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Objectives HPV16-positive oropharyngeal cancer (OPC) patients experience better outcomes compared to HPV16-negative patients. Currently, strategies for treatment de-escalation are based on HPV status, smoking history and disease stage. However, the appropriate cut-point for smoking and the role of other non-clinical factors in OPC survival remains uncertain. Materials and Methods We examined factors associated with OPC outcome in 321 patients recruited in a large European multi-center study. Seropositivity for HPV16 E6 was used as a marker of HPV16 positive cancer. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox proportional models adjusted for potential confounders. Results Overall 5-year survival following OPC diagnosis was 50%. HPV16-positive OPC cases were at significantly lower risk of death (aHR = 0.51, 95% CI: 0.32–0.80). A significant effect on OPC survival was apparent for female sex (aHR 0.50: 95% CI: 0.29–0.85) and being underweight at diagnosis (aHR: 2.41, 95% CI: 1.38–4.21). A 10 pack year smoking history was not associated with overall survival. Higher stage at diagnosis appeared as the only factor significantly associated with OPC recurrence (aHR: 4.88, 95% CI: 2.12–11.21). Conclusion This study confirms that HPV16 status is an independent prognostic factor for OPC survival while female sex lowers risk of death and being underweight at diagnosis increases the risk of death. Smoking was not an independent predictor of OPC survival.

Background Cancer notification has been mandatory in Ukraine since 1953, with the National Cancer Registry of Ukraine (NCRU) established in 1996. The aim of this study was to provide a comprehensive evaluation of the data quality at the NCRU. Methods Qualitative and semi-quantitative methods were used to assess the comparability, completeness, validity and timeliness of cancer incidence data from the NCRU for the period 2002–2012. Results Cancer registration procedures at the NCRU are in accordance with international standards and recommendations. Semi-quantitative methods suggested the NCRU’s data was reasonably complete, although decreases in age-specific incidence and mortality rates in the elderly indicated some missing cases at older ages. The proportion of microscopically-verified cases increased from 73.6% in 2002 to 82.3% in 2012, with death-certificate-only (DCO) proportions stable at around 0.1% and unknown stage recorded in 9.6% of male and 7.5% of female solid tumours. Timeliness was considered acceptable, with reporting >99% complete within a turn-around time of 15 months. Conclusion While timely reporting of national data reflects the advantages of a mandatory data collection system, a low DCO% and observed age-specific declines suggest possible underreporting of incidence and mortality data, particularly at older ages. Overall, the evaluation indicates that the data are reasonably comparable and thus may be used to describe the magnitude of the cancer burden in Ukraine. Given its central role in monitoring and evaluation of cancer control activities, ensuring the sustainability of NCRU operations throughout the process of healthcare system reform is of utmost importance.

The aim of this study was to analyse trends of malignant melanoma incidence in Croatia for men and women of different age groups by birth cohorts and time periods, and to interpret them in the context of national socioeconomic changes over time and the possible implications for future prevention in South-Eastern European postcommunist countries with high mortality rates. We used the Croatian National Cancer Registry data to analyse incidence trends of malignant melanoma of the skin (ICD-9 code 172 and ICD-10 code C43) in men and women aged 25-79 years by age-period-cohort modelling. Over the 25-year period, the incidence was increasing by 5.0% annually in men and 4.6% in women. The age-period model provided the best fit for data in both sexes, with steeply increasing incidence rates, followed by a stabilization after the 2000s. On the cohort scale, incidence rates increased in successive generations of men, whereas in women, the risk of malignant melanoma attenuated in recent cohorts. Even if some progress has been achieved in recent years, the increasing melanoma incidence without concomitant declines in mortality would indicate a need to rekindle prevention efforts in the country taking the specific socioeconomic context into account.

The increasing rates of kidney cancer incidence, reported in many populations globally, have been attributed both to increasing exposures to environmental risk factors, as well as increasing levels of incidental diagnosis due to widespread use of imaging. To better understand these trends, we examine long-term cancer registry data worldwide, focusing on the roles of birth cohort and calendar period, proxies for changes in risk factor prevalence and detection practice respectively. We used an augmented version of the Cancer Incidence in Five Continents series to analyze kidney cancer incidence rates 1978-2007 in 16 geographically representative populations worldwide by sex for ages 30-74, using age-period-cohort (APC) analysis. The full APC model provided the best fit to the data in most studied populations. While kidney cancer incidence rates have been increasing in successive generations born from the early twentieth century in most countries, equivalent period-specific rises were observed from the late-1970s, although these have subsequently stabilized in certain European countries (the Czech Republic, Lithuania, Finland, Spain) as well as Japan from the mid-1990s, and from the mid-2000s, in Colombia, Costa Rica and Australia. Our results indicate that the effects of both birth cohort and calendar period contribute to the international kidney cancer incidence trends. While cohort-specific increases may partly reflect the rising trends in obesity prevalence and the need for more effective primary prevention policies, the attenuations in period-specific increases (observed in 8 of the 16 populations) highlight a possible change in imaging practices that could lead to mitigation of overdiagnosis and overtreatment.

