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The available data from preclinical and pharmacological studies on the role of gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in brain GABAergic system activity contributes to the vulnerability to bipolar affective disorders (BPAD). Moreover, the localization of the alpha3 subunit GABA receptor GABRA3 gene on the Xq28, a region of interest in certain forms of bipolar illness, suggests that GABRA3 may be a candidate gene in BPAD. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentric case-control sample, matched for sex and ethnogeographical origin. Allele and genotype (in females) frequencies were compared in 185 BPAD patients and 370 controls. A significant increase of genotype 1-1 was observed in BPAD females compared to controls (P=0.0004). Furthermore, when considering recessivity of allele 1 (females with genotype 1-1 and males carrying allele 1), results were even more significant (P= 0.00002). Our findings suggest that the GABRA3 polymorphism may confer susceptibility to or may be in linkage disequilibrium with another gene involved in the genetic etiology of BPAD.

This introduction provides a general overview of the aims, methods and procedures used in the EUROCARE II study and the types of analyses presented in each article of this Special Issue of the European Journal of Cancer. The main aims of the EUROCARE II project are the updating of the survival database of the European Cancer Registries, the study of recent trends in relative survival rates and the interpretation of the survival differences observed both in time and across populations. Once having completed the preliminary stage of data checking, a total of 3,473,659 individual records from patients of all cancer sites, diagnosed between 1978 and 1989 and provided by 45 cancer registries in 17 European countries were accepted to build up the EUROCARE database. The quality of these data, in terms of the accuracy of the diagnosis and the validity of vital status assessment, was checked by indirect indicators, based on cross-validation analysis of consistency of the relevant variables. Statistical analysis was based on age-specific relative survival rates, computed for each cancer sites as the ratio of observed survival to the expected survival of the general population of the same area, gender and age, according to the Hakulinen method. An estimate of the European survival was computed as a weighted mean of the corresponding survival of the different countries, using as weights the expected yearly number of incident cases in each country. For comparison purposes, age-standardised survival was also calculated for Europe and for each country involved in the study.

This study estimates the incidence and prevalence of larynx and lung cancers using a mathematical model based on available data on specific mortality and survival. In Italy, larynx and lung cancers account for more than 95% of respiratory cancers. In this paper, estimates of age/sex-specific and age-standardized incidence rates and prevalence are presented for the years 1970 and 1987. Age and birth-cohort effects on incidence are also presented by sex and broad geographical area. The procedure was firstly validated using data from four cancer registries: Varese (Northern Italy), Parma (North-Central Italy), Florence (Central Italy), and Ragusa (Southern Italy). Estimates were then carried out at the national level and for each major geographical area (i.e. North, Center and South). Larynx cancer age-standardized incidence rates increased for men by about 25% from 1970 to 1987. Age-specific rates increased for ages greater than 44 years, but decreased for younger ages. Cohort effects are low for older cohorts; they steeply increase and plateau for the 1900-1905 cohorts, and then peak for the 1930 cohort. The risk for cohorts born after 1930 systematically decreases. We estimated that the 1930 birth cohort has a risk five times higher than the 1890 cohort. For women, the incidence rates increased by about 30% from 1970 to 1987, for all age classes. Cohort effects steadily increase from the 1886 birth cohort to the 1960 cohort. The estimated prevalence between ages 30 and 84 increased from about 24,400 cases in 1970 (23,000 males and 1,400 females) to about 51,400 cases in 1987 (48,600 males and 2,800 females). For men, 42% of the increase can be attributed to an increase in the incidence of the disease; 45% can be attributed to population aging, and only 13% to an increase in the survival probability. Corresponding figures for women are 42%, 48%, and 10%. For lung cancer, we estimated 32,000 incident cases for 1987 (28,000 men and 4,000 women), two times the corresponding figures for 1970 (14,000 men and 2,000 women). Looking at age-adjusted rates, the overall risk of lung cancer increased by about 60% for men and 52% for women during a period of 17 years. Age-specific incidence rates increased proportionally with age for ages greater than 50 years. By contrast, there was a slight but systematic risk reduction in younger age classes.(ABSTRACT TRUNCATED AT 400 WORDS)