Download Associations Between Anthropometry, Cigarette Smoking, Alcohol

American Journal of Epidemiology
Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2010.
Vol. 171, No. 12
DOI: 10.1093/aje/kwq085
Advance Access publication:
May 21, 2010
Original Contribution
Associations Between Anthropometry, Cigarette Smoking, Alcohol Consumption,
and Non-Hodgkin Lymphoma in the Prostate, Lung, Colorectal, and Ovarian
Cancer Screening Trial
Jesse D. Troy, Patricia Hartge, Joel L. Weissfeld, Martin M. Oken, Graham A. Colditz,
Leah E. Mechanic, and Lindsay M. Morton*
* Correspondence to Dr. Lindsay M. Morton, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120
Executive Blvd., EPS 7040, MSC 7238, Rockville, MD 20852-7238 (e-mail: [email protected]).
Initially submitted November 11, 2009; accepted for publication March 24, 2010.
Prospective studies of lifestyle and non-Hodgkin lymphoma (NHL) are conflicting, and some are inconsistent
with case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was used to
evaluate risk of NHL and its subtypes in association with anthropometric factors, smoking, and alcohol consumption in a prospective cohort study. Lifestyle was assessed via questionnaire among 142,982 male and female
participants aged 55–74 years enrolled in the PLCO Trial during 1993–2001. Hazard ratios and 95% confidence
intervals were calculated using Cox proportional hazards regression. During 1,201,074 person-years of follow-up
through 2006, 1,264 histologically confirmed NHL cases were identified. Higher body mass index (BMI; weight (kg)/
height (m)2) at ages 20 and 50 years and at baseline was associated with increased NHL risk (Ptrend < 0.01 for all;
e.g., for baseline BMI 30 vs. 18.5–24.9, hazard ratio ¼ 1.32, 95% confidence interval: 1.13, 1.54). Smoking was
not associated with NHL overall but was inversely associated with follicular lymphoma (ever smoking vs. never:
hazard ratio ¼ 0.62, 95% confidence interval: 0.45, 0.85). Alcohol consumption was unrelated to NHL (drinks/week:
Ptrend ¼ 0.187). These data support previous studies suggesting that BMI is positively associated with NHL, show
an inverse association between smoking and follicular lymphoma (perhaps due to residual confounding), and do
not support a causal association between alcohol and NHL.
alcoholic beverages; anthropometry; body height; body mass index; body weight; life style; lymphoma; nonHodgkin; smoking
Abbreviations: CI, confidence interval; CLL, chronic lymphocytic leukemia; HR, hazard ratio; NHL, non-Hodgkin lymphoma; PLCO,
Prostate, Lung, Colorectal, and Ovarian; SLL, small lymphocytic lymphoma.
Non-Hodgkin lymphomas (NHL), a heterogeneous group
of malignant neoplasms arising in lymphoid cells throughout the body, represent the sixth most common cancer in the
United States (1). Diffuse large B-cell lymphoma, follicular
lymphoma, chronic lymphocytic leukemia (CLL)/small
lymphocytic lymphoma (SLL), and plasma cell neoplasms
are the most common NHL subtypes (1). NHL incidence
and mortality increased steadily during the last half of the
20th century in the United States, with rates approximately
doubling in both sexes during this time (1–3). The ageadjusted (2000 US standard population) incidence of NHL
in the United States during 2006 was 29.9 per 100,000
person-years (4). The rise in NHL rates was not entirely
explained by the acquired immunodeficiency syndrome epidemic, changes in coding practices, or changes in NHL
detection and diagnosis (2). The strongest known risk factors for NHL, infectious agents and immune system dysfunction, account for only a small proportion of cases (2).
Previous research suggests that NHL is associated with
obesity, cigarette smoking, and alcohol consumption, and
effects may vary by NHL subtype. Pooled analyses of results from case-control studies suggest increased risk of
diffuse large B-cell lymphoma with obesity (5, 6), increased
risk of follicular lymphoma with cigarette smoking (7), and
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Am J Epidemiol 2010;171:1270–1281
Lifestyle and NHL in the PLCO Trial
decreased risk of all types of NHL with alcohol consumption (8). Few cohort studies have examined lifestyle factors
and NHL risk; results from these studies are conflicting, and
some are inconsistent with those from case-control studies.
Specifically, some prospective studies have suggested that
body mass index (weight (kg)/height (m)2) affects NHL risk
in women and men (9–18), whereas others have shown no
association (19–23). Cohort studies have not identified an
association between smoking status and the risk of NHL
overall (24–28), yet some studies have shown an increased
risk of follicular lymphoma (24, 25), whereas others observed an inverse association with follicular lymphoma or
no association (26, 28). The few cohort studies that have
examined alcohol and NHL risk have all shown an inverse
association, with conflicting evidence for the effect of alcoholic beverage type (28–31).
