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Introduction With increasing tobacco product varieties, understanding tobacco use (TU) profiles and their associations with tobacco dependence (TD) has also become increasingly challenging. Aims and Methods We aimed to identify TU profiles and their associations with TD over time, and to identify subgroups with high risk of TD. We included 3463 adult recent tobacco users who had complete TU and TD data across waves 1–4 of the Population Assessment of Tobacco and Health (PATH) study. We used a composite index of TD and a summed TD score from an established 16-item TD measure. We applied a latent class analysis to identify TU profiles based on participants' usage of eight common tobacco product groups at each survey wave and to check the stability of the TU profiles over time. We then used generalized estimating equations regressions to evaluate the longitudinal TU–TD association, adjusting for potential confounders. Results We identified three distinct TU profiles that remained consistent across four survey waves: Dominant cigarette users (62%–68%), poly users with high propensity of using traditional cigarettes, e-cigarettes, and cigars (24%–31%), and dominant smokeless product users (7%–9%). Covariate-adjusted models showed that TD was significantly lower among the poly users and the dominant smokeless users, compared to that among the dominant cigarette users. Conclusions Both TU profiles and their associations with TD were stable over time at the population level. Poly users and smokeless product users were consistently associated with lower TD than cigarette-dominant users, suggesting the need for tailored tobacco cessation interventions for users with different TU profiles. Implications The finding of consistent TU profiles across four survey waves extends the current literature in capturing TU patterns in an evolving tobacco product landscape. The finding of the overall higher level of TD among the cigarette-dominant users compared to the other TU latent profiles (the Cig+eCig+Cigar dominant poly users and the dominant smokeless product users) can help identify high-risk groups for potential interventions. Our application of innovative statistical methods to high-quality longitudinal data from the PATH study helps improve the understanding of the dynamic TU–TD relationship over time. [ABSTRACT FROM AUTHOR]

Objectives Glyphosate is the most commonly used herbicide in the USA; however, its safety is still under debate. We assessed glyphosate levels and their association with overall mortality in a representative sample of the US adult population from the 2013 to 2016 National Health and Nutrition Examination Survey. Methods We extracted data on urinary glyphosate (N  = 2910) measured by ion chromatography isotope-dilution tandem mass spectrometry. Associations between glyphosate concentrations and demographic, lifestyle and other exposures were analyzed. Data were linked to public-use Mortality Files for 2019. Results The mean (STD) glyphosate level was 0.53 (0.59) ng/ml, with 25.7% of the subjects having glyphosate levels at or below the detection limit. At multivariate analysis, age and creatinine were associated with glyphosate urinary levels (both P  < 0.0001). There was a borderline association between glyphosate levels and mortality (HRadj 1.33; 95% CI 0.99–1.77 P  = 0.06). When 3,5,6-trichloropyridinol was excluded from the Cox model, glyphosate exhibits a significant association with mortality (HRadj 1.33; 95% CI 1.00–1.77; P  = 0.0532). Conclusions These nationally representative data suggest that recent exposure to glyphosate could be associated with increased mortality. More studies are necessary to understand population-level risk associated with the product, given its widespread use in agriculture. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Non-small-cell lung cancer mortality has declined at a faster rate than incidence due to multiple factors, including changes in smoking behaviour, early detection which shifts diagnosis, and novel therapies. Limited resources require that we quantify the contribution of early detection versus novel therapies in improving lung cancer survival outcomes. METHODS Non-small-cell lung cancer patients from the Surveillance, Epidemiology, and End Results-Medicare data were queried and divided into: (i) stage IV diagnosed in 2015 (n  = 3774) and (ii) stage I–III diagnosed in 2010–2012 (n  = 15 817). Multivariable Cox-proportional hazards models were performed to assess the independent association of immunotherapy or diagnosis at stage I/II versus III with survival. RESULTS Patients treated with immunotherapy had significantly better survival than those who did not (HRadj: 0.49, 95% confidence interval: 0.43–0.56), as did those diagnosed at stage I/II versus stage III (HRadj: 0.36, 95% confidence interval: 0.35–0.37). Patients on immunotherapy had a 10.7-month longer survival than those who were not. Stage I/II patients had an average survival benefit of 34 months, compared to stage III. If 25%% of stage IV patients not on immunotherapy received it, there would be a gain of 22 292 person-years survival per 100 000 diagnoses. A switch of only 25% from stage III to stage I/II would correspond to 70 833 person-years survival per 100 000 diagnoses. CONCLUSIONS In this cohort study, earlier stage at diagnosis contributed to life expectancy by almost 3 years, while gains from immunotherapy would contribute ½ year of survival. Given the relative affordability of early detection, risk reduction through increased screening should be optimized. [ABSTRACT FROM AUTHOR]

