1. The Triana, Alabama Cohort: A Study of Women Highly Exposed to Organochlorine Compounds Jennifer A. Rusiecki, Ph.D. Uniformed Services University APHA 2007

2. OBJECTIVES To investigate associations between serum levels of organochlorines and: –Mammographic Density –Reproductive Health To investigate which factors influence decay of DDT and DDE over 20 year period (1979-1998)

3. BACKGROUND: History of Triana DDT Contamination : Late 1970’s –Extensive DDT pollution in Indian Creek, Tennessee River –DDT linked to Redstone Arsenal Leased to DDT Manufacturer : 1947-70 Discharged DDT-contaminated wastewater into river 22 years ops  ~4,000 tons DDT in sediment –Fish : DDT levels = 40 x Federal Limit (200 ppm)

4. Triana, Alabama

5. BACKGROUND: History of Triana DDT Contamination : Tennessee River, Huntsville Spring Branch –Flows through town of Triana Residents ate fish from local waters –Food chain exposure Early 1970’s fish along river died in large numbers CDC measured blood from selected residents for DDT exposure assessment –Levels in blood 3 x found in other U.S. studies Like levels in workers at DDT plants

6. BACKGROUND: 1998 Study of Women in Triana National Cancer Institute (NCI) U. Alabama in Huntsville, College of Nursing –Study of potential assoc between DDT and benign breast conditions N = 230 –Women – members of Triana Area Medical Fund Breast cancer screening/mammographies Standard blood chemistry analysis Questionnaire

7. BACKGROUND: Why Mammographic Density? High density: major breast cancer risk factor –Women (older than 45) with > 75% dense tissue have elevated risk of developing breast cancer Associated with estrogen exposure –Organochlorines : estrogenic properties

8. BACKGROUND: Why Reproductive Health? Concern arises from accidental exposure and animal studies Hospital based and case-control studies: –Menstrual cycle abnormalities –Spontaneous abortions –Prolonged waiting time to pregnancy –Altered age of sexual development

9. METHODS: How to measure mammographic density? Mammograms –Area of dense tissue –Overall area of breast RELATIVE density: (PERCENT density) –Dense Area / Total Area ABSOLUTE density: –Dense Area

10. METHODS: Mammographic Density (MD) 2 metrics –Avg (of L & R) absolute MD Log(Avg. Absolute) –Avg (of L & R) percent MD Log(Avg. Percent)

11. METHODS: Measurement of Reproductive Health Questionnaire: –Age at menopause (contin) –Age at menarche (≤11, 12 or 13, >13) –Stillbirth or spontaneous abortion (ever, never) –Fertility (ever, never) –Length of monthly cycle (20-25 da, 26-30 da) –Change in BMI (1979 to 1998)

12. METHODS: Serum OCC Measurements Via gas chromatography (lipid adjusted) –DDT –DDE –Β-HCCH –H.epoxy –Oxychlordane –Trans-nonachlor –Mirex –PCB congeners : 74, 99, 118, 138, 153, 170, 180, 183, 187, 194, 206 ppt = pg/g 1979 measurements: 89 women

13. METHODS: Statistical Analyses Mammographic Density (n=230) : –Spearman Correlation Coefficients (r) –Linear regression analyses Reproductive Health (n=230): –Spearman Correlation Coefficients (r) –Chi 2 tests of association OCC decay (n=89) : –Variables of interest DDT, p,p’DDE, o,p’DDE serum concentrations in 1979 and 1998 Demographic and medical variables –Regression Modeling Linear regression predicting log difference in p,p’-DDE 1979 - 1998

14. RESULTS: General Characteristics 230 women enrolled (212 with mammograms) –Age: 19 – 91 mean = 49.4 (16.0) –Race: 80% African American; 20% Caucasian –Menopausal status: Pre: 58.4% Post: 41.6% –Age at menarche: μ=12.7 (1.6) –Total months breastfed: μ = 35 (48) –Taking HRT: Yes: 15.2% No: 84.8% –Number of full term pregnancies: 1: 18% 2: 49% 3: 29% 4: 4%

15. RESULTS: Reproductive Characteristics Taking HRT : Menopausal Status : Age at menarche: Total months breastfed: μ = 35 (48) Number full term pregnancies :

