Publications by authors named "P Boffetta"

1,353 Publications

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Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium.

Br J Cancer 2021 Mar 26. Epub 2021 Mar 26.

International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, Lyon, France.

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.

Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.

Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.

Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.
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http://dx.doi.org/10.1038/s41416-021-01347-4DOI Listing
March 2021

Red Meat Consumption and Risk of Nonalcoholic Fatty Liver Disease in a Population With Low Meat Consumption: The Golestan Cohort Study.

Am J Gastroenterol 2021 Mar 24. Epub 2021 Mar 24.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Departments of Biology, School of Art and Sciences, Utica College, Utica, New York, USA; Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Radiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, Maryland, USA; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA; Departments of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Genetic Epidemiology Group, Section of Genetics, International Agency for Research on Cancer, the World Health Organization, Lyon, France; Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Introduction: Nonalcoholic fatty liver disease (NAFLD), as the most common liver disease in the world, can range from simple steatosis to steatohepatitis. We evaluated the association between meat consumption and risk of NAFLD in the Golestan Cohort Study (GCS).

Methods: The GCS enrolled 50,045 participants, aged 40-75 years in Iran. Dietary information was collected using a 116-item semiquantitative food frequency questionnaire at baseline (2004-2008). A random sample of 1,612 cohort members participated in a liver-focused study in 2011. NAFLD was ascertained through ultrasound. Total red meat consumption and total white meat consumption were categorized into quartiles based on the GCS population, with the first quartile as the referent group. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: The median intake of total red meat was 17 and total white meat was 53 g/d. During follow-up, 505 individuals (37.7%) were diagnosed with NAFLD, and 124 of them (9.2%) had elevated alanine transaminase. High total red meat consumption (ORQ4 vs Q1 = 1.59, 95% CI = 1.06-2.38, P trend = 0.03) and organ meat consumption (ORQ4 vs Q1 = 1.70, 95% CI = 1.19-2.44, P trend = 0.003) were associated with NAFLD. Total white meat, chicken, or fish consumption did not show significant associations with NAFLD.

Discussion: In this population with low consumption of red meat, individuals in the highest group of red meat intake were at increased odds of NAFLD. Furthermore, this is the first study to show an association between organ meat consumption and NAFLD (see Visual Abstract, http://links.lww.com/AJG/B944).
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http://dx.doi.org/10.14309/ajg.0000000000001229DOI Listing
March 2021

Oral health and risk of upper gastrointestinal cancers in a large prospective study from a high-risk region: Golestan Cohort Study.

Cancer Prev Res (Phila) 2021 Mar 17. Epub 2021 Mar 17.

Division of Cancer Epidemiology and Genetics, National Cancer Institute.

Tooth loss and periodontal disease have been associated with several cancers, and poor oral health may be an important risk factor for upper gastrointestinal (UGI, i.e., esophageal and gastric) cancers. We assessed the relationship between oral health and UGI cancers using a large prospective study of over 50,000 adults living in Golestan Province, Iran, a high-incidence area for these cancers. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between three different measures of oral health [frequency of tooth brushing; number of missing teeth; and the sum of decayed, missing, and filled teeth (DMFT)] and UGI cancers. During a median follow-up duration of 13 years, there were 794 incident UGI cancers (396 esophageal and 398 gastric cancers). Daily tooth brushing was associated with a decreased risk of developing both esophageal (HR = 0.670; 95% CI: 0.486, 0.924) and gastric (HR = 0.741; 95% CI: 0.544, 1.01) cancers (combined UGI cancer HR = 0.697; 95% CI: 0.558, 0.871) compared to never brushing. Tooth loss in excess of the loess smoothed, age- and sex-specific median number of teeth lost was significantly associated with esophageal (HR = 1.64; 95% CI: 1.08, 2.47) and gastric cancers (HR = 1.58; 95% CI: 1.05, 2.38). There were some adverse associations between DMFT and UGI cancers but most were not statistically significant. These results suggest increased risk of developing UGI cancers among individuals with poor oral health, and those who do not perform regular oral hygiene.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0577DOI Listing
March 2021

Determinants of SARS-CoV-2 infection in Italian healthcare workers: a multicenter study.

Sci Rep 2021 03 11;11(1):5788. Epub 2021 Mar 11.

Department of Biomedical and Dentistry Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.

