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Genetic predisposition to cutaneous malignant melanoma (CMM) involves highly penetrant predisposing genes and low and intermediate penetrant predisposing alleles. However, the missing heritability in (CMM) is still high. For such and in order to identify new genetic factors for CMM, we conducted an exome sequencing study in high-risk CMM patients. Two rounds of exome sequencing were successively performed in 33 and 27 high-risk patients. We focused on genes carrying rare nonsense, frameshift, and splice variants (allelic frequency1%) that were present in both series of exomes. An extension study was then conducted in a large cohort (1 079 CMM patients and 1 230 Caucasian ethnically matched healthy controls), and the inactivating variants frequency was compared between groups using two-sided Fisher exact test. Two TP53AIP1 truncating mutations were identified in four patients: a frameshift c.63_64insG, p.Q22Afs*81 in two patients from the same family and in the proband of a second family; and a nonsense mutation c.95 C A, p.Ser32Stop in a patient with multiple CMMs. In all patients, TP53AIP1 truncating variants were strongly associated with CMM risk (two-sided Fisher exact test = 0.004, OR = 3.3[1.3-8.5]). Additionally, we showed that TP53AIP1 mRNA was strongly down-regulated throughout different phases of melanoma progression. TP53AIP1 gene is a TP53 target which plays a key role by inducting apoptosis in response to UV-induced DNA damage. Constitutional mutations of TP53AIP1 had previously been involved in susceptibility to prostate cancer. Our results show that constitutional truncating TP53AIP1 mutations predispose to CMM in the French population. Replication studies in other populations should be performed.

Although nevus count is an established risk factor for melanoma, relationships between nevus number and patient and tumor characteristics have not been well studied and the influence of nevus count on melanoma-specific survival is equivocal. Using data from the Genes, Environment and Melanoma (GEM) study, a large population-based study of primary cutaneous melanoma, we evaluated associations between number of nevi and patient features, including sun-sensitivity summarized in a phenotypic index, and tumor characteristics. We also assessed the association of nevus count with melanoma-specific survival. Higher nevus counts were independently and positively associated with male gender and younger age at diagnosis, and they were inversely associated with lentigo maligna histology. We observed a borderline significant trend of poorer melanoma-specific survival with increasing quartile of nevus count, but little or no association between number of nevi and pigmentary phenotypic characteristics or prognostic tumor features.

A model has been proposed whereby melanomas arise through two distinct pathways dependent on the relative influence of host susceptibility and sun exposure. Such pathways may explain site-specific patterns of melanoma occurrence. To explore this model, we investigated the relationship between melanoma risk and general markers of acute (recalled sunburns) and chronic (prevalent solar keratoses) sun exposure, stratified by anatomic site and host phenotype. Our working hypothesis was that head and neck melanomas have stronger associations with solar keratoses and weaker associations with sunburn than trunk melanomas. We conducted a collaborative analysis using original data from women subjects of 11 case-control studies of melanoma (2,575 cases, 3,241 controls). We adjusted for potential confounding effects of sunlamp use and sunbathing. The magnitude of sunburn associations did not differ significantly by melanoma site, nevus count or histologic subtype of melanoma. Across all sites, relative risk of melanoma increased with an increasing number of reported lifetime "painful" sunburns, lifetime "severe" sunburns and "severe" sunburns in youth (p(trend) < 0.001), with pooled odds ratios (pORs) for the highest category of sunburns versus no sunburns of 3.22 [95% confidence interval (CI) 2.04-5.09] for lifetime "painful" sunburns, 2.10 (95%CI 1.30-3.38) for lifetime "severe" sunburns and 2.43 (95%CI 1.61-3.65) for "severe" sunburns in youth. Solar keratoses strongly increased the risk of head and neck melanoma (pOR 4.91, 95%CI 2.10-11.46), but data were insufficient to assess risk for other sites. Reported sunburn is strongly associated with melanoma on all major body sites.

Rationale, aims and objectives Lung cancer is a disease with high consumption of health care resources. The aim of this study was to describe hospital costs due to lung cancer care from diagnosis until death or end of the study follow-up, in a cohort of incident cases, by using administrative data. Methods Particular attention was given to the determinants of total costs and the impact of the initial treatment approach on the process of costs accumulation. Incident cases were identified by the local Cancer Registry (January 2000–December 2003) among the residents of Turin (Italy). Per patient hospital care has been determined from administrative databases (outpatient radiotherapy records and hospital discharge records). Costs determinants were identified via a multivariable generalized linear model (GLM), with a Gamma cost distribution and a logarithmic link function. To assess the time effect over the cost accumulation process for non-small-cell lung cancer cases, the same GLM Gamma model was repeated at different follow-up periods. Analyses were stratified by cancer histotype. Results Results evidenced the relevant role of initial patterns of care on the cost accumulation process, with increased midterm costs associated with curative patterns of care. Conclusion The use of administrative data enabled hospital lung cancer care to be described, and related costs to be estimated.