16. RESULTS: Chemical Characteristics (Select OCCs)

17. Mammog. Density RESULTS: Spearman Correlation Coefficient (r) Avg % mamm dens vs. OCC PCBrp-valueChemicalrp-value pcb 74-0.28<0.01b-HCCH-0.43<0.01 pcb 99-0.21<0.01h.epoxy-0.21<0.01 pcb 118-0.24<0.01oxychlor-0.23<0.01 pcb 153-0.180.01t_nonachlor-0.26<0.01 pcb 170-0.180.01pp-DDE-0.27<0.01 pcb 180-0.20<0.01 pcb 183-0.180.01 pcb 187-0.20<0.01 If LOG transformed: similar results

18. Mammog. Density RESULTS: Spearman Correlation Coefficient (r) Avg Absolute mamm dens vs. OCC PCBrp-valueChemicalrp-value 74-0.29<0.01b_HCCH-0.37<0.01 99-0.21<0.01h_epox-0.180.01 118-0.24<0.01oxychlor-0.23<0.01 153-0.21<0.01t_nonachlor-0.25<0.01 170-0.22<0.01ppDDE-0.22<0.01 180-0.23<0.01ppDDT-0.30<0.01 183-0.190.01mirex-0.190.01 187-0.23<0.01 If LOG transformed: similar results

19. Mammog. Density RESULTS: Linear Regression Results Age 19-40 years: –No significant estimates Avg PERCENT, Avg ABSOLUTE, log x-formed metrics Age 41-54 years: –Positive linear relationship for: PCB153, B-HCCH (percent) PCB 183, Mirex (absolute) Age 55-91 years: –Positive linear relationship for: DDE (percent) Oxychlordane (absolute)

20. Reproductive Health RESULTS Age at menopause: no associations Age at menarche: –PCB 183: young age & low exp: χ2 p-value=0.02 –PCB 170: r 2 = 0.14; p=0.05 Stillbirths: –PCB 74: + assoc, χ2 p-value < 0.01 –PCB 118: + assoc, χ2 p-value = 0.03 –Trans-nonachlor: + assoc, χ2 p-value = 0.03 Spontaneous Abortions: –B-HCCH: + assoc, χ2 p-value = 0.02 –H.epoxy: + assoc, χ2 p-value = 0.05

21. Reproductive Health RESULTS (cont’d) Fertility (sex 1 yr w/out pregnancy) –No associations Monthly Cycle (<25 days, 26-30 days) –Assoc between shorter cycle and higher serum: PCB 183: χ2 p-value = 0.03 Change in BMI (if increased 1979 to 1998) –Consistently negative r 2 ’s for PCBs –Negative r 2 ’s for oxychlordane, trans-nonachlor, mirex

22. DDT/DDE Decay RESULTS Average serum concentrations: –1979 97.6 ng/ml (DDT) 73.4 ng/ml (DDE) –1998 0.44 ng/ml (DDT) 44.0 ng/ml (DDE) 1979 -1998: p,p’-DDT levels declined to ~ 0 p,p’-DDE declines less steep and more variable Individual factors independently related to decrease in p,p’-DDT and p,p’-DDE over time : –Older age, higher body mass index (BMI) in 1979, greater parity, breastfed children

23. Conclusions Mammographic Density and OCCs –Consistently negative correlations Not strong (~-0.18 - -0.43), yet significant For both metrics (PERCENT and ABSOLUTE) –Older women negative linear relationships PCB183, B-HCCH, Mirex, DDE, Oxychlor

24. Reproductive Health CONCLUSIONS Reproductive Health and OCCs –Only a few chemicals for each endpoint –All Bivariate associations –Need further investigation, particularly for: Age at menarche Stillbirths & Spontaneous Abortions Monthly cycle Change in BMI

25. Organochlorine Decay CONCLUSIONS Decay to ~ 0 Factors influencing: –Older age, higher BMI in 1979, higher parity, if breast fed children.

26. Overall Conclusions &Future Directions Potential association : –↓ mammographic density with ↑ serum OCCs –Why? Potential association: –Some adverse reproductive health outcomes –But these need to be further studied Age in 1979 most strongly influenced the decay of DDT and DDE over time Follow-up for other outcomes Follow-up of children of these women

27. Acknowledgements National Cancer Institute (NCI) –Aaron Blair –Louise Brinton –Robert Hoover –Susan Sieber * –Shelia Zahm Centers for Disease Control (CDC) –Larry Needham –Wayman Turner *deceased U. Alabama, Huntsville –Fay Raines –Jane Cash U. South Florida –Tom Mason SUNY Buffalo –Matthew Bonner U. Michigan –Julia Gray Triana Area Medical Fund *** The Women of Triana ***