Immunotherapy has increased survival for non–small cell lung cancer (NSCLC), especially for those diagnosed with late-stage disease. However, it is not known if its use is equally distributed across races. We assessed immunotherapy use in 21 098 pathologically confirmed stage IV NSCLC patients according to race in the Surveillance Epidemiology, and End Results–Medicare linked dataset. Multivariable models were conducted to evaluate the independent association of receipt of immunotherapy with race and overall survival according to race. Black patients had statistically significantly lower odds of receiving immunotherapy (adjusted odds ratio = 0.60, 95% confidence interval = 0.44 to 0.80); receipt of immunotherapy was lower in Asian and Hispanic patients but not statistically significant. When immunotherapy was received, survival was similar across races. Immunotherapy for NSCLC is not used equally among races, underscoring the racial disparities that exist in access to the newest cancer treatment. Efforts should be directed toward expanding access to novel, efficacious treatments for advanced stage lung cancer. [ABSTRACT FROM AUTHOR]

The 2-fold excess thyroid cancer risk reported in multiple World Trade Center (WTC) disaster exposed cohorts cannot entirely be explained by surveillance and physician bias thus highlighting the need to investigate the potential consequences of the dust exposure, containing carcinogenic and endocrine disruptive elements, on the thyroid. This study investigated the presence of TERT promoter and BRAF V600E mutations in 20 WTC-exposed versus 23 matched non-exposed thyroid cancers as potential mechanism explaining the excess risk. Although no significant difference in BRAF V600E mutation was found, TERT promoter mutations were significantly more prevalent in WTC thyroid cancer versus non-exposed thyroid cancers (P = 0.021). The odds of a TERT promoter mutation was significantly higher in the WTC versus the non-WTC thyroid cancers after adjustment [ORadj: 7.11 (95% CI: 1.21–41.83)]. These results may indicate that exposure to the mixture of pollutants present in the WTC dust resulted in an excess thyroid cancer risk and potentially more aggressive thyroid cancer, warranting investigating WTC responders on thyroid-associated symptoms during their health checkups. Future studies should include long-term follow-up to provide important insights in whether thyroid-specific survival is negatively affected by WTC dust exposure and whether this is because of the presence of one or more driver mutations. [ABSTRACT FROM AUTHOR]

Background Patients with cancer are at risk for severe COVID-19. Previous studies examining mortality in cancer patients with COVID-19 have produced inconclusive results. Several published meta-analyses have aimed to estimate this association; however, because of methodological limitations in study selection and data aggregation, these studies do not reliably estimate the independent association between cancer and COVID-19 mortality. We conducted this systematic review and meta-analysis to determine whether cancer is an independent risk factor for COVID-19 mortality. Methods A literature search was performed in PubMed to identify studies that compared COVID-19 mortality in adult patients with and without cancer. Selection criteria included polymerase chain reaction–confirmed COVID-19, multivariate adjustment and/or matching for mortality risk estimates, and inclusion of hospitalized noncancer controls. Adjusted odds ratios and/or hazard ratios for mortality based on cancer status were extracted. Odds ratio and hazard ratio estimates were pooled using a random effects model. Results The analysis included 42 studies comprising 129 840 patients: 8612 cancer patients and 121 228 noncancer patients. Of these studies, 18 showed a null difference in survival between cancer and noncancer patients with COVID-19, and 24 studies showed statistically significantly worse survival in cancer patients with COVID-19. Meta-analysis revealed an increased risk of mortality in patients with cancer compared with noncancer patients with COVID-19 (odds ratio = 1.93, 95% confidence interval = 1.55 to 2.41; hazard ratio = 1.54, 95% confidence interval = 1.29 to 1.84). Conclusion We conclude that cancer is an independent risk factor for mortality in unvaccinated patients admitted for or diagnosed with COVID-19 during hospitalization. [ABSTRACT FROM AUTHOR]

