Paola Zambon

Lung cancer and cigarette smoking in Europe: An update of risk estimates and an assessment of inter-country heterogeneity

Ten case‐control studies have been carried out in 6 European countries to investigate the major risk factors for lung cancer. Carcinogenic effect from cigarette smoke was the most relevant interest in our study, which has included 7,609 cases of lung cancer and 10,431 controls, mainly population based. The results indicate elevated odds ratios (ORs; 23.9 among men and 8.7 among women) with attributable risks exceeding 90% for men and close to 60% for women. A large, and statistically significant, variability of the results across countries was detected after adjusting for the most common confounding variables, and after controlling, at least in part, for the instability of the ORs due to the small number of non‐smokers in some of the study subsets. This pattern of lung cancer risk associated with cigarettes smoke, across different European regions, reflects inherent characteristics of the studies as well as differences in smoking habits, particularly calender periods of starting, and it is likely to have been influenced by effect modifiers like indoor radon exposure, occupation, air pollution and dietary habits.

Food groups and risk of squamous cell esophageal cancer in Northern Italy

To better understand the nutritional etiology of squamous cell esophageal cancer, we conducted a case‐control study in 3 areas of northern Italy. A total of 304 incident, histologically confirmed cases of squamous cell carcinoma of the esophagus (275 men, 29 women) and 743 hospital controls (593 men, 150 women) with acute, non‐neoplastic conditions, not related to smoking, alcohol consumption or long‐term diet modification, were interviewed during 1992 to 1997. The validated food‐frequency questionnaire included 78 questions on food items or recipes, which were then categorized into 19 main food groups, and 10 questions on fat intake pattern. After allowance for age, sex, education, area of residence, tobacco smoking, alcohol drinking and non‐alcohol energy, a significant increased risk emerged for high consumption of soups (OR=2.1 for the highest vs. lowest quintile), whereas inverse associations with esophageal cancer risk were observed for pasta and rice (OR=0.7), poultry (OR=0.4), raw vegetables (OR=0.3), citrus fruit (OR=0.4) and other fruit (OR=0.5). The associations with dietary habits were consistent in different strata of tobacco smoking and alcohol drinking. Among added lipids, olive oil intake showed a significant reduction of esophageal cancer risk, even after allowance for total vegetable consumption (OR=0.4), while butter consumption was directly associated with this risk (OR=2.2). Our results thus provide further support to the evidence that raw vegetables and citrus fruit are inversely related to the risk of squamous cell esophageal cancer and suggest that olive oil may also reduce this risk. Int. J. Cancer 87:289–294, 2000.

The advantage of women in cancer survival: an analysis of EUROCARE-4 data.

We analysed 1.6 million population-based EUROCARE-4 cancer cases (26 cancer sites, excluding sex-specific sites, and breast) from 23 countries to investigate the role of sex in cancer survival according to age at diagnosis, site, and European region. For 15 sites (salivary glands, head and neck, oesophagus, stomach, colon and rectum, pancreas, lung, pleura, bone, melanoma of skin, kidney, brain, thyroid, Hodgkin disease and non-Hodgkins lymphoma) age- and region-adjusted relative survival was significantly higher in women than men. By multivariable analysis, women had significantly lower relative excess risk (RER) of death for the sites listed above plus multiple myeloma. Women significantly had higher RER of death for biliary tract, bladder and leukaemia. For all cancers combined women had a significant 5% lower RER of death. Age at diagnosis was the main determinant of the womens advantage, which, however, decreased with increasing age, becoming negligible in the elderly, suggesting that sex hormone patterns may have a role in womens superior ability to cope with cancer.

Pattern of cancer risk in persons with AIDS in Italy in the HAART era

A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16–69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997–2004 compared with 1986–1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997–2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.

