SETIL: Italian multicentric epidemiological case-control study on risk factors for childhood leukaemia, non hodgkin lymphoma and neuroblastoma: study population and prevalence of risk factors in Italy.

BACKGROUND: Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case-control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. METHODS: The study was carried out in 14 Italian regions (78.3% of Italian population aged 0-10). It included leukaemia, NHL and neuroblastoma cases incident in 0-10 year olds in 1998-2001, registered by the Italian Association of Paediatric Haematology and Oncology (AIEOP) (accrual over 95% of estimated incidence). Two controls for each leukaemia case were randomly sampled from the Local Health Authorities rolls, matched by gender, birthdate and residence. The same controls were used in NHL and neuroblastoma studies. Parents were interviewed at home on: physical agents (ELF-MF and ionizing radiation), chemicals (smoking, solvents, traffic, insecticides), occupation, medical and personal history of children and parents, infectious diseases, immunizations and associated factors. Occupational exposure was collected using job specific modules. ELF-MF was measured in the main rooms (spot measurement) and close to child's bed (48 hours measurement). RESULTS: The study included: 683 leukaemia cases (87% ALL, 13% AnLL), 97 NHL, 155 neuroblastomas, and 1044 controls. CONCLUSIONS: SETIL represents a data source on exposure of Italian children to a broad array of potential carcinogenic factors.

What reasons lie behind long-term survival differences for gastric cancer within Europe?

BACKGROUND: Wide geographic variations in survival for gastric cancer in Europe have been reported. The aim of this study was to analyse the effect of stage at diagnosis, treatment and cancer characteristics on long-term survival for gastric cancer in populations covered by cancer registries. METHODS: We analysed survival in 4620 cases of gastric cancer from 17 European population-based cancer registries from 8 countries. Univariate and multivariate regression of relative survival were performed. RESULTS: Five-year relative survival varied between 10.6% and 24.0%, while 10-year survival ranged from 7.7% to 23.0%. After adjustment for age and sex, the regional excess hazard ratio (EHR) of death was significantly higher in Ragusa, Granada, Yorkshire, Slovakia, Slovenia and Poland than in France, Northern Italy, The Netherlands and the Basque Country. After further adjustment for surgical resection versus no resection (a proxy of stage), the EHR of death remained significantly higher only in Granada and Yorkshire than in the reference country (France). After adjustment for stage, the EHR was significantly higher only in Yorkshire (EHR: 1.51; 95% confidence interval (CI): 1.29-1.77). The EHR in this area was limited to the first year following diagnosis. CONCLUSION: Differences across Europe in gastric cancer survival depend to a large extent on differences in stage at diagnosis. However they do not explain all variations. Quality of management and treatment can explain some differences.

Socio-economic and other correlates of Kaposi sarcoma-associated herpesvirus seroprevalence among older adults in Sicily.

The virus that causes Kaposi sarcoma, KS-associated herpesvirus (KSHV, also known as human herpesvirus 8) has an unusual distribution and poorly characterized modes of transmission. To clarify these issues, socio-demographic correlates of KSHV seroprevalence were examined in a population-based study. In 1,154 randomly sampled adults (aged 32- 92, mean 71 years) throughout Sicily, KSHV antibodies were detected with four assays and a conservative algorithm. Seroprevalence was re-weighted to the population. Odds ratios with 95% confidence intervals (OR, CI) from multivariate logistic regression were used to estimate associations of seroprevalence with interview data. KSHV seroprevalence was 8.5%, including 5.3% among men (N = 848) and 11.5% among women (N = 306, P = 0.22). Seroprevalence was higher with residence in a smaller community during childhood (P(trend) = 0.03) and working with plants/soil during adulthood (OR 2.9, CI 1.1-7.9); these were especially strong among women. Among men, seroprevalence was significantly associated with lower education (OR 2.6, CI 1.1-5.9) and migration to a larger community (OR 0.3, CI 0.1-0.9). Other demographic and household variables were unrelated to seroprevalence. From these data, KSHV in Sicily appears to be related to low socio-economic status, but micro-endemicity in small communities cannot be excluded.

Oral contraceptive use and BRCA penetrance: a case-only study.

