Cigarette smoking and malignant melanoma: a case-control study

1. Cigarette smoking and malignant melanoma: a case-control study American Federation for Medical Research Eastern Regional Meeting, Washington D.C. April 15, 2009 Presented by: Maria Christina Kessides M.S.

2. Disclosures • This work is funded by the Doris Duke Charitable Foundation

3. Background • Smoking is well-known to be associated with cancers of several internal organs, including the lung, bladder, pancreas, larynx and cervix • Knowledge of numerous carcinogens in cigarette smoke and their link to cancers of internal organs eventually led to studies on smoking and skin cancer (NMSC and melanoma)

4. Previous studies: Ever smoker and melanoma risk OR or RR

5. Previous studies: Former smoker and melanoma risk OR or RR

6. Previous studies: Current smoker and melanoma risk OR or RR

7. Distribution of adjusted variables in previous studies

8. Background • Inverse association is somewhat puzzling, especially in light of well-known risks of smoking • High probability of a confounder • Inconsistent controlling for skin type and history of UV exposure, or history of blistering sunburns among previous studies

9. Hypothesis When carefully adjusting for sun exposure, skin type, and history of blistering sunburns, cigarette smoking will either: • Show no association with risk for melanoma OR 2. Confer an increased risk for melanoma OR 3. Show a persistent inverse association

10. Materials/Methods: the CLUE database • CLUE II est. in 1989 by the Johns Hopkins School of Public Health • 32,000 volunteers gave blood samples, social and medical histories • Follow-up questionnaires sent in 1996, 1998, 2000, 2003, 2007 • 2007 questionnaire collected information on hours spent outdoors, tanning salon use, history of sunburning, and sun protection practices Source: www.jhsph.edu/comstockcenter

11. Materials/Methods: study design • Case-control study • Over 8,000 subjects responded to the 2007 questionnaire • Identified 103 confirmed cases of malignant melanoma who fulfilled our inclusion and exclusion criteria • Matching criteria • Each case matched to two controls along the following variables • Race • Age (± 5 years) • Sex • Skin type • Statistics: Chi-square and logistic regression analysis

12. Study Design • Inclusion criteria • Cases: confirmed history of melanoma (Maryland tumor registry) • Controls: no history of melanoma • Exclusion criteria: • Cases with a history of another cancer diagnosed before melanoma • Controls with history of melanoma or confirmed history of any other cancer • Anyone missing matching data

13. Methods: skin typedetermination If you went into the sun at noon for 1 hour in the summer…

14. Methods: determiningnumber of blistering sunburns • How many blistering sunburns have you had in a lifetime: • None • 1 or 2 • 3 or 4 • 5-9 • 10+

15. Methods: determining UV exposure history On a typical weekday/weekend in the summer…how many hours (w/o sun protection) in the midday sun?

16. Results:UV exposure history-WEEKENDS* *Excluding subjects for which there was missing data

17. Results:UV exposure history-WEEKDAYS* *Excluding subjects for which there was missing data

18. Results: Sunburn history andsun protective practices* *Excluding subjects for which there was missing data

19. Results: Odds ratios and 95%CI’s for smoking and melanoma Logistics regression analysis with matched variables and Adjusted for history of sunburns and sun exposure history

20. CONCLUSIONS • After carefully controlling for age, sex, race, skin type, UV exposure history, and history of blistering sunburns we did not find evidence that cigarette smoking is associated with either an increased or decreased risk of cutaneous malignant melanoma.

21. CONCLUSIONS Limitations Strengths More precise adjustment of UV exposure history, skin type, history of sunburns Average age of 69.2 at 2007 follow-up for cases and controls allows for adequate time for observation • Recall bias with any survey • Low number of subjects • 80% power to detect an OR ≤ 2.0 or ≥ 0.5 • No information on number of overall nevi

22. ACKNOWLEDGEMENTS • Dr. Rhoda M. Alani • Dr. Anthony J. Alberg • Mr. Lee Wheless • Ms. Sandy Clipp • Ms. Judy Hoffman • Doris Duke Charitable Foundation • American Federation of Medical Research

23. THANK YOU! Can I take any question/comments?

24. References • Source: www.jhsph.edu/comstockcenter • Coups EJ, Manne SL, Heckman CJ. Multiple skin cancer risk behaviors in the U.S. population. Am J Prev Med. 2008;34(2):87-93. 10.1016/j.amepre.2007.09.032. • Freedman DM, Sigurdson A, Doody MM, Rao RS, Linet MS. Risk of melanoma in relation to smoking, alcohol intake, and other factors in a large occupational cohort. Cancer Causes Control. 2003;14(9):847-857. • Osterlind A, Tucker MA, Stone BJ, Jensen OM. The danish case-control study of cutaneous malignant melanoma. IV. no association with nutritional factors, alcohol, smoking or hair dyes. Int J Cancer. 1988;42(6):825-828.

25. References • Odenbro A, Gillgren P, Bellocco R, Boffetta P, Hakansson N, Adami J. The risk for cutaneous malignant melanoma, melanoma in situ and intraocular malignant melanoma in relation to tobacco use and body mass index. Br J Dermatol. 2007;156(1):99-105. 10.1111/j.1365-2133.2006.07537.x. • Shors AR, Solomon C, McTiernan A, White E. Melanoma risk in relation to height, weight, and exercise (united states). Cancer Causes Control. 2001;12(7):599-606. • Grant WB. A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer: Additional evidence that solar ultraviolet-B irradiance reduces the risk of internal cancers. J Steroid Biochem Mol Biol. 2007;103(3-5):668-674. 10.1016/j.jsbmb.2006.12.030.

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