Smoking, type of alcoholic beverage and squamous-cell oesophageal cancer in northern Italy

Between 1992 and 1997, we conducted a case‐control study of oesophageal cancer in 3 areas of northern Italy. Cases were 275 men, ages 39–77 years (median age 60), with a first incident squamous‐cell carcinoma of the oesophagus. Controls were 593 men, ages 36–77 years (median age 60) admitted for acute illnesses, unrelated to tobacco and alcohol, to major hospitals of the areas under surveillance. Number of daily cigarettes was strongly associated with risk [odds ratio (OR) for ≥25 cigarettes/day = 7.0)]. Long‐duration smoking showed particularly elevated ORs (OR = 6.4 for ≥35 years), and excess risk declined after smoking cessation (OR = 1.5 after ≥10 years). Oesophageal cancer risk steeply rose with increasing level of alcohol consumption. ORs were 6.2 for 35–55 drinks and 24.5 for 84 drinks or more per week. No trend in risk emerged for duration of alcohol drinking or age at start of drinking. The risk in the highest joint level of alcohol drinking and current smoking was increased 130 folds (i.e., compatible with a multiplicative model). Excess risk in drinkers chiefly derived from wine. In conclusion, alcohol drinking and cigarette smoking were both important, but the roles of dose and duration of exposure differed. The association with alcohol was stronger than the one with smoking by exposure intensity, but apparently unaffected by duration or other temporal variables. Int. J. Cancer 86:144–149, 2000.

Gender differences in lung cancer risk by smoking: a multicentre case-control study in Germany and Italy.

Several studies in the past have shown appreciably higher lung cancer risk estimates associated with smoking exposure among men than among women, while more recent studies in the USA report just the opposite. To evaluate this topic in a European population we conducted a case–control study of lung cancer in three German and three Italian centres. Personal interviews and standardized questionnaires were used to obtain detailed life-long smoking and occupational histories from 3723 male and 900 female cases and 4075 male and 1094 female controls. Lung cancer risk comparing ever-smokers with never-smokers was higher among men (odds ratios (OR) adjusted for age and centre = 16.1, 95% confidence interval (CI) 12.8–20.3) than among women (OR = 4.2, CI 3.5–5.1). Because the smoking habits of women were different from men, we conducted more detailed analyses using comparable levels of smoking exposure. After restriction to smokers and adjustment for other smoking variables, risk estimates did not differ appreciably between genders. The analysis of duration of smoking (0–19, 20–39, 40+ years) adjusted for cigarette consumption and time since quitting smoking revealed similar risk estimates in men (OR = 1.0, 3.3 [CI 2.6–4.2], 4.1 [CI 3.1–5.6]) and women (OR = 1.0, 2.7 [CI 1.7–4.1], 3.3 [CI 1.9–5.8]). The same was true of the analysis of average or cumulative smoking consumption, and also of analyses stratified by different histological types. We conclude that for comparable exposure to tobacco smoke, the risk of lung cancer is comparable in women and men.

Role of macronutrients, vitamins and minerals in the aetiology of squamous-cell carcinoma of the oesophagus.

Between 1992 and 1997 we conducted a case‐control study of oesophageal cancer in 3 areas of northern Italy. Cases were 304 patients (29 women), ages 39–77 years (median age 60 years), with a first incident squamous‐cell carcinoma (SCC) of the oesophagus. Controls were 743 patients (150 women), ages 35–77 years (median age 60 years), admitted for acute illnesses, unrelated to tobacco and alcohol, to major hospitals of the areas under surveillance. We derived estimates of daily dietary intake of 6 macronutrients, cholesterol, and 20 micronutrients or minerals from a validated food‐frequency questionnaire, including 78 food groups and recipes and 15 questions on individual eating patterns. After allowance for age, gender, area of residence, education, body mass index, physical activity, smoking habit, alcohol consumption and energy intake, most micronutrients were inversely associated with oesophageal SCC risk. Highly significant associations emerged for monounsaturated fatty acids [odds ratio (OR) in highest vs. lowest intake quintile = 0.5]; carotene (OR = 0.3); lutein + zeaxanthin (OR = 0.4); vitamin C (OR = 0.4); and niacin (OR = 0.5). Only retinol appeared to be positively related to risk (OR = 1.9). The effect of the above nutrients, expressed as ORs, appeared to be similar in non‐smokers and smokers, and non/light drinkers and heavy drinkers. Int. J. Cancer 86:626–631, 2000.