Healthcare workers (HCWs) are at increased risk of being infected with SARS-CoV-2, yet limited information is available on risk factors of infection. We pooled data on occupational surveillance of 10,654 HCW who were tested for SARS-CoV-2 infection in six Italian centers. Information was available on demographics, job title, department of employment, source of exposure, use of personal protective equipment (PPEs), and COVID-19-related symptoms. We fitted multivariable logistic regression models to calculate odds ratios and 95% confidence intervals of infection. The prevalence of infection ranged from 3.0 to 22.0%, and was correlated with that of the respective areas. Women were at lower risk of infection compared to men. Fever, cough, dyspnea and malaise were the symptoms most strongly associated with infection, together with anosmia and ageusia. No differences in the risk of infection were detected according to job title, or working in a COVID-19 designated department. Reported contact with a patient inside or outside the workplace was a risk factor. Use of a mask was strongly protective against risk of infection as was use of gloves. The use of a mask by the source of exposure (patient or colleague) had an independent effect in reducing infection risk.
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http://dx.doi.org/10.1038/s41598-021-85215-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970984PMC
March 2021

The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens.

BMC Cancer 2021 Mar 6;21(1):227. Epub 2021 Mar 6.

Cardno ChemRisk, Boston, MA, USA.

Introduction: Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies.

Methods: We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis.

Results: Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML.

Conclusions: Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.
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http://dx.doi.org/10.1186/s12885-021-07908-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936449PMC
March 2021

Re: Dutheil et al. Prostate Cancer and Asbestos: A Systematic Review and Meta-Analysis.

Perm J 2021 Jan;25

Department of Public Health Sciences and Pediatrics, University of Turin, Turin, Italy.

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http://dx.doi.org/10.7812/TPP/20.215DOI Listing
January 2021

Methodological issues in descriptive environmental epidemiology. The example of study Sentieri.

Med Lav 2021 Feb 23;112(1):15-33. Epub 2021 Feb 23.

Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Background: Descriptive epidemiology identifies associations between environmental exposures and health effects that require results from methodologically stronger studies before causation can be considered.

Objective: To critically review the methodology and results of Sentieri, a descripitive study on residence in areas with one or more industrial source of pollution.

Methods: We systematically reviewed the literature quoted by Sentieri for the selection of health effects of nine types of pollution sources of a-priori interest. We also reviewed and meta-analyzed the results of the first report of Sentieri, that analyzed mortality in 44 polluted sites (PS), and 17 causes of deaths during 1995-2002.

Results: Among 159 study results quoted by Sentieri, 23.9 % were supportive of an association between residence near a pollution source and a health effect, 30.2 % were partially supportive, 10.7 % were not supportive, and 35.2 % were not relevant. Among 653 standardized mortality ratios for associations between PS-specific pollution sources and causes of death, 14.4% were significantly above 1.02, and 9.0% were significantly below 0.98. Among 48 meta-analysis, seven were significantly above 1.0, including five on exposure to asbestos.

Conclusions: Sentieri exemplifies the limitations of descriptive environmental epidemiology studies, in which most hypotheses have limited prior support, most results do not show associations, data on potential confounders and other sources of bias are not available. Such studies tend to replicate well-known associations and occasionally can identify critical situations requiring more investigation, but cannot be used to infer causality either in general or in specific circumstances.
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http://dx.doi.org/10.23749/mdl.v112i1.10099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023053PMC
February 2021

Dose-Response Analysis of Exposure to Arsenic in Drinking Water and Risk of Skin Lesions: A Systematic Review of the Literature.

Dose Response 2020 Oct-Dec;18(4):1559325820957823. Epub 2020 Oct 21.

New York Genome Center, NY, USA.

Background: Exposure to high arsenic concentrations in drinking water has been associated with skin lesions. Our goal was to conduct a systematic review of studies on skin lesions and arsenic exposure, with emphasis on results at low level of exposure.

Methods: We conducted a systematic review of studies reporting estimates of either prevalence or risk of skin lesions associated with exposure to more than 2 levels of arsenic in drinking water. We reviewed and abstracted the relevant results, with the aim of conducting a dose-response meta-analysis.

