Three cohorts including the Fire Department of the City of New York (FDNY), the World Trade Center Health Registry (WTCHR), and the General Responder Cohort (GRC), each funded by the World Trade Center Health Program have reported associations between WTC-exposures and cancer. Results have generally been consistent with effect estimates for excess incidence for all cancers ranging from 6 to 14% above background rates. Pooling would increase sample size and de-duplicate cases between the cohorts. However, pooling required time consuming steps: obtaining Institutional Review Board (IRB) approvals and legal agreements from entities involved; establishing an honest broker for managing the data; de-duplicating the pooled cohort files; applying to State Cancer Registries (SCRs) for matched cancer cases; and finalizing analysis data files. Obtaining SCR data use agreements ranged from 6.5 to 114.5 weeks with six states requiring >20 weeks. Records from FDNY (n = 16,221), WTCHR (n = 29,372), and GRC (n = 33,427) were combined de-duplicated resulting in 69,102 unique individuals. Overall, 7894 cancer tumors were matched to the pooled cohort, increasing the number cancers by as much as 58% compared to previous analyses. Pooling resulted in a coherent resource for future research for studies on rare cancers and mortality, with more representative of occupations and WTC- exposure.

Background Statistically significantly increased cancer incidence has been reported from 3 cohorts of World Trade Center (WTC) disaster rescue and recovery workers. We pooled data across these cohorts to address ongoing public concerns regarding cancer risk 14 years after WTC exposure. Methods From a combined deduplicated cohort of 69 102 WTC rescue and recovery workers, a sample of 57 402 workers enrolled before 2009 and followed through 2015 was studied. Invasive cancers diagnosed in 2002-2015 were identified from 13 state cancer registries. Standardized incidence ratios (SIRs) were used to assess cancer incidence. Adjusted hazard ratios (aHRs) were estimated from Cox regression to examine associations between WTC exposures and cancer risk. Results Of the 3611 incident cancers identified, 3236 were reported as first-time primary (FP) cancers, with an accumulated 649 724 and 624 620 person-years of follow-up, respectively. Incidence for combined FP cancers was below expectation (SIR = 0.96, 95% confidence interval [CI] = 0.93 to 0.99). Statistically significantly elevated SIRs were observed for melanoma-skin (SIR = 1.43, 95% CI = 1.24 to 1.64), prostate (SIR = 1.19, 95% CI = 1.11 to 1.26), thyroid (SIR = 1.81, 95% CI = 1.57 to 2.09), and tonsil (SIR = 1.40, 95% CI = 1.00 to 1.91) cancer. Those arriving on September 11 had statistically significantly higher aHRs than those arriving after September 17, 2001, for prostate (aHR = 1.61, 95% CI = 1.33 to 1.95) and thyroid (aHR = 1.77, 95% CI = 1.11 to 2.81) cancers, with a statistically significant exposure-response trend for both. Conclusions In the largest cohort of 9/11 rescue and recovery workers ever studied, overall cancer incidence was lower than expected, and intensity of WTC exposure was associated with increased risk for specific cancer sites, demonstrating the value of long-term follow-up studies after environmental disasters.

BackgroundThe World Trade Center (WTC) attacks on 11 September 2001 created a hazardous environment with known and suspected carcinogens. Previous studies have identified an increased risk of prostate cancer in responder cohorts compared with the general male population.ObjectivesTo estimate the length of time to prostate cancer among WTC rescue/recovery workers by determining specific time periods during which the risk was significantly elevated.MethodsPerson-time accruals began 6 months after enrolment into a WTC cohort and ended at death or 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. New York State was the comparison population. We used Poisson regression to estimate hazard ratios and 95% CIs; change points in rate ratios were estimated using profile likelihood.ResultsThe analytic cohort included 54 394 male rescue/recovery workers. We observed 1120 incident prostate cancer cases. During 2002–2006, no association with WTC exposure was detected. Beginning in 2007, a 24% increased risk (HR: 1.24, 95% CI 1.16 to 1.32) was observed among WTC rescue/recovery workers when compared with New York State. Comparing those who arrived earliest at the disaster site on the morning of 11 September 2001 or any time on 12 September 2001 to those who first arrived later, we observed a positive, monotonic, dose-response association in the early (2002–2006) and late (2007–2015) periods.ConclusionsRisk of prostate cancer was significantly elevated beginning in 2007 in the WTC combined rescue/recovery cohort. While unique exposures at the disaster site might have contributed to the observed effect, screening practices including routine prostate specific antigen screening cannot be discounted.

