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Cancer Atlas, 2nd edition Major risk factors for cancer Prof Paolo Vineis Imperial College London Session code: CTS.4.230 www.worldcancercongress.org Cancer as a multifactorial process The Hallmarks of Cancer From D Hanahan, The Lancet, February 8, 2014 Genes or environment? Stomach cancer incidence in Hawaii Japanese and Caucasians by place of birth, 1973-77 Heredity Can Affect Many Types of Cancer Inherited Conditions That Increase Risk for Cancer (5-10% of cases) Heritability of Colorectal Cancer Familial High Penetrance APC (FAP), MMR (Lynch), TGFβR2, POLD, SMAD4 (Familial CRC) Sporadic Low Penetrance 8q23, 8q24, 10p14, 11q23, 14q22, 15q13, 18q21 (SMAD7), 19q31, 20p12, GSTM1 null, NAT2 G/G Modifier Alleles Genes Environment 2 Smoking is associated with at least 16 types of cancers. Nasal cavity and paranasal sinus Oral cavity Laryn x Pharynx Esophag us Bone marrow (acute myeloid leukemia) Cancer can be caused by a variety of known risk factors, many of them preventable. 3 43% Exposure to betanaphthylamine Liv er 23% Stoma ch 1 80— RATE PER 100,000 60— 40— Rates in Japanese Hawaiians are more similar to cancer rates of white Hawaiians, rather than Japanese 23.9 in22.4 Japan. Japanese 20— in Hawaii 6.3 91.4 13% 0.7% General male populatio n Colon Cancer Ovari es Cerv ix Benzidine manufactur e Mixed exposure to carcinogenic amines 40 30 20 10 0 1. Be as lean as possible without becoming underweight. 2. Be physically active for at least 30 minutes every day. 3. Avoid sugary drinks. Limit consumption of energy-dense foods (particularly processed foods high in added sugar, low in fiber, or high in fat). 4. Eat a variety of vegetables, fruits, whole grains, and pulses such as beans. ESTIMATED HPV PREVALENCE (%), ALL TYPES COMBINED, AMONG WOMEN BY REGION, 1995-2009 5. Limit consumption of red meats (such as beef, pork and lamb) and avoid processed meats. 6. Limit alcoholic drinks to 2 drinks per day for men and 1 drink per day for women. 14% Europe 9% Asia 16% 7. Limit consumption of salty foods and foods processed with salt (sodium). 21% Latin America & the Caribbean Hawaii Whites 50 4 Northern America 34.9 60 The World Cancer Research Fund (WCRF/AICR) has released (and periodically updates) guidelines for cancer prevention: Compared with Northern America, the estimated prevalence of human papillomavirus (HPV), the leading cause of cervical cancer, is about three times as high in Europe and Latin America, and four times as high in Africa. 5% Africa 17.4 Japanese in Japan 0— Urinary bladder Dietary recommendations from the WCRF/AICR 90 70 Uret er Colorect um 100— 100 80 Kidne ys CANCER INCIDENCE AGESTANDARDIZED RATES (WORLD) PER 100,000, CIRCA 1970 Distillers of betanaphthylamine Lungs Pancre as Cancer is more often caused by the environment a person lives in, rather than his or her innate biology. 5 100% Increasing intensity of occupational exposure to carcinogens carries increasing risk of developing cancer. 8. Don’t use supplements to protect against cancer. Instead, choose a balanced diet with a variety of foods. Human papillomavirus types 16 and 18 are the most prevalent types of HPV worldwide, Stomach Cancer accounting for over 70% of all cervical cancer cases. 19 Tobacco Use and Cancer Cancer sites for which there is “sufficient” evidence of carcinogenicity of tobacco smoking according to the IARC Working Group: number of studies on which the evaluation was based and average relative risk. CC=case-control Cancer site Lung Urinary tract Upper aero-digestive tract: Oral cavity, Oro-and hypopharynx Oesophagus Larynx Pancreas Stomach Liver Kidney Uterine cervix Number of studies CC Cohort >100 37 50 24 RR 28 45 25 38 44 29 13 49 4-5 1.5-5 10 2-4 1.5-2 1.5-2.5 1.5-2.0 1.5-2.5 (Vineis et al, JNCI 2004 Jan 21;96(2):99-106) 6 19 5 27 27 29 8 14 15-30 3 Trends in Overweight and Obesity WHO, 2010 Colorectal cancer and dietary fibre S. Bingham et al. , The