Results: Nine studies of skin lesions were reviewed. Strong heterogeneity in the results did not meet the criteria for performing a meta-analysis. The relative risks for an increase of 10 μg/L arsenic in drinking water ranged from 1.002 to 1.140 (p-value of heterogeneity < 0.0001). Protection from bias and confounding was inadequate in most studies.

Conclusion: Current studies are inadequate to conduct meta-analysis on dose-response relationship between exposure to arsenic in drinking water and skin lesions. Studies with complete exposure histories indicate skin lesions are associated with arsenic exposure in excess of 50 µg/L or higher.
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http://dx.doi.org/10.1177/1559325820957823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887677PMC
October 2020

European cancer mortality predictions for the year 2021 with focus on pancreatic and female lung cancer.

Ann Oncol 2021 04 21;32(4):478-487. Epub 2021 Feb 21.

Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, Milan, Italy.

Background: We predicted cancer mortality statistics for 2021 for the European Union (EU) and its five most populous countries plus the UK. We also focused on pancreatic cancer and female lung cancer.

Materials And Methods: We obtained cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2015. We predicted numbers of deaths and age-standardised (world population) rates for 2021 for total cancers and 10 major cancer sites, using a joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2021.

Results: We predicted 1 267 000 cancer deaths for 2021 in the EU, corresponding to age-standardised rates of 130.4/100 000 men (-6.6% since 2015) and 81.0/100 000 for women (-4.5%). We estimated further falls in male lung cancer rates, but still trending upward in women by +6.5%, reaching 14.5/100 000 in 2021. The breast cancer predicted rate in the EU was 13.3/100 000 (-7.8%). The rates for stomach and leukaemias in both sexes and for bladder in males are predicted to fall by >10%; trends for other cancer sites were also favourable, except for the pancreas, which showed stable patterns in both sexes, with predicted rates of 8.1/100 000 in men and 5.6/100 000 in women. Rates for pancreatic cancer in EU men aged 25-49 and 50-64 years declined, respectively, by 10% and 1.8%, while for those aged 65+ years increased by 1.3%. Rates fell for young women only (-3.4%). Over 1989-2021, about 5 million cancer deaths were avoided in the EU27 compared with peak rates in 1988.

Conclusion: Overall cancer mortality continues to fall in both sexes. However, specific focus is needed on pancreatic cancer, which shows a sizeable decline for young men only. Tobacco control remains a priority for the prevention of pancreatic and other tobacco-related cancers, which account for one-third of the total EU cancer deaths, especially in women, who showed less favourable trends.
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http://dx.doi.org/10.1016/j.annonc.2021.01.006DOI Listing
April 2021

Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study.

Eur J Prev Cardiol 2021 Mar;28(1):98-106

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran.

Aims: Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.

Methods And Results: In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.

Conclusion: Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.
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http://dx.doi.org/10.1093/eurjpc/zwaa006DOI Listing
March 2021

Occupational socioeconomic risk associations for head and neck cancer in Europe and South America: individual participant data analysis of pooled case-control studies within the INHANCE Consortium.

J Epidemiol Community Health 2021 Feb 23. Epub 2021 Feb 23.

School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.

Background: The association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures.

Methods: Pooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige-Treiman's Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position-International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs.

Results: For the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94).

Conclusions: These findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.
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http://dx.doi.org/10.1136/jech-2020-214913DOI Listing
February 2021

Dietary quality using four dietary indices and lung cancer risk: the Golestan Cohort Study (GCS).

Cancer Causes Control 2021 May 21;32(5):493-503. Epub 2021 Feb 21.

Stony Brook Cancer Center, New York, NY, USA.

Purpose: The lung cancer incidence in Iran has increased almost ten times over the past three decades. In addition to the known causes such as smoking and certain occupational exposure, dietary quality has been suggested to play a role in lung cancer. We aim to explore the association between dietary pattern and lung cancer risk among a Middle East population.

Methods: Data came from Golestan Cohort Study which included 48,421 participants with 136 lung cancer cases diagnosed during a median follow-up of 12 years. Multivariable Cox proportional hazards regression models were used to calculate the HRs and 95% CI of lung cancer risk by tertile of the four dietary index scores-the Health Eating Index (HEI)-2015, the Alternative Health Eating Index (AHEI)-2010, the Alternative Mediterranean Diet (AMED), and the Dietary Approach to Stop Hypertension (DASH)-Fung.

