CANCER EXCESSES IN THE CLINICAL COHORT OF THE RAMAZZINI INSTITUTE Ramazzini Days October 27, 2017 - Carpi Angela Guaragna, MD Director of the Cancer Clinical Center of the Ramazzini Institute, Bologna

Cancer in Italy in 2016 366,000 new diagnoses of cancer every year, 55% among men, 45 % among women. and 176,000 deaths due to cancer 6,000-16,000 (?) estimated new diagnoses of occupational cancers (1.6-4.3 %, probably understimated)

Cancer in Italy in 2016 Incidence of cancer in Italy by age: 0-49 11 % 0-49 11 % 50-69 39 % 70 + 50 % Incidence and the type of tumor changes in different age groups.

Cancer in Italy in 2016 Rank Males Females 1° Prostate (19%) Breast (30%) 2° Lung (15%) Colorectal (13%) 3° Lung (6%) 4° Bladder (11%) Body of uterus (5%) 5° Stomach (4%) Thyroid (5%) Top five most frequently diagnosed cancers by sex. Pool Airtum 2008-2012. Cancer in Italy Airtum 2016.

Cancer in Italy in 2016 Rank Males Females 1° Lung (26%) Breast (17%) 2° Colorectal (10%) Colorectal (12%) 3° Prostate (8%) Lung (11%) 4° Liver (7%) Pancreas (7%) 5° Stomach (6%) Top five most frequent causes of cancer death by sex. Pool Airtum 2008-2012. Cancer in Italy Airtum 2016.

Cancer in Italy in 2016 Survival The survival rate at 5 years has increased significantly for both men and women: Men: 57% Women: 63% It was 39% for men and 53% for women between 1990-1992. Pool Airtum 2008-2012. Cancer in Italy Airtum 2016.

Cancer in Italy in 2016 Survival The improvement in 5 year survival rate is marked in frequent tumors such as: Prostate cancer: 91% survival Breast cancer: 87% Colorectal cancer: 64% for men and 63% for women Type of cancers for which early detection may be effective. Pool Airtum 2008-2012. Cancer in Italy Airtum 2016.

What are the annual costs for Cancer in Italy What are the annual costs for oncological disease? Total healthcare cost (1): € 112 bn Oncological healthcare cost (2): € 7.5 bn (6.7% of total healthcare cost). Future: increase in costs (more specific but more expensive treatments) and prevalence (aging population, increased survival). (1) ISTAT - 2011 (2) Economist Intelligence Unit - 2009

Manca da Ralph Cancer is not a single disease with a single cause or treatment (multifactorial disease). It develops when cells in the body grow in an uncontrolled and abnormal way. An individual’s risk of developing a cancer is influenced by a combination of factor including personal habits such as smoking and alcohol consumption, exposure to carcinogens in the general and occupational environment, genetics, sex, ethnicity, age, and so on.

To fight cancer, as a major public health problem, we need to revise the present control strategies, reinforcing: Primary prevention: identification of carcinogenic agents Secondary prevention: early detection of oncological lesions of certain types of tumor

Primary prevention: with the Cesare Maltoni Cancer Research Center. For more than 30 years the Ramazzini Institute has pursued this strategy for: Primary prevention: with the Cesare Maltoni Cancer Research Center. This Center, with over 200 compounds studies, is the second largest program in the world for the experimental identification of carcinogens.

Secondary prevention: with the Clinical Center for Cancer Prevention.

The aims of this presentation are: To illustrate the Ramazzini Institute Clinical activity for early detection of oncological lesions To show if the various types of tumors detected among unselected patients, referring to our Clinical Center are affected by the type of occupational activity – administrative/managerial (white collar) or workers (blue collar) – and To show if there are some occupationally-related types of tumor

Ramazzini Institute, Bologna Structures and Activity Clinical Center for Cancer Prevention Ramazzini Institute, Bologna Structures and Activity

Clinical Center for Cancer Prevention The Clinical Center for Cancer Prevention at the Ramazzini Institute was opened in Bologna in June 2002. The aim of the Center is the EARLY DETECTION of oncological lesions among people particularly at risk of developing cancer by age and/or by occupation.

Clinical Center for Cancer Prevention THE STRUCTURE The Center has: five surgeries for specialistic visits a digital mammography unit a bone densitometry (DEXA) unit a ultrasonography unit a cytopathology laboratory blood tests and lab analysis

Clinical Center for Cancer Prevention For each patient questionnaire data are collected: demographics data and family history, occupational activity, lifestyle, noteworthy symptoms, past pathologies. This enables stratification of people at risk of developing oncological lesions.

