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Verhoeven R.H.A.,Comprehensive Cancer Center South | Gondos A.,German Cancer Research Center | Janssen-heijnen M.L.G.,Comprehensive Cancer Center South | Janssen-heijnen M.L.G.,Viecuri Medical Center | And 17 more authors.
Annals of Oncology | Year: 2013

Background: Despite high curability, some testicular cancer (TC) patient groups may have increased mortality. We provide a detailed age- and histology-specific comparison of population-based relative survival of TC patients in Europe and the USA. Design: Using data from 12 European cancer registries and the USA Surveillance, Epidemiology and End Results 9 database, we report survival trends for patients diagnosed with testicular seminomas and nonseminomas between 1993-1997 and 2003-2007. Additionally, a model-based analysis was used to compare survival trends and relative excess risk (RER) of death between Europe and the USA adjusting for differences in age and histology. Results: In 2003-2007, the 5-year relative survival of patients with testicular seminoma was at least 98% among those aged <50 years, survival of patients with nonseminoma remained 3%-6% units lower.Despite improvements in the relative survival of nonseminoma patients aged ≥50 years by 13%-18% units, survival remained markedly lower than the survival of seminoma patients of the same age. Model-based analyses showed increased RERs for nonseminomas, older, and European patients. Conclusions: There remains little room for survival improvement among testicular seminoma patients, especially for those aged <50 years. Older TC patients remain at increased risk of death, which seems mainly attributable to the lower survival among the nonseminoma patients. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Mukherjee B.,University of Michigan | Delancey J.O.,University of Michigan | Raskin L.,University of Michigan | Everett J.,University of Michigan | And 15 more authors.
Journal of the National Cancer Institute | Year: 2012

The purpose of this study was to quantify the risk of cancers other than melanoma among family members of CDKN2A mutation carriers using data from the Genes, Environment and Melanoma study. Relative risks (RRs) of all non-melanoma cancers among first-degree relatives (FDRs) of melanoma patients with CDKN2A mutations (n = 65) and FDRs of melanoma patients without mutations (n = 3537) were calculated as the ratio of estimated event rates (number of cancers/total person-years) in FDRs of carriers vs noncarriers with exact Clopper-Pearson-type tests and 95% confidence intervals (CIs). All statistical tests were two-sided. There were 56 (13.1%) non-melanoma cancers reported among 429 FDRs of mutation carriers and 2199 (9.4%) non-melanoma cancers in 23452 FDRs of noncarriers. The FDRs of carriers had an increased risk of any cancer other than melanoma (56 cancers among 429 FDRs of carrier probands vs 2199 cancers among 23452 FDRs of noncarrier probands; RR = 1.5, 95% CI = 1.2 to 2.0, P = .005), gastrointestinal cancer (20 cancers among 429 FDRs of carrier probands vs 506 cancers among 23452 FDRs of noncarrier probands; RR = 2.4, 95% CI = 1.4 to 3.7, P = .001), and pancreatic cancer (five cancers among 429 FDRs of carrier probands vs 41 cancers among 23452 FDRs of noncarrier probands; RR = 7.4, 95% CI = 2.3 to 18.7, P = .002). Wilms tumor was reported in two FDRs of carrier probands and three FDRs of noncarrier probands (RR = 40.4, 95% CI = 3.4 to 352.7, P = .005). The lifetime risk of any cancer other than melanoma among CDKN2A mutation carriers was estimated as 59.0% by age 85 years (95% CI = 39.0% to 75.4%) by the kin-cohort method, under the standard assumptions of Mendelian genetics on the genotype distribution of FDRs conditional on proband genotype. © 2012 The Author.


Wiegell S.R.,Copenhagen University | Fabricius S.,Copenhagen University | Heydenreich J.,Copenhagen University | Enk C.D.,Hebrew University of Jerusalem | And 4 more authors.
British Journal of Dermatology | Year: 2013