Results: A higher DASH-Fung score was inversely associated with risk of lung cancer after adjusting for potential confounders (tertile three vs. tertile one: HR = 0.59 (0.38-0.93); p for trend = 0.07), and p with smoking was 0.46. Similar findings were observed among current smokers with the HEI-2015 score (tertile three vs. tertile one: HR = 0.22 (0.08-0.60): p for trend < 0.01), and p between smoking and the HEI-2015 score was 0.03.

Conclusion: In the GCS, consuming a diet more closely aligned with the DASH diet was associated with a reduced risk of lung cancer, which appeared to be independent of smoking status. There was also an inverse link between the HEI-2015 score and lung cancer risk among current smokers. Our finding is particularly important for the Middle East population, as diet may play an important role in cancer prevention and overall health.
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http://dx.doi.org/10.1007/s10552-021-01400-wDOI Listing
May 2021

Caffeinated Coffee Consumption and Health Outcomes in the US Population: A Dose-Response Meta-Analysis and Estimation of Disease Cases and Deaths Avoided.

Adv Nutr 2021 Feb 11. Epub 2021 Feb 11.

Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro," Università degli Studi di Milano, Milan, Italy.

To explore the role of coffee on health outcomes in the United States, where coffee consumption is common, we conducted a meta-analysis of prospective studies investigating the magnitude (any compared with no consumption) and the dose-response shape (cups per day) of the associations between caffeinated coffee consumption and incidence/mortality of cardiovascular disease (CVD), as well as incidence of type 2 diabetes (T2D), hepatocellular carcinoma (HCC), endometrial cancer, melanoma, and nonmelanoma skin cancer. We selected the desirable health outcomes that have been shown to be positively associated with coffee consumption. Studies were identified by searching PubMed/Embase databases up to September 2019. Inclusion criteria included prospective studies that investigated the relation of ≥3 categories of caffeinated coffee consumption and the outcomes of interest. Twenty-six studies (42 distinct cohorts), with 93,706 cases/deaths and 3,713,932 participants, met the inclusion criteria. In any coffee consumers, there was a significant inverse association with the risk of CVD (RR = 0.90; 95% CI: 0.84, 0.96), T2D (RR = 0.90; 95% CI: 0.85, 0.96), endometrial cancer (RR = 0.85; 95% CI: 0.78, 0.92), melanoma (RR = 0.89; 95% CI: 0.80, 0.99), and nonmelanoma skin cancer (RR = 0.92; 95% CI: 0.89, 0.95). Coffee consumption was also inversely associated with HCC (RR = 0.93; 95% CI: 0.80, 1.08), without reaching statistical significance. The dose-response relation was nonlinear uniquely for CVD (P-nonlinearity = 0.01). In particular, the largest risk reduction was observed for 3-4 cups/d (∼120 mL/cup) and no reduction thereafter. For other outcomes, the risk decreased linearly over the whole coffee consumption range. Current patterns of consumption in the United States would account for a fraction of avoided cases/deaths ranging from 6% to 12% according to the outcome considered. This study confirms the beneficial health effects of caffeinated coffee consumption in the US population on the health outcomes considered, and quantifies their possible magnitude.
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http://dx.doi.org/10.1093/advances/nmaa177DOI Listing
February 2021

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

Int J Environ Res Public Health 2021 Feb 3;18(4). Epub 2021 Feb 3.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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 ( = 16,221), WTCHR ( = 29,372), and GRC ( = 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.
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http://dx.doi.org/10.3390/ijerph18041386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913216PMC
February 2021

Memorial in honour of Andrea Farioli.

Scand J Public Health 2021 Feb;49(1):123

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.1177/1403494821989930DOI Listing
February 2021

Trends in male breast cancer mortality: a global overview.

Eur J Cancer Prev 2021 Jan 18. Epub 2021 Jan 18.

Department of Clinical Sciences and Community Health Department of Biomedical and Clinical Sciences L. Sacco, Università degli Studi di Milano, Milan, Italy Department of Epidemiology and Health Services Research, Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.

Objectives: Recent trends in male breast cancer have been inadequately studied. We updated mortality trends in selected countries and regions worldwide using most recent available data and we predicted figures for 2020.