Lancet, May 21, 2003 RR estimate 1.0 corrected upper limit 0.8 corrected 0.6 corrected lower limit 0.4 0.2 10.0 15.0 20.0 25.0 30.0 35.0 40.0 fibre (g/day) Statistical model adjusted for : energy, height, weight, physical activity, alcohol and tobacco SCFA! Butyrate! Lower pH! Bacterial metabolism in colon! Bacterial mass! Apopotosis?! Reduced transit time, dilution,less ! mucosal contact! Physical activity level around the world Source: WHO Cancer Research Fund) RECOMMENDATIONS Be as lean as possible within the normal range of body weight Be as lean as possible within the normal range of body weight Be physically active as part of everyday life Be physically active as part of everyday life Limit consumption of energy-dense foods Avoid sugary drinks Limit consumption of energy-dense foods Avoid sugary drinks Eat mostly foods of plant origin Eat mostly foods of plant origin Limit intake of red meat and avoid processed meat Limit intake of red meat and avoid processed meat Limit alcoholic drinks Limit alcoholic drinks Limit consumption of salt Avoid mouldy cereals (grains) or pulses (legumes) Avoid mouldy cereals (grains) or pulses (legumes) Aim to meet nutritional needs through diet alone Aim to meet nutritional needs through diet alone Mothers to breastfeed; children to be breastfed Mothers to breastfeed; children to be breastfed Follow the recommendations for cancer prevention Follow the recommendations for cancer prevention Infectious Agents and Cancer agents worldwide • 25% in Africa • <10% in Europe (1 in 33 in UK) Agent Cancer HPV (16,18) Cervix, Head and Neck EBV Hodgkin’s Lymphoma, Burkitts HCV, HBV Liver H. Pylori Stomach Occupational Carcinogens Some Carcinogens in the Workplace Mesothelioma deaths by sex and year in England and Wales. From Hodgson et al, 2005 Parkin’s estimate of preventable cancers (Parkin et al, 2012) => 5 servings of fruit and vegetables; =>23 g/day of fibers; <=6 g/day of salt; BMI<=25 kgm-2; physical activity=> 30 min 5 times/week; breastfeeding at least 6 months 14 risk factors and 18 cancer sites have been considered. The result is that 45% of cancers in men and 40% in women could have been prevented had risk factors been reduced to the optimal levels or eliminated (like tobacco). Reduction/elimination of the same risk factors would lead to a substantial reduction also of cases of cardiovascular disease, renal disease, hepatic disease, diabetes and possibly some neurological diseases. Advantages of primary prevention (P Vineis, C Wild. Global cancer patterns: causes and prevention.The Lancet 2014 Feb 8;383(9916): 549-57) Primary prevention decreases social inequalities, when it is effective. Current structural reforms increase inequalities within/between countries Primary preventive activities have an impact that go beyond those who are directly affected by it, for example for an indirect effect. The typical instance is herd immunity. Similarly, banning smoking in public places has a positive effect not only in those potentially exposed to secondhand smoke (the target population), but also in smokers, who will smoke less. Prevention is usually effective on more than one disease (cancer CVD, diabetes, hypertension, neurological diseases) and does not require to be renewed at each generation like therapies. Threats to primary prevention Primary prevention acts on exposures to risk factors. An exclusively individualized approach is unlikely to have a strong impact, while societal actions are more likely to be effective. However, the tendency to reduce public expenditure and privatize parts of the health care systems will impact on preventive activities such as health promotion, which are not appealing for private enterprises. In the US, Europe and Canada less than 4% of the current public budget is spent in cancer prevention (including all types)(Sullivan et al, 2012) The spread of the cancer epidemic to low-income countries should and could be stopped now. Thank you