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.
1
Disclosures
• This work is funded by the Doris Duke
Charitable Foundation
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2
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)
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OR or RR
Previous studies: Ever
smoker and melanoma risk
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4
OR or RR
Previous studies: Former
smoker and melanoma risk
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5
OR or RR
Previous studies: Current
smoker and melanoma risk
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Distribution of adjusted
variables in previous studies
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Background
• Inverse association is somewhat
puzzling, especially in light of wellknown 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
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Hypothesis
When carefully adjusting for sun exposure, skin
type, and history of blistering sunburns,
cigarette smoking will either:
1. Show no association with risk for melanoma
OR
2. Confer an increased risk for melanoma
OR
3. Show a persistent inverse association
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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
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
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Study Design
• Inclusion criteria
– Cases: confirmed
history of melanoma
(Maryland tumor
registry)
– Controls: no history
of melanoma
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• 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
12
Methods: skin type
determination
If you went into the sun at noon for 1 hour in the summer…
ANSWERS
Fitzpatrick Skin Skin Type description
Type
a. Blistering sunburn
I
Always burn, no tan
b. Sunburn w/o blisters
I/II
Always burn, no
tan/Always burn,
sometimes tan
c. Mild sunburn w/o
blisters
III
Sometimes burn/always
tan
d. Tan or darken w/o
burn
IV
Never burn/always tan
e. No change in color
V/VI
Never burn/tan
profusely
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Methods: determining
number of blistering sunburns
• How many blistering sunburns have you
had in a lifetime:
a.
b.
c.
d.
e.
None
1 or 2
3 or 4
5-9
10+
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Methods: determining UV
exposure history
On a typical weekday/weekend in the summer…how many
hours (w/o sun protection) in the midday sun?
LOW
MEDIUM
HIGH
Teens
20s
30s
Last 10
yrs
0
0
0
0
1
1
1
1
2
2
2
2
3
3
3
3
4
4
4
4
5
5
5
5
6
6
6
6
Results:
UV exposure history-WEEKENDS*
Case
Control
p value
Exposure to midday sun - teens
Low
Medium
High
N = 87
14.9 %
32.2 %
52.9 %
N= 186
16.1 %
32.3 %
51.6 %
0.97
Exposure to midday sun - 20s
Low
Medium
High
N = 88
15.9 %
45.5 %
38.6 %
N = 189
18.0 %
45.5 %
36.5 %
0.89
Exposure to midday sun - 30s
Low
Medium
High
N = 89
21.4 %
51.7 %
21.4 %
N = 188
30.9 %
40.4 %
28.7 %
0.19
N = 90
54.4 %
30.0 %
15.6 %
N = 193
47.7 %
33.7 %
18.7 %
0.56
Exposure to midday sun - past decade
Low
Medium
High
*Excluding subjects for which there was missing data
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Results:
UV exposure history-WEEKDAYS*
Case s
Control
Exposure to midday sun - teens
Low
Medium
High
N = 91
N = 187
Exposure to midday sun - 20s
Low
Medium
High
N = 92
Exposure to midday sun - 30s
Low
Medium
High
Exposure to midday sun - past decade
Low
Medium
High
15.4 %
35.2 %
49.5 %
p value
0.89
15.5 %
38.0 %
46.5 %
N = 188
29.4 %
35.9 %
34.8 %
N = 91
0.54
29.8 %
41.5 %
28.7 %
0.31
N = 188
42.9 %
44.0 %
13.2 %
N = 92
46.8 %
35.1 %
18.1 %
N = 192
59.8 %
29.4 %
10.9 %
0.92
59.4 %
28.1 %
12.5 %
*Excluding subjects for which there was missing data
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Results: Sunburn history and
sun protective practices*
Cases
Controls
Total blistering sunburns in lifetime
Never
1-4
5-9
10+
N = 99
N = 195
Sunscreen Use
Regular
Non-regular
N = 103
Sun-protective clothing use
Regular
Non-regular
N = 100
29.3 %
43.4 %
19.2 %
8.1 %
P value
0.06
33.9 %
51.8 %
9.2 %
5.1 %
N = 206
29.1 %
70.9 %
0.13
21.4 %
78.4 %
N = 203
35.0 %
65.0 %
0.07
25.1 %
74.9 %
*Excluding subjects for which there was missing data
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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
Smoking history
Cases (n = 103)
Controls (n=206)
Odds Ratio (95% Confidence interval)
%
%
Never
59.2
55.8
1.00 (reference)
Former
27.2
33.5
0.75 (0.39-1.45)
Current
13.6
10.7
1.29 (0.47-3.58)
Smoking frequency
Odds Ratio (95% Confidence interval)
%
%
None
59.2
55.8
1.00 (reference)
<20 / day
14.6
18.0
0.68 (0.29-1.56)
20+ /day
26.2
26.2
1.00 (0.48-2.11)
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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.
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CONCLUSIONS
Limitations
• 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
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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
21
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
March 19, 2016
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THANK YOU!
Can I take any question/comments?
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References
•
•
•
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