Background Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated methyl aminolaevulinate PDT (daylight-PDT) is a simple and painless treatment procedure for PDT. All daylight-PDT studies have been performed in the Nordic countries. To be able to apply these results in other parts of the world we have to compare the daily protoporphyrin IX (PpIX) light dose in other countries with the PpIX light doses found in Nordic countries. Objectives To calculate where and when daylight-PDT of AKs was possible in six different geographical locations using ground stations measuring PpIX-weighted daylight doses. Methods PpIX-weighted daylight doses were measured using a dosimeter with a customer-specific photodiode with a detector sensitivity that mimics the PpIX absorption spectrum and measures in 'PpIX doses'. The dosimeters were built into ground stations that were placed in six geographical locations measuring from July to December 2008. Temperature data for each location were obtained from the internet. The maximal ultraviolet (UV) index for Copenhagen was obtained for the measuring period of the dosimeters. Results If the PpIX light dose should be above 8 J cm-2 and the maximum temperature of the day at least 10 °C, it was possible to treat patients on nearly all days until the middle of September in Reykjavik and Oslo, until the last week of October in Copenhagen and Regensburg, until the middle of November in Turin and all year in Israel. Conclusions Where and when to perform daylight-PDT depends on the PpIX light dose and outdoor temperature. The PpIX light dose was influenced by the geographical location (latitude), weather condition and time of year. The UV index was not more suitable than temperature and weather to predict if the intensity of daylight would be sufficient for daylight-PDT. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.


Verhoeven R.H.A.,Comprehensive Cancer Center South | Janssen-Heijnen M.L.G.,Comprehensive Cancer Center South | Janssen-Heijnen M.L.G.,Viecuri Medical Center | Saum K.U.,German Cancer Research Center | And 8 more authors.
European Journal of Cancer | Year: 2013

Introduction: Penile cancer is a rare neoplasm in Western countries, and detailed studies on trends in population-based survival of penile cancer have never been published before. We examined population-based trends in survival in Europe and the United States of America (USA). Methods: Data from 3297 European and 1820 American penile cancer patients, contributed by 12 European cancer registries and the Surveillance, Epidemiology, and End Results (SEER) Program of the USA were included in this study. Period analysis techniques were used to examine relative survival trends overall, as well as for four geographic regions in Europe, and for the age groups 15-54, 55-64, 65-74 and 75+ for both populations between 1990-1995 and 2002-2007. Survival trends were assessed in a multiple regression model of relative excess risk including period of diagnosis, age and continent. Results: The 5-year relative survival of penile cancer patients increased statistically non-significantly from 65% to 70% in Europe and decreased (significantly) from 72% to 63% in the USA. Trends in age-specific 5-year relative survival did not find any significant improvement in either Europe or the USA. The multiple regression analysis confirmed the lack of survival trend, and found significantly higher relative excess risk with age, and, apparently due to lower survival before 2002-2007, higher risk in Europe. Conclusion: Survival for penile cancer patients has not improved in either Europe or the USA since at least 1990. The reasons for the decrease of survival in the USA remain unknown and to be explored. Stronger international cooperation in clinical research may be important to facilitate clinical progress in treatment and thereby improvement of survival of this rare malignancy. © 2012 Elsevier Ltd. All rights reserved.


Rosso S.,Center for Epidemiology and Prevention in Oncology in Piedmont | Gondos A.,German Cancer Research Center | Zanetti R.,Center for Epidemiology and Prevention in Oncology in Piedmont | Bray F.,Institute of Population based Cancer Research | And 8 more authors.
European Journal of Cancer | Year: 2010

Introduction: We investigated survival in breast cancer patients by age group, focussing on those covered by screening programmes, using data from 12 European population-based cancer registries participating in the European Network for Indicators on Cancer Survival Working Group. Methods: We calculated period estimates of 5-year relative survival for 2000-2004 and examined the change in survival estimates for four age groups between 1990-1994 and 2000-2004. Trends in age specific incidence, survival and mortality were additionally compared to those in the United States based on results from the Surveillance Epidemiology and End Results (SEER) programme. Results: Breast cancer survival uniformly increased particularly in areas with lower breast cancer survival for patients diagnosed in 1990-1994. With the exception of Geneva, Scotland and Estonia, the rise in survival was always larger among the younger age groups than in the 70+ age group and the age-gradient widened over time. The 5-year relative survival of patients aged 70 and above in the European registries was at least 7 percentage points lower than the 5-year relative survival of patients in the same age group in the US in 2000-2004. During the study period, incidence increased in all age groups and populations with a few exceptions, an observation paralleled by declining mortality. Conclusions: Results showed that some of the geographical differences in overall survival are even larger when considering age groups, in particular between Western and Eastern European countries. Furthermore, some of the differences in survival within the Northern and Western European areas could be due to variations in the implementation of screening programmes rather than economic inequalities. © 2010 Elsevier Ltd. All rights reserved.