There is increased incidence of prostate cancer (PC) among World Trade Center (WTC)-exposed responders and community members, with preliminary evidence suggestive of more aggressive disease. While previous research is supportive of differences in DNA methylation and gene expression as a consequence of WTC exposure, as measured in blood of healthy individuals, the epigenetics of WTC PC tissues has yet to be explored. Patients were recruited from the World Trade Center Health Program. Non-WTC PC samples were frequency matched on age, race/ethnicity and Gleason score. Bisulfite-treated DNA was extracted from tumor tissue blocks and used to assess global DNA methylation with the MethylationEPIC BeadChip. Differential and pathway enrichment analyses were conducted. RNA from the same tumor blocks was used for gene expression analysis to further support DNA methylation findings. Methylation data were generated for 28 samples (13 WTC and 15 non-WTC). Statistically significant differences in methylation were observed for 3,586 genes; on average WTC samples were statistically significantly more hypermethylated (P = 0.04131). Pathway enrichment analysis revealed hypermethylation in epithelial mesenchymal transition (EMT), hypoxia, mitotic spindle, TNFA signaling via NFKB, WNT signaling, and TGF beta signaling pathways in WTC compared to non-WTC samples. The androgen response, G2M and MYC target pathways were hypomethylated. These results correlated well with RNA gene expression. In conclusion, long-term epigenic changes associated with WTC dust exposure were observed in PC tissues. These occurred in genes of critical pathways, likely increasing prostate tumorigenesis potential. This warrants analysis of larger WTC groups and other cancer types. [ABSTRACT FROM AUTHOR]

Background Although immunotherapy can increase survival in non-small cell lung cancer (NSCLC), response rates are low. It is unclear which characteristics contribute to variability in immunotherapy efficacy and survival. Research is needed to identify reasons for heterogeneity in response rates to better tailor treatments. Methods Web of Science, Ovid EMBASE, and MEDLINE were queried from 2013 to January 2021, and all studies reporting overall or progression-free survival for patients treated with immunotherapy for NSCLC of at least stage IIIB were screened. Results Included were 18 randomized controlled trials (RCTs; 6534 immunotherapy RCTs; 11 192 nonimmunotherapy RCTs) and 16 observational studies (n = 9073 immunotherapy patients). Among RCTs, there was improved survival with the addition of immunotherapy in patients aged younger than 65 years in 10 of 17 studies; smokers in 8 of 15 studies; and males in 10 of 17 studies and 6 of 17 females. Only 5 studies reported outcomes by race. Among observational studies, younger patients (aged younger than 60, younger than 65, or younger than 70 years in most studies) had better survival than older patients (aged 60 years and older, 65 years and older, or 70 years and older) in 4 of 13 studies, ever-smokers in 7 of 13, and females in 2 of 14. Three studies reported race with mixed results. Conclusion Although evidence is mixed, younger patients, smokers, and males may derive more benefit from immunotherapy. Evidence on racial differences is limited. Physicians should be mindful of personal characteristics when formulating treatment plans. Further research is needed to understand underlying mechanisms and to identify the best immunotherapy candidates and alternative treatments for those unlikely to benefit. [ABSTRACT FROM AUTHOR]

Dementia and cancer occur commonly in older adults. Yet, little is known about the effect of dementia on cancer treatment and outcomes in patients diagnosed with cancer, and no guidelines exist. We performed a mixed studies review to assess the current knowledge and gaps on the impact of dementia on cancer treatment decision-making, cancer treatment, and mortality. A search in PubMed, Medline, and PsycINFO identified 55 studies on older adults with a dementia diagnosis before a cancer diagnosis and/or comorbid cancer and dementia published in English from January 2004 to February 2020. We described variability using range in quantitative estimates, ie, odds ratios (ORs), hazard ratios (HRs), and risk ratios (RR) when appropriate and performed narrative review of qualitative data. Patients with dementia were more likely to receive no curative treatment (including hospice or palliative care) (OR, HR, and RR range = 0.40-4.4, n = 8), while less likely to receive chemotherapy (OR and HR range = 0.11-0.68, n = 8), radiation (OR range = 0.24-0.56, n = 2), and surgery (OR range = 0.30-1.3, n = 4). Older adults with cancer and dementia had higher mortality than those with cancer alone (HR and OR range = 0.92-5.8, n = 33). Summarized findings from qualitative studies consistently revealed that clinicians, caregivers, and patients tended to prefer less aggressive care and gave higher priority to quality of life over life expectancy for those with dementia. Current practices in treatment-decision making for patients with both cancer and dementia are inconsistent. There is an urgent need for treatment guidelines for this growing patient population that considers patient and caregiver perspectives. [ABSTRACT FROM AUTHOR]