Methods: We extracted official death certification data for male breast cancer and population estimates from the WHO and the Pan American Health Organization databases, from 2000 to 2017. We computed age-standardized (world population) death rates for selected countries and regions worldwide. We used joinpoint regression analysis to identify significant changes in trends and to predict death numbers and rates for 2020.

Results: In 2015-2017, Central-Eastern Europe had a rate of 2.85/1 000 000, and Russia of 2.22, ranking among the highest. North-Western and Southern Europe, the European Union as a whole and the USA showed rates ranging between 1.5 and 2.0. Lower rates were observed in most Latin American countries, with values below 1.35/1 000 000, in Australia, 1.22, and Japan, 0.58. Between 2000-2004 and 2015-2017, age-adjusted death rates decreased between 10 and 40% in North-Western Europe, Russia, and the USA, and between 1.5 and 25% in the other areas under study, except Latin America (+0.8%). Except for Central-Eastern Europe, predicted rates for 2020 were favourable.

Conclusion: Advancements in management are likely the main drivers of the favourable trends in male breast cancer death rates over the last decades. Delayed diagnosis and limited access to effective care explain the higher mortality in some areas.
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http://dx.doi.org/10.1097/CEJ.0000000000000651DOI Listing
January 2021

Beta-blockers have no impact on survival in pancreatic ductal adenocarcinoma prior to cancer diagnosis.

Sci Rep 2021 Jan 13;11(1):1038. Epub 2021 Jan 13.

Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1069, New York, NY, 10029, USA.

Previous studies have suggested that β-adrenergic signaling may regulate the growth of various cancers. The aim of our study is to investigate the association between the incidental use of beta-blockers for various conditions on the overall survival of patients with pancreatic ductal adenocarcinoma (PDAC). Patients with histologically-confirmed PDAC between 2007 and 2011 were extracted from Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database. Kaplan Meier and multivariable Cox Proportional-Hazard models were used to examine the association between beta-blocker usage before diagnosis and overall survival adjusting for appropriate confounders. As an additional analysis we also examined continuous beta-blocker use before and after diagnosis. From 2007 to 2011, 13,731 patients were diagnosed with PDAC. Of these, 7130 patients had Medicare Part D coverage in the 6-month period before diagnosis, with 2564 (36%) of these patients using beta-blockers in this period. Patients receiving beta-blockers had a mean survival time of 5.1 months compared to 6 months for non-users (p < 0.01). In multivariable analysis, beta-blockers usage was not associated with improved survival (Hazard Ratio (HR) 1.04, 95%, Confidence Interval (CI) 0.98-1.1, p = 0.2). When patients were stratified by conditions with indications for beta-blocker usage, such as hypertension, coronary artery disease and cardiac arrhythmia, differences in survival were insignificant compared to non-users in all groups (p > 0.05). After stratification by receptor selectivity, this lack of association with survival persisted (p > 0.05 for all). As a subgroup analysis, looking at patients with continuous Medicare Part D coverage who used beta-blockers in the 6-month period before and after cancer diagnosis, we identified 7085 patients, of which 1750 (24.7%) had continuous beta blocker use. In multivariable analysis, continuous beta-blockers usage was associated with improved survival (Hazard Ratio (HR) 0.86, 95%, Confidence Interval (CI) 0.8-0.9, p < 0.01). Beta-blocker usage before diagnosis does not confer a survival advantage in patients with PDAC, though continuous use before and after diagnosis did confer a survival advantage. Prospective studies into the mechanism for this advantage are needed.
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http://dx.doi.org/10.1038/s41598-020-79999-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807087PMC
January 2021

Colorectal Cancer Mortality in Young Adults Is Rising in the United States, Canada, United Kingdom, and Australia but Not in Europe and Asia.

Gastroenterology 2021 Apr 6;160(5):1860-1862.e2. Epub 2021 Jan 6.

Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.12.070DOI Listing
April 2021

Exposure to emissions from Mount Etna (Sicily, Italy) and incidence of thyroid cancer: a geographic analysis.

Sci Rep 2020 12 4;10(1):21298. Epub 2020 Dec 4.

Department of Experimental Oncology, Istituto Oncologico del Mediterraneo, Viagrande, Italy.