Aim To determine if preoperative treatment with a topical non-steroidal anti-inflammatory drug (NSAID) lowers the concentration of intraocular interleukin (IL)-12 and the incidence of postoperative macular edema in patients with non-proliferative diabetic retinopathy undergoing cataract surgery. Methods A total of 55 patients were randomized to diclofenac (n = 27) or placebo (n = 28). Patients receiving diclofenac started preoperative treatment with 0.1% topical diclofenac four times a day 7 days before cataract surgery and the therapy was discontinued 30 days after surgery. Patients in the control group were administered placebo 7 days preoperatively and a standard postoperative therapy with 0.1% topical dexamethasone four times a day for 30 days after surgery. All patients received postoperative antibiotic prophylaxis with tobramycin eye drops four times daily for 30 days. Seven days before the cataract surgery, on the day of surgery, and 1, 7, 30, and 90 days after surgery, central foveal thickness (CFT) was measured with optical coherence tomography (OCT) and the aqueous humor was sampled at the beginning of cataract surgery for the analysis of IL-12 concentration. Due to loss to follow-up and insufficient aqueous humor samples, the data of 3 patients treated with diclofenac and 8 patients receiving placebo were not analyzed. Results The aqueous humor IL-12 concentration was significantly lower in the diclofenac group than in the placebo group (t=−2.85, P = 0.007). The diclofenac group had a significantly smaller increase in CFT after phacoemulsification (F = 13.57, p

Rapid increases in testicular cancer incidence have marked the second half of the last century. While these secular rises, observed mainly in countries attaining the highest levels of human development, appear to have attenuated in the last decade, rates continue to increase in countries transiting toward high developmental levels. The purpose of our study was to provide a comprehensive analysis and presentation of the cohort-specific trends in testicular cancer incidence rates in 38 countries worldwide.We used an augmented version of the Cancer Incidence in Five Continents series to analyze testicular cancer incidence in men aged 15-54 in 38 countries, via age-period-cohort analysis.In many European countries, the USA, Canada, Australia, and New Zealand, there is a continuation of the increasing risk among successive generations, yet rates are attenuating in male cohorts born since the 1970s in several Northern European countries, in contrast to the steeply increasing trends in recent cohorts in Southern Europe. Incidence rates have also been increasing in the populations traditionally at rather low risk, such as in the Philippines, Singapore, China, and Costa Rica.The attenuation of testicular cancer risk in younger generations (in the most developed countries) alongside concomitant increases (in countries undergoing developmental change) is indicative of a global transition in the risk of testicular cancer. While identifying the underlying causes remains a major challenge, increasing awareness and adapting national healthcare systems to accommodate a growing burden of testicular cancer may prevent future avoidable deaths in young men.

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 – 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 – 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

Context Testicular cancer (TC) is the most common cancer in men aged 15–44 yr in many countries that score high or very high on the Human Development Index (HDI). Despite the very good prognosis for TC, wide variations in mortality rates have been reported internationally. Objective To describe and contrast global variations and recent trends in TC incidence and mortality rates. Evidence acquisition To compare TC incidence and mortality rates, we used GLOBOCAN 2008 estimates. We used the Cancer Incidence in Five Continents series to analyse recent trends in TC incidence in 41 countries by way of joinpoint analysis. To examine recent trends in mortality, we used the World Health Organisation mortality database. Evidence synthesis Northern Europe remains the highest TC incidence area, with the highest rates observed in Norway and Denmark. Incidence rates continue to increase in most countries worldwide, more markedly in Southern Europe and Latin America, while attenuating in Northern Europe, the United States, and Australia. Mortality from TC shows a different pattern, with higher rates in some countries of medium to high HDI. The highest mortality rates were seen in Chile and Latvia, as well as in selected Central European and Eastern European countries. In high-income countries, TC mortality rates are declining or stable at very low levels of magnitude, while no significant decreases were observed in middle-income regions in Latin America and Asia. Conclusions The rises in TC incidence appear to be recently attenuating in countries with the highest HDIs, with corresponding mortality rates either continuing to decline or stabilising at very low levels. In a number of countries transiting towards higher levels of development, the TC incidence is increasing while mortality rates are stable or increasing. Patient summary In this study we looked at international testicular cancer trends. We found that testicular cancer is becoming more common in low- and middle-income countries, where the optimal treatment might not yet be available.

BACKGROUND: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.METHODS: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.RESULTS: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.CONCLUSIONS: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.

