Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

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

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.

Mammographic breast density and characteristics of invasive breast cancer.

INTRODUCTION: Inconclusive data exist on the association between breast density and breast cancer characteristics. MATERIALS AND METHODS: We conducted a case-only study on 667 invasive breast cancers, using data from the Piedmont Cancer Registry. We applied a multivariate logistic regression model to estimate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of high breast density (Breast Imaging Reporting and Data System, BI-RADS 3-4) versus low (BI-RADS 1-2) in relation to histologic grade, pathological tumour size and lymph node status, histotype, estrogen and progesterone receptor, HER2 and Ki67 status. Histopathological data were assessed according to the American Joint Committee on Cancer (AJCC) Staging Manual guidelines. The model includes terms for age at diagnosis, education level, body mass index, reproductive factors, family history of breast cancer, smoking and diabetes. RESULTS: As regards histologic grade, compared to well differentiated tumours, the OR of high (versus low) breast density cases was 0.61 (95% CI 0.38-0.98) for moderately-poorly differentiated tumours. No other associations with hormonal and histopathological characteristics were observed. DISCUSSION: Our results indicate that low breast density is associated with moderately-poorly differentiated breast tumours.

European cancer mortality predictions for the year 2020 with a focus on prostate cancer.

BACKGROUND: Current cancer mortality figures are important for disease management and resource allocation. We estimated mortality counts and rates for 2020 in the European Union (EU) and for its six most populous countries. MATERIALS AND METHODS: We obtained cancer death certification and population data from the World Health Organization and Eurostat databases for 1970-2015. We estimated projections to 2020 for 10 major cancer sites plus all neoplasms and calculated the number of avoided deaths over 1989-2020. RESULTS: Total cancer mortality rates in the EU are predicted to decline reaching 130.1/100 000 men (-5.4% since 2015) and 82.2 in women (-4.1%) in 2020. The predicted number of deaths will increase by 4.7% reaching 1 428 800 in 2020. In women, the upward lung cancer trend is predicted to continue with a rate in 2020 of 15.1/100 000 (higher than that for breast cancer, 13.5) while in men we predicted further falls. Pancreatic cancer rates are also increasing in women (+1.2%) but decreasing in men (-1.9%). In the EU, the prostate cancer predicted rate is 10.0/100 000, declining by 7.1% since 2015; decreases for this neoplasm are ∼8% at age 45-64, 14% at 65-74 and 75-84, and 6% at 85 and over. Poland is the only country with an increasing prostate cancer trend (+18%). Mortality rates for other cancers are predicted to decline further. Over 1989-2020, we estimated over 5 million avoided total cancer deaths and over 400 000 for prostate cancer. CONCLUSION: Cancer mortality predictions for 2020 in the EU are favourable with a greater decline in men. The number of deaths continue to rise due to population ageing. Due to the persistent amount of predicted lung (and other tobacco-related) cancer deaths, tobacco control remains a public health priority, especially for women. Favourable trends for prostate cancer are largely attributable to continuing therapeutic improvements along with early diagnosis.

Cancer mortality in Europe in 2015 and an overview of trends since 1990.

BACKGROUND: Cancer mortality in Europe has been decreasing since the late 1980s or 1990s in some countries with different patterns in many areas. In this study, we updated trends in cancer mortality in Europe. MATERIALS AND METHODS: We extracted data from the World Health Organization mortality database for 24 cancer sites, 36 European countries and the European Union (EU) as a whole over the 1990-2017 period. We computed age-standardized death rates per 100 000 person-years, and we carried out a joinpoint regression analysis of mortality trends from all cancers and selected major neoplasms. The estimated annual percent change (APC) for each identified linear segment, and the weighted average APC (AAPC) over the entire study period were provided as summary measures of the changes in rates over the time period. RESULTS: In 2015, the age-standardized mortality rates from all cancers in the EU were 137.5 deaths per 100 000 in men and 85.7 in women. Eastern European countries showed the highest rates with values over 150 deaths per 100 000 in men and over 100 deaths per 100 000 in women. Mortality from all cancers in the EU declined annually by 1.5% in men since 2006 and by 0.8% in women since 2007. Most cancer sites showed decreasing trends, with steady declines over the whole period for cancers of stomach, intestines, lung in men, breast and prostate. Unfavourable mortality trends persisted for cancers of liver, lung in women, pancreas, besides skin and kidney in men. CONCLUSIONS: The downward trends in total cancer mortality in Europe still continue over the last decade. However, the trends were less favourable in most eastern European countries. Tobacco control in men (but not in women), improvements in diagnosis and therapy were the main underlying factors of these trends.