Clinical Center for Cancer Prevention On the basis of the data collected select basic diagnostic investigations are recommended, if necessary, for cancer screening and prevention, such as ultrasound-scan, mammography, fecal occult blood test and cytological examinations (sputum, breast fine needle aspiration and secretions, urine and cervical tests).

Clinical Center for Cancer Prevention After making a precise record of job details (type of job performed, duration, exposure to potential carcinogens, type and duration of exposure), we divide the people in blue collar and white collar. All are examinated following a standardized and systematic protocol.

Clinical Center for Cancer Prevention: Results

Clinical Center for Cancer Prevention Clinical Cohort Sex Blue collar White collar Total Males 1.531 706 2.237 Females 3.109 2.654 5.763 4.640 3.360 8.000

Clinical Center for Cancer Prevention Clinical Cohort performed from June 2002 to December 2016, by sex and age

Cancer Clinical Center The Ramazzini Institute, with the support of members, through various initiatives, can guarantee a free oncological check for people over sixty-five, as well as free follow-up for patients with neoplastic disease. Meaning 11% of our examinations are free

Asymptomatic tumors are in most cases completely curable! Total malignant tumors observed from June 2002 to December 2016, distributed by sex and symptoms Malignant tumours 2002-2016 Males Females Total Asymptomatic 89 164 253 55% Symptomatic 39 167 206 45% 128 331 459 100% Asymptomatic tumors are in most cases completely curable!

Total malignant tumors observed from June 2002 to December 2016, distributed by site and by sex Syte Males Females Total Prostate 43 Breast 250 252 Skin_no Mel 24 21 45 Colorectal 16 Skin_Melanoma 15 Cervix 8 31 Bladder 10 7 23 Kidney 9 Uterus 6 Other sytes 11 Tyroid TOTAL 128 5 12 331 19 459

Total malignant tumors observed from June 2002 to December 2016, distributed by working categories, sex and age group BLUE: Total 267 of which 88 (33%) Males and 179 (67%) Females WHITE: Totale 192 di cui 40 (21%) Males and 152 (79%) Females TOTAL: 459 cases of which 128 (28%) Males and 331 (72%) Females

Comparison of the incidence of some types of tumor among blue or white collar Blue Collar White Collar Male 1531 706 Female 3109 2654 TOTAL 4640 3360   Syte (%) Prostate 34 (2.0) 9 (1.0) Skin Non-Mel 14 10 Colon 2 (0.3) Bladder 7 (0.4) 3 Melanoma 5 Kidney 4 (0.2) Breast 139 (4.0) 97 Skin Non -Mel 12 (0.1) 13 (0.5) Cervix Uterus

Case report showing the consistency of the approch S. R. M 73 years old Carcinogens : asbestos, railway tobacco smoke Entered follow-up at the R.I. Clinical Cancer Prevention Center from the age of 59 60 years: bladder cancer in early stage, diagnosed by cytological examination of urine sediment (trans-uretral bladder resection) 68 years: left kidney cancer, diagnosed by abdominal ultrasonography (lumpectomy) 70 years: left kidney cancer, diagnosed by abdominal ultrasonography (lumpectomy) This case shows the importance of early detection by cancer surveillance

Conclusion The small number of cases in our clinical cohort does not allow us to draw definitive conclusions regarding some cancers excesses: However it is interesting to note the incidence of cases of melanoma among white collar males and females. At the moment and on the basis of the data available, no specific explanation is possible.

Conclusion Collection of information on occupational cancers is of primary importance in planning targeted prevention programs. Occupational cancers are of major concern in terms of mortality and lost economic productivity. Some occupational cancers are often preventable and, if detected in early stages (often asymptomatic), completely curable Preventive campaigns to evaluate ongoing risk and current exposure are strongly recommended to health policy-makers.

Most types of cancer are not caused by bad luck! Conclusion Our experience once more highlights the importance of cancer surveillance during the development of neoplastic disease. This lowers mortality rates for cancer, significantly increasing survival and improving the quality of life. However the first goal is to decrease the incidence of cancer through the reducing and remedying environmental carcinogens and correcting the risk factors related to lifestyle. Most types of cancer are not caused by bad luck!