Toporcov, Tatiana Natasha Znaor, Ariana Zhang, Zuo-Feng Yu, Guo-Pei Winn, Deborah M Wei, Qingyi Vilensky, Marta Vaughan, Thomas Thomson, Peter Talamini, Renato Szeszenia-Dabrowska, Neonila Sturgis, Erich M Smith, Elaine Shangina, Oxana Schwartz, Stephen M Schantz, Stimson Rudnai, Peter Richiardi, Lorenzo Ramroth, Heribert Purdue, Mark P Olshan, Andrew F Eluf-Neto, Jose Muscat, Joshua Moyses, Raquel Ajub Morgenstern, Hal Menezes, Ana McClean, Michael Matsuo, Keitaro Mates, Dana Macfarlane, Tatiana V Lissowska, Jolanta Levi, Fabio Lazarus, Philip La Vecchia, Carlo Lagiou, Pagona Koifman, Sergio Kjaerheim, Kristina Kelsey, Karl Holcatova, Ivana Herrero, Rolando Healy, Claire Hayes, Richard B Franceschi, Silvia Fernandez, Leticia Fabianova, Eleonora Daudt, Alexander W Curioni, Otavio Alberto Maso, Luigino Dal Curado, Maria Paula Conway, David I Chen, Chu Castellsague, Xavier Canova, Cristina Cadoni, Gabriella Brennan, Paul Boccia, Stefania Antunes, Jose Leopoldo Ferreira Ahrens, Wolfgang Agudo, Antonio Boffetta, Paolo Hashibe, Mia Lee, Yuan-Chin Amy Filho, Victor Wunsch eng FIRCA TW01500/TW/FIC NIH HHS/ K07CA104231/CA/NCI NIH HHS/ P01CA068384/CA/NCI NIH HHS/ P30ES010126/ES/NIEHS NIH HHS/ P50CA90388/CA/NCI NIH HHS/ R01CA048996/CA/NCI NIH HHS/ R01CA100264/CA/NCI NIH HHS/ R01CA30022/CA/NCI NIH HHS/ R01CA51845/CA/NCI NIH HHS/ R01CA61188/CA/NCI NIH HHS/ R01DA11386/DA/NIDA NIH HHS/ R01DE012609/DE/NIDCR NIH HHS/ R01DE11979/DE/NIDCR NIH HHS/ R01DE13110/DE/NIDCR NIH HHS/ R01DE13158/DE/NIDCR NIH HHS/ R01ES11740/ES/NIEHS NIH HHS/ R03CA113157/CA/NCI NIH HHS/ R03CA77954/CA/NCI NIH HHS/ R03DE016611/DE/NIDCR NIH HHS/ R21ES011667/ES/NIEHS NIH HHS/ T32CA09142/CA/NCI NIH HHS/ U01CA96134/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2015/01/24 06:00 Int J Epidemiol. 2015 Feb;44(1):169-85. doi: 10.1093/ije/dyu255. Epub 2015 Jan 22.; International audience; BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults 45 years old ('older adults', 17700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI=9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking=5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR=2.27 (95% CI=1.26, 4.10)], but not in the older adults [OR=1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.

Conway, David I Brenner, Darren R McMahon, Alex D Macpherson, Lorna M D Agudo, Antonio Ahrens, Wolfgang Bosetti, Cristina Brenner, Hermann Castellsague, Xavier Chen, Chu Curado, Maria Paula Curioni, Otavio A Dal Maso, Luigino Daudt, Alexander W de Gois Filho, Jose F D'Souza, Gypsyamber Edefonti, Valeria Fabianova, Eleonora Fernandez, Leticia Franceschi, Silvia Gillison, Maura Hayes, Richard B Healy, Claire M Herrero, Rolando Holcatova, Ivana Jayaprakash, Vijayvel Kelsey, Karl Kjaerheim, Kristina Koifman, Sergio La Vecchia, Carlo Lagiou, Pagona Lazarus, Philip Levi, Fabio Lissowska, Jolanta Luce, Daniele Macfarlane, Tatiana V Mates, Dana Matos, Elena McClean, Michael Menezes, Ana M Menvielle, Gwenn Merletti, Franco Morgenstern, Hal Moysich, Kirsten Muller, Heiko Muscat, Joshua Olshan, Andrew F Purdue, Mark P Ramroth, Heribert Richiardi, Lorenzo Rudnai, Peter Schantz, Stimson Schwartz, Stephen M Shangina, Oxana Simonato, Lorenzo Smith, Elaine Stucker, Isabelle Sturgis, Erich M Szeszenia-Dabrowska, Neonila Talamini, Renato Thomson, Peter Vaughan, Thomas L Wei, Qingyi Winn, Deborah M Wunsch-Filho, Victor Yu, Guo-Pei Zhang, Zuo-Feng Zheng, Tongzhang Znaor, Ariana Boffetta, Paolo Chuang, Shu-Chun Ghodrat, Marianoosh Amy Lee, Yuan-Chin Hashibe, Mia Brennan, Paul eng DE016631/DE/NIDCR NIH HHS/ K07CA104231/CA/NCI NIH HHS/ NIDCR R01DE11979/DE/NIDCR NIH HHS/ NIDCRR01DE13110/DE/NIDCR NIH HHS/ NIH FIRCA TW01500/TW/FIC NIH HHS/ P01CA068384/CA/NCI NIH HHS/ P30ES010126/ES/NIEHS NIH HHS/ P50CA090388/CA/NCI NIH HHS/ R01 CA078609/CA/NCI NIH HHS/ R01 CA100679/CA/NCI NIH HHS/ R01CA030022/CA/NCI NIH HHS/ R01CA048996/CA/NCI NIH HHS/ R01CA051845/CA/NCI NIH HHS/ R01CA061188/CA/NCI NIH HHS/ R01CA078609/CA/NCI NIH HHS/ R01CA100264/CA/NCI NIH HHS/ R01CA100679/CA/NCI NIH HHS/ R01CA90731/CA/NCI NIH HHS/ R01DA011386/DA/NIDA NIH HHS/ R01DA026815/DA/NIDA NIH HHS/ R01DE012609/DE/NIDCR NIH HHS/ R01DE013158/DE/NIDCR NIH HHS/ R01ES011740/ES/NIEHS NIH HHS/ R03CA077954/CA/NCI NIH HHS/ R03CA113157/CA/NCI NIH HHS/ R03DE016611/DE/NIDCR NIH HHS/ R21ES011667/ES/NIEHS NIH HHS/ T32CA009142/CA/NCI NIH HHS/ U01CA096134/CA/NCI NIH HHS/ Intramural NIH HHS/ Comparative Study Multicenter Study Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2014/07/06 06:00 Int J Cancer. 2015 Mar 1;136(5):1125-39. doi: 10.1002/ijc.29063. Epub 2014 Aug 23.; International audience; Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

