Hugo Pomares-Millan's scientific contributions

Introduction: We examined nationwide trends in urinary bladder cancer incidence and mortality focusing on 1999-2019. A separate analysis of data from 2020 revealed how these rates were affected by the onset of the COVID-19 pandemic. Methods: State-specific bladder cancer (in situ and invasive) incidence and mortality rates were ascertained from the United States (US) Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database for 1999-2020 overall and according to age, gender, and geographic region. All rates were age-adjusted to the 2000 US Census population, except age-specific rates. We used Joinpoint software to calculate the 20-year average annual percent change and annual percent change for specific periods identified by data-driven joinpoint placement with 95% confidence intervals (CI). Results: In 2019, the US bladder cancer incidence rate was 18.8 (CI, 18.6 to 18.9) cases per 100,000. Bladder cancer incidence decreased 0.9% annually (CI, 0.8 to 1.0% decrease) during 1999-2019, with a 3.3% annual decrease (CI, 2.5 to 4.1% decrease) during 2016-2019 specifically. Among men, the 20-year annual decrease was 1.1% (CI, 1.0 to 1.1% decrease), with a 3.8% annual decrease (CI, 2.8 to 4.6% decrease) during 2017-2019 specifically. Among women, the 20-year annual decrease was 1.0% (CI, 0.9 to 1.2% decrease), with a 2.6% annual decrease (CI, 1.7 to 4.2% decrease) during 2016-2019 specifically. Largest annual decreases in incidence rates were seen among 55-59-year-olds (1.8%, CI, 1.6 to 2.0% decrease), and in the western US (2.3%, CI, 2.0 to 2.6% decrease). Conversely, some southern states showed an increase in incidence. In Tennessee, there was a 20-year annual increase of 1.2% (CI, 0.9 to 1.6% increase). In 2019, the US bladder cancer mortality rate was 4.1 (CI, 4.0 to 4.2) deaths per 100,000. Bladder cancer mortality decreased 0.4% annually (CI, 0.2 to 0.5% decrease) during 1999-2019, with a 2.5% annual decrease (CI, 1.3 to 4.7% decrease) during 2016-2019 specifically. Mortality rate trends were generally similar among men and women (0.4% and 0.7% decrease annually, respectively). Largest annual decreases in mortality rates were seen among 50-54-year-olds (1.5%, CI, 0.6 to 2.4% decrease) and in the northeast US (0.8%, CI, 0.7 to 1.0% decrease). Reflecting the initial impact of the COVID-19 pandemic, bladder cancer incidence decreased by 8.6% (CI, 7.7 to 9.6% decrease) and bladder cancer mortality decreased by 2.7% (CI, 0.6 to 4.8% decrease) comparing 2020 with 2019. Conclusions: After decades remaining relatively constant, bladder cancer incidence and mortality rates in the US began to decrease around 2016-2017. This trend was less apparent in the southern part of the country, where incidence trended upward in some states. As evident for other common cancers, bladder cancer incidence rates decreased sharply during the first year of the COVID-19 pandemic. Forthcoming data for 2021-2024 will provide a clearer picture of the magnitude of this disruption and the possibility of a rebound. Citation Format: Grace B. Gallant, Hugo Pomares-Millan, Judy R. Rees, Margaret R. Karagas, Michael N. Passarelli. Urinary bladder cancer incidence and mortality in the United States: 20-year trends and initial impact of the COVID-19 pandemic [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B001.

Environmental arsenic and genetic susceptibility have both been shown to increase bladder cancer risk, yet little is known about their respective interaction. We conducted a gene-environment interaction (GxE) study to characterize lifetime arsenic exposure from drinking water, inherited susceptibility, and bladder cancer risk in the New England Bladder Cancer Study. Exposures were estimated from arsenic measured in water samples collected at home and workplace. We evaluated common single-nucleotide polymorphisms (SNPs) i) from the latest bladder cancer genome-wide association study (n= 28), ii) from candidate gene studies of arsenic or bladder cancer (n= 16 SNPs), and iii) SNPs from a large genome-wide association study of arsenic metabolism (n = 4 SNPs) as potential effect modifiers of the arsenic-bladder cancer relationship. We coded SNPs as the absence or presence of a risk/effect allele for bladder cancer or arsenic metabolism in 2,019 adults (928 bladder cancer cases and 1,091 controls) and arsenic exposures as tertiles. Odds ratios (OR) with 95% confidence intervals (CI) adjusted for age, sex, smoking status, high-risk occupation, and principal components of genetic ancestry were estimated using logistic regression models. P-values for multiplicative interaction were calculated. Out of 48 SNPs, we found evidence of interaction for 7 SNPs at the statistical significance level of P<0.05. Most SNPs involved in GxE interactions are mapped to genomic regions known or suspected to function in arsenic metabolism. For the association between cumulative lifetime water arsenic (mg) and bladder cancer, the strongest evidence of an interaction was with rs1046428 (near GSTZ1 on 14q23); among those with one or two copies of the T risk allele, ORT2vsT1: 1.52, CI: 1.11 - 2.07; ORT3 vsT1: 1.44, CI: 1.05 - 1.98, Pinteraction = 0.01; among those with no risk allele copy, ORT2vsT1: 0.91, CI: 0.62 - 1.35; ORT3 vsT1: 0.97, CI: 0.65 - 1.44. For average daily water arsenic (µg/day), we found evidence of interaction among those with risk allele for rs1801133 (A/A, A/G; MTHFR on 1p36) ORT2 vsT1: 1.70, CI: 1.18 - 2.44; ORT3 vsT1: 1.53, CI: 1.06 - 2.23, Pinteraction = 0.02, in those with no copies of risk allele ORT2vsT1: 0.85, CI: 0.61 - 1.17; ORT3 vsT1: 1.11, CI: 0.79 - 1.54; and rs1801131 (G/G; G/T; MTHFR ) ORT2 vsT1: 1.59, CI: 1.14 - 2.22; ORT3 vsT1: 1.63, CI: 1.16 - 2.29, Pinteraction = 0.01, whereas in those with no risk allele ORT2vsT1: 0.84, CI: 0.59 - 1.19; ORT3 vsT1: 1, CI: 0.69 - 1.44. For 40-year lagged cumulative lifetime water arsenic (mg) and average daily water arsenic (µg/day), we found suggestive interactions with rs2234636 (SLC39A2 on 14q11), and rs1495741 (NAT2 on 8p22). Our study provides evidence of interactions between lifetime arsenic exposure and genetic variants that function in xenobiotic metabolism on bladder cancer occurrence. Citation Format: Hugo Pomares-Millan, Stella Koutros, Nathaniel Rothman, Dalsu Baris, Molly Schwenn, Alison Johnson, Debra T. Silverman, Margaret R. Karagas, Michael N. Passarelli. Gene-environment interactions for lifetime water arsenic exposure and bladder cancer risk in the New England Bladder Cancer study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6140.