Rationale, aims and objectives Record linkage (RL) has become increasingly useful in health care administration, demographic studies, provision of health statistics and medical research. Linkage failure may occur when databases are affected by missing or inaccurate information. In particular, if the subsets of those who are not linked are not representative of the original population, the results obtained from linked data may be biased. This paper discusses the impact of incomplete RL on survival analysis. Methods In our study we assess by simulations the potential impact of such bias, that we will refer to as RL, on the effect of the covariates in the Cox regression model. We also evaluate the RL bias introduced by an incomplete linkage procedure on the analysis of survival in a cohort of patients with breast cancer. Results Our simulation study shows that the relative bias of the factors, which the linking probability depends on, reaches the threshold of 20%, and is never less than 5%. The bias observed in the simulation for a comparable scenario is consistent with the actual one estimated from the breast cancer records. Conclusions Incomplete RL is rarely explicitly taken into account in the models for survival analysis. This study indicates that such a practice is potentially leading to inefficient and biased results, in particular in presence of medium or small sample sizes.

Prostate specific antigen (PSA) screening was introduced to detect prostate cancer at an early stage and to reduce prostate cancer-specific mortality. Until results from clinical trials are available, the efficacy of PSA screening in reducing prostate cancer mortality can be estimated by surveillance of prostate cancer mortality trends. Our study analyzes recent trends in prostate cancer mortality in 38 countries. We used the IARC-WHO cancer mortality database and performed joinpoint analysis to examine prostate cancer mortality trends and identified 3 patterns. In USA, and to a lesser extent in Germany, Switzerland, Canada, France, Italy and Spain, prostate cancer-specific mortality decreased to a level lower than before the introduction of PSA screening. In Australia, New Zealand, Austria, Finland, The Netherlands, Norway, United Kingdom, Hungary, Slovakia, Israel, Singapore, Sweden and Portugal, mortality from prostate cancer decreased but rates remain higher than before the introduction of PSA screening. Prostate cancer mortality continued to increase in Belgium, Denmark, Greece, Ireland, Bulgaria, Czech Republic, Belarus, Ukraine, Russian Federation, Romania, Poland, Argentina, Chile, Cuba, Mexico, Japan, China Hong Kong and the Republic of Korea. The trends in prostate cancer mortality rates in examined countries suggest that PSA screening may be effective in reducing mortality from prostate cancer.

Eumelanins are brown-black pigments present in the hair and in the epidermis which are acknowledged as protection factors against cell damage caused by ultraviolet radiation. The quantity of eumelanin present in hair has recently been put forward as a means of identifying subjects with a higher risk of skin tumours. For epidemiological studies, chromatographic methods of determining pyrrole-2,3,5-tricarboxylic acid (PTCA; the principal marker of eumelanin) are long, laborious and unsuitable for screening large populations. We suggest near infrared (NIR) spectroscopy as an alternative method of analysing eumelanin in hair samples. PCTA was determined on 93 samples of hair by means of oxidizing with hydrogen peroxide in a basic environment followed by chromatographic separation. The same 93 samples were then subjected to NIR spectrophotometric analysis. The spectra were obtained in reflectance mode on hair samples which had not undergone any preliminary treatment, but had simply been pressed and placed on the measuring window of the spectrophotometer. The PTCA values obtained by means of HPLC were correlated with the near infrared spectrum of the respective samples. A correlation between the PTCA values obtained by means of HPLC and the PTCA values obtained from an analysis of the spectra was obtained using the principal component regression (PCR) algorithm. The correlation obtained has a coefficient of regression (R(2)) of 0.89 and a standard error of prediction (SEP) of 13.8 for a mean value of 108.6 ng PTCA/mg hair. Some considerations about the accuracy of the obtained correlation and the main sources of error are made and some validation results are shown.

We report the first results of a comparison between the Italian Registry on AIDS (RAIDS) and 13 population-based cancer registries (about 8 million population in 1991) with respect to the notification of Kaposi's sarcoma and non-Hodgkin's lymphoma. Routine indicators of data quality and completeness have been found in both types of registry, consistent with the best international standards. A linkage process was carried out on about 339,000 cancer notifications and 3,134 AIDS notifications and was herein restricted to individuals under the age of 50. Out of 243 Kaposi's sarcomas at either type of registry, 90 (37%) were reported as such by both; 68% of individuals with Kaposi's sarcoma at cancer registries could be identified at the AIDS registry, including AIDS-defining illnesses other than Kaposi's sarcoma; 62% of individuals with Kaposi's sarcoma at RAIDS could be found at cancer registries. Of 2,104 non-Hodgkin's lymphomas at either type of registry, 55 were reported as such by both; 65% of individuals reported as having non-Hodgkin's lymphoma at the AIDS registry were found at cancer registries. Our present results indicate the scope for improving cancer assessment in individuals with HIV infection and AIDS and the potential of AIDS and cancer registries for such a purpose. Int. J. Cancer 75:831–834, 1998. © 1998 Wiley-Liss, Inc.