Cancer and Environmental Chemicals: Why is there Concern?

Transcription

1 Cancer and Environmental Chemicals: Why is there Concern? (Cancer trends in Ontario) Eric Holowaty Population Studies & Surveillance, December 3, 2009

2 Fundamental questions Why is there a concern about environmental links to cancer risk? Which chemicals in our food, in the air we breathe, in our drinking water, in our homes and in our workplaces are associated with increased risks of cancer? What do we know about endocrine disrupting chemicals and cancer risk? What can we learn from animal cancer bioassays? From zoologic studies? What challenges do we face in evaluating linkages between environmental chemicals and cancer risk? 2

3 Example : environmental links to cancer Scandinavian Twins Study and Breast Cancer Contribution of inherited vs. environmental factors to breast cancer risk Inherited factors, 27% of risk Environmental factors, 73% of risk Suggests environmental (or at least, non-hereditary) factors play a major role in determining breast cancer risk Ref: Lichtenstein et al., N. Engl. J. Med., 343:78-85, 85,

4 How are we exposed to environmental chemicals? Routes of exposure Air we breath Food we eat & beverages we drink Contact with our skin Contact with eyes Some chemicals cross the placenta Some can appear in breast milk 4

5 Exposure to environmental chemicals Each chemical is unique Some can be stored in body fat Others are quickly eliminated Some need to be activated by the body Others are quickly detoxified Some pose no cancer risk Some are potent carcinogens Others may be hormone mimics and support tumor growth of hormonally sensitive cancers Some may act as anti-cancer agents 5

6 Chemicals in the workplace Dwindling number of high quality cancer studies in the workplace Few high quality cancer studies of women in the workplace Many studies very small Follow-up time often too short Records of actual exposures often lacking Methods for estimating exposures often crude Frequently have exposures to multiple chemicals 6

7 Chemicals in the workplace and breast cancer what do we know? Some evidence of higher breast cancer risk Acid mists Benzene Carbon tetrachloride Ethylene Oxide Formaldehyde Lead oxide Methylene chloride Styrene Refs: Blair and Kazerouni, Cancer Causes & Control, 8: , 1997 Cantor et al., J. Occup. Environ. Med., 37: , 1995 Goldberg and Labreche, Occup. Environ. Med., 53: , 1996 Hansen, Am. J. Ind. Med., 36:43-47, 1999 Norman et al., Int. J. Epidemiology, 24: , 1995 Spiritas et al., Br. J. Ind. Med., 48: ,

8 The workplace and breast cancer what do we know? Light at night May disrupt the synthesis of the hormone melatonin Changes in melatonin may affect levels of estrogen Breast cancer risk is higher in women who worked the grave yard shift for many years Refs: Steven and Rea, Cancer Causes Control, 12: , 287, 2001 Davis et al., JNCI, 93: , 2001 Hansen et al., Epidemiology, 12:74-77, 77, 2001 Schernhammer et al, JNCI, 93: , 1568,

9 Chemicals in the workplace what do we need to know? Workers that need further evaluation Chemical manufacturing workers Pharmaceutical industry workers Laboratory and biomedical workers Cosmetologists and hairdressers Printers and dye workers Health care workers Metal plate workers Airline personnel 9

10 Chemicals in the home what are we exposed to? Cape Cod Breast Study Silent Spring Institute Measured household exposures to 89 hormone-like and cancer-causing causing chemicals in air and dust samples of 120 Cape Cod homes Chemicals identified included plasticizers, disinfectants, certain flame retardants, persistent organochlorine pesticides and contemporary (permethrin)) pesticides Exposure is one step in the risk assessment process Results will help prioritize chemicals that should be studied further Refs: Rudel et al., J. Air Waste Manage. Assoc. 51: , 513, 2001 Rudel et al., Environ. Science and Technol., 37: , 53,

11 Pesticides and cancer risk exposure concerns 11

12 U.S. Conventional Pesticide Use historical trends Ref: Aspelin and Grub, Pesticide industry sales and usage, 1996 and 1997 market estimates, Figure 10.b, US EPA, November

13 Pesticides and cancer risk why is there concern? Higher cancer risk in male farmers Lip Skin Stomach Brain Lymphoma Prostate Ref: Blair and Zahm,, Environ. Health Perspect (Suppl( 8): , 208,

