Rena R Jones

Associations of self-identified race and ethnicity and genetic ancestry with mortality among cancer survivors

Abstract Self-identified race and ethnicity (SIRE) and genetic ancestry are potentially associated with disparities in health outcomes; however, independent effects of SIRE and genetic ancestry on mortality in cancer survivors including when adjusting for multiple risk factors are understudied. Among 23 445 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Screening Trial, SIRE was associated with mortality among prostate, colorectal, lung, ovarian, and breast cancer survivors; genetic ancestry was associated with mortality among prostate, colorectal, and breast cancer survivors. Associations were strong when adjusting for age at cancer diagnosis, sex, and tumor characteristics but attenuated when adjusting for individual-level factors and population-level socioeconomic status. For example, mortality risk was higher among Black vs White prostate cancer survivors and African genetic ancestry vs European genetic ancestry, but associations were attenuated after multilevel adjustment. Results suggest that SIRE and genetic ancestry do not solely reflect biologic variation; rather, social factors may drive mortality differences by SIRE and genetic ancestry.

Fine Particulate Matter, Noise Pollution, and Greenspace and Prostate Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Cohort

Abstract Background: Greenspace is hypothesized as being protective against cancer, whereas noise pollution and fine particulate matter (<2.5 μm in diameter, PM2.5) are both potential risk factors. Findings from recent studies of greenspace and PM2.5 with prostate cancer are not conclusive and the association between noise exposure and cancer has not been evaluated in a U.S. study. Methods: We assessed PM2.5, noise, and greenspace exposure using spatiotemporal models and satellite-based estimates at enrollment addresses for N = 43,184 male participants of the prospective Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial cohort (enrolled 1994–2001). We used Cox regression models adjusted for age, race and ethnicity, study center, family history of prostate cancer, and Area Deprivation Index to estimate associations between ambient PM2.5 (μg/m3), greenspace (index range from –1 to 1), and noise pollution (loudest 10% of total existing sound, decibels) and incident prostate cancer risk through December 2017. Results: A total of 6,327 cases of prostate cancer were diagnosed among male participants during follow-up. PM2.5 and noise exposures were moderately positively correlated (Spearman ρ = 0.46), and PM2.5 and greenspace were not correlated (ρ = 0.10); greenspace and noise were inversely correlated (ρ = −0.32). In single-pollutant and multipollutant models mutually adjusted for coexposures, we found no associations with prostate cancer risk. Conclusions: We did not find evidence that PM2.5, greenspace, and noise pollution were associated with prostate cancer risk in this large, geographically spread cohort. Impact: This study contributes to a small body of existing literature investigating these biologically plausible associations.

State-Specific Incidence of Endometrial Cancer in the United States by Histologic Subtype Corrected for Hysterectomy Prevalence from 2010 to 2019

Abstract Background: Accurate reporting of state-specific endometrial cancer incidence is important for informing cancer control efforts and may lead to new hypotheses about environmental and/or geographic risk factors. Previous studies have demonstrated the importance of accounting for hysterectomy prevalence when estimating state-level endometrial cancer incidence rates as hysterectomy prevalence varies by geographic region. Methods: We used the Cancer in North America Public Use Dataset produced by the North American Association of Central Cancer Registries to identify incident endometrial cancer cases among women ≥20 years of age diagnosed from 2010 to 2019. We estimated state-specific hysterectomy-corrected, age-adjusted incidence rates overall and by histology. State-specific hysterectomy prevalence data were obtained from the Behavioral Risk Factor Surveillance System. Results: Hysterectomy prevalence was highest in Southern and Midwestern states and lowest in the Northeast. Although uncorrected endometrial cancer incidence rates were highest in the Northeast, hysterectomy-corrected rates were highest in states within the Midwest and Appalachia. Geographic patterns of the hysterectomy-corrected incidence of endometrioid cancer resembled those of endometrial cancer overall. In contrast, corrected rates of non-endometrioid cancer were highest in the South and in certain states within the Northeast and Midwest. There was no overlap in the top 10 states with the highest rates of endometrioid and non-endometrioid cancers, respectively. Conclusions: State-specific, hysterectomy-corrected incidence rates of endometrial cancer vary by histology, suggesting potential differences in behavioral, sociodemographic, and/or environmental exposures at the state level. Impact: This study presents an accurate assessment of US endometrial cancer rates and emphasizes the importance of hysterectomy correction for geographic comparisons.