This study aims to compare serum cotinine levels in e-cigarette and combustible cigarette smokers, in an attempt to quantify the potential chronic nicotine addiction risk that e-cigarettes pose. We analyzed 428 participants in 2015–2016 NHANES: 379 (87.03%) smoked combustible cigarettes alone and 49 (12.97%) smoked e-cigarettes. Serum cotinine levels were measured by isotope-dilution high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometric method with a detection limit of 0.015 ng/ml. Electronic cigarette smokers were younger than combustible cigarette smokers (mean age 36.79 versus 42.69 years, P = 0.03), more likely to be male (64.93% versus 48.32%, P = 0.09) and significantly less likely to live with other smokers (50.17% versus 90.07%, P < 0.01). Serum cotinine levels increased linearly with self-reported days of smoking in both electronic cigarette and combustible cigarette smokers, after accounting for living with a smoker. The analysis of the subgroup who reported daily use show non-statistically significantly higher serum cotinine levels in electronic cigarette smokers versus combustible cigarette smokers (β adj = 52.50, P = 0.10). This analysis of recent US data demonstrates that electronic cigarettes expose users to nicotine levels proportionate to, and potentially higher than combustible cigarettes, and thus pose a serious risk of chronic nicotine addiction. This could be particularly relevant in otherwise tobacco naive individuals; future risk of tobacco-related dependence, addiction and relapse, as well as of tobacco-related cancers in these subjects needs to be investigated. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer, and early detection is associated with better survival. Mesothelin, fibulin-3 and osteopontin have been suggested as screening biomarkers. The study conducted a meta-analysis of the mean differences of mesothelin, osteopontin and fibulin-3 in blood and pleural samples. PubMed searches were conducted for studies that measured levels of mesothelin, osteopontin and fibulin-3 in participants with MPM compared with malignancy, benign lung disease or healthy participants. Thirty-two studies with mesothelin levels, 12 studies with osteopontin levels and 9 studies with fibulin-3 levels were included in the meta-analysis. Statistically significant mean differences were seen between MPM patients and all other comparison groups for mesothelin blood and pleural levels. Statistically significant differences in blood osteopontin levels were seen between participants with benign lung disease and healthy participants compared with participants with MPM, but not when comparing participants with cancer with MPM participants. There were not enough studies that reported osteopontin levels in pleural fluid to complete a meta-analysis. Statistically significant differences were seen in both blood and pleural levels of fibulin-3 in MPM patients compared with all other groups. On the basis of these results, mesothelin and fibulin-3 levels appear to be significantly lower in all control groups compared with those with MPM, making them good candidates for screening biomarkers. Osteopontin may be a useful biomarker for screening healthy individuals or those with benign lung disease but would not be useful for screening patients with malignancies. [ABSTRACT FROM AUTHOR]

The article discusses the importance of lung cancer screening and the need to improve access to it globally. It emphasizes the need to identify high-risk individuals and incorporate relevant risk factors, such as family history and exposure to asbestos, into screening criteria. The authors argue that investing in lung cancer CT screenings can save more lives than other treatments like chemotherapy or targeted therapy. While radiomics shows promise for the future, the immediate priority should be expanding access to screenings and enhancing early detection. [Extracted from the article]

Acute promyelocytic leukemia (APL) is a particularly aggressive subtype of acute myeloid leukemia (AML), with high rates of early death. It is important to examine how epidemiological characteristics, clinical and treatment factors, cytogenetic and genetic data affect survival and differ between APL and non-APL AML patients. We analyzed population data from the New York State Cancer Registry to characterize AML including APL incidence rates by demographics. APL incidence rates were higher among Hispanics than non-Hispanics [incidence rate ratio = 1.22; 95% confidence interval (CI) = 1.02–1.43]; and among foreign-born than USA-born persons. APL incidence rates increased more rapidly through 1995–2014 than non-APL AML; and its frequency increased faster among foreign-born persons. In a hospital cohort of 390 AML patients, the risk of death was significantly higher among APL patients with FLT3-internal tandem duplications than those without [hazard ratio (HR) = 11.74; 95% CI = 1.03–134.5]; and among APL patients with secondary versus de novo disease (HR = 17.32; 95% CI = 1.56–192.1). Among non-APL AML patients, risk of death was significantly associated with prior chemotherapy with antitubulin agents after adjusting for age, gender and ethnicity (adjusted HR = 3.30; 95% CI = 1.49–7.32); and separately with older age, unfavorable cytogenetics and complex karyotype. This study highlights FLT3 -internal tandem duplications as a prognostic factor in APL and proposes consideration of prior antitubulin therapy as a prognostic factor in non-APL AML. [ABSTRACT FROM AUTHOR]

In the midst of widespread community transmission of coronavirus disease 2019 (COVID-19) in New York, residents have sought information about COVID-19. We analyzed trends in New York State (NYS) and New York City (NYC) data to quantify the extent of COVID-19-related queries. Data on the number of 311 calls in NYC, Google Trend data on the search term 'Coronavirus' and information about trends in COVID-19 cases in NYS and the USA were compiled from multiple sources. There were 1228 994 total calls to 311 between 22 January 2020 and 22 April 2020, with 50 845 calls specific to COVID-19 in the study period. The proportion of 311 calls related to COVID-19 increased over time, while the 'interest over time' of the search term 'Coronavirus' has exponentially increased since the end of February 2020. It is vital that public health officials provide clear and up-to-date information about protective measures and crucial communications to respond to information-seeking behavior across NYC. [ABSTRACT FROM AUTHOR]

