Renato Talamini

A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25.

Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 × 10-10). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 × 10-20 overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N′-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.

Interaction between tobacco and alcohol use and the risk of head and neck cancer: Pooled analysis in the international head and neck cancer Epidemiology consortium

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (ψ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases <45 years, 73% for cases >60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

Hepatitis C and Non-Hodgkin Lymphoma Among 4784 Cases and 6269 Controls From the International Lymphoma Epidemiology Consortium

BACKGROUND & AIMS Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkins lymphoma (NHL) subtypes after HCV infection. METHODS The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. RESULTS HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40-2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44-4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68-2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14-5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65-1.60). CONCLUSIONS These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).

Food groups, oils and butter, and cancer of the oral cavity and pharynx

SummaryTo elucidate the role of dietary habits, a study was carried out in 1992–1997 in the province of Pordenone in Northeastern Italy, and those of Rome and Latina in central Italy. Cases were 512 men and 86 women with cancer of the oral cavity and pharynx (lip, salivary glands and nasopharynx excluded) and controls were 1008 men and 483 women who had been admitted to local hospitals for a broad range of acute non-neoplastic conditions. The validated dietary section of the questionnaire included 78 foods or recipes and ten questions on fat intake patterns. After allowance for education, smoking, alcohol and total energy intake, significant trends of increasing risk with increasing intake emerged for soups, eggs, processed meats, cakes and desserts, and butter. Risk was approximately halved in the highest compared to the lowest intake quintile for coffee and tea, white bread, poultry, fish, raw and cooked vegetables, citrus fruit, and olive oil. The inverse association with oils, especially olive oil, was only slightly attenuated by allowance for vegetable intake. Thus, frequent consumption of vegetables, citrus fruit, fish and vegetable oils were the major features of a low-risk diet for cancer of the oral cavity and pharynx.

Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study

Objective: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. Methods: This was a case–control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. Results: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for ≥25 cigarettes/day) and for duration of smoking (OR = 37.2 for ≥40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for ≥56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). Conclusions: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Effect of obesity and other lifestyle factors on mortality in women with breast cancer.

A few lifestyle characteristics before cancer diagnosis have been suggested to modify the prognosis of breast cancer. Follow‐up information from 1,453 women with incident invasive breast cancer, diagnosed between 1991 and 1994 and interviewed within the framework of an Italian multicenter case‐control study, was used to assess the effect of obesity and of a large spectrum of other factors on breast cancer mortality. Five hundred and three deaths, including 398 breast cancer deaths, were identified. Hazard ratios (HR) for all‐cause and breast cancer mortality and corresponding 95% confidence intervals (CI), were calculated using Cox proportional hazards models and adjusted for age and breast cancer characteristics (stage and receptor status). Increased risk of death for breast cancer emerged for body mass index (BMI) ≥ 30 kg/m2 (HR = 1.38; 95% CI: 1.02–1.86), compared to <25, or waist‐to‐hip ratio (WHR) ≥ 0.85 (HR = 1.27; 95% CI: 0.98–1.64), compared to <0.80, and the strongest association was observed for women with BMI ≥30 and high WHR (≥0.85), compared to women with BMI <25 and WHR < 0.85 (HR = 1.57, 95% CI: 1.08–2.27). The unfavorable effect of high BMI was similar in women <55 and ≥55 years of age, whereas it was stronger in women with I–II stage than III–IV stage breast cancer. Low vegetable and fruit consumption and current or past smoking were also associated to marginally worse breast cancer survival. No significant relationship with survival after breast cancer emerged for several other major lifestyle factors, including physical activity, alcohol drinking, exogenous hormones use and fat intake. High BMI was the lifestyle risk factor that most consistently modified breast cancer prognosis in our study.

Clinical Features and Outcome of Primary Effusion Lymphoma in HIV-Infected Patients: A Single-Institution Study

PURPOSE To describe the clinical features and outcome of HIV-associated primary effusion lymphoma (PEL) and to compare them with those of the other HIV-associated non-Hodgkins lymphomas (NHLs). PATIENTS AND METHODS From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated in our institution. Clinical features and outcome of PEL patients were compared with the features and outcomes of 162 patients belonging to the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75). RESULTS Among the 277 NHL patients, PEL was diagnosed in 11 patients (4%). Eight of 11 patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimen. Complete remission was reached in 42% of patients, with a median survival time of 6 months. When the clinical features and outcome of 11 PEL patients were compared with the other three groups of patients affected by NHL, at the onset of the disease, no statistically significant differences were observed in demographic data, CD4 absolute number, HIV viremia plasma levels, and clinical characteristics. When we compared the outcome of PEL patients with the CBCL group, a statistically significant worse outcome was observed; however, the clinical outcome of PEL patients was not significantly different from the outcome observed in the other two groups (PBLOC and IBL groups). CONCLUSION PEL is a rare HIV-associated NHL type occurring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients.

Nutrition, social factors and prostatic cancer in a Northern Italian population

The relationship between prostate cancer and indicators of nutrition, diet and social factors was evaluated in a case-control study of 166 patients with histologically confirmed prostatic carcinoma and 202 control subjects hospitalized for acute diseases other than malignant, hormonal or urogenital. The relative risk increased with increasing body mass index, men being moderately overweight showing a 2.3 elevated risk, and those grossly overweight an over four-fold higher risk of prostate cancer, when allowance was made for several identified potential confounding factors. Cases also reported more frequent consumption of milk and other dairy products and meat, but no significant difference was noted for vegetable intake. The risk of prostate cancer was unrelated to marital status or indicators of social class based on occupation.

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.

Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy plus highly active antiretroviral therapy in patients with human immunodeficiency virus‐related, non‐Hodgkin lymphoma

The feasibility and efficacy of concomitant chemotherapy and highly active antiretroviral therapy (HAART) is still unknown in patients with human immunodeficiency virus (HIV)‐related malignancies. To evaluate the impact of chemotherapy plus HAART on the clinical course of patients with HIV‐related, systemic, non‐Hodgkin lymphoma (HIV‐NHL), the authors compared retrospectively a group of 24 patients with HIV‐NHL who were treated with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen plus HAART with a group of 80 patients who were treated with CHOP chemotherapy or a CHOP‐like regimen (i.e., cyclophosphamide, doxorubicin, teniposide, and prednisone with vincristine plus bleomycin) without receiving antiretroviral therapy.