BACKGROUND: Women with deleterious mutations in BRCA genes are at increased risk of breast cancer. However, the penetrance of the genetic trait may be regulated through environmental factors. This multinational case-only study tested the interaction between oral contraceptive use and genetic susceptibility in the occurrence of breast cancer. METHODS: We recruited 3,123 patients diagnosed with breast cancer before the age of 45 years. Participants were classified according to their probability of carrying a BRCA mutation on the basis of their family history of breast and ovarian cancer. According to a case-only approach, the frequency of relevant exposures among breast cancer cases with high probability of BRCA mutation ("genetic cases") was compared with the frequency of the same exposures among breast cancer cases with a low probability of BRCA mutation ("sporadic cases"). The interaction odds ratios (OR) and 95% confidence intervals (CI) for oral contraceptive use were estimated by unconditional logistic regression, after controlling for potentially confounding variables. RESULTS: The analysis was carried out comparing 382 "genetic" and 1,333 "sporadic" cases. We found a borderline significant interaction between genetic breast cancer and oral contraceptive use for ever users compared with never users (OR, 1.3; 95% CI, 1.0-1.7). The greatest interaction OR was found for women who started using pill at 18 to 20 years (OR, 1.6; 95% CI, 1.1-2.3). CONCLUSION: These results suggest that BRCA mutation carriers, as well as women with a significant family history of breast and ovarian cancer are more vulnerable to exogenous hormones in oral contraceptives.

Risk factors for classical Kaposi sarcoma in a population-based case-control study in Sicily.

BACKGROUND: Classical Kaposi sarcoma is a rare complication of Kaposi sarcoma-associated herpes virus (KSHV) infection. We conducted a population-based, frequency-matched case-control study in Sicily to further investigate the reported inverse relationship between smoking and classical Kaposi sarcoma and to identify other factors associated with altered risk. METHODS: All incident, histologically confirmed classical Kaposi sarcoma cases in Sicily were eligible. A two-stage cluster sample design was applied to select population controls. KSHV seropositivity was determined using four antibody assays (K8.1 and orf73 enzyme immunoassays and two immunofluorenscence assays). Using SAS-callable SUDAAN, we compared the characteristics of classical Kaposi sarcoma cases and KSHV-seropositive controls. Odds ratios (OR) and 95% confidence intervals (CI) are presented. RESULTS: In total, 142 classical Kaposi sarcoma cases and 123 KSHV-seropositive controls were recruited. Current cigarette smoking was associated with reduced risk of classical Kaposi sarcoma amongst males (OR, 0.20; 95% CI, 0.06-0.67). Edema was associated with classical Kaposi sarcoma, but only when it presented on the lower extremities (OR, 3.65; 95% CI, 1.62-8.23). Irrespective of presentation site, diabetes and oral corticosteroid medications were associated with increased risk (OR, 4.73; 95% CI, 2.02-11.1 and OR, 2.34; 95% CI, 1.23-4.45, respectively). Never smoking, diabetes, and oral corticosteroid medication use were all independently associated with classical Kaposi sarcoma risk. DISCUSSION: We confirmed previous reports that cigarette smoking was associated with a reduced risk of classical Kaposi sarcoma, and we found that risk was lowest among current smokers. We also found that classical Kaposi sarcoma risk was strongly and independently associated with oral corticosteroid use and diabetes. Corroboration of these observations and investigation of possible underlying mechanisms are warranted.

Occupation and skin cancer: the results of the HELIOS-I multicenter case-control study.