The unexpected nature of disasters leaves little time or resources for organized health surveillance of the affected population, and even less for those who are unaffected. An ideal epidemiologic study would monitor both groups equally well, but would typically be decided against as infeasible or costly. Exposure and health outcome data at the level of the individual can be difficult to obtain. Despite these challenges, the health effects of a disaster can be approximated. Approaches include 1) the use of publicly available exposure data in geographic detail, 2) health outcomes data-collected before, during, and after the event, and 3) statistical modeling designed to compare the observed frequency of health outcomes with the counterfactual frequency hidden by the disaster itself. We applied these strategies to Hurricane Sandy, which struck the northeastern United States in October 2012. Hospital admissions data from the state of New York with information on primary payer as well as patient demographic characteristics were analyzed. To illustrate the method, we present multivariate logistic regression results for the first 2 months after the hurricane. Inferential implications of admissions data on nearly the entire target population in the wake of a disaster are discussed. [ABSTRACT FROM AUTHOR]

This study was performed to quantify the association between mortality and known and unknown secondhand smoke (SHS) exposure as measured by cotinine levels in non-smokers. Data collected from 1999 to 2010 in the National Health and Nutrition Examination Survey (NHANES) were linked to the National Death Index. Self-reported non-smokers aged ≥20 years (N = 20 175) were studied. Serum cotinine was measured at recruitment; non-smokers were those with cotinine below the reported race-specific cut-off points (5.92, 4.85 and 0.84 ng/ml for non-Hispanic blacks, non-Hispanic whites and Mexican Americans, and 3.08 ng/ml for all other groups). Serum cotinine levels were significantly associated with overall survival (HRadj 1.17, 95% CI: 1.13-1.22 per natural-log unit change in cotinine), death for all medical causes, lung cancer, all cancers and heart diseases, after adjustment for gender, race/ethnicity, body mass index, smoking history and education. Similar results were observed when non-smokers reporting no SHS exposure at home or work were analyzed. There was a statistically significant trend in years of life lost (YLL), adjusted for confounders, across cotinine categories both in nonsmokers (YLLadj: 5.6, 6.4, 6.8, 7.5; P for trend < 0.0001) and non-smokers reporting no SHS exposure (YLLadj: 5.5, 6.1, 6.3, 6.7; P for trend = 0.002). Serum cotinine levels identify SHS-attributable mortality in subjects who would have otherwise been overlooked by questionnaire data, providing further evidence that the economic toll of SHS may be substantially higher than what was reported based on questionnaires. [ABSTRACT FROM AUTHOR]

We found that MM patients with germline BAP1 mutations have a 7-fold increase in long-term survival. This information is critical for appropriate genetic counseling and clinical management of MM that develops in germline BAP1 mutation carriers.BRCA1-associated protein-1 (BAP1) mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared with sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the United States Surveillance, Epidemiology, and End Results (SEER) data from 1973 to 2010. We identified 23 MM patients—11 alive—with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM and three MM in both locations. Thirteen patients had one or more malignancies in addition to MM. Actuarial median survival for the MM patients with germline BAP1 mutations was 5 years, as compared with <1 year for the median survival in the United States SEER MM group. Five-year survival was 47%, 95% confidence interval (24–67%), as compared with 6.7% (6.2–7.3%) in the control SEER group. Analysis of the pooled cohort of germline BAP1 mutation MM showed that patients with peritoneal MM (median survival of 10 years, P = 0.0571), or with a second malignancy in addition to MM (median survival of 10 years, P = 0.0716), survived for a longer time compared with patients who only had pleural MM, or MM patients without a second malignancy, respectively. In conclusion, we found that MM patients with germline BAP1 mutations have an overall 7-fold increased long-term survival, independently of sex and age. Appropriate genetic counseling and clinical management should be considered for MM patients who are also BAP1 mutation carriers. [ABSTRACT FROM AUTHOR]

Of the studies in this meta-analysis, only 3 included noncancer controls, with pooled fatality rates of 23.4% and 5.9% for cancer and noncancer patients, and high statistical heterogeneity (87% and 85%, respectively). Cancer patients are likely to be older and male and to have more comorbidities than noncancer patients, factors consistently shown to be associated with poor COVID-19 outcomes (4); thus, appropriate matching or multivariate adjustments are critical for obtaining valid relative estimates. We recently published higher COVID-19 case fatality rates in cancer than noncancer hospitalized patients (30.6% and 24.8%, respectively) (5). [Extracted from the article]