Cancer mortality in the elderly in 11 countries worldwide, 1970-2015.

BACKGROUND: Population ageing results in an increasing cancer burden in the elderly. We aimed to evaluate time-trends in cancer mortality for adults aged 65 and over for 17 major cancer types and all cancers combined in 11 countries worldwide over the period 1970-2015. MATERIALS AND METHODS: We obtained cancer death certification and population figures from the WHO and PAHO databases. We computed age-standardised (world standard population) rates for individuals aged 65 and over, and applied joinpoint regression models. RESULTS: Age-standardised mortality rates for all cancers combined showed a heterogeneous, but widespread decline. Lung cancer mortality rates have been decreasing among men, and increasing among women. Pancreatic cancer had unfavourable trends in all countries for both sexes. Despite variability across countries, other tobacco-related cancers (except kidney) showed overall favourable trends, except in Poland and Russia. Age-standardised mortality rates from stomach cancer have been declining in all countries for both sexes. Colorectal mortality has been declining, except in Poland and Russia. Liver cancer mortality increased in all countries, except in Japan, France and Italy, which had the highest rates in the past. Breast cancer mortality decreased for most countries, except for Japan, Poland and Russia. Trends for age-standardised uterine cancer rates in the USA, Canada and the UK were increasing over the last decade. Ovarian cancer rates showed declines in most countries. With the exception of Russia, prostate cancer rates showed overall declines. Lymphoid neoplasms rates have been declining in both sexes, except in Poland and Russia. CONCLUSION: Over the last decades, age-standardised cancer mortality in the elderly has been decreasing in major countries worldwide and for major cancer sites, with the major exception of lung and uterine cancer in women and liver, pancreatic and kidney cancers in both sexes. Cancer mortality for the elderly in central and eastern Europe remains comparatively high.

European cancer mortality predictions for the year 2019 with focus on breast cancer.

BACKGROUND: To overcome the lag with which cancer statistics become available, we predicted numbers of deaths and rates from all cancers and selected cancer sites for 2019 in the European Union (EU). MATERIALS AND METHODS: We retrieved cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2014. We obtained estimates for 2019 with a linear regression on number of deaths over the most recent trend period identified by a logarithmic Poisson joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2019. RESULTS: We estimated about 1 410 000 cancer deaths in the EU for 2019, corresponding to age-standardized rates of 130.9/100 000 men (-5.9% since 2014) and 82.9 women (-3.6%). Lung cancer trends in women are predicted to increase 4.4% between 2014 and 2019, reaching a rate of 14.8. The projected rate for breast cancer was 13.4. Favourable trends for major neoplasms are predicted to continue, except for pancreatic cancer. Trends in breast cancer mortality were favourable in all six countries considered, except Poland. The falls were largest in women 50-69 (-16.4%), i.e. the age group covered by screening, but also seen at age 20-49 (-13.8%), while more modest at age 70-79 (-6.1%). As compared to the peak rate in 1988, over 5 million cancer deaths have been avoided in the EU over the 1989-2019 period. Of these, 440 000 were breast cancer deaths. CONCLUSION: Between 2014 and 2019, cancer mortality will continue to fall in both sexes. Breast cancer rates will fall steadily, with about 35% decline in rates over the last three decades. This is likely due to reduced hormone replacement therapy use, improvements in screening, early diagnosis and treatment. Due to population ageing, however, the number of breast cancer deaths is not declining.

Cancer mortality and predictions for 2018 in selected Australasian countries and Russia.