BACKGROUND: Non-melanoma skin cancer (NMSC) is the most frequent tumour among Caucasian populations worldwide. Among the risk factors associated with this tumour, there are host-related factors and several environmental agents. A greater likelihood of high exposure to physical agents (with the exception of solar radiation) and chemical agents depends on the work setting. Our objective is to evaluate the role of occupational exposures in NMSC, with special emphasis on risk factors other than solar radiation and skin type. METHODS: We analysed 1585 cases (1333 basal cell carcinoma (BCC) and 183 squamous cell carcinoma (SCC)) and 1507 controls drawn from the Helios-I multicenter study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression mixed models. RESULTS: For NMSC as a whole (both histological types), miners and quarrymen, secondary education teachers, and masons registered excess risk, regardless of exposure to solar radiation and skin type (OR 7.04, 95% CI 2.44-20.31; OR 1.75, 95% CI 1.05-2.89 and OR 1.54, 95% CI 1.04-2.27, respectively). Frequency of BCC proved higher among railway engine drivers and firemen (OR 4.55; 95% CI 0.96-21.57), specialised farmers (OR 1.65; 95% CI 1.05-2.59) and salesmen (OR 3.02; 95% CI 1.05-2.86), in addition to miners and quarrymen and secondary education teachers (OR 7.96; 95% CI 2.72-23.23 and OR 1.76; 95% CI 1.05-2.94 respectively). The occupations that registered a higher risk of SCC (though not of BCC) were those involving direct contact with livestock, construction workers not elsewhere classified (OR 2.95, 95% CI 1.12-7.74), stationary engine and related equipment operators not elsewhere classified (OR 5.31, 95% CI 1.13-21.04) and masons (OR 2.55, 95% CI 1.36-4.78). CONCLUSION: Exposure to hazardous air pollutants, arsenic, ionizing radiations and burns may explain a good part of the associations observed in this study. The Helios study affords an excellent opportunity for further in-depth study of physical and chemical agents and NMSC based on matrices of occupational exposure.

Correlates of Human Herpesvirus-8 DNA detection among adults in Italy without Kaposi sarcoma.

BACKGROUND: The presence of Human Herpesvirus-8 (HHV8) DNA is predictive of Kaposi sarcoma (KS) among patients with HIV-associated or iatrogenic immunosuppression. However, correlates of HHV8-DNA detection in the general population remain undefined. METHODS: We assessed correlates of HHV8-DNA detection among Italian adults without KS who had antibodies against HHV8-latent nuclear antigen by immunofluorescence assay. HHV8-K6 DNA sequences were detected in peripheral blood mononuclear cells using TaqMan PCR. RESULTS: Of the 158 subjects 26 (16.5%) had detectable HHV8-DNA [median copies/million cells, 53; (13-2128)]. Adjusted for age, sex, and laboratory, HHV8-DNA was detected more frequently in participants with >7 total residents in the childhood home [OR = 3.7 (1.5-9.1)], >2 younger siblings [OR = 2.6 (1.1-6.5)], and current cardiovascular [OR = 3.6 (1.3-9.7)] or renal [OR = 3.1 (1.2-8.0)] disease. Excluding the participants using immune modulating drugs, HHV8-DNA was more frequent among those with low red blood cells (RBC) [<4.5 10(6)/microl; OR = 5.3 (1.7-16.2)], slightly elevated mean corpuscular volume [>92 microm3/red cell; OR = 2.8 (1.0-7.8)], and mild thrombocytopenia [<151 K/microl; OR = 5.6 (1.9-16.3)]. CONCLUSIONS: Presence of HHV8-DNA in elderly Italians is associated with childhood crowding, low RBCs, and platelets, perhaps indicating roles for early infection and chronic inflammation. These risk factors are the first to be reported for non-immunosuppressed HHV8-seropositive adults.

Upper gastrointestinal tract cancers: oesophagus, stomach, liver, gallbladder and biliary ducts, pancreas.

In this paper temporal trend of the upper gastrointestinal tract cancers in the Italian Network of Cancer Registries (pool AIRT) are analysed during the period 1986-1997. Oesophagus cancer (4477 cases and 4226 deaths analysed) showed a decrease in incidence rates that was statistically significant among males and less evident in recent years among females. Mortality is significantly decreasing both among males (since 1993) and females. Stomach cancer (34282 cases and 26430 deaths) had a stable decreasing trend, in both sexes, for both incidence which decreased at a rate of more 3% every year, and of mortality, mean annual rate decrease over 4%. As regards liver cancer (13893 cases 13655 deaths) an increasing incidence trend (up to 1993 among males) has been documented; mortality was stable. Cancers of the biliary tract (6662 cases and 5065 deaths) showed stable rates both in incidence (slightly decreasing among females) than in mortality. Pancreas cancer (13300 cases and 12937 deaths) presented increasing incidence in both sexes with stable mortality rates.

Breast carcinoma survival in Europe and the United States.

