Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological ...studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting.
A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. Heterogeneity among studies and their publication bias were further assessed by the χ(2)-based Q statistic test and Egger's test, respectively.
The results showed that shorter telomeres were significantly associated with cancer risk (OR = 1.35, 95% CI = 1.14-1.60), compared with longer telomeres. In the stratified analysis by tumor type, the association remained significant in subgroups of bladder cancer (OR = 1.84, 95% CI = 1.38-2.44), lung cancer (OR = 2.39, 95% CI = 1.18-4.88), smoking-related cancers (OR = 2.25, 95% CI = 1.83-2.78), cancers in the digestive system (OR = 1.69, 95% CI = 1.53-1.87) and the urogenital system (OR = 1.73, 95% CI = 1.12-2.67). Furthermore, the results also indicated that the association between the relative telomere length and overall cancer risk was statistically significant in studies of Caucasian subjects, Asian subjects, retrospective designs, hospital-based controls and smaller sample sizes. Funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis (P = 0.532).
The results of this meta-analysis suggest that the presence of shortened telomeres may be a marker for susceptibility to human cancer, but single larger, well-design prospective studies are warranted to confirm these findings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Research suggests better survival among Hispanics with diffuse large B-cell lymphoma (DLBCL) compared to non-Hispanic Whites (NHW); however, less is known about racial/ethnic survival ...differences in follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL).
Methods
We identified incident FL and CLL cases diagnosed between 2005 and 2016 at Montefiore Medical Center in the Bronx, NY. Cox proportional hazards regression assessed the association between race/ethnicity and all-cause mortality among FL and CLL separately.
Results
Of the 201 FL patients, 39.3% were NHW, 19.4% non-Hispanic Black (NHB), and 41.3% Hispanic, with a similar distribution among CLL patients. After adjusting for International Prognostic Index factors, sex, and chemotherapy, Hispanics with FL had lower all-cause mortality compared to NHWs (HR = 0.22; 95% CI 0.08–0.63), similar to prior DLBCL findings. All-cause mortality did not differ between NHBs and NHWs for FL or by any race/ethnicity for CLL.
Conclusion
In our diverse, urban population, we found that Hispanic diagnosed with FL had lower all-cause mortality compared to NHWs. We found no significant difference in all-cause mortality between Hispanics and NHWs diagnosed with CLL. Our study adds to the growing literature on racial and ethnic differences in survival among Hispanics with hematologic malignancies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Background: Domestic fuel combustion from cooking and heating is an important public health issue because roughly 3 billion people are exposed worldwide. Recently, the International Agency for ...Research on Cancer classified indoor emissions from household coal combustion as a human carcinogen (group 1) and from biomass fuel (primarily wood) as a probable human carcinogen (group 2A). Objectives: We pooled seven studies from the International Lung Cancer Consortium (5,105 cases and 6,535 controls) to provide further epidemiological evaluation of the association between in-home solid-fuel use, particularly wood, and lung cancer risk. Methods: Using questionnaire data, we classified subjects as predominant solid-fuel users (e. g., coal, wood) or nonsolid-fuel users (e.g., oil, gas, electricity). Unconditional logistic regression was used to estimate the odds ratios (ORs) and to compute 95% confidence intervals (CIs), adjusting for age, sex, education, smoking status, race/ethnicity, and study center. Results: Compared with nonsolid-fuel users, predominant coal users (OR = 1.64; 95% CI, 1.49-1.81), particularly coal users in Asia (OR = 4.93; 95% CI, 3.73-6.52), and predominant wood users in North American and European countries (OR = 1.21; 95% CI, 1.06-1.38) experienced higher risk of lung cancer. The results were similar in never-smoking women and other subgroups. Conclusions: Our results are consistent with previous observations pertaining to in-home coal use and lung cancer risk, support the hypothesis of a carcinogenic potential of in-home wood use, and point to the need for more detailed study of factors affecting these associations.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Indoor gas stove use for cooking is associated with an increased risk of current asthma among children and is prevalent in 35% of households in the United States (US). The population-level ...implications of gas cooking are largely unrecognized. We quantified the population attributable fraction (PAF) for gas stove use and current childhood asthma in the US. Effect sizes previously reported by meta-analyses for current asthma (Odds Ratio = 1.34, 95% Confidence Interval (CI) = 1.12−1.57) were utilized in the PAF estimations. The proportion of children (<18 years old) exposed to gas stoves was obtained from the American Housing Survey for the US, and states with available data (n = 9). We found that 12.7% (95% CI = 6.3−19.3%) of current childhood asthma in the US is attributable to gas stove use. The proportion of childhood asthma that could be theoretically prevented if gas stove use was not present (e.g., state-specific PAFs) varied by state (Illinois = 21.1%; California = 20.1%; New York = 18.8%; Massachusetts = 15.4%; Pennsylvania = 13.5%). Our results quantify the US public health burden attributed to gas stove use and childhood asthma. Further research is needed to quantify the burden experienced at the county levels, as well as the impacts of implementing mitigation strategies through intervention studies.