Delahaye-Sourdeix, Manon Anantharaman, Devasena Timofeeva, Maria N Gaborieau, Valerie Chabrier, Amelie Vallee, Maxime P Lagiou, Pagona Holcatova, Ivana Richiardi, Lorenzo Kjaerheim, Kristina Agudo, Antonio Castellsague, Xavier Macfarlane, Tatiana V Barzan, Luigi Canova, Cristina Thakker, Nalin S Conway, David I Znaor, Ariana Healy, Claire M Ahrens, Wolfgang Zaridze, David Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Fabianova, Eleonora Mates, Ioan Nicolae Bencko, Vladimir Foretova, Lenka Janout, Vladimir Curado, Maria Paula Koifman, Sergio Menezes, Ana Wunsch-Filho, Victor Eluf-Neto, Jose Boffetta, Paolo Fernandez Garrote, Leticia Polesel, Jerry Lener, Marcin Jaworowska, Ewa Lubinski, Jan Boccia, Stefania Rajkumar, Thangarajan Samant, Tanuja A Mahimkar, Manoj B Matsuo, Keitaro Franceschi, Silvia Byrnes, Graham Brennan, Paul McKay, James D eng 1R03DE020116/DE/NIDCR NIH HHS/ R01CA092039 05/05S1/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural 2015/04/04 06:00 J Natl Cancer Inst. 2015 Apr 2;107(5). pii: djv037. doi: 10.1093/jnci/djv037. Print 2015 May.; International audience; Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

The current cancer landscape within transitional economies in central and Eastern Europe and the Mediterranean area is not particularly optimistic. Current perceptions are often based on extrapolations from other countries and regions; and hence the authors collaborated with the South Eastern Europe Oncology Group (SEEROG) to collect information on cancer registration in Central and Eastern Europe, Israel and Turkey. Healthcare authorities and specialist oncology centres in 21 countries in the region were contacted for information on cancer registries in their countries. Based on this information, the authors believe that the recording and reporting of data on cancer in the region is at an acceptable level. The authors discuss and compare institution- and population-based registries, and present opinions on elements of an 'ideal registry' based on the survey replies and comparisons with other registries. A comparison with the sources used for GLOBOCAN 2008 illustrates the need for consistent data to be communicated, published and utilised throughout the region and the oncology community. The authors conclude by considering the potential value of collaboration between health authorities across the region, as well as between the clinical and epidemiological communities, to ensure that cancer data are consistently collected, verified and made public.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility., Author Summary We have used a two-phased study approach to identify common genetic variation involved in susceptibility to upper aero-digestive tract cancer. Using Illumina HumanHap300 beadchips, 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls, were genotyped for a panel 317,000 genetic variants that represent the majority of common genetic in the human genome. The 19 top-ranked variants were then studied in an additional series of 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies. Five variants were significantly associated with UADT cancer risk after the completion of both stages, including three residing within the alcohol dehydrogenase genes (ADH1B, ADH1C, ADH7) that have been previously described. Two additional variants were found, one near the ALDH2 gene and a second variant located in HEL308, a DNA repair gene. These results implicate two variants 4q21 and 12q24 and further highlight three ADH variants UADT cancer susceptibility.