BACKGROUND: Breast carcinoma survival rates were found to be higher in the U.S. than in Europe. METHODS: Multiple regression analysis of breast carcinoma survival rates among women diagnosed between 1990 and 1992 was performed using clinical data from population-based case series from the Surveillance, Epidemiogy, and End Results (SEER) program (13,172 women) and the European Concerted Action on survival and Care of Cancer Patients (EUROCARE) project (4478 women). RESULTS: Early-stage tumors (T1N0M0) were more frequent in the SEER data (41% of cases) than in the EUROCARE data (29%). In the SEER data, early tumors were more frequent in women age > or = 65 years (43%) than in younger women (38%), whereas the reverse was true in the European data (25% vs. 31%). In both case series, > 90% of women underwent surgery and 81-82% underwent lymphadenectomy, but the number of axillary lymph nodes evaluated was higher in the SEER data than in the EUROCARE data. The 5-year survival rate was higher in the U.S. case series (89%) than in the European series (79%). This differential was observed for each stage category evaluated: early (T1N0M0), large lymph node-negative (T2-3N0M0), lymph node-positive (T1-3N+M0), locally advanced (T4M0), and metastatic (M1) tumors. The overall relative excess risk (RER) of death was significantly higher (RER, 1.37; 95% confidence interval [95% CI], 1.25-1.50) among European women compared with U.S. women (referent group). Adjustment for stage, age, surgery, and the number of lymph nodes evaluated explained most of the excess risk (RER, 1.07; 95% CI, 0.98-1.17). CONCLUSIONS: Transatlantic differences in the 5-year survival rates for women diagnosed with breast carcinoma between 1990 and 1992 were attributable mainly to differences in stage of disease. Resources should be invested to achieve earlier diagnosis of breast carcinoma in Europe, especially for elderly women.

Risk factors for classical Kaposi's sarcoma.

BACKGROUND: Classical Kaposi's sarcoma (KS) is a malignancy of lymphatic endothelial skin cells. Although all forms of KS are associated with the KS-associated herpesvirus (KSHV), classical KS occurs in a small fraction of KSHV-infected people. We sought to identify risk factors for classical KS in KSHV-infected individuals. METHODS: Lifestyle and medical history data from case patients with biopsy-proven non-AIDS (non-acquired immunodeficiency syndrome) KS in Italy were compared by logistic regression analysis with data from population-based KSHV-seropositive control subjects of comparable age and sex. After KSHV immunofluorescence testing, randomly selected patients on the rosters of local physicians were identified as control subjects. Risk of KS was estimated by odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: From April 13, 1998, through October 8, 2001, we enrolled 141 classical KS case patients and 192 KSHV-seropositive control subjects of similar age (mean = 72 years for case patients and 73 years for control subjects) and sex (30% female case patients and 35% female control subjects). The strongest association was a reduced risk of KS with cigarette smoking (OR = 0.25, 95% CI = 0.14 to 0.45). Cigarette smoking intensity and duration could be evaluated for men, among whom the risk for KS was inversely related to the amount of cumulative smoking (P(trend)<.001). KS risk decreased approximately 20% (OR = 0.81, 95% CI = 0.74 to 0.89) for each 10 pack-years reported, and it was decreased sevenfold (OR = 0.14, 95% CI = 0.07 to 0.30) with more than 40 pack-years. In multivariable analysis, a decreased KS risk was associated with smoking (OR = 0.23, 95% CI = 0.12 to 0.44); but an increased KS risk was associated with topical corticosteroid use (OR = 2.73, 95% CI = 1.35 to 5.51), infrequent bathing (OR = 1.85, 95% CI = 1.04 to 3.33), and a history of asthma (OR = 2.18, 95% CI = 0.95 to 4.97) or of allergy among men (OR = 2.59, 95% CI = 1.15 to 5.83) but not among women (OR = 0.09, 95% CI = 0.003 to 2.76). KS was not related to other exposures or illnesses examined. CONCLUSION: Risk for classical KS was approximately fourfold lower in cigarette smokers, a result that requires confirmation by other studies. Identification of how smoking affects KS risk may lead to a better understanding of the pathogenesis of this malignancy and interventions for its prevention.