Background While well known for its Viking past, Norway's population history and the influences that have shaped its genetic diversity are less well understood. This is particularly true with respect to its demography, migration patterns, and dialectal regions, despite there being curated historical records for the past several centuries. In this study, we undertook an analysis of mitochondrial DNA (mtDNA) diversity within the country to elaborate this history from a matrilineal genetic perspective. Methods We aggregated 1174 partial modern Norwegian mtDNA sequences from the published literature and subjected them to detailed statistical and phylogenetic analysis by dialectal regions and localities. We further contextualized the matrilineal ancestry of modern Norwegians with data from Mesolithic, Iron Age, and historic period populations. Results Modern Norwegian mtDNAs fell into eight West Eurasian (N, HV, JT, I, U, K, X, W), five East Eurasian (A, F, G, N11, Z), and one African (L2) haplogroups. Pairwise analysis of molecular variance (AMOVA) estimates for all Norwegians indicated they were differentiated from each other at 1.68% (p < 0.001). Norwegians within the same dialectal region also showed genetic similarities to each other, although differences between subpopulations within dialectal regions were also observed. In addition, certain mtDNA lineages in modern Norwegians were also found among prehistoric and historic period populations, suggesting some level of genetic continuity over hundreds to many thousands of years. Conclusions This analysis of mtDNA diversity provides a detailed picture of the genetic variation within Norway in light of its topography, settlement history, and historical migrations over the past several centuries.

Determining if specific cell type(s) are responsible for an association between DNA methylation (DNAm) and a given phenotype is important for understanding the biological mechanisms underlying the association. Our EWAS of gestational age (GA) in 953 newborns from the Norwegian MoBa study identified 13,660 CpGs significantly associated with GA (pBonferroni<0.05) after adjustment for cell type composition. When the CellDMC algorithm was applied to explore cell-type specific effects, 2,330 CpGs were significantly associated with GA, mostly in nucleated red blood cells [nRBCs; n = 2,030 (87%)]. Similar patterns were found in another dataset based on a different array and when applying an alternative algorithm to CellDMC called Tensor Composition Analysis (TCA). Our findings point to nRBCs as the main cell type driving the DNAm–GA association, implicating an epigenetic signature of erythropoiesis as a likely mechanism. They also explain the poor correlation observed between epigenetic age clocks for newborns and those for adults.

Background A recent study of World Trade Center (WTC)‐exposed firefighters and emergency medical service workers demonstrated that elevated thyroid cancer incidence may be attributable to frequent medical testing, resulting in the identification of asymptomatic tumors. We expand on that study by comparing the incidence of thyroid cancer among three groups: WTC‐exposed rescue/recovery workers enrolled in a New York State (NYS) WTC‐medical monitoring and treatment program (MMTP); WTC‐exposed rescue/recovery workers not enrolled in an MMTP (non‐MMTP); and the NYS population. Methods Person‐time began on 9/12/2001 or at enrollment in a WTC cohort and ended at death or on 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. We used Poisson regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for MMTP and non‐MMTP participants. NYS rates were used as the reference. To estimate potential changes over time in WTC‐associated risk, change points in RRs were estimated using profile likelihood. Results The thyroid cancer incidence rate among MMTP participants was more than twice that of NYS population rates (RR = 2.31; 95% CI = 2.00–2.68). Non‐MMTP participants had a risk similar to NYS (RR = 0.96; 95% CI = 0.72–1.28). We observed no change points in the follow‐up period. Conclusion Our findings support the hypothesis that no‐cost screening (a benefit provided by WTC‐MMTPs) is associated with elevated identification of thyroid cancer. Given the high survival rate for thyroid cancer, it is important to weigh the costs and benefits of treatment, as many of these cancers were asymptomatic and may have been detected incidentally.

Background World Trade Center (WTC)‐exposed responders may be eligible to receive no‐cost medical monitoring and treatment for certified conditions, including cancer. The survival of responders with cancer has not previously been investigated. Methods This study compared the estimated relative survival of WTC‐exposed responders who developed cancer while enrolled in two WTC medical monitoring and treatment programs in New York City (WTC‐MMTP responders) and WTC‐exposed responders not enrolled (WTC‐non‐MMTP responders) to non‐responders from New York State (NYS‐non‐responders), all restricted to the 11‐southernmost NYS counties, where most responders resided. Parametric survival models estimated cancer‐specific and all‐cause mortality. Follow‐up ended at death or on December 31, 2016. Results From January 1, 2005 to December 31, 2016, there were 2,037 cancer cases and 303 deaths (248 cancer‐related deaths) among WTC‐MMTP responders, 564 cancer cases, and 143 deaths (106 cancer‐related deaths) among WTC‐non‐MMTP responders, and 574,075 cancer cases and 224,040 deaths (158,645 cancer‐related deaths) among the NYS‐non‐responder population. Comparing WTC‐MMTP responders with NYS‐non‐responders, the cancer‐specific mortality hazard ratio (HR) was 0.72 (95% confidence interval [CI] = 0.64–0.82), and all‐cause mortality HR was 0.64 (95% CI = 0.58–0.72). The cancer‐specific HR was 0.94 (95% CI = 0.78–1.14), and all‐cause mortality HR was 0.93 (95% CI = 0.79–1.10) comparing WTC‐non‐MMTP responders to the NYS‐non‐responder population. Conclusions WTC‐MMTP responders had lower mortality compared with NYS‐non‐responders, after controlling for demographic factors and temporal trends. There may be survival benefits from no‐out‐of‐pocket‐cost medical care which could have important implications for healthcare policy, however, other occupational and socioeconomic factors could have contributed to some of the observed survival advantage.

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