Iako odvojeni, pulpa i parodont su komunikacijama koje čine apikalni otvor, akcesorni kanali, dentinski tubuli, povezani dijelovi zuba. Upravo im ta povezanost omogućuje prijenos ne samo metaboličkog, već i inficiranog sadržaja iz jednog tkiva u drugo. Na taj način inficirana pulpa može primjerice dovesti do nastanka periapikalnog procesa koji se može proširiti i zahvatiti parodont. S druge strane, inficirani parodont može se proširiti preko apeksa i ugroziti i oštetiti pulpu. Na taj se način formira pulpo-parodontni sindrom, stanje kojem je teško odrediti primaran uzrok lezije. U rijetkim slučajevima mogu nastati i dvije nepovezane lezije na zubu. Klasifikacija koja odjeljuje lezije prema mjestu nastanka primarne lezije je ona prema kojoj razlikujemo pet tipova lezija. Primarno endodontska je lezija koja se može zbrinuti samo endodontskim postupkom. Primarno endodontska sa sekundarnim zahvaćanjem parodonta, gdje je potrebno prvo provesti endodontsko liječenje a zatim nakon toga možda parodontnu terapiju. Primarno parodontna lezija je onda gdje je dovoljna samo parodontna terapija. Primarno parodontna sa sekundarno zahvaćenom pulpom iziskuje i endodontsku i parodontnu terapiju. Prava kombinirana lezija je ona kod koje odvojeno nastaju lezije i kod nje su potrebne obje vrste terapije. Although separated, pulp and periodont are connected through numerous communications. Pathways like apical foramen, accessory canals and dentinal tubules represent transport ways not only for metabolic, but also for toxic products. This makes it possible for an infected pulp to compromise vital periodontal tissue and vice versa. In this way are the endodontic-periodontal lesions formed. It is difficult to determine which lesion happened first, but there is a classification based on the determination of the primary disease. Primary endodontal lesion is curable after endodontic treatment. Primary endodontal lesion with secondary periodontal involvement requires first endodontic treatment, and then after that, if necessary, periodontal therapy. Primary periodontal lesion can be successful after periodontal therapy. Primary periodontal lesion with secondary endodontal involvement needs periodontal and endodontc therapy. True combined lesions occur when an endodonticaly induced lesion exists at a tooth that is also affected by marginal periodontitis. This requires both endodontic and periodonal therapy.

Background Many countries in the Eastern Mediterranean region (EMR) are undergoing marked demographic and socioeconomic transitions that are increasing the cancer burden in region. We sought to examine the national cancer incidence and mortality profiles as a support to regional cancer control planning in the EMR. Methods GLOBOCAN 2012 data were used to estimate cancer incidence and mortality by country, cancer type, sex and age in 22 EMR countries. We calculated age-standardized incidence and mortality rates (per 100,000) using direct method of standardization. Results The cancer incidence and mortality rates vary considerably between countries in the EMR. Incidence rates were highest in Lebanon (204 and 193 per 100,000 in males and females, respectively). Mortality rates were highest in Lebanon (119) and Egypt (121) among males and in Somalia (117) among females. The profile of common cancers differs substantially by sex. For females, breast cancer is the most common cancer in all 22 countries, followed by cervical cancer, which ranks high only in the lower-income countries in the region. For males, lung, prostate, and colorectal cancer in combination represent almost 30% of the cancer burden in countries that have attained very high levels of human development. Conclusions The most common cancers are largely amenable to preventive strategies by primary and/or secondary prevention, hence a need for effective interventions tackling lifestyle risk factors and infections. The high mortality observed from breast and cervical cancer highlights the need to break the stigmas and improve awareness surrounding these cancers.

Mongolia has a high burden from noncommunicable diseases, with cancer now the second leading cause of mortality. Given the paucity of situation analyses from the country, this study reports cancer data based on new cases 2008-12 from the National Cancer Registry of Mongolia covering the entire population (2.87 million). New cancer cases of 21,564 were diagnosed over the 5-year period, with a slight predominance of cases (52%) in men. Liver cancer was the leading cancer site in both sexes (ASRs of 114.7 and 74.6 per 100,000 males and females), and responsible for almost two-fifths of all cancer diagnoses, followed by cancers of stomach, lung and oesophagus in men and cervix, stomach and oesophagus in women. The cumulative risk of incidence for all cancers (27.7% and 20.8% in men and women, respectively) positions Mongolia above China (20.2% and 13.3%), below the United States (34.1% and 28.5%) and similar to Russia (26.1% and 19.1%). These figures shed light on the considerable magnitude of cancer in the country and the large fraction of cancers that can be prevented by lifestyle modifications and vaccine implementation. An expansion of activities of the cancer registry and the continued development of research are necessary steps in support of national cancer control planning in Mongolia.

Leoncini, Emanuele Ricciardi, Walter Cadoni, Gabriella Arzani, Dario Petrelli, Livia Paludetti, Gaetano Brennan, Paul Luce, Daniele Stucker, Isabelle Matsuo, Keitaro Talamini, Renato La Vecchia, Carlo Olshan, Andrew F Winn, Deborah M Herrero, Rolando Franceschi, Silvia Castellsague, Xavier Muscat, Joshua Morgenstern, Hal Zhang, Zuo-Feng Levi, Fabio Dal Maso, Luigino Kelsey, Karl McClean, Michael Vaughan, Thomas L Lazarus, Philip Purdue, Mark P Hayes, Richard B Chen, Chu Schwartz, Stephen M Shangina, Oxana Koifman, Sergio Ahrens, Wolfgang Matos, Elena Lagiou, Pagona Lissowska, Jolanta Szeszenia-Dabrowska, Neonila Fernandez, Leticia Menezes, Ana Agudo, Antonio Daudt, Alexander W Richiardi, Lorenzo Kjaerheim, Kristina Mates, Dana Betka, Jaroslav Yu, Guo-Pei Schantz, Stimson Simonato, Lorenzo Brenner, Hermann Conway, David I Macfarlane, Tatiana V Thomson, Peter Fabianova, Eleonora Znaor, Ariana Rudnai, Peter Healy, Claire Boffetta, Paolo Chuang, Shu-Chun Lee, Yuan-Chin Amy Hashibe, Mia Boccia, Stefania eng Netherlands 2013/11/26 06:00 Eur J Epidemiol. 2014 Jan;29(1):35-48. doi: 10.1007/s10654-013-9863-2. Epub 2013 Nov 24.; International audience; Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95 % CI 0.86-0.95 for men; adjusted OR = 0.86, 95 % CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.