Video-assisted thoracic surgery (VATS) lobectomy is an appealing alternative to open lobectomy via thoracotomy for non-small-cell lung cancer. However, there is no clear consensus in regard to the superior approach for long-term outcomes. The data are limited to small series, which precludes further clarification. Meta-analysis of these studies was performed in order to obtain a more objective determination of the oncological feasibility of VATS lobectomy. A systematic review of the PubMed and Embase databases was performed. Twenty observational studies reporting long-term outcomes were included, involving 2106 VATS and 2661 thoracotomy patients. There was an advantage in long-term mortality for patients who underwent VATS vs patients who underwent thoracotomy (meta difference in survival: 5%; 95% CI: 3–6%) with large heterogeneity among studies (Q = 42.6; P-value: 0.001; I2 = 55.7%). There was no evidence of publication bias. Compared with open lobectomy, VATS lobectomy appears to have improved long-term outcomes. [ABSTRACT FROM AUTHOR]

Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case–control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83–0.97 and OR 0.88, 95% CI: 0.82–0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01–1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46–0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene–environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent. [ABSTRACT FROM AUTHOR]

Head and neck cancer represents 3.3% of all new malignancies and 2.0% of cancer deaths in the USA, the majority of which are squamous in origin. The overall 5 year survival is 60% and worsens with increasing stage at diagnosis. Thus, novel biomarkers for early detection of squamous cell carcinoma of the head and neck (SCCHN) are needed. MicroRNA-137 (miR-137) plays a role in cell cycle control and seems to undergo promoter methylation in oral squamous cell carcinoma tissue. The main objectives of this study were to ascertain whether miR-137 promoter methylation is detectable in oral rinse samples, assess its association with SCCHN and identify potential risk factors for its occurrence. Oral rinse samples were collected from 99 SCCHN patients with no prior history of cancer and 99 cancer-free controls, frequency matched on gender; tumor tissue for 64 patients was also tested. Methylation of the miR-137 promoter, assessed using methylation-specific polymerase chain reaction, was detected in 21.2% oral rinses from SCCHN patients and 3.0% from controls [odds ratio (OR) = 4.80, 95% confidence interval (CI): 1.23–18.82]. Among cases, promoter methylation of miR-137 was associated with female gender (OR = 5.30, 95% CI: 1.20–23.44) and inversely associated with body mass index (BMI) (OR = 0.88, 95% CI: 0.77–0.99). Promoter methylation of miR-137 appears to be a relatively frequently detected event in oral rinse of SCCHN patients and may have future utility as a biomarker in DNA methylation panels. The observed associations with gender and BMI help to shed light on potential risk factors for an altered methylation state in SCCHN. [ABSTRACT FROM PUBLISHER]

Lung cancer is the leading cause of cancer mortality worldwide. A possible carcinogenic role of human papillomavirus (HPV) has been investigated for >20 years and has major clinical and public health implications. We performed a meta-analysis to assess the prevalence of HPV16 and HPV18 in primary lung cancers (2435 subjects from 37 published studies). The overall HPV prevalence ranged from 0.0 to 78.3% with large heterogeneity across geographic regions and histological tissue types. A higher proportion, 50% (7/14), of the European studies reported low or no HPV prevalence (0–10%) compared with the Asian studies, 22% (4/18). When the analysis was limited to HPV16 and HPV18 prevalence, a higher prevalence in Asia (HPV16 = 11.6% and HPV18 = 8.8%) than in Europe (HPV16 = 3.5% and HPV18 = 3.6%) was observed. Studies using HPV-specific primers resulted in higher prevalence rates than consensus HPV primers (HPV16: Asia = 13% and Europe = 6%; HPV18: Asia = 13% and Europe = 5%). Further studies are needed to elucidate the role of HPV in lung carcinogenesis with careful thought given to study design and laboratory detection methods for a more accurate assessment of HPV status in lung tumors. [ABSTRACT FROM PUBLISHER]

