and RCC-specific mortality even after adjusting for neighborhood socioeconomic factors and surgical treatment patterns. Although statistically not significant after adjusting for neighborhood-level socioeconomic factors and surgical treatment patterns, AI/AN had an elevated risk of mortality. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Racial and ethnic disparities in preoperative surgical wait time and renal cell carcinoma tumor characteristics

Racial/ethnic minority groups have a disproportionate burden of kidney cancer. The objective of this study was to assess if race/ethnicity was associated with a longer surgical wait time (SWT) and upstaging in the pre-COVID-19 pandemic time with a special focus on Hispanic Americans (HAs) and American Indian/Alaska Natives (AIs/ANs). Medical records of renal cell carcinoma (RCC) patients who underwent nephrectomy between 2010 and 2020 were retrospectively reviewed (n = 489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination to date of nephrectomy. Out of a total of 363 patients included, 34.2% were HAs and 8.3% were AIs/ANs. While 49.2% of HA patients experienced a longer SWT (≥90 days), 36.1% of Non-Hispanic White (NHW) patients experienced a longer SWT. Longer SWT had no statistically significant impact on tumor characteristics. Patients with public insurance coverage had increased odds of longer SWT (OR 2.89, 95% CI: 1.53–5.45). Public insurance coverage represented 66.1% HA and 70.0% AIs/ANs compared to 56.7% in NHWs. Compared to NHWs, HAs had higher odds for longer SWT in patients with early-stage RCC (OR, 2.38; 95% CI: 1.25–4.53). HAs (OR 2.24, 95% CI: 1.07–4.66) and AIs/ANs (OR 3.79, 95% CI: 1.32–10.88) had greater odds of upstaging compared to NHWs. While a delay in surgical care for early-stage RCC is safe in a general population, it may negatively impact high-risk populations, such as HAs who have a prolonged SWT or choose active surveillance. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

In Situ Geochronology for the Next Decade: Mission Designs for the Moon, Mars, and Vesta

Geochronology is an indispensable tool for reconstructing the geologic history of planets, essential to understanding the formation and evolution of our solar system. Bombardment chronology bounds models of solar system dynamics, as well as the timing of volatile, organic, and siderophile element delivery. Absolute ages of magmatic products provide constraints on the dynamics of magma oceans and crustal formation, as well as the longevity and evolution of interior heat engines and distinct mantle/crustal source regions. Absolute dating also relates habitability markers to the timescale of evolution of life on Earth. However, the number of terrains important to date on worlds of the inner solar system far exceeds our ability to conduct sample return from all of them. In preparation for the upcoming Decadal Survey, our team formulated a set of medium-class (New Frontiers) mission concepts to three different locations (the Moon, Mars, and Vesta) where sites that record solar system bombardment, magmatism, and habitability are uniquely preserved and accessible. We developed a notional payload to directly date planetary surfaces, consisting of two instruments capable of measuring radiometric ages, an imaging spectrometer, optical cameras to provide site geologic context and sample characterization, a traceelement analyzer to augment sample contextualization, and a sample acquisition and handling system. Landers carrying this payload to the Moon, Mars, and Vesta would likely fit into the New Frontiers cost cap in our study (∼$1B). A mission of this type would provide crucial constraints on planetary history while also enabling a broad suite of complementary investigations 2021. The Author(s). Published by the American Astronomical Society. © 2021. The Author(s). Published by the American Astronomical Society.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]