Outdoor light at night and risk of endometrial cancer in the NIH-AARP diet and health study

Outdoor light at night (LAN) can result in circadian disruption and hormone dysregulation and is a suspected risk factor for some cancers. Our study is the first to evaluate the association between LAN and risk of endometrial cancer, a malignancy with known relationship to circulating estrogen levels. We linked enrollment addresses (1996) for 97,677 postmenopausal women in the prospective NIH-AARP cohort to satellite imagery of nighttime radiance to estimate LAN exposure. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for LAN quintiles and incident endometrial cancer overall (1,669 cases) and endometrioid adenocarcinomas (991 cases) through follow-up (2011). We tested for interaction with established endometrial cancer risk factors. We observed no association for endometrial cancer overall (HR Our study did not find an association between outdoor LAN and endometrial cancer risk, but was limited by the inability to account for individual-level exposure determinants. Future studies should consider approaches to improve characterization of personal exposures to light.

Serum perfluorooctane sulfonate and perfluorooctanoate and risk of postmenopausal breast cancer according to hormone receptor status: An analysis in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Per‐ and polyfluoroalkyl substances (PFAS) are highly persistent endocrine‐disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case‐control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography‐tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype‐specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs] = 1.59 [1.01‐2.50], 2.34 [1.29‐4.23], and 2.19 [1.21‐3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER−, PR−, ER+/PR−, and ER−/PR− tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor‐positive tumors, and possibly between PFOA and receptor‐negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology.

Serum concentrations of perfluoroalkyl and polyfluoroalkyl substances and risk of ovarian cancer

Abstract Background Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent, widespread environmental contaminants, and some are endocrine disrupting. Studies of gynecologic cancers are limited; we evaluated ovarian cancer, a rare, often fatal malignancy. Methods This nested case-control study included 318 ovarian cancer cases and 472 individually matched female controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which recruited participants aged 55-74 years from 10 US study centers (1993-2001). We looked at cases through 2016 and quantitated 8 PFAS in prediagnostic serum samples. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for continuous (log2-transformed) and categorized PFAS concentrations by using conditional logistic regression models, implicitly adjusting for matching factors (age, center, year of random assignment, year of blood draw, race and ethnicity) and adjusting for smoking, body mass index, family history of cancer, menopausal hormone therapy and oral contraceptive use, parity, and number of freeze-thaw cycles. Results We found a positive association with ovarian cancer for a doubling in 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) concentrations (OR for log2 = 1.24, 95% CI = 1.03 to 1.49) and 62% greater risk among those in the highest quartile (OR for quartile 4 vs quartile 1 = 1.62, 95% CI = 1.03 to 2.54; P for trend = .02). Perfluorooctane sulfonic acid (PFOS) was associated with increased risk (OR for log2 = 1.47, 95% CI = 1.05 to 2.06), with no quartile trend (P for trend = .79). Associations with perfluorononanoic acid (OR for log2 = 1.36, 95% CI = 0.95 to 1.95) and perfluorodecanoic acid (OR for log2 = 1.35, 95% CI = 0.94 to 1.95) were suggested, with nonmonotonic quartile trends (P for trend = .12 to .21). The MeFOSAA associations were strongest in women aged 55-59 years (OR for log 2 = 1.60, 95% CI = 1.13 to 2.27), more moderate in women aged 60-64 years (OR for log2 = 1.31, 95% CI = 0.90 to 1.90), and null among women 65 years of age and older (OR for log2 = 1.02, 95% CI = 0.73 to 1.43; P for heterogeneity = .22). Associations persisted in cases diagnosed 8 years or more after blood collection. Conclusions These findings offer novel evidence for PFAS as ovarian cancer risk factors, particularly PFOS and MeFOSAA, a PFOS precursor.