Background: Predicted cancer mortality figures and rates are useful for public health planning. Materials and methods: We retrieved cancer death certification data for 10 major cancer sites and total cancers from the World Health Organization (WHO) database and population data from WHO and United Nations Population Division databases. We obtained figures for Russia, Israel, Hong Kong, Japan, the Philippines, Korea, and Australia in 1970-2015. We predicted numbers of deaths by age group and age-standardized rates (world population) for 2018 by applying a linear regression to mortality data of each age group over the most recent trend segment identified by a joinpoint regression model. Results: Russia had the highest predicted total cancer mortality rates, 158.5/100 000 men and 84.1/100 000 women. Men in the Philippines showed the lowest rates for 2018 (84.6/100 000) and Korean males the most favourable predicted fall (21% between 2012 and 2018). Women in Korea had the lowest total cancer predicted rate (52.5/100 000). Between 1993 and 2018, i.e. by applying the 1993 rates to populations in subsequent years, a substantial number of cancer deaths was avoided in Russia (1 000 000 deaths, 821 000 in men and 179 000 in women), Israel (40 000 deaths, 21 000 in men and 19 000 in women), Hong Kong (63 000 deaths, 40 000 in men and 23 000 in women), Japan (651 000 deaths, 473 000 in men and 178 000 in women), Korea (327 000 deaths, 250 000 in men and 77 000 in women), and Australia (181 000 deaths, 125 000 in men and 56 000 in women). No appreciable reduction in cancer deaths was found in the Philippines. Conclusion: Overall, we predicted falls in cancer mortality. However, these are less marked and later compared with the European Union and United States. Substantial numbers of deaths were avoided in all countries considered except the Philippines. Lung cancer mortality remains exceedingly high in Russian men, despite recent falls.

Relation between mortality trends of cardiovascular diseases and selected cancers in the European Union, in 1970-2017. Focus on cohort and period effects.

AIM: To characterise mortality trends from major non-communicable diseases in the European Union (EU) analysing data from the World Health Organization (WHO) Mortality Database. METHODS: We obtained EU population and death certification data for major non-communicable diseases, i.e. seven cancer sites (stomach, intestine, pancreas, lung, breast, prostate and haematopoietic), total cancers, coronary heart diseases (CHDs) and cerebrovascular diseases (CVDs) from the WHO Mortality Database over the 1970 and 2012 period. We computed age-standardised rates (world standard population) and applied joinpoint regression models to identify temporal trends and age period cohort (APC) models to disentangle the effects of age, period of death and cohort of birth on mortality. RESULTS: In 2012, 2.4 million deaths were recorded in the EU (1.3 million from cancers and 1.1 million from CHD and CVD combined). Over the last decade, mortality from cancer fell by 14% in men and 8% in women, resulting in age-standardised rates of 144 and 88/100,000 persons, respectively, in 2012. The only exceptions to the general downward trends were pancreatic cancer and female lung cancer. Both cardiovascular diseases mortality fell over 35% in both sexes with rates of 60 and 28/100,000 for CHD, and of 30 and 23/100,000 for CVD, in men and women, respectively, in 2012. CONCLUSIONS: Overall trends in mortality rates from non-communicable diseases in the EU were favourable, and the joinpoint and APC models indicated these trends are likely to continue in the near future. Lack of progress in tobacco-related mortality in women underlines the importance of female-specific anti-tobacco policies.

European cancer mortality predictions for the year 2018 with focus on colorectal cancer.

Background: We projected cancer mortality statistics for 2018 for the European Union (EU) and its six more populous countries, using the most recent available data. We focused on colorectal cancer. Materials and methods: We obtained cancer death certification data from stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers from the World Health Organisation database and projected population data from Eurostat. We derived figures for France, Germany, Italy, Poland, Spain, the UK, and the EU in 1970-2012. We predicted death numbers by age group and age-standardized (world population) rates for 2018 through joinpoint regression models. Results: EU total cancer mortality rates are predicted to decline by 10.3% in men between 2012 and 2018, reaching a predicted rate of 128.9/100 000, and by 5.0% in women with a rate of 83.6. The predicted total number of cancer deaths is 1 382 000 when compared with 1 333 362 in 2012 (+3.6%). We confirmed a further fall in male lung cancer, but an unfavourable trend in females, with a rate of 14.7/100 000 for 2018 (13.9 in 2012, +5.8%) and 94 500 expected deaths, higher than the rate of 13.7 and 92 700 deaths from breast cancer. Colorectal cancer predicted rates are 15.8/100 000 men (-6.7%) and 9.2 in women (-7.5%); declines are expected in all age groups. Pancreatic cancer is stable in men, but in women it rose +2.8% since 2012. Ovarian, uterine and bladder cancer rates are predicted to decline further. In 2018 alone, about 392 300 cancer deaths were avoided compared with peak rates in the late 1980s. Conclusion: We predicted continuing falls in mortality rates from major cancer sites in the EU and its major countries to 2018. Exceptions are pancreatic cancer and lung cancer in women. Improved treatment and-above age 50 years-organized screening may account for recent favourable colorectal cancer trends.