Context Bladder cancer has become a common cancer globally, with an estimated 430 000 new cases diagnosed in 2012. Objective We examine the most recent global bladder cancer incidence and mortality patterns and trends, the current understanding of the aetiology of the disease, and specific issues that may influence the registration and reporting of bladder cancer. Evidence acquisition Global bladder cancer incidence and mortality statistics are based on data from the International Agency for Research on Cancer and the World Health Organisation (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organisation Mortality). Evidence synthesis Bladder cancer ranks as the ninth most frequently-diagnosed cancer worldwide, with the highest incidence rates observed in men in Southern and Western Europe, North America, as well in certain countries in Northern Africa or Western Asia. Incidence rates are consistently lower in women than men, although sex differences varied greatly between countries. Diverging incidence trends were also observed by sex in many countries, with stabilising or declining rates in men but some increasing trends seen for women. Bladder cancer ranks 13th in terms of deaths ranks, with mortality rates decreasing particularly in the most developed countries; the exceptions are countries undergoing rapid economic transition, including in Central and South America, some central, southern, and eastern European countries, and the Baltic countries. Conclusions The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking, although infection with Schistosoma haematobium and other risk factors are major causes in selected populations. Differences in coding and registration practices need to be considered when comparing bladder cancer statistics geographically or over time. Patient summary The main risk factor for bladder cancer is tobacco smoking. The observed patterns and trends of bladder cancer incidence worldwide appear to reflect the prevalence of tobacco smoking.

Prema navedenom istraživanju na uzorku od 30 poreznih službenika i 30 poduzetnika, obrtnika, te zaposlenika raznih privatnih poduzeća možemo zaključiti da je velika većina svih ispitanika nezadovoljna visokim poreznim stopa u našoj državi. Porezni službenici drže do ugleda svoje službe i profesionalnog ponašanja u službenim nadzorima poreznih obveznika, s druge strane većina poduzetnika nema povjerenja u rad porezne uprave kao državnog tijela smatraju da se nema smisla natezati s državom ukoliko dođe do propusta službenika. Poduzetnici bi se trebali moralno pridržavati društveno odgovornog poslovanja, na navedenom istraživanju pokazalo se da samo polovina njih se pridržava istog dok ostali nemaju predodžbu što bi trebao značiti DOP. Korupcija je prisutna u svim društvima, čak je i postala normalna pojava. Prema rezultatima istraživanja poreznim službenicima je rijetko ili nikada ponuđen mito koji predstavlja najčešći oblik korupcije. Poduzetnici smatraju da uredno vode svoje poslovanje i nema potrebe za tim. U manjoj mjeri postoji korupcija što se tiče poreznog nadzora, no zloupotreba položaja nije upitna i porezni službenici profesionalno obavljaju svoj terenski rad. Raduju nas zadovoljavajući rezultati što se tiču korektnih međusobnih odnosa među poreznim službenicima i s druge strane zaposlenika u raznim privatnim poduzećima. Naravno istraživanje pokazuje da u svakoj tvrtki ili službi ima nezadovoljnih kolega, međutim takvi postotci nisu značajni. Po mišljenju poreznih službenika najgori porezni zakon za poduzetnike i društvo u cjelini smatraju da je to zakon o predstečajnoj nagodbi ili kako su ga slikovito opisali „zakon o prijateljima“. Dok prema mišljenju poduzetnika najgori porezni zakon je porez na dobit, naravno jel on utječe na profit koji poduzeće ostvaruje, na koncu taj profit bi se mogao uložiti u napredak poduzeća što je s stopom od 20% poreza na dobit djelomično onemogućeno. Zaposlenici pak smatraju da je to porez na dohodak jer izravno utječe na njihove prihode, s tim se slažu i porezni službenici. Na pitanje samog prihoda izgleda da porezni službenici nisu zadovoljni s plaćom koju primaju za svoj obim posla i odgovornosti, na što smatram da su u pravu i kad kažu da žele zaštitu i dostojanstvo kao i suci. Zaposleni građani koji imaju sreće što su u radnom odnosu i primaju plaću za svoj rad, smatraju da bi trebali imati veću plaću u odnosu na skup život u Hrvatskoj državi. Based on this research on the sample of 30 tax officials and 30 entrepreneurs, craftsmen and employees of various private companies, we can conclude that the vast majority of the respondents are dissatisfied with the high tax rate in our country. Tax officials uphold to the reputation of their service and professional conduct in the official control of taxpayers. On the other hand, most business owners have no confidence in the work of the tax administration as a government body and consider it to be useless to fight the state if failures by tax officers occur. Entrepreneurs should uphold moral and social responsibility in conducting business operations. However, the same research showed that only half of them adhere to the abovementioned, while others have conception that the CSR means. Corruption is present in all societies, and has even become a normal occurrence. According to the results of the research, tax officials have rarely or never been offered a bribe, which is the most common form of corruption. Entrepreneurs believe that if they would conduct their business regularly, there would be no need for it. To a lesser extent, there is corruption when it comes to tax inspection, but the abuse of position by tax officers is in question and they are found to be professional in conducting their field work. We have received satisfactory results related to good mutual relations among tax officials and, on the other side, employees in various private companies. As expected, the research shows that in each company or service there are dissatisfied colleagues. However, those are found by this research to be in insignificant percentages. In tax officials' opinion, the worst tax law for entrepreneurs and society in general is presumed to be the Law of pre-bankruptcy settlement or how it was vividly described - the "Law of Friends". In the entrepreneurs’ opinion, the worst tax law is tax on profits; quite logically since it affects the profits that the company gains. Ultimately, gained profit could be invested in the improvement of the enterprises, which is partially disabled with income tax and its current rate of 20%. Respectively, employees consider the income tax to be the worst because it directly affects their income, with which tax officials are in accordance. On the issue of the income itself, it seems that tax officials are not satisfied with the salary they receive in respect to their workload and responsibilities. I agree with them on that issue as well as with statement that they are entitled to the same level of protection as is available for the judicial officers. Employees who are lucky to be employed and are regularly paid a salary for their work, feel that they should have higher wages in relation to the expensive lifestyle in Croatia.