14 Pesticides and cancer risk cancer risks on the farm Environmental exposures on the farm Sunlight / UV radiation Nitrates Pesticides Solvents Fuel exhaust Mycotoxins (toxins formed by mold on crops; some are cancer-causing) causing) 14

15 Pesticides and cancer risk cancer risks on the farm Agricultural Health Study Evaluating health effects of agricultural chemicals in a 10 year, prospective study - 55,300 men and 30,000 women Cancer risks - Prostate cancer risk elevated 14% in male pesticide applicators Ref: Alavanja et al., Am. J. Epidemiology, vol. 157, pp , 814,

16 Breast cancer risk of farm women Few studies on cancer risks of farm women; most studies on men North Carolina Study Overall, breast cancer rates lower in women living on or near farms In farm women who applied pesticides,, breast cancer risk 2X higher if protective clothing or gloves not worn Reducing exposure reduces risk Ref: Duell et al., Epidemiology, 11: , 531,

17 Pesticides and breast cancer risk -organochlorine (OC) pesticides DDT and DDE Early descriptive studies suggested a positive association between blood or adipose tissue DDE levels and breast cancer risk Over 20 of the recent, well controlled, large-scale studies have not shown that levels of DDT or DDE predict breast cancer risk in North American or European white women 17

18 Pesticides and breast cancer risk DDT/DDE possible explanations Exposure Issues - Chemical form matters Predominant exposure in western white women - Was not to estrogenic form that was sprayed (o,p( o,p -DDT) - But to very weak estrogenic form (p,p( p,p -DDE) in food Heavily exposed populations less studied Few studies of breast cancer risk in countries that currently use DDT (estrogenic form) for malaria control Critical windows of exposure Little information on whether exposure to DDT during early breast development affects breast cancer risk Ref: Snedeker,, Environ. Health Perspect., 109 (suppl( 1): 3547,

19 Chemicals and breast cancer risk laboratory animal studies Why use laboratory animal studies? Human studies have the most weight when evaluating cancer risk For most chemicals we have no information on human exposures and later cancer risk Use controlled animal laboratory studies to: - Identify the hazard - Estimate cancer risks to humans National Toxicology Program bioassays Animal cancer - Of 509 chemicals tested, 42 (8%) cause mammary (breast) tumors in i laboratory animals 19

20 Endocrine disrupting chemicals (Hormonally Active Agents) We know that many hormones and local growth factors play a role both in normal tissue/organ growth and development and in the cancer process Hormones (chemical messengers) - Estrogen - Progesterone - Prolactin - Growth Hormone Growth Factors (local chemical messengers) - Epidermal Growth Factor family - Insulin Growth Factor (IGFs( IGFs) 20

21 Endocrine disrupting chemicals What s the evidence? What we know Pharmaceuticals that act like estrogen or estrogen / progesterone (E + P) can increase breast cancer risk - Diethylstilbestrol Prescribed to 5 to10 million women In mothers - moderate increase in BC risk In daughters - data not in yet - E + P post-menopausal hormone therapy Risk increases with duration of use Small risk (8 cases per 10,000), but widely prescribed May increase risk of more aggressive tumors 21

22 Endocrine Disrupting Chemicals Need to know more Polybrominated diphenyl ethers (PBDEs( PBDEs) Flame retardant Used in plastics, textiles, carpets, & furniture foam Detected in marine life and human breast milk globally Can stimulate breast tumors cells to grow in the lab Plasticizers Nonyl phenol, bisphenol A - estrogenic Phthalates - some may cause premature breast development in children (studies from Puerto Rico) Heavy Metals Cadmium and arsenite - environmental estrogens Pesticides 22

23 Genes influence response to environmental chemicals Gene-environmental environmental interactions Many chemicals need to be activated to become cancer-causing causing agents Certain genes control important enzymes involved in activation pathways Variations in these genes can affect the activation pathway This may affect the level of cancer-causing causing chemicals 23

24 Challenges of studying EDCs and cancer Complexity of the disease Many risk factors involved Complex biology of onchogenesis Takes long time for most tumors to develop Exposure issues Difficult to measure low-level level exposures to multiple chemicals from the distant past Few chemicals have validated biomarkers Levels of exposure to chemicals at critical periods of organ development (in( utero through puberty) is lacking Exposures to many chemicals in the home and workplace are not well characterized 24