Lung cancer and cigarette smoking in women: a multicenter case-control study in Europe

The association between cigarette smoking and lung cancer risk in women was investigated within the framework of a case‐control study in 9 centres from 6 European countries. Cases were 1,556 women up to 75 years of age with histologically confirmed primary lung cancer; 2,450 controls with age distribution similar to cases were selected. The predominant cell type was adenocarcinoma (33.5%), with similar proportions for squamous‐cell type (26.4%) and small‐cell carcinoma (22.3%). Overall, smoking cigarettes at any time was associated with a 5‐fold increase in lung cancer risk (odds ratio 5.21, 95% confidence interval 4.49–6.04); corresponding figures for current smoking habits were 8.94, 7.54–10.6. The association showed a dose‐response relationship with duration of the habit and daily and cumulative lifetime smoking. A significant excess risk of 70% was associated with every 10 pack‐years smoked. After 10 years of smoking cessation, the relative risk decreased to 20% compared to current smokers. The following characteristics were associated with a higher relative risk: inhalation of smoke, smoking non‐filter cigarettes, smoking dark‐type cigarettes and starting at young age. The association was observed for all major histological types, being the strongest for small‐cell type carcinoma, followed by squamous‐cell type and the lowest for adenocarcinoma. The proportion of lung‐cancer cases in the population attributable to cigarette smoking ranged from 14% to 85%. We concluded that women share most features of the association between cigarette smoking and lung cancer observed in men. Int. J. Cancer 88:820–827, 2000.

Occupational risk factors for lung cancer in men and women: a population-based case-control study in Italy*

AbstractObjective: We investigated the role of occupation in lung cancerogenesis in two Northern Italian areas. Methods: During 1990–1992, occupational histories were obtained for 1171 incident lung cancer cases (956 men, 176 women) and 1553 population controls (1253 men, 300 women) and were evaluated for having been employed in jobs entailing exposure to known or suspected lung carcinogens. A further exploratory analysis on other job titles and branches of industry was conducted. Results: Among men, we found a smoking-adjusted odds ratio (OR) of 2.1 (95% confidence interval: 1.6–2.8) for exposure to known carcinogens, corresponding to a population attributable risk of 9.5%(6.0–13.0). Non-ferrous metal workers and painters had a significantly increased risk. No association was found for exposure to suspected carcinogens. In the exploratory analysis, the OR was increased for cleaners (OR: 2.7; 1.0–7.4), bakers (5.7; 1.4–24), tailors (6.9; 1.2–39), plumbers and pipe fitters (2.6; 1.0–6.4), welders and flame–cutters (5.6; 2.1–15), dockers and freight handlers (1.7; 1.0–2.7) and construction workers (1.4; 1.1–1.9). Female glass workers, laundry/dry cleaners and workers in rubber industry had an increased risk. Conclusions: The study indicates that a sizable proportion of lung cancers among men may be due to occupational exposures and suggests that exposure to lung carcinogens occurs in different jobs in women compared to men.

Flavonoids and risk of squamous cell esophageal cancer

The relation between 5 classes of flavonoids (flavanones, flavan‐3‐ols, flavonols, flavones and anthocyanidines) and esophageal cancer was investigated using data from a case‐control study conducted between 1992 and 1997 in 3 areas of northern Italy. The study included 304 cases (275 men, 29 women) with a first diagnosis of squamous‐cell carcinoma of the esophagus and 743 controls (593 men, 150 women) with no history of cancer, admitted for acute illnesses, unrelated to tobacco and alcohol consumption, to major hospitals of the areas under surveillance. Dietary habits were investigated using a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CI) were computed after allowance for age, sex, study centre, years of education, alcohol drinking, tobacco smoking, body mass index and energy intake. An inverse association emerged between flavanone intake and esophageal cancer risk (OR = 0.38 for the highest vs. the lowest quintile, 95% CI = 0.23–0.66). The inverse relation between flavanones and esophageal cancer tended to be stronger in those who drank ≥6 drinks/day. In conclusion, this study suggests that flavanone intake is inversely associated with esophageal cancer risk and may account, with vitamin C, for the protective effect of fruit, especially citrus fruit, on esophageal cancer.