The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Nucleated red blood cells explain most of the association between DNA methylation and gestational age.

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.

Phylogeographic history of mitochondrial haplogroup J in Scandinavia.

BACKGROUND: Mitochondrial DNA haplogroup J is the third most frequent haplogroup in modern-day Scandinavia, although it did not originate there. To infer the genetic history of haplogroup J in Scandinavia, we examined worldwide mitogenome sequences using a maximum-likelihood phylogenetic approach. METHODS: Haplogroup J mitogenome sequences were gathered from GenBank (n = 2245) and aligned against the ancestral Reconstructed Sapiens Reference Sequence. We also analyzed haplogroup J Viking Age sequences from the European Nucleotide Archive (n = 54). Genetic distances were estimated from these data and projected onto a maximum likelihood rooted phylogenetic tree to analyze clustering and branching dates. RESULTS: Haplogroup J originated approximately 42.6 kya (95% CI: 30.0-64.7), with several of its earliest branches being found within the Arabian Peninsula and Northern Africa. J1b was found most frequently in the Near East and Arabian Peninsula, while J1c occurred most frequently in Europe. Based on phylogenetic dating, subhaplogroup J1c has its early roots in the Mediterranean and Western Balkans. Otherwise, the majority of the branches found in Scandinavia are younger than those seen elsewhere, indicating that haplogroup J dispersed relatively recently into Northern Europe, most plausibly with Neolithic farmers. CONCLUSIONS: Haplogroup J appeared when Scandinavia was transitioning to agriculture over 6 kya, with J1c being the most common lineage there today. Changes in the distribution of haplogroup J mtDNAs were likely driven by the expansion of farming from West Asia into Southern Europe, followed by a later expansion into Scandinavia, with other J subhaplogroups appearing among Scandinavian groups as early as the Viking Age.

Evolution and dispersal of mitochondrial DNA haplogroup U5 in Northern Europe: insights from an unsupervised learning approach to phylogeography.

BACKGROUND: We combined an unsupervised learning methodology for analyzing mitogenome sequences with maximum likelihood (ML) phylogenetics to make detailed inferences about the evolution and diversification of mitochondrial DNA (mtDNA) haplogroup U5, which appears at high frequencies in northern Europe. METHODS: Haplogroup U5 mitogenome sequences were gathered from GenBank. The hierarchal Bayesian Analysis of Population Structure (hierBAPS) method was used to generate groups of sequences that were then projected onto a rooted maximum likelihood (ML) phylogenetic tree to visualize the pattern of clustering. The haplogroup statuses of the individual sequences were assessed using Haplogrep2. RESULTS: A total of 23 hierBAPS groups were identified, all of which corresponded to subclades defined in Phylotree, v.17. The hierBAPS groups projected onto the ML phylogeny accurately clustered all haplotypes belonging to a specific haplogroup in accordance with Haplogrep2. By incorporating the geographic source of each sequence and subclade age estimates into this framework, inferences about the diversification of U5 mtDNAs were made. Haplogroup U5 has been present in northern Europe since the Mesolithic, and spread in both eastern and western directions, undergoing significant diversification within Scandinavia. A review of historical and archeological evidence attests to some of the population interactions contributing to this pattern. CONCLUSIONS: The hierBAPS algorithm accurately grouped mitogenome sequences into subclades in a phylogenetically robust manner. This analysis provided new insights into the phylogeographic structure of haplogroup U5 diversity in northern Europe, revealing a detailed perspective on the diversity of subclades in this region and their distribution in Scandinavian populations.

Temporal Aspects of the Association between Exposure to the World Trade Center Disaster and Risk of Cutaneous Melanoma.

Rescue/recovery workers who responded to the World Trade Center (WTC) attacks were exposed to known/suspected carcinogens. Studies have identified a trend toward an elevated risk of cutaneous melanoma in this population; however, few found significant increases. Furthermore, temporal aspects of the association have not been investigated. A total of 44,540 non-Hispanic White workers from the WTC Combined Rescue/Recovery Cohort were studied between March 12, 2002 and December 31, 2015. Cancer data were obtained through linkages with 13 state registries. Poisson regression was used to estimate hazard ratios and 95% confidence intervals using the New York State population as the reference; change points in hazard ratios were estimated using profile likelihood. We observed 247 incident cases of melanoma. No increase in incidence was detected during 2002-2004. From 2005 to 2015, the hazard ratio was 1.34 (95% confidence interval = 1.18-1.52). A dose‒response relationship was observed by arrival time at the WTC site. Risk was elevated just over 3 years after the attacks. Whereas WTC-related exposures to UVR or other agents might have contributed to this result, exposures other than those at the WTC site, enhanced medical surveillance, and lack of a control group with a similar proportion of rescue/recovery workers cannot be discounted. Our results support continued study of this population for melanoma.

Cancer Incidence in World Trade Center Rescue and Recovery Workers: 14 Years of Follow-Up.

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.

Temporal association of prostate cancer incidence with World Trade Center rescue/recovery work.

BACKGROUND: The 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. OBJECTIVES: To 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. METHODS: Person-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. RESULTS: The 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. CONCLUSIONS: Risk 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.

Cancer survival among World Trade Center rescue and recovery workers: A collaborative cohort study.

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.

Impact of healthcare services on thyroid cancer incidence among World Trade Center-exposed rescue and recovery workers.

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.

Matrilineal diversity and population history of Norwegians.

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.

Combining Three Cohorts of World Trade Center Rescue/Recovery Workers for Assessing Cancer Incidence and Mortality.

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.