An increased incidence of thyroid cancer has been reported in the area close to Mount Etna, the largest volcano in Europe located in Northeastern Sicily. We tested the hypothesis that exposure to the emissions from the volcano is associated with thyroid cancer in 186 municipalities from three provinces surrounding the volcano (1.9 million inhabitants). We measured the angle between the bearing of the municipalities and each direction, with special focus on South-East, the prevalent direction of the plume, and conducted a regression analysis on 2003-2016 incidence rates of thyroid cancer, adjusting for distance from Mount Etna, population size, and income. A 10-degree increase in the angle with South-East was associated with a decrease in thyroid cancer rates in the whole population (- 0.67 cases/100,000, p = 0.002) and in women (- 1.54/100,000, p < 0.001), and were robust to several sensitivity analyses. Similar results were obtained for East-South-East direction. These results support the hypothesis of a potential role of exposure to the plume from Mount Etna in determining the high rates of thyroid cancer. The results need to be confirmed in analytical studies, in which information of exposure to chemicals originating from the volcano, as well as other possible causes, should be carefully measured, molecular characteristics of the tumors and taken into account.
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http://dx.doi.org/10.1038/s41598-020-77027-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718918PMC
December 2020

Cancer mortality and predictions for 2020 in selected Australasian countries, Russia and Ukraine.

Eur J Cancer Prev 2021 Jan;30(1):1-14

Department of Clinical Sciences and Community Health.

Objectives: Predicted cancer mortality figures are useful for public health planning. We predicted cancer mortality rates in Israel, Hong Kong, Japan, the Philippines, Korea, Australia, Russia and Ukraine for the year 2020 using the most recent available data. We focused on breast cancer.

Methods: We obtained cancer death certification and population data from the WHO and the United Nations Population Division databases. We derived figures for 10 major cancer sites and total cancers over 1970-2017. We predicted numbers of deaths and age-standardized mortality rates for 2020 through joinpoint regression models. We calculated the number of avoided deaths from 1994-2020.

Results: Overall, total cancer mortality is predicted to decline. Russia had the highest all cancers rates in 2020, 151.9/100 000 men and 79.6 women; the Philippines had the lowest rate in men, 78.0/100 000, Korea in women, 47.5. Stomach cancer rates declined over the whole period in all countries considered, colorectal cancer since the late 1990s. Trends for pancreas were inconsistent. Predicted rates for lung and breast cancer were favourable; women from Hong Kong, Korea and Australia had lung cancer death rates higher than breast ones. Predicted rates for uterine, ovarian, prostate and bladder cancers and leukaemias were downward for most countries. Between 1994 and 2020, over 3.3 million cancer deaths were avoided in the considered countries, except for the Philippines where no reduction was observed.

Conclusion: Predicted cancer rates were lower than in the European Union and the USA, even though falls started later and were less marked.
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http://dx.doi.org/10.1097/CEJ.0000000000000639DOI Listing
January 2021

Systematic review and meta-analysis of recent high-quality studies on exposure to particulate matter and risk of lung cancer.

Environ Res 2020 Nov 10:110440. Epub 2020 Nov 10.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA. Electronic address:

Background: Several aspects of the association between exposure to air pollution and risk of lung cancer remain unclear.

Objective: We aimed at performing a meta-analysis of high-quality cohort studies on exposure to particulate matter (PM) 10 and PM2.5 and risk of lung cancer.

Methods: We identified cohort studies published since 2004, that reported risk estimates of lung cancer for exposure to PM2.5 and PM10 adjusted for tobacco smoking and socioeconomic status, and conducted a meta-analysis based on random-effects models, including stratification by outcome, sex, country, tobacco smoking, and age.

Results: Results on PM2.5 exposure were available from 15 studies; the summary relative risk (RR) for an increase of 10 μg/m was 1.16 (95% confidence interval [CI] 1.09, 1.23). The corresponding RR for PM10 exposure was 1.23 (95 CI 1.05, 1.40; seven studies). A higher risk was suggested in studies based on lung cancer mortality and in studies conducted in East Asia, while no difference was shown according to sex, smoking status or age. There was no suggestion of publication bias.

Conclusions: Our meta-analysis supported the hypothesis of an association between exposure to PM2.5 or PM10 and risk of lung cancer, and provided evidence that the magnitude of the risk might be higher than previously estimated, and might be modified by outcome and geographic region.
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http://dx.doi.org/10.1016/j.envres.2020.110440DOI Listing
November 2020

Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium.