Lung cancer is considered an age-associated disease, whose progression is in part due to accumulation of genomic instability as well as age-related decline in system integrity and function. Thus even ...among individuals exposed to high levels of genotoxic carcinogens, such as those found in cigarette smoke, lung cancer susceptibility may vary as a function of individual differences in the rate of biological aging. We recently developed a highly accurate candidate biomarker of aging based on DNA methylation (DNAm) levels, which may prove useful in assessing risk of aging-related diseases, such as lung cancer. Using data on 2,029 females from the Women's Health Initiative, we examined whether baseline measures of "intrinsic epigenetic age acceleration" (IEAA) predicted subsequent lung cancer incidence. We observed 43 lung cancer cases over the nearly twenty years of follow-up. Results showed that standardized measures of IEAA were significantly associated with lung cancer incidence (HR: 1.50, P=3.4x10-3). Furthermore, stratified Cox proportional hazard models suggested that the association may be even stronger among older individuals (70 years or above) or those who are current smokers. Overall, our results suggest that IEAA may be a useful biomarker for evaluating lung cancer susceptibility from a biological aging perspective.
Purpose
Lung cancer mortality has been shown to vary by race and ethnicity in cancer registries; however, studies often do not account for smoking status. We sought to summarize the independent ...contribution of race and ethnicity to survival in US lung cancer patients, accounting for important variables including smoking status.
Methods
PubMed was used to identify 1,877 potentially eligible studies of which 27 were included. Studies were excluded if they did not account for age, race and/or ethnicity, and smoking status. Fixed- and random-effects meta-analyses were conducted using the reported adjusted hazard ratios (HR) of Hispanic ethnicity and Asian and African-American race compared to Non-Hispanic whites (NHWs) on overall survival in lung cancer.
Results
Hispanic ethnicity and Asian race were associated with decreased adjusted risk of death (Hispanic:
N
studies
= 5,
N
subjects
= 108,810, HR = 0.95, 95% CI 0.90–1.00; Asian:
N
studies
= 6,
N
subjects
= 128,950, HR = 0.86, 95% CI 0.81–0.90). The results were similar when excluding studies of solely never-smokers. There was no significant difference in survival between African-American and white race after adjustment (
N
studies
= 10,
N
subjects
= 131,378, HR = 0.98, 95% CI 0.96–1.01). Other prognostic factors were female gender (HR = 0.88, 95% CI 0.87–0.89), unmarried status (HR = 1.08, 95% CI 1.04–1.11), ever-smoking status (HR = 1.11, 95% CI 1.08–1.15), having comorbidities (HR = 1.39, 95% CI 1.24–1.56), and treatment receipt (surgery: HR = 0.33, 95% CI 0.32–0.34; radiation: HR = 0.87, 95% CI 0.85–0.88; chemotherapy: HR = 0.64, 95% CI 0.63–0.65).
Conclusions
Even after adjustment for clinical factors and smoking status, Hispanics and Asians experienced improved survival compared to NHWs. Future studies are needed to elucidate the drivers of these survival disparities.
Mitochondria are eukaryotic organelles responsible for energy production. Mitochondrial DNA (mtDNA) lack introns and protective histones, have limited DNA repair capacity and compensate for damage by ...increasing the number of mtDNA copies. As a consequence, mitochondria are more susceptible to reactive oxygen species, an important determinant of cancer risk, and it is hypothesized that increased mtDNA copy number may be associated with carcinogenesis. We assessed the association of mtDNA copy number and lung cancer risk in 227 prospectively collected cases and 227 matched controls from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age at randomization, smoking years and number of cigarettes smoked per day. There was suggestion of a dose-dependent relationship between mtDNA copy number and subsequent risk of lung cancer, with a prominent effect observed in the highest mtDNA copy number quartile ORs (95% CI) by quartile: 1.0 (reference), 1.3 (0.7–2.5), 1.1 (0.6–2.2) and 2.4 (1.1–5.1); Ptrend = 0.008. This is the first report, to the best of our knowledge, to suggest that mtDNA copy number may be positively associated with subsequent risk of lung cancer in a prospective cohort study; however, replication is needed in other studies and populations.
During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and ...three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, which we term the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment--the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (<0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and ...significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval CI: 1.0, 1.4 0.8-2.5, and 2.2 1.2-4.0, respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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