Predmet istraživanja ovog rada je primjena i procjena koncepta BIM u izradi varijantnih rješenja tradicijske kuće dalmatinskog zaleđa kroz različite odnose prema izvornoj kamenoj kući. Rad se sastoji od teorijskog i od praktičnog dijela. U teorijskom dijelu se postavio okvir za koncipiranje varijantnih rješenja, slijedeći postavke autora Rapoporta (1999) o odnosu prema narodnoj ili pučkoj gradnji. Pregledom literature zaključene su i osnovne vrijednosti i pouke gradnje kamene kuće koje su bile podloga za razvoj varijantnih rješenja. U praktičnom dijelu rada su izrađena četiri 5D BIM modela na temelju nacrta obiteljske kuće u Vinovu Gornjem, Donji Gotovci iz izvora „Hrvatsko tradicijsko graditeljstvo“ autora Zdravka Živkovića. Za izradu BIM modela korišten je softver Revit Architecture od Autodesk-a. Za polazni model kamene kuće odabran je ogledni primjer regionalne arhitekture dalmatinskog zaleđa. Varijantni modeli su izrađeni na temelju tri od četiri stava u pogledu narodnog graditeljstva (Rapoport, 1999) pri čemu je izrađen model 0 - izvorni model, model 1 – pseudo tradicijski, model 2 – djelomično tradicijski i model 3 u kojem smo u potpunosti zanemarili tradiciju. Varijantni modeli mijenjani su u pogledu geometrije i graditeljskih elemenata čime se uspostavljao različit odnos prema početnom modelu. U radu se izradio troškovnik i dinamički plan za čiju su izradu količine pojednih stavki odnosno radova dobivene izravno iz Revit modela. Rezultati usporedbe troškova i trajanje izvedbe pojednih modela potvrđuju arhitektonske koncepte te se može vidjeti kako se vrijednost tradicije očituje i u većim troškovima radova odnosno duljem trajanju izgradnje. Primjenom alata za ocjenu zrelosti BIM-a u projektu dobiven je rezultat ocjene srednje zrelosti za arhitekturu i niske zrelosti na razini cijelog projekta.

Background: Cigarette smoking is a major risk factor for head and neck cancer (HNC). To our knowledge, low cigarette smoking (0-3, >3-5, >5-10 cigarettes per day. Results: Smoking >0-3 cigarettes per day was associated with a 50% increased risk of HNC in the study population [ odds ratio (OR) = 1.52, 95% confidence interval (CI): (1.21, 1.90). Smoking >3-5 cigarettes per day was associated in each subgroup from OR = 2.01 (95% CI: 1.22, 3.31) among never alcohol drinkers to OR = 2.74 (95% CI: 2.01, 3.74) among women and in each cancer site, particularly laryngeal cancer (OR = 3.48, 95% CI: 2.40, 5.05). However, the observed increased risk of HNC for low smoking frequency was not found among smokers with smoking duration shorter than 20 years. Conclusion: Our results suggest a public health message that low frequency of cigarette consumption contributes to the development of HNC. However, smoking duration seems to play at least an equal or a stronger role in the development of HNC.

Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.

