Skin melanoma deaths within 1 or 3 years from diagnosis in Europe.

The steep increase in incidence of cutaneous malignant melanoma in white populations mainly applies to thin lesions with good survival suggesting overdiagnosis. Based on population-based cancer registries (CRs), we have investigated changes in aggressive melanoma, selecting only cases who died within 1 or 3 years after diagnosis in 11 European countries between 1995 and 2012. Trends in fatal cases were analysed by period of diagnosis, sex, tumour thickness, histologic subtype of the lesion, tumour site and CR with a multivariate generalised linear mixed effects model, where geographical area was considered as a random effect. We collected data on 123 360 invasive melanomas, with 5133 fatal cases at 1 year (4%) and 12 330 (10%) at 3 years. The number of fatal cases showed a 16% decrease at 1 year and 8% at 3 years between the first (1995-2000) and the last (2007-2012) period. The highest proportion of fatal cases was seen for men, older age (≥65 years), thick lesions (>1 mm), nodular melanoma, melanoma on the trunk and for poorly documented cases, lacking information about thickness and histologic subtype. The mixed-effects model showed a remarkable variability among European countries. The majority of registries showed a decreasing trend in fatal cases, but a few registries showed an opposite pattern. Trends in fatal melanoma cases, highlighting real changes in risk not related to overdiagnosis, showed a decrease in most European countries, with a few exceptions. Stronger efforts for early detection could lead to a more efficient treatment of melanoma in general.

The relative risk of second primary cancers in Switzerland: a population-based retrospective cohort study.

BACKGROUND: More people than ever before are currently living with a diagnosis of cancer and the number of people concerned is likely to continue to rise. Cancer survivors are at risk of developing a second primary cancer (SPC). This study aims to investigate the risk of SPC in Switzerland. METHODS: The study cohort included all patients with a first primary cancer recorded in 9 Swiss population-based cancer registries 1981-2009 who had a minimum survival of 6 months, and a potential follow-up until the end of 2014. We calculated standardized incidence ratios (SIR) to estimate relative risks (RR) of SPC in cancer survivors compared with the cancer risk of the general population. SIR were stratified by type of first cancer, sex, age and period of first diagnosis, survival period and site of SPC. RESULTS: A total of 33,793 SPC were observed in 310,113 cancer patients. Both male (SIR 1.18, 95%CI 1.16-1.19) and female (SIR 1.20, 95%CI 1.18-1.22) cancer survivors had an elevated risk of developing a SPC. Risk estimates varied substantially according to type of first cancer and were highest in patients initially diagnosed with cancer of the oral cavity and pharynx, Hodgkin lymphoma, laryngeal, oesophageal, or lung cancer. Age-stratified analyses revealed a tendency towards higher RR in patients first diagnosed at younger ages. Stratified by survival period, risk estimates showed a rising trend with increasing time from the initial diagnosis. We observed strong associations between particular types of first and SPC, i.e. cancer types sharing common risk factors such as smoking or alcohol consumption (e.g. repeated cancer of the oral cavity and pharynx (SIRmales 20.12, 95%CI 17.91-22.33; SIRfemales 37.87, 95%CI 30.27-45.48). CONCLUSION: Swiss cancer survivors have an increased risk of developing a SPC compared to the general population, particularly patients first diagnosed before age 50 and those surviving more than 10 years. Cancer patients should remain under continued surveillance not only for recurrent cancers but also for new cancers. Some first and SPCs share lifestyle associated risk factors making it important to promote healthier lifestyles in both the general population and cancer survivors.

Correction to: The relative risk of second primary cancers in Switzerland: a population-based retrospective cohort study.

Following publication of the original article [1], an error was reported in the author group. The correct author group should read as follows.

Comparison between opportunistic and organised breast cancer mammography screening in the Swiss canton of Fribourg.