25 So, what are the predominant temporal and spatial patterns for cancer in Ontario? 25

26 Most common cancers in Ontario by sex (2010 estimates) Males N=36,565 Females N=31,867* Stomach 798 Oral cavity and pharynx 958 Kidney 1,063 Leukemia 1,157 Melanoma 1,304 Non-Hodgkin lymphoma 1,482 All other cancers 7,241 2% 3% 3% 3% 4% 20% 4% 4% Bladder 1,578 12% Lung 4,250 13% 32% Prostate 11,878 Colon and rectum 4,856 Kidney 744 Leukemia 761 Melanoma 1,013 Ovary 1,057 All other cancers 7,208 2% 2% 3% Non-Hodgkin lymphoma 1,356 Thyroid 1,409 3% 4% 23% 4% 6% Body of uterus 1,985 12% Lung 3,845 27% 12% Breast 8,539 Colon and rectum 3,951 *Total of rounded numbers may not equal rounded total number Source: Cancer Care Ontario (Ontario Cancer Registry: 2010 estimates provided by Informatics July 2007) 26

27 Cancer by age group New cases diagnosed, Ontario, 2010 Both sexes combined by age group N=68,432* Age 85+ 5,358 (8%) Age (1%) Age ,010 (1%) Age ,172 (10%) Age ,770 (49%) Age ,774 (30%) *Total of rounded numbers may not equal rounded total number Source: Cancer Care Ontario (Ontario Cancer Registry: 2010 estimates provided by Informatics July 2007) 27

28 But aren t we winning the war against cancer? - Cancer mortality rates are finally falling! Males Females 0 28 Mortality per 100,

29 Recent Changes in Cancer Mortality Males All Cancers (chgpt 1988, 2002) main components: Lung Ca (chgpt: 1983, 1989) Prostate Ca (chgpt: 1994) Colorectal Ca (chgpt: 1986) Stomach Ca (chgpt. 1991) Bladder Ca (chgpt 2000) Pancreas Ca (chgpt 1985) Leukemia (no chgpt) NH Lymphoma (chgpt 2000) -2.5(-5.1) deaths per 100,000 popn/yr average annual change in rates (since 1988) -1.6(-1.4) deaths per 100,000 popn/yr -0.8 deaths per 100,000 pop'n per year -0.4 deaths per 100,000 pop'n per year -0.2 deaths per 100,000 pop'n per year -0.1(-0.3) deaths per 100,000 popn/yr -0.1 deaths per 100,000 pop'n per year -0.1 deaths per 100,000 pop'n per year +0.1(-0.2) deaths per 100,000 popn/yr Females All Cancers (chgpt 1987) main components: Breast Ca (chgpt: 1986, 1995, 1998) Colorectal Ca (chgpt: 1980) Stomach Ca (no chgpt) Cervix Ca (no chgpt) Ovarian Ca (no chgpt) Leukemia (no chgpt) NH Lymphoma (chgpt 1997) Lung Ca (chgpt: 1985, 2000) in Ontario -0.7 deaths per 100,000 pop'n per year average annual change in rates (since 1988) -0.6(-0.4) deaths per 100,000 popn/yr -0.3 deaths per 100,000 pop'n per year -0.1 deaths per 100,000 pop'n per year -0.1 deaths per 100,000 pop'n per year -0.1 deaths per 100,000 pop'n per year -0.1 deaths per 100,000 pop'n per year +0.1(-0.1) deaths per 100,000 popn/yr +0.5(-0.1) deaths per 100,000 popn/yr 29

30 Why? Were these changes planned? Cancers Reason Planned? Lung Smoking Partly Large bowel & stomach Breast Cervix Diet Screening and treatment Screening No Partly Partly 30

31 What else have we achieved? Quality of life Probably Consumer satisfaction Uncertain Inequalities Possibly Efficiency Probably Early gains - free Screening gains - $20-30,000 per PYL saved Treatment gains - uncertain 31

32 Aren t Cancer Incidence Rates Still Rising in Ontario? 500 Rate per 100,000 pop'n (CAN'91) 3 yr moving ave Male (se=1%) Female (se=1%) Year 32

33 Changes in Cancer Incidence All Cancers Lung Breast CRC Prostate Stomach Bladder Leukemias NHL Brain Melanoma Thyroid Liver Larynx Testis Ontario male males all ages Age-standardized rates Canada 1991 All Cancers Lung (2003) Breast CRC Endometrium Stomach Bladder Leukemias NHL Brain Melanoma Thyroid Liver Larynx Ovary n.a. Ontario females 33