This book provides an overview of measures in the Rural Development Programme of Croatia 2014-2020 which contribute to nature protection. It covers organic farming (Measure 11); agri-environment/climate measures (Measure 10); areas with natural constraints (Measure 13) and support for non-productive investments for environmental purposes/public amenity (Measure 4.4). The chapter on organic farming provides an overview on basic principles and practices and contribution of organic farming to nature protection.

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10 â'8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci - 9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1∗1301-HLA-DQA1∗0103-HLA-DQB1∗0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers. © 2016 Nature America, Inc. part of Springer Nature, All Rights reserved.

Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood. Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression. Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer. Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.

It is not clear to what extent mammographic density represents a risk factor for breast cancer among women with moderate risk for disease. We conducted a population-based study to estimate the independent effect of breast density on breast cancer risk and to evaluate the potential of breast density as a marker of risk in an intermediate risk population. From November 2006 to April 2009, data that included American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density categories and risk information were collected on 52,752 women aged 50-69 years without previously diagnosed breast cancer who underwent screening mammography examination. A total of 257 screen-detected breast cancers were identified. Logistic regression was used to assess the effect of breast density on breast carcinoma risk and to control for other risk factors. The risk increased with density and the odds ratio for breast cancer among women with dense breast (heterogeneously and extremely dense breast), was 1.9 (95% confidence interval, 1.3-2.8) compared with women with almost entirely fat breasts, after adjustment for age, body mass index, age at menarche, age at menopause, age at first childbirth, number of live births, use of oral contraceptive, family history of breast cancer, prior breast procedures, and hormone replacement therapy use that were all significantly related to breast density (p < 0.001). In multivariate model, breast cancer risk increased with age, body mass index, family history of breast cancer, prior breast procedure and breast density and decreased with number of live births. Our finding that mammographic density is an independent risk factor for breast cancer indicates the importance of breast density measurements for breast cancer risk assessment also in moderate risk populations.

Malignant melanoma of the skin is a cancer originating in melanocytes, the pigment-producing cells of the skin (1). Unlike basal and squamous cell cancers of the skin that are rarely fatal, its five-year relative survival in Europe is 83.1% (2). With 286 new cases and 118 yearly deaths in men and 275 new cases and 79 deaths in women in Croatia in 2008, melanoma represented 2.6% of male cancer incidence and 1.1% of cancer deaths in men, and 2.9% of female cancer incidence and 1.4% of cancer deaths in women (3). The strongest environmental risk factor for malignant melanoma in white populations is exposure to UV light (4). Intermittent sun exposure, especially before the age of 10 is considered to be a stronger risk factor than a continuous exposure (5,6). Other risk factors for malignant melanoma include invasive melanoma of the skin in one or more first degree-relatives, history of primary invasive melanoma, more than a hundred banal melanocytic nevi, three or more clinically atypical (dysplastic) nevi, pale Caucasian skin (type 1 or 2), red or blond hair, history of one or more severe blistering sunburns, sunbed use (especially before the age of 30), and history of pesticide exposure (6). Generally, melanoma incidence rates in Caucasian populations increase with proximity to the Equator (7). However, there are variations across Europe, with Switzerland, Denmark, Norway, Sweden, and the Netherlands having the highest rates (15-18/100 000 in men and 16-22/100 000 in women) and Central and Southeastern Europe countries the lowest (4.4/100 000 for men and 4.3/100 000 for women) (8). Until now, recent trends in melanoma incidence and mortality have been less studied in the Mediterranean and Eastern European populations. The aim of this study was to analyze the melanoma incidence and mortality trends in Croatia 1988-2008, compare them with the trends in other populations, and identify possible changes.

An increase in the incidence of breast cancer in women aged

AIM: To describe and interpret prostate cancer incidence and mortality trends in Croatia between 1988 and 2008. ----- METHODS: Incidence data for the period 1988-2008 were obtained from the Croatian National Cancer Registry. The number of prostate cancer deaths was obtained from the World Health Organization mortality database. We also used population estimates for Croatia from the Population Division of the Department of Economic and Social Affairs of the United Nations. Age standardized incidence and mortality rates were calculated by the direct standardization method. To describe time trends of incidence and mortality, joinpoint regression analysis was used. ----- RESULTS: Average age-standardized incidence rate between the first and last five-year period doubled, from 19.0/100,000 in 1988-1992 to 39.1 per 100,000 in 2004-2008. Age-standardized mortality rate increased by 6.9%, from 14.5 to 15.5 per 100,000. Joinpoint analysis of incidence identified two joinpoints. The increasing incidence trend started from 1997, with the estimated annual percent of change (EAPC) of 12.9% from 1997-2002 and of 4.1% from 2002-2008. Joinpoint analyses of mortality identified one joinpoint. Mortality trend first decreased, with EAPC of -3.0% from 1988-1995 to increase later with EAPC of 2.0% from 1995-2008. ----- CONCLUSION: The incidence of prostate cancer in Croatia has been on the increase since 1997. Trend in mortality is increasing, contrary to the trends in some higher-income countries. An improvement in the availability of different treatment modalities as well as establishing prostate cancer units could have a positive impact on prostate cancer mortality in Croatia.