Objective: This study explored whether average urinary estrogen metabolites in breast cancer high-risk women can be used to identify a subgroup of women at particularly high risk to develop breast cancer, to which prevention strategies should be addressed. Methods: The population consisted of 77 high-risk women, 30 breast cancer patients and 41 controls. All subjects answered a standardized questionnaire; height and weight and spot urine samples were also obtained. Urine hydroxyestrogen metabolites were measured in triplicate by enzyme immunoassay, and the estrogen metabolite ratios for each individual were calculated. Results: The 2:16 OHE ratio (2-hydroxyestrone/16-alpha-hydroxyestrone) in women at high risk for breast cancer was similar to that observed in the breast cancer group (1.76 ± 2.33 versus 1.29 ± 0.80) and lower than in controls (2.47 ± 1.14; P = 0.00). At the multivariate linear regression model, the 2:16 OHE ratio was significantly associated with diagnosis (P = 0.000 for both the high risk and breast cancer group versus the controls) and body mass index (P = 0.005), but not with age (P = 0.604), or smoking history (P = 0.478). Conclusions: This study suggests that lower urinary 2:16 OHE ratios are predictors of breast cancer risk. Profiling estrogen metabolites may identify women who are more probably to develop breast cancer within a population of women with known risk factors and may help to further elucidate the clinical relevance of urinary 2:16 OHE ratios as clinical markers and prognostic indicators in this population. [ABSTRACT FROM PUBLISHER]

Background: Despite the great public concern for the health status of professional soccer players, no formal study on mortality from all causes in soccer players has been performed so far. A study on mortality rates of professional soccer players in Italy between 1975 and 2003 was conducted. Methods: A total of 5389 players, age 14-35 years at enrollment were identified from public sources, and actively followed up for vital status from birth up to 31 December 2003, for 204 125 subject-years of follow-up. Overall and cause-specific mortality rates were calculated; expected number of deaths was calculated by applying the calendar period and age cause-specific mortality rates for men to the cohort of soccer players. The ratios between the observed and expected deaths gave the Standardized Mortality Ratios. Results: Deaths from diseases of the circulatory system, cancer and immune deficiency were significantly lower than expected. The SMR for car accidents was 2.23 (95% Cl 1.46-3.27). There were four deaths for Amyotrophic Lateral Sclerosis (ALS), and 0.2 expected, giving a SMR of 18.18 (95% CI 5.00-46.55). Conclusion: The public health impact of these findings has to be balanced against the significant observed lower mortality for cancer and cardiovascular disease. However, the early age at death, and the youthful composition of the cohort pose questions on the relative weight of ALS mortality in this population in the coming years. [ABSTRACT FROM AUTHOR]

Leptin is an important regulator of the mass of adipose tissue and of body weight; it operates by inhibiting food intake and stimulating energy expenditure. Some polymorphic genes involved in the regulation of leptin—the leptin gene (LEP A19G), the leptin receptor gene (LEPR Q223R, K109R, and K656N), and the peroxisome proliferator-activated receptor-gamma gene (PPARG P12A and C161T)—have been investigated as possible factors associated with obesity. Allelic frequencies of these polymorphisms show ethnic variation. The authors performed a meta-analysis of the available data on the association between these polymorphisms and obesity based on case-control studies. Odds ratios and 95% confidence intervals for obesity associated with leptin polymorphisms were calculated by using both fixed- and random-effects models. Results suggest no evidence of association between the genes under study and obesity. The lack of association could be due to the complex pathogenesis of obesity, which involves a number of genetic and environmental factors. Large studies including testing of multiple genes in both obese and lean subjects, with epidemiologic data on dietary habits in different ethnic groups, are necessary to better understand the role of leptin in regulating weight in human populations. [ABSTRACT FROM AUTHOR]

The recent completion of the first draft of the human genome sequence and advances in technologies for genomic analysis are generating tremendous opportunities for epidemiologic studies to evaluate the role of genetic variants in human disease. Many methodological issues apply to the investigation of variation in the frequency of allelic variants of human genes, of the possibility that these influence disease risk, and of assessment of the magnitude of the associated risk. Based on a Human Genome Epidemiology workshop, a checklist for reporting and appraising studies of genotype prevalence and studies of gene-disease associations was developed. This focuses on selection of study subjects, analytic validity of genotyping, population stratification, and statistical issues. Use of the checklist should facilitate the integration of evidence from these studies. The relation between the checklist and grading schemes that have been proposed for the evaluation of observational studies is discussed. Although the limitations of grading schemes are recognized, a robust approach is proposed. Other issues in the synthesis of evidence that are particularly relevant to studies of genotype prevalence and gene-disease association are discussed, notably identification of studies, publication bias, criteria for causal inference, and the appropriateness of quantitative synthesis. [ABSTRACT FROM PUBLISHER]