BACKGROUND: Breast cancer screening mammography is widespread in industrialised countries within the framework of public health program or opportunist form. Only few data exist on the comparison of effectiveness between organised and opportunistic screening. The aim of this study is to compare organised and opportunistic screening using population-based data from the Fribourg cancer registry, Switzerland. METHODS: We included all first primary breast adenocarcinoma diagnosed between 2006 and 2014 in women aged 50-69 years resident in the canton of Fribourg. We considered only breast cancer discovered by mammography screening. We compared patients, tumour characteristics and treatment modalities between breast cancer detected by the organised screening program versus opportunistic screening using logistic regression. RESULTS: Out of 989 patients diagnosed with breast cancer, 402 (40.6%) were diagnosed by organised and 205 (20.7%) by opportunistic screening. Women with breast cancer detected within the screening program were more likely to be from rural areas (P = 0.035) and lived less frequently in high favoured regions (P = 0.020). They presented more frequently in situ than invasive cancer (P = 0.022). For patients with invasive breast cancer, those detected by the program were less likely to undergo mastectomy (P = 0.06) and consequently, they were more likely to undergo radiation therapy (P = 0.003). Adjustment for area of residence and financial context of the region did not modify the results presented. CONCLUSIONS: The present study reports an increased rate of detection of carcinoma in situ in organised screening program as compared to opportunistic screening mammographies, an indirect evidence of a higher radiologic sensitivity. Furthermore, the results show a trend towards more mastectomies among patients with breast cancer discovered after opportunistic than after organized mammography screening, reflecting lower treatment burden. Those results were independent of socio-economic factors which differed across screening groups.

Skin cancer screening in Switzerland: Cross-sectional trends (1997-2012) in socioeconomic inequalities.

INTRODUCTION: Skin cancer is one of the most common malignancies. Despite controversy over its efficacy, skin cancer screening has become widespread although socioeconomic screening inequalities have been documented. Switzerland has the highest rate of melanoma in Europe but Swiss trends in skin cancer screening and social disparities have not been investigated. This study aims to evaluate trends in skin cancer screening and its association with socioeconomic indicators in Switzerland between 1997 and 2012. METHOD: We used data from four waves (from 1997 to 2012) of the population-based Swiss Health Interview Survey. Multivariable Poisson regressions with robust variance were used to estimate weighted prevalence ratio (PR) and 95% Confidence Intervals (CI) adjusting for demographics, health status and use of healthcare. RESULTS: This study included 60,764 participants with a mean age of 49.1 years (standard deviation (SD) 17.2) and 53.6% of women. Between 1997 and 2012, the weighted prevalence of ever life-time skin examination and skin examination in the current year increased by 38.2% and 35.3% respectively (p-value <0.001). Participants with a lower education level, lower income and living in non-metropolitan areas were less often screened than their counterparts. Educational differences in ever life-time skin examination increased over time (p-value for trend = 0.036). CONCLUSION: While skin cancer screening prevalence in Switzerland increased from 1997 to 2012, most social inequalities persisted over time and educational inequalities increased. Dermatologists should be alerted that populations with lower education should be given special attention.

Testicular cancer in Geneva, Switzerland, 1970-2012: incidence trends, survival and risk of second cancer.

BACKGROUND: This paper describes the testicular cancer trends for incidence, survival, socio-economic status (SES) disparities and second cancer occurrence in Geneva, Switzerland, a high-risk population. METHODS: We included all testicular germ-cell tumors recorded in the population-based Geneva cancer registry during the period 1970-2012. Changes in incidence trends were assessed using Joinpoint regression to calculate the annual percentage change (APC). Overall and cancer-specific survivals (OS, CSS) were estimated by Kaplan Meyer methods. To evaluate the risk of a second cancer we calculated the Standardized Incidence Ratios (SIR) using the Geneva population incidence rates. RESULTS: The average annual testicular cancer rate was 7.32/100 000 men, with a non-significant increasing trend during the study period. The highest rates were observed among men younger than 39 years. Despite a trend toward earlier diagnosis, 14% of patients were diagnosed at a late stage. Patients with non-seminoma tumours and patients with low SES were more often diagnosed with an advanced stage. Both OS and CSS improved during the study period but with strong differences by age, stage, morphology and SES. The risk for developing a second cancer was more than doubled. This risk was particularly high for a contralateral testicular cancer, bladder cancer and pancreatic cancer. CONCLUSIONS: Overall, there was no substantial increase in the incidence of testicular cancer in Geneva in recent decades, however the prognosis has improved. The high risk of developing a second cancer, the differences in stage at diagnosis and survival by SES, require enhanced awareness and surveillance by clinicians, patients and men in general.

Organised population-based programmes and change in socioeconomic inequalities in mammography screening: A 1992-2012 nationwide quasi-experimental study.