Cancer mortality predictions for 2017 in Latin America.

BACKGROUND: From most recent available data, we predicted cancer mortality statistics in selected Latin American countries for the year 2017, with focus on lung cancer. MATERIALS AND METHODS: We obtained death certification data from the World Health Organization and population data from the Pan American Health Organization database for all neoplasms and selected cancer sites. We derived figures for Argentina, Brazil, Chile, Colombia, Cuba, Mexico and Venezuela. Using a logarithmic Poisson count data joinpoint model, we estimated number of deaths and age-standardized (world population) mortality rates in 2017. RESULTS: Total cancer mortality rates are predicted to decline in all countries. The highest mortality rates for 2017 are in Cuba, i.e. 132.3/100 000 men and 93.3/100 000 women. Mexico had the lowest predicted rates, 64.7/100 000 men and 60.6/100 000 women. In contrast, the total number of cancer deaths is expected to rise due to population ageing and growth. Men showed declines in lung cancer trends in all countries and age groups considered, while only Colombian and Mexican women had downward trends. Stomach and (cervix) uteri rates are predicted to continue their declines, though mortality from these neoplasms remains comparatively high. Colorectal, breast and prostate cancer rates were predicted to decline moderately, as well as leukaemias. There was no clear pattern for pancreatic cancer. Between 1990 and 2017 about 420 000 cancer deaths were avoided in 5 of the 7 countries, no progress was observed in Brazil and Cuba. CONCLUSION: Cancer mortality rates for 2017 in seven selected Latin American countries are predicted to decline, though there was appreciable variability across countries. Mortality from major cancers-including lung and prostate-and all cancers remains comparatively high in Cuba, indicating the need for improved prevention and management.

European cancer mortality predictions for the year 2017, with focus on lung cancer.

BACKGROUND: We predicted cancer mortality figures in the European Union (EU) for the year 2017 using most recent available data, with a focus on lung cancer. MATERIALS AND METHODS: We retrieved cancer death certification data and population figures from the World Health Organisation and Eurostat databases. Age-standardized (world standard population) rates were computed for France, Germany, Italy, Poland, Spain, the UK and the EU overall in 1970-2012. We obtained estimates for 2017 by implementing a joinpoint regression model. RESULTS: The predicted number of cancer deaths for 2017 in the EU is 1 373 500, compared with 1 333 400 in 2012 (+3%). Cancer mortality rates are predicted to decline in both sexes, reaching 131.8/100 000 men (-8.2% when compared with 2012) and 84.5/100 000 women (-3.6%). Mortality rates for all selected cancer sites are predicted to decline, except pancreatic cancer in both sexes and lung cancer in women. In men, pancreatic cancer rate is stable, in women it increases by 3.5%. Lung cancer mortality rate in women is predicted to rise to 14.6/100 000 in 2017 (+5.1% since 2012, corresponding to 92 300 predicted deaths), compared with 14.0/100 000 for breast cancer, corresponding to 92 600 predicted deaths. Only younger (25-44) women have favourable lung cancer trends, and rates at this age group are predicted to be similar in women (1.4/100 000) and men (1.2/100 000). In men lung cancer rates are predicted to decline by 10.7% since 2012, and falls are observed in all age groups. CONCLUSION: European cancer mortality projections for 2017 confirm the overall downward trend in rates, with a stronger pattern in men. This is mainly due to different smoking prevalence trends in different generations of men and women. Lung cancer rates in young European women are comparable to those in men, confirming that smoking has the same impact on lung cancer in the two sexes.

Global trends and predictions in ovarian cancer mortality.

BACKGROUND: Over the last two decades, ovarian cancer mortality rates have levelled or declined. There are, however, persisting and substantial differences in ovarian cancer patterns and trends. PATIENTS AND METHODS: We updated global trends in ovarian cancer mortality to 2012, and predicted trends in rates to 2020 using data from the World Health Organization database. RESULTS: In the EU, age-adjusted ovarian cancer mortality rates decreased 10% between 2002 and 2012, to 5.2/100 000. The decline was ∼16% in the USA, to 4.9/100 000 in 2012. Latin American countries had lower rates, and declines were observed in Argentina and Chile. Likewise, modest declines (-2.1%) were observed in Japan, whose rate remained low (3.2/100 000 in 2012). Australia had a rate of 4.3/100 000 in 2012, and a 12% decline. The falls were larger in young women, than in middle or old age. Recent rates at age 20-49 were higher in Japan than in the EU and the USA. Predictions to 2020 indicate a further 15% decline in the USA and 10% in the EU and Japan. CONCLUSIONS: The main reason for the favourable trends is the use of oral contraceptives (OCs), particularly, in the USA and countries of the EU where OCs were introduced earlier. Declines in menopausal hormone use may also have played a favourable role in elderly women, as well as improved diagnosis, management and treatment.