Smoking is a known risk factor for bladder cancer. The product of the GSTM1 gene, glutathione S-transferase M1 (GSTM1), is involved in the detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke; a homozygous deletion of this gene in approximately 50% of Caucasians and Asians results in a lack of GSTM1 enzyme activity. Most studies examining the relation between bladder cancer and GSTM1 have reported an increased risk associated with a lack of GSTM1 activity. The authors performed meta- and pooled analyses of published and unpublished, case-control, genotype-based studies that examined this association (17 studies, 2,149 cases, 3,646 controls) and excluded studies conducted in populations with a high prevalence of exposure to known bladder cancer risk factors other than tobacco smoke. Using random effects models in the meta-analysis, the authors obtained a summary odds ratio of 1.44 (95% confidence interval (CI): 1.23, 1.68) for GSTM1 null status with all studies included. Results from studies with at least 100 cases and 100 controls produced a summary odds ratio of 1.42 (95% CI: 1.26, 1.60). Pooled analyses using original data sets from 10 studies (1,496 cases and 1,444 controls) and adjusting for age, sex, and race produced similar results. There was no evidence of multiplicative interaction between the GSTM1 null genotype and ever smoking in relation to bladder cancer, although there was a suggestion of additive interaction (additive interaction = 0.45, 95% CI: –0.03, 0.93). These results indicate that, among populations studied to date, GSTM1 null status is associated with a modest increase in the risk of bladder cancer. Am J Epidemiol 2002;156:95–109. [ABSTRACT FROM PUBLISHER]

Statistical data on smoking and dietary habits in northern and southern Italy were compared and related to mortality rates for lung cancer. Age-adjusted mortality rates for lung cancer in the years 1980 and 1982 were lower in southern than in northern Italy. The proportion of smokers, as surveyed in 1977, was similar in the two geographical areas. Dietary habits in southern Italy, however, were characterized during the years 1960 through 1965, by a low consumption of saturated and polyunsaturated lipids, and a high consumption of foods of vegetable origin. Our data suggest that diet may modify the carcinogenic effect of tobacco in lung cancer. [ABSTRACT FROM PUBLISHER]

Nicolosi A (Preventive and Rehabilitative Medicine Project National Research Council, Milan, Italy), Casati S, Taioli E and Polli E. Death from cardiovascular disease in Italy, 1972–1981: decline in mortality rates and possible causes. 1988, 17: 766–772. Mortality rates for cardiovascular disease vary widely between countries, and epidemiological patterns (trends in incidence rates, prevalence of risk factors, availability of medical care) are heterogeneous even among industrialized nations. We studied mortality from cardiovascular disease in Italy from 1972 to 1981 and compared mortality to trends in risk factors during the same period. Age-adjusted mortality rates for acute ischaemic heart disease (IHD) have increased in Italy from 1972 to reach a peak in 1978 (180.53/100 000 in males, 51.55/100 000 in females), then declined between 1978 and 1981, by 7% in males and 5% in females. The decline was more evident in males and in the younger age groups. Deaths from chronic IHD reached a peak in 1973 in females and in 1975 in males, then decreased, respectively by 24.8% and 35.7% unti 1981. Mortality for cerebrovascular disease declined from 1972 to 1981 by 16.2% in males and 21.5% in females. Data from national statistics and sample surveys in different areas of Italy show an increase in total calorie intake, in animal proteins, fats and dairy products and raised average serum cholesterol levels plus an increase in smoking prevalence but a possible decline in blood pressure levels. The roles of hypertension treatment and of access to specialized medical care are discussed as possible contributors to the new declining trend of IHD, and the need is stressed for preventive strategies in health promotion. [ABSTRACT FROM PUBLISHER]

The task of identifying genetic determinants for complex, multigenetic diseases is hampered by small studies, publication and reporting biases, and lack of common standards worldwide. The authors propose the creation of a network of networks that include groups of investigators collecting data for human genome epidemiology research. Twenty-three networks of investigators addressing specific diseases or research topics and representing several hundreds of teams have already joined this initiative. For each field, the authors are currently creating a core registry of teams already participating in the respective network. A wider international registry will include all other teams also working in the same field. Independent investigators are invited to join the registries and existing networks and to join forces in creating additional ones as needed. The network of networks aims to register these networks, teams, and investigators; be a resource for information about or connections to the many networks; offer methodological support; promote sound design and standardization of analytical practices; generate inclusive overviews of fields at large; facilitate rapid confirmation of findings; and avoid duplication of effort. [ABSTRACT FROM AUTHOR]

A new Mspl RFLP in the CYP1A1 gene has been found in genomic DNA from African-Americans. The polymorphism results from a single A-T to G-C transition in the 3' noncoding region ˜300 bp upstream from the polyadenylation site. This mutation leads to cleavage of the normal 2.3 kb l restriction fragment into 1.3 and 1.0 kb fragments. The heterozygous mutation has been seen in 8 of 47 African-Americans, but was not detected in 191 Caucasians or 30 Asians. No linkage was observed with either of the two previously described polymorphisms in this gene. [ABSTRACT FROM PUBLISHER]