Organised mammography screening programmes may reduce socioeconomic inequalities in breast cancer screening, but evidence is contradictory. Switzerland has no national organised mammography screening programme, but regional programmes were progressively introduced since 1999, giving the opportunity to conduct a nationwide quasi-experimental study. We examined the evolution of socioeconomic inequalities in mammography screening in Switzerland and if exposure to regional organised programmes reduced socioeconomic inequalities. Data of 10,927 women aged 50 to 70 years old were collected from the Swiss Health Interview Survey, a nationally representative cross-sectional survey repeated 5 times (1992-2012). Socioeconomic characteristics were assessed using education, income, employment status, and occupational class. Adjusted prevalence ratios of up-to-date mammography screening were estimated with Poisson regressions and weighted for sampling strategy and non-participation bias. In the absence of organised screening programmes (1992-1997), prevalence of mammography screening increased by 23% and was associated with tertiary education and working part time. During the period of progressive introduction of regionally organised programmes (2002-2012), prevalence of mammography screening increased by 19% every 5 years and was associated with exposure to regional programmes and with independent/artisan occupations. Tertiary education and working part time were no longer associated. Exposure to organised programmes did not modify socioeconomic inequalities except for employment status: not employed women benefitted more from organised programmes compared to women working full time. In conclusion, socioeconomic inequalities in mammography screening decreased over time but organised programmes did not greatly modify them, except women not employed whose prevalence passed employed women.

Socioeconomic and demographic disparities in breast cancer stage at presentation and survival: A Swiss population-based study.

We explored socioeconomic and demographic disparities in breast cancer (BC) stage at presentation and survival in a Swiss population-based sample of female BC patients linked to the census-based Swiss National Cohort. Tumor stage was classified according to Surveillance, Epidemiology and End Results Program summary stage (in situ/localized/regional/distant). We used highest education level attained to estimate SEP (low/middle/high). Further demographic characteristics of interest were age at presentation (30-49/50-69/70-84 years), living in a canton with organized screening (yes/no), urbanity of residence (urban/peri-urban/rural), civil status (single/married/widowed/divorced) and nationality (Swiss/non-Swiss). We used ordered logistic regression models to analyze factors associated with BC stage at presentation and competing risk regression models for factors associated with survival. Odds of later-stage BC were significantly increased for low SEP women (odds ratio 1.19, 95%CI 1.06-1.34) compared to women of high SEP. Further, women living in a canton without organized screening program, women diagnosed outside the targeted screening age and single/widowed/divorced women were more often diagnosed at later stages. Women of low SEP experienced an increased risk of dying from BC (sub-hazard ratio 1.22, 95%CI 1.05-1.43) compared to women of high SEP. Notably, these survival inequalities could not be explained by socioeconomic differences in stage at presentation and/or other sociodemographic factors. It is concerning that these social gradients have been observed in a country with universal health insurance coverage, high health expenditures and one of the highest life expectancies in the world.

Breast cancer family history leads to early breast cancer detection and optimal management.

PURPOSE: We investigated whether the relationship between family history (FH) of breast cancer and survival of women with breast cancer is related to the quality of care received, once adjusted for other prognostic variables using data from the Geneva population-based cancer registry and quality of care indicators defined by the European Society of breast cancer specialists (EUSOMA). METHODS: We included non-metastatic malignant breast tumor patients who had their surgery between 2001 and 2010. We assessed the association between FH and patient and tumor characteristics on one hand, and each quality of care indicator and an overall score of quality of care, on the other hand, through logistic regression. We assessed the impact of FH and the quality of care-score on 5-year survival with Cox regression adjusting for patient and tumor characteristics. RESULTS: 2,672 patients were included in the study. Women with a positive FH were younger, more likely from Switzerland, screen detected, had positive estrogen and progesterone receptor status, and had smaller and ductal tumors. A positive FH was also associated with better management for several quality indicators. Women with a positive FH had a better crude survival (Hazard Ratio 0.61, p = 0.006). This association was not substantially affected when adjusting for quality of care. However, the effect of FH did not persist when also adjusting for patient and tumor characteristics. CONCLUSIONS: A positive FH of breast cancer is associated with earlier breast cancer diagnosis, better tumor features, and higher quality of care. These factors explain the better survival observed among breast cancer women with a positive FH as compared to women without positive FH.