Occup Environ Med 2021 Apr 28;78(4):269-278. Epub 2020 Oct 28.

International Agency for Research on Cancer, Lyon, France

Objectives: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project.

Methods: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens.

Results: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0).

Conclusions: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.
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http://dx.doi.org/10.1136/oemed-2020-106770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958079PMC
April 2021

Polyphenol Intake and Gastric Cancer Risk: Findings from the Stomach Cancer Pooling Project (StoP).

Cancers (Basel) 2020 Oct 20;12(10). Epub 2020 Oct 20.

Research Group in Gene-Environment Interactions and Health, Instituto de Biomedicina (IBIOMED), University of León, 24071 León, Spain.

Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer (GC). However, selected polyphenol classes have not been adequately investigated in relation to GC. The aim of this study is to evaluate the association between the intake of polyphenols in relation to GC risk. We used data from the Stomach cancer Pooling (StoP) Project, including 10 studies from six countries (3471 GC cases and 8344 controls). We carried out an individual participant data pooled analysis using a two-stage approach. The summary odds ratios (ORs) of GC for each compound, and the corresponding 95% confidence intervals (95% CI), were computed by pooling study specific ORs obtained through multivariate logistic regression, using random effect models. Inverse associations with GC emerged for total polyphenols (OR = 0.67, 95% CI = 0.54-0.81, for the highest versus lowest quartile of intake), total flavonoids (OR = 0.73, 95% CI = 0.55-0.90), anthocyanidins (OR = 0.74, 95% CI = 0.56-0.92), flavanols (OR = 0.77, 95% CI = 0.66-0.88), flavanones (OR = 0.57, 95%CI = 0.44-0.69), total phenolic acids (OR = 0.75, 95%CI = 0.55-0.94), and hydroxybenzoic acids (OR = 0.73, 95%CI = 0.57-0.89). Results were consistent across strata of age, sex, social class, and smoking habit. Suggestive inverse associations were also found for flavonols (OR = 0.76, 95%CI = 0.51-1.01) and hydroxycinnamic acids (OR = 0.82, 95%CI = 0.58-1.06). Further investigations from longitudinal data are needed to confirm this association.
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http://dx.doi.org/10.3390/cancers12103064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588964PMC
October 2020

Systematic review of the potential respiratory carcinogenicity of metallic nickel in humans.

Crit Rev Toxicol 2020 08;50(7):605-639

Gradient, Boston, MA, USA.

The inhalation of dust containing certain nickel compounds has been associated with an increased risk of lung and nasal cancers in occupational studies of workers who process or refine sulfidic nickel ores and are exposed to relatively high levels of mixtures of water-soluble, sulfidic, oxidic, and/or metallic forms of nickel. We conducted a systematic review of the potential carcinogenicity of metallic nickel, focusing on cancers of the respiratory tract. We evaluated the quality and risk of bias (RoB) of the relevant epidemiology, experimental animal, and in vitro mechanistic studies using the National Toxicology Program's Office of Health Assessment and Translation (OHAT) RoB Rating Tool. We then used a systematic review protocol based on the OHAT approach to critically assess whether metallic nickel should be considered a human respiratory carcinogen. Our evaluation of the epidemiology studies indicates that there is no substantive evidence of increased respiratory cancer risk in workers exposed predominantly to metallic nickel. Animal evidence indicates that metallic nickel does not increase the incidence of respiratory tumors in rodents exposed by inhalation. The in vitro studies are limited in value, as they bypass normal clearance mechanisms. Nevertheless, the mechanistic evidence indicates that metallic nickel is not mutagenic but can induce DNA strand breaks under certain conditions. Based on a standard framework for assessing causality, we conclude that the evidence does not support a causal relationship between metallic nickel exposure and respiratory cancer in humans.
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http://dx.doi.org/10.1080/10408444.2020.1803792DOI Listing
August 2020

Habitual dietary intake of flavonoids and all-cause and cause-specific mortality: Golestan cohort study.

Nutr J 2020 09 28;19(1):108. Epub 2020 Sep 28.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Flavonoids are the most important group of polyphenols with well-known beneficial effects on health. However; the association of intake of total flavonoid or their subclasses with all-cause or cause-specific mortality is not fully understood. The present study aims to evaluate the association between intake of total flavonoid, flavonoid subclasses, and total and cause-specific mortality in a developing country.