European cancer mortality predictions for the year 2016 with focus on leukaemias.

BACKGROUND: Current cancer mortality statistics are important for public health decision-making and resource allocation. Age-standardized rates and numbers of deaths are predicted for 2016 in the European Union (EU). PATIENTS AND METHODS: Population and death certification data for stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukaemias and total cancers were obtained from the World Health Organization database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected numbers of deaths by age group were obtained for 2016 by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: Projected total cancer mortality trends for 2016 in the EU are favourable in both sexes with rates of 133.5/100 000 men and 85.2/100 000 women (8% and 3% falls since 2011) corresponding to 753 600 and 605 900 deaths in men and women for a total number of 1 359 500 projected cancer deaths (+3% compared with 2011, due to population ageing). In men, lung, colorectal and prostate cancer have fallen 11%, 5% and 8%, respectively, since 2011. Breast and colorectal cancer trends in women are favourable (8% and 7% falls, respectively), but lung and pancreatic cancer rates have risen 5% and 4% since 2011 reaching rates of 14.4 and 5.6/100 000 women. Leukaemias show favourable projected mortality for both sexes and all age groups, with stronger falls in the younger age groups. All ages rates are 4.0/100 000 men and 2.5/100 000 women, with falls of 14% and 12% respectively. CONCLUSION: The 2016 predictions for EU cancer mortality confirm the favourable trends in rates particularly for men. Lung cancer is likely to be the leading site for female cancer rates. Continuing falls in mortality, larger in children and young adults, are predicted in leukaemias, essentially due to advancements in management and therapy, and their subsequent adoption across Europe.

Risk factors for neuroendocrine neoplasms: a systematic review and meta-analysis.

BACKGROUND: Neuroendocrine neoplasms (NENs) are rare cancers mainly of lung and digestive tract. Little is known on risk factors. The aim of this work is to define the risk factors for NEN development by extensive review and meta-analysis of published data. METHODS: The search was conducted on Medline, Scopus, and Web of Science following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Newcastle-Ottawa scale was used for study quality. Meta-analyses were conducted by primary site. Odds ratio (OR), hazard ratio, risk ratio, standardized incidence ratio, and associated 95% confidence intervals (CIs) were abstracted. Data were combined and analyses carried out for risk factors considered by at least two studies. Random-effects model was adopted for study variation. RESULTS: Of 1535 extracted articles, 24 were enrolled. Meta-analyses were possible for pancreas, small intestine, and rectum. Risk for NEN associated with: (i) family history of cancer at all investigated sites (lung, stomach, pancreas, small intestine, appendix, and colon; OR 2.12 [95% CI 1.40-3.22, I(2) = 0.0%, P = 0.681] at meta-analysis in pancreas); (ii) body mass index (BMI) or diabetes (stomach, pancreas, and small intestine; OR of 2.76 [95% CI 1.65-4.64, I(2) = 58.5%, P = 0.090] for diabetes at meta-analysis in pancreas); (iii) cigarette smoking (lung, stomach, pancreas, and small intestine; OR of 1.34 [95% CI 1.10-1.63, I(2) = 0.0%, P = 0.780] and of 1.59 [95% CI 1.07-2.37, I(2) = 32.9%, P = 0.225] for smokers versus never-smokers at meta-analysis for pancreas and small intestine); (iv) alcohol consumption (pancreas and rectum; OR of 2.44 [95% CI 1.07-5.59, I(2) = 65.8%, P = 0.054] and of 1.53 [95% CI 0.99-2.35, I(2) = 0.0%, P = 0.630] for heavy drinkers versus never-drinkers at meta-analysis for pancreas and rectum). CONCLUSIONS: Family history of cancer is the most relevant risk factor for NEN development at all investigated sites, followed by BMI and diabetes. Cigarette smoking and alcohol consumption are potential risk factors for selected anatomical sites.