Introduction of an organised programme and social inequalities in mammography screening: A 22-year population-based study in Geneva, Switzerland.

In developed countries, breast cancer mortality has decreased during the last decades due to, at least partially, the advent of mammography screening. Organised programmes aim, among other objectives, to increase participation and decrease social inequalities in screening access. We aimed to characterise the evolution of socioeconomic disparities in mammography screening before and after the implementation of an organised programme in Geneva, Switzerland. We included 5345 women, aged 50-74years, without past history of breast cancer who participated in the cross-sectional Bus Santé study, between 1992 and 2014. Outcome measures were: 1) never had a mammography (1992-2014) and 2) never had a mammography or not screened in the two years before being surveyed (subgroup analysis, 2007-2014). Educational attainment was divided in three groups (primary, secondary and tertiary) and period in two (before/after introduction of a screening programme in 1999). We calculated measures of relative and absolute change, including the relative (RII) and slope (SII) indices of social inequality adjusted for age and nationality. We compared the prevalence of screening before and after screening programme implementation using Poisson models. The proportion of unscreened women decreased during the study period from 30.5% to 3.6%. Lower educated women were more frequently unscreened (RII=2.39, p<0.001; SII=0.10, p<0.001). Organised screening decreased the proportion of unscreened women independently of education (prevalence ratiobefore vs. after=4.41, p<0.001), but absolute and relative inequalities persisted (RII=2.11, p=0.01; SII=0.04, p=0.01). Introduction of an organised programme increased women's adherence to mammography screening but did not eliminate social disparities in screening participation.

Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/µL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/µL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/µL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer.

Prognostic models in male breast cancer.

PURPOSE: Breast cancer in men is uncommon; it accounts for 1 % of all patients with primary breast cancer. Its treatment is mostly extrapolated from its female counterpart. Accurate predictions are essential for adjuvant systemic treatment decision-making and informing patients. Several predictive models are available for female breast cancer (FBC) including the Morphometric Prognostic Index (MPI), Nottingham Prognostic Index (NPI), Adjuvant! Online and Predict. The aim of this study was to examine and compare the prognostic performance of these models for male breast cancer (MBC). METHODS: The population of this study consists of 166 MBC patients. The prognostic scores of the patients are categorized by good, (moderate) and poor, defined by the test itself (MPI and NPI) or based on tertiles (Adjuvant! Online and Predict). Survival according to prognostic score was compared by Kaplan-Meier analysis and differences were tested by logRank. The prognostic performances were evaluated with C-statistics. Calibration was done with the aim to estimate to what extent the survival rates predicted by Predict were similar to the observed survival rates. RESULTS: All prediction models were capable of discriminating between good, moderate and poor survivors. P-values were highly significant. Comparison between the models using C-statistics (n = 88) showed equal performance of MPI (0.67), NPI (0.68), Adjuvant! Online (0.69) and Predict (0.69). Calibration of Predict showed overestimation for MBC patients. CONCLUSION: In conclusion, MPI, NPI, Adjuvant! and Predict prognostic models, originally developed and validated for FBC patients, also perform quite well for MBC patients.

Prostate cancer screening in Switzerland: 20-year trends and socioeconomic disparities.

BACKGROUND: Despite important controversy in its efficacy, prostate cancer (PCa) screening has become widespread. Important socioeconomic screening disparities have been reported. However, trends in PCa screening and social disparities have not been investigated in Switzerland, a high risk country for PCa. We used data from five waves (from 1992-2012) of the population-based Swiss Health Interview Survey to evaluate trends in PCa screening and its association with socioeconomic indicators. METHODS: We used multivariable Poisson regression to estimate prevalence ratios (PR) and 95% Confidence Intervals (CI) adjusting for demographics, health status, and use of healthcare. RESULTS: The study included 12,034 men aged ≥50 years (mean age: 63.9). Between 1992 and 2012, ever use of PCa screening increased from 55.3% to 70.0% and its use within the last two years from 32.6% to 42.4% (p-value <0.05). Income, education, and occupational class were independently associated with PCa screening. PCa screening within the last two years was greater in men with the highest (>$6,000/month) vs. lowest income (≤$2,000) (46.5% vs. 38.7% in 2012, PR for overall period =1.29, 95%CI: 1.13-1.48). These socioeconomic disparities did not significantly change over time. CONCLUSIONS: This study shows that about half of Swiss men had performed at least one PCa screening. Men belonging to high socioeconomic status are clearly more frequently screened than those less favored. Given the uncertainty of the usefulness of PCa screening, men, including those with high socioeconomic status, should be clearly informed about benefits and harms of PCa screening, in particular, the adverse effect of over-diagnosis and of associated over-treatment.