Methods: A total number of 49,173 participants from the Golestan cohort study, who completed a validated food frequency questionnaire at recruitment, were followed from 2004 till 2018. Phenol-Explorer database was applied to estimate dietary intakes of total flavonoid and different flavonoid subclasses. Associations were examined using adjusted Cox proportional hazards models.

Results: During a mean follow-up of 10.63 years, 5104 deaths were reported. After adjusting for several potential confounders, the hazard ratios (HRs) of all-cause mortality for the highest versus the lowest quintile of dietary flavanones, flavones, isoflavonoids, and dihydrochalcones were 0.81 (95% confidence interval = 0.73-0.89), 0.83(0.76-0.92), 0.88(0.80-0.96) and 0.83(0.77-0.90), respectively. However, there was no association between total flavonoid intake or other flavonoid subclasses with all-cause mortality. In cause-specific mortality analyses, flavanones and flavones intakes were inversely associated with CVD mortality [HRs: 0.86(0.73-1.00) and 0.85(0.72-1.00)] and isoflavonoids and dihydrochalcones were the only flavonoid subclasses that showed a protective association against cancer mortality [HR: 0.82(0.68-0.98)].

Conclusion: The results of our study suggest that certain subclasses of flavonoids can reduce all-cause mortality and mortality rate from CVD and cancer.
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http://dx.doi.org/10.1186/s12937-020-00627-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523365PMC
September 2020

High mobility group A protein-2 as a tumor cancer diagnostic and prognostic marker: a systematic review and meta-analysis.

Eur J Cancer Prev 2020 11;29(6):565-581

Department of Epidemiology, University of Pittsburgh Graduate School of Public Health.

High mobility group A protein-2 (HMGA2) is an architectural transcription factor that binds to the A/T-rich DNA minor groove and is responsible for regulating transcriptional activity of multiple genes indirectly through chromatin change and assembling enhanceosome. HMGA2 is overexpressed in multiple tumor types, suggesting its involvement in cancer initiation and progression, thus, making it an ideal candidate for cancer diagnostic and prognostic. We performed a systematic review to examine the role of HMGA2 as a universal tumor cancer diagnostic and prognostic marker. We used Reporting Recommendations for Tumor Marker Prognostic Studies to systematically search OvidMedline, PubMed, and the Cochrane Library for English language studies, published between 1995 and June 2019. Meta-analysis provided pooled risk estimates and their 95% confidence intervals (CIs) for an association between overall survival and recurrence of cancers for studies with available estimates. We identified 42 eligible studies with a total of 5123 tumor samples in 15 types of cancer. The pooled percentage of HMGA2 gene expression in tumor samples was 65.14%. Meta-analysis showed that cancer patients with HMGA2 positive have significantly reduced survival, compared to patients without HMGA2 gene [pooled-hazard ratio (HR) = 1.85, 95% CI 1.48-2.22]. There was a positive association between cancer patients with HMGA2 overexpression and cancer recurrence though this association did not reach significance (pooled-HR = 1.44, 95% CI 0.80-2.07). Overexpression of HMGA2 was found in 15 types of cancer. There was an association between HMGA2 overexpression with reduced survival of cancer patients. HMGA2 is thus considered a promising universal tumor marker for prognostics.
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http://dx.doi.org/10.1097/CEJ.0000000000000602DOI Listing
November 2020

Opium use and the risk of head and neck squamous cell carcinoma.

Int J Cancer 2021 Mar 9;148(5):1066-1076. Epub 2020 Oct 9.

Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.

Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case-control study-Iran Opium and Cancer study, we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx and 28 other subsites within the head and neck) and 3065 frequency-matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95% confidence intervals (95% CIs) were obtained using mixed-effects logistic regression because of heterogeneity among centers. The adjusted OR (95% CI) for regular opium use was 3.76 (2.96-4.79) for all HNSCC combined. Strong dose-response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx and other subsites within the head and neck with OR (95% CI) of 2.90 (1.40-6.02), 6.55 (4.69-9.13) and 5.95 (2.41-14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20-10.74). For the first time, the current study showed opium users have an increased risk of several anatomic subsites of HNSCC.
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http://dx.doi.org/10.1002/ijc.33289DOI Listing
March 2021