PubMed | Cancer Care Ontario, University of California at Irvine, University of New South Wales, British Columbia Cancer Agency and 7 more.
Type: Journal Article | Journal: Cancer medicine | Year: 2016

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI)=0.27-0.81, P=0.02) and a decrease in Breslow thickness (P=0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P=0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI=1.11-1.94, P=0.03; rs510432 CC, OR 1.84; 95% CI=1.12-3.02, P=0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P=0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI=0.21-0.88, P=0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI=0.34-0.87, P=0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression.


PubMed | University of California at Irvine, University of New South Wales, Center for Epidemiology and Prevention in Oncology in Piedmont, Cancer Control Research and 7 more.
Type: Journal Article | Journal: Carcinogenesis | Year: 2016

Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic variation influences survival in patients with cutaneous melanoma. The analysis involved 3566 incident single and multiple primary melanoma cases enrolled in the international population-based Genes, Environment, and Melanoma Study. Melanoma-specific survival outcomes were calculated for each of 38 VDR SNPs using a competing risk analysis after adjustment for covariates. There were 254 (7.1%) deaths due to melanoma during the median 7.6 years follow-up period. VDR SNPs rs7299460, rs3782905, rs2239182, rs12370156, rs2238140, rs7305032, rs1544410 (BsmI) and rs731236 (TaqI) each had a statistically significant (trend P values < 0.05) association with melanoma-specific survival in multivariate analysis. One functional SNP (rs2239182) remained significant after adjustment for multiple testing using the Monte Carlo method. None of the SNPs associated with survival were significantly associated with Breslow thickness, ulceration or mitosis. These results suggest that the VDR gene may influence survival from melanoma, although the mechanism by which VDR exerts its effect does not seem driven by tumor aggressiveness. Further investigations are needed to confirm our results and to understand the relationship between VDR and survival in the combined context of tumor and host characteristics.


PubMed | Cancer Care Ontario, University of California at Irvine, University of New South Wales, British Columbia Cancer Agency and 8 more.
Type: Comparative Study | Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | Year: 2015

Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case-control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma.


Ferlay J.,International Agency for Research on Cancer IARC | Steliarova-Foucher E.,International Agency for Research on Cancer IARC | Lortet-Tieulent J.,International Agency for Research on Cancer IARC | Rosso S.,Center for Epidemiology and Prevention in Oncology in Piedmont | And 5 more authors.
European Journal of Cancer | Year: 2013

Introduction: Cancer incidence and mortality estimates for 25 cancers are presented for the 40 countries in the four United Nations-defined areas of Europe and for the European Union (EU-27) for 2012. Methods: We used statistical models to estimate national incidence and mortality rates in 2012 from recently-published data, predicting incidence and mortality rates for the year 2012 from recent trends, wherever possible. The estimated rates in 2012 were applied to the corresponding population estimates to obtain the estimated numbers of new cancer cases and deaths in Europe in 2012. Results: There were an estimated 3.45 million new cases of cancer (excluding non-melanoma skin cancer) and 1.75 million deaths from cancer in Europe in 2012. The most common cancer sites were cancers of the female breast (464,000 cases), followed by colorectal (447,000), prostate (417,000) and lung (410,000). These four cancers represent half of the overall burden of cancer in Europe. The most common causes of death from cancer were cancers of the lung (353,000 deaths), colorectal (215,000), breast (131,000) and stomach (107,000). In the European Union, the estimated numbers of new cases of cancer were approximately 1.4 million in males and 1.2 million in females, and around 707,000 men and 555,000 women died from cancer in the same year. Conclusion: These up-to-date estimates of the cancer burden in Europe alongside the description of the varying distribution of common cancers at both the regional and country level provide a basis for establishing priorities to cancer control actions in Europe. The important role of cancer registries in disease surveillance and in planning and evaluating national cancer plans is becoming increasingly recognised, but needs to be further advocated. The estimates and software tools for further analysis (EUCAN 2012) are available online as part of the European Cancer Observatory (ECO) (http://eco.iarc.fr). © 2013 Elsevier Ltd. All rights reserved.

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