The incidence of colon cancer among patients diagnosed with left colonic or sigmoid acute diverticulitis is higher than in the general population.

BACKGROUND: Considering the low incidence of colon cancer after an initial episode of colonic diverticulitis in some categories of patients, some authors suggested to exempt them from colonoscopy. However, this incidence has never been compared to that of a reference population, and predictors of cancer are still poorly investigated. We aimed to determine the 1-year incidence of colon cancer at the site of diverticulitis in patients diagnosed with left colonic or sigmoid acute diverticulitis, to compare this incidence to a reference population to state whether endoscopy is required or not, and to identify predicting factors of cancer to better target subpopulations needing that examination. METHODS: All patients admitted at the University Hospitals of Geneva for left colonic or sigmoid acute diverticulitis were included. Patients with a previous history of colon cancer or non-available for follow-up were excluded. Demographic data, haemoglobin values, and the Hinchey score were documented. This cohort was matched with the Geneva Cancer Registry to look for cancer occurrence at the site of diverticulitis within 1 year. Predictors of cancer were assessed using univariate logistic regression and the risk of cancer by comparing observed cases to a reference population using standardized incidence ratios. RESULTS: The final cohort included 506 patients. Eleven (2.2 %) had a diagnosis of cancer at the site of diverticulitis within 1 year. The mean age was significantly different between patients with cancer and others. No predictor of cancer could be identified, except a trend for an increased risk with advancing age (p = 0.067). The standardized incidence ratios showed a 44-fold increased risk of cancer among the cohort compared to the reference population. CONCLUSIONS: Colonoscopy should be continued after an initial diagnosis of left colonic or sigmoid acute diverticulitis, irrespective of the clinical or radiological presentations.

Determinants of genetic counseling uptake and its impact on breast cancer outcome: a population-based study.

Genetic counseling and BRCA1/BRCA2 genes testing are routinely offered in a clinical setting. However, no data are available on the proportion of breast cancer patients with a positive family history undergoing genetic counseling. By linking databases of the Oncogenetics and Cancer Prevention Unit at the Geneva University Hospitals and the population-based Geneva Cancer Registry, we evaluated the uptake of genetic counseling among 1709 breast cancer patients with familial risk of breast cancer and the determinants of such a consultation process. We also studied the impact of genetic counseling on contralateral breast cancer occurrence and survival. Overall, 191 (11.2 %) breast cancer patients had genetic counseling; this proportion was 25.1 % within the high familial risk group. Recent period of diagnosis, early-onset breast cancer, female offspring, high familial risk, tumor size, and chemotherapy treatment were statistically significantly associated with genetic counseling uptake in multivariate analysis. More than 2 % of patients had developed contralateral metachronous breast cancer. An increased risk of contralateral breast cancer of borderline significance was found for patients who had genetic counseling versus those who had not (Cox model adjusted hazard ratio 2.2, 95 % confidence intervals 1.0-5.2, P = 0.063). Stratification by BRCA1/BRCA2 mutation status showed that the occurrence of contralateral breast cancer was 8-fold higher among mutation carriers compared with non-carriers. Age-adjusted overall survival and breast cancer-specific survival were not significantly different between patients who underwent genetic counseling and those who did not. In conclusion, we observed a significant increase in the use of genetic counseling over time and found that breast cancer patients with high familial risk had more often genetic counseling than those with moderate familial risk. A more thorough evaluation of sociodemographic and clinical predictors to attend the cancer genetic unit may help improving the use of genetic counseling services for at-risk individuals at a population level.

Determinants and effects of positive surgical margins after prostatectomy on prostate cancer mortality: a population-based study.