34 Changes in Cancer Incidence All Cancers Lung Breast CRC Prostate Stomach Bladder Leukemias NHL Brain Melanoma Thyroid Liver Larynx Testis n.a. Ontario malemales male Younger adults yrs Age-standardized rates Canada 1991 All Cancers Lung Breast CRC Endometrium Stomach Bladder Leukemias NHL Brain Melanoma Thyroid Liver Larynx Ovary Ontario females 34

35 Overall, Incidence Rates (all sites combined) seem to be stabilizing Male Rate per 100,000 pop'n (CAN'91) 3 yr moving ave Male Lung/Pr Female - Lung/Br Female Year 35

36 Hormone-related cancers Breast cancer Prostate cancer Endometrial cancer Testicular cancer Thyroid cancer 36

37 Breast cancer incidence, , Ontario 1000 Female 60-74yr Female 60-74yr Rate per 100,000 pop'n (CAN'91) 3 yr moving ave Female all ages Male all ages Female 45-59yr Female 30-44yr Female 15-29yr Year 37

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39 Breast cancer rates worldwide USA Ontario Gambia Korea China India Kenya Peru Japan Mexico Philipines Portugal Italy Germany UK Israel Denmark Netherlands Breast Cancer Incidence Rates 39

40 Risks Related to Breast Cancer Advancing Age Early Menarche Lack of Exercise Alcohol Overweight Hormone Replacement Therapy Gender Late Menopause Diet Benign Breast Disease Close Relative Age at First Birth Education & Income Ionizing Radiation EDCs??? Genetics Passive Smoke Chemicals -Work -Home -Garden Recreation 40

41 Exposure to Hormones Early Menarche Lack of Exercise Alcohol Gender Late Menopause Overweight Hormone Replace t Therapy Advancing Age Some Chemicals -Work -Home -Garden Recreation 41

42 Prostate cancer incidence, , Ontario 1000 Male 60-74yr Male 60-74yr Rate per 100,000 pop'n (CAN'91) 3 yr moving ave Male all ages Male 45-59yr Male 30-44yr Year 42

43 Prostate cancer incidence, , Ontario Rate per 100,000 pop'n (CAN'91) 3 yr moving ave Year Male all ages Male 60-74yr Male 60-74yr Male 45-59yr Male 30-44yr 43

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45 Endometrial cancer incidence, , Ontario 1000 Rate per 100,000 pop'n (CAN'91) 3 yr moving ave. 10 Female 60-74yr Female 75+yr Female 45-59yr Female all ages Female 30-44yr Year 45

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47 Testis cancer incidence, , Ontario 1000 Rate per 100,000 pop'n (CAN'91) 3 yr moving ave. 10 Male all ages Male 30-44yr Male 15-29yr Male 45-59yr Male 60-74yr Year 47

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49 Testicular cancer There is no accepted explanation for the rising trend Rise also seen in other developed countries Known causes, including undescended testicle, previous testicular cancer and family history of the disease, do not explain the increasing trend Other causes of testicular cancer are poorly understood 49

50 Thyroid cancer incidence, , Ontario 1000 Rate per 100,000 pop'n (CAN'91) 3 yr moving ave Female all ages Male all ages Female 30-44yr Female 45-59yr Female 60-74y Female 15-29yr Year 50

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52 Thyroid cancer Since 1985, thyroid cancer incidence dramatically in Ontario, particularly among females Reasons for this remain unknown but likely include both: Changes in diagnostic practices Changing risk factor exposure and/or immigration patterns Particularly rapid rise in females and geographic variation may be due to: Differences in health care seeking behaviours Differences in diagnostic services availability/utilization 52

53 That s it for now! 53

54 What about first primaries only? 500 Male - all 450 Rate per 100,000 pop'n (CAN'91) Male-1st Female-1st Female - all Year 54

55 May be a problem in comparing rates with other areas different criteria for registering second and later primaries Rate per 100,000 pop'n (CAN'91) All sites combined All sites combined USA = SEER original 9 registries Male - SEER Male - Ont Female - SEER Female - Ont Year 55

56 May be a problem in comparing rates with other areas restricting comparisons to first primaries helps to standardize our comparisons 700 All sites combined All sites combined USA = SEER original 9 registries Rate per 100,000 pop'n (CAN'91) Male - SEER Male - Ont Female - Ont Female - SEER Year 56