BACKGROUND: The objective of this population-based study was to assess patient, physician and tumour determinants associated with positive surgical margins after prostatectomy, and to assess the effects of positive surgical margins on prostate cancer-specific survival. METHODS: We included 1'254 prostate cancer patients recorded at the Geneva Cancer Registry who had radical prostatectomy during 1990-2008. To assess factors associated with positive margins, we used logistic regression. We assessed the effects of positive margins on prostate cancer-specific survival by Cox proportional hazard models accounting for numerous other prognostics factors including prostate and tumour volume, the total percentage of tumour, radiotherapy, surgical approach and surgeon's caseload. RESULTS: Among men undergoing prostatectomy, 479 (38%) had positive margins. In the multivariate logistic regression analysis, period, clinical- and pathological T stage, Prostate Specific Antigen (PSA) level, Gleason score and percentage of tumour in the prostate were significantly associated to positive margins. Ten-year prostate cancer-specific survival was 96.6% for the negative margins group and 92.0% for the positive margins group (log rank p = 0.008). In the Cox survival analysis adjusted for tumour characteristics, surgical margin status per se was not an independent prognostic factor while age, pathological T, PSA level and Gleason score remained associated with prostate cancer-specific survival. CONCLUSIONS: More aggressive tumour characteristics were strong determinants for positive margins. Furthermore, surgical margin status per se was not an independent prognostic factor for prostate cancer-specific survival after adjusting by the gravity of the disease in the multivariate analysis.

A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

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.

Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study.

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/µL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/µL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ≥500 cells/µL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.

Hierarchical modeling identifies novel lung cancer susceptibility variants in inflammation pathways among 10,140 cases and 11,012 controls.

Recent evidence suggests that inflammation plays a pivotal role in the development of lung cancer. In this study, we used a two-stage approach to investigate associations between genetic variants in inflammation pathways and lung cancer risk based on genome-wide association study (GWAS) data. A total of 7,650 sequence variants from 720 genes relevant to inflammation pathways were identified using keyword and pathway searches from Gene Cards and Gene Ontology databases. In Stage 1, six GWAS datasets from the International Lung Cancer Consortium were pooled (4,441 cases and 5,094 controls of European ancestry), and a hierarchical modeling (HM) approach was used to incorporate prior information for each of the variants into the analysis. The prior matrix was constructed using (1) role of genes in the inflammation and immune pathways; (2) physical properties of the variants including the location of the variants, their conservation scores and amino acid coding; (3) LD with other functional variants and (4) measures of heterogeneity across the studies. HM affected the priority ranking of variants particularly among those having low prior weights, imprecise estimates and/or heterogeneity across studies. In Stage 2, we used an independent NCI lung cancer GWAS study (5,699 cases and 5,818 controls) for in silico replication. We identified one novel variant at the level corrected for multiple comparisons (rs2741354 in EPHX2 at 8p21.1 with p value = 7.4 × 10(-6)), and confirmed the associations between TERT (rs2736100) and the HLA region and lung cancer risk. HM allows for prior knowledge such as from bioinformatic sources to be incorporated into the analysis systematically, and it represents a complementary analytical approach to the conventional GWAS analysis.

Cancer survivors in Switzerland: a rapidly growing population to care for.

BACKGROUND: Cancer survivors are a heterogeneous group with complex health problems. Data concerning its total number and growing dynamics for Switzerland are scarce and outdated. METHODS: Population and mortality data were retrieved from the Swiss Federal Statistical Office (FSO). Incidence and relative survival for invasive cancers were computed using data from the cancer registries Geneva (1970-2009), St. Gallen - Appenzell (1980-2010), Grisons & Glarus (1989-2010), and Valais (1989-2010). We estimated prevalence for 1990-2010 using the Prevalence, Incidence Approach MODel (PIAMOD) method. We calculated trends in prevalence estimates by Joinpoint analysis. Projections were extrapolated using the above models and based on time trends of the period 2007-2010. RESULTS: The estimated number of cancer survivors increased from 139'717 in 1990 (2.08% of the population) to 289'797 persons in 2010 (3.70%). The growth rate shows an exponential shape and was 3.3% per year in the period 2008 to 2010. Almost half of the survivors have a history of breast, prostate or colorectal cancer. Among cancer survivors, 55% are women but the increases have been more marked in men (p < 0.01, 3.9% annual increase in men vs. 2.7% in women since 2008). By the end of 2020 372'000 cancer survivors are expected to live in Switzerland. CONCLUSIONS: There is a rapidly growing population of cancer survivors in Switzerland whose needs and concerns are largely unknown.