Prospective studies of lifestyle factors and NHL have
provided conflicting results and have lacked either an adequate sample size or the histologic information required for
examining NHL subtype. Therefore, we evaluated the associations between anthropometric factors, smoking, and
alcohol consumption and incident NHL and major NHL
subtypes in a population-based cohort of older US men
and women.
MATERIALS AND METHODS
Study population
The study population for this analysis was derived from
the National Cancer Institute’s Prostate, Lung, Colorectal,
and Ovarian (PLCO) Cancer Screening Trial, which has
been described previously (32). Briefly, 154,910 men and
women aged 55–74 years with no prior history of the
cancers under study were enrolled during 1993–2001 at 10
centers around the United States in a randomized, controlled
trial designed to evaluate the impact of cancer screening on
mortality. Participants completed a baseline questionnaire
that assessed demographic information and self-reported
anthropometric factors and tobacco use. Beginning in
1998, data on alcohol consumption were collected with
other dietary data on a food frequency questionnaire (validated via 24-hour recall) from control-arm participants at
baseline and from intervention-arm participants during their
fourth year of participation. Both questionnaires were selfadministered and returned by mail, self-administered in
person; or administered by telephone. Starting in 2006, anthropometric factors and smoking behavior were reassessed
on a supplemental questionnaire that was returned by mail
(32, 33). Follow-up in the PLCO Trial is ongoing.
Of the 154,910 PLCO participants, 149,984 (96.8%)
completed the baseline questionnaire. After excluding
6,789 subjects with a history of previous cancer, 99 subjects
diagnosed with cancer prior to completing the questionnaire, and 114 subjects with invalid follow-up time (e.g.,
the start date followed the stop date), we included 142,982
participants (70,905 women and 72,077 men) in our smoking and anthropometry analyses. A total of 116,736 PLCO
participants (75.4%) completed the dietary history questionnaire. After excluding 5,221 subjects with invalid questionAm J Epidemiol 2010;171:1270–1281
1271
naires (e.g., incomplete data or data outside of expected
ranges), 4,885 subjects with a history of previous cancer,
4,741 subjects diagnosed with cancer prior to completing
the questionnaire, and 76 subjects with invalid follow-up
time, we included 101,813 participants (52,280 women
and 49,533 men) in our alcohol analyses. Nonmelanoma
skin cancer was excluded when considering participants’
cancer history.
For participants who provided responses on both the baseline and supplemental questionnaires, we evaluated changes
over time in current body mass index (n ¼ 91,937), height
(n ¼ 93,766), weight (n ¼ 93,894), and smoking status (n ¼
90,543). The mean time between completion of the questionnaires was 9.1 years.
The National Cancer Institute’s institutional review board
approved the PLCO Trial protocol.
Follow-up and case ascertainment
We followed participants from the date of completion of
the baseline or dietary history questionnaire to the earliest of
the following: diagnosis with any NHL or any other first
primary cancer (excluding in-situ disease and nonmelanoma
skin cancer), death, loss to follow-up, or the end of the study
period (December 31, 2006). Deaths in the PLCO Trial are
ascertained by means of annual questionnaires as well as
through linkage with state vital statistics and the National
Death Index (32, 33). We considered subjects lost to followup at the date of last contact if they were not known to be
deceased and were unresponsive to the most recent attempts
at contact.
Cancer cases in the PLCO Trial are identified through
annually mailed follow-up questionnaires and telephone
calls and are confirmed by medical record review at the
screening centers. Histologic type is recorded by a certified
tumor registrar at each screening center on the basis of
collected medical records and pathology reports using the
International Classification of Diseases for Oncology (32).
We defined a case as any first primary NHL diagnosed prior
to censoring, death, or withdrawal from the study. We defined NHL subtypes using International Classification of
Diseases for Oncology codes specified by the World Health
Organization-based classification of lymphoid neoplasms
recommended by the Pathology Working Group of the International Lymphoma Epidemiology Consortium (34, 35).
Exposure data
Anthropometric factors. Baseline height (in feet and
inches) and weight (in pounds) at ages 20 and 50 years and
at baseline were solicited on the baseline questionnaire and
converted to centimeters and kilograms, respectively, for analysis and for calculation of body mass index at each age. Quartiles of height, weight (at each age), and body mass index (at
each age) were created separately for men and women. Body
mass index was also analyzed according to World Health Organization categories (<18.5, 18.5–24.9, 25–29.9, and 30).
We also analyzed the effects of lifetime weight change by
examining weight change in 10-year increments from age 20
years to baseline. We conducted analyses in the total
1272 Troy et al.
population (adjusted for sex) and for each sex separately to
evaluate potential sex-specific effects on disease risk.
Smoking. Smokers were defined as participants with
a minimum 6-month regular smoking history, as reported
on the baseline questionnaire. Additional data on age at
which participants started smoking, current smoking status,
age at which participants stopped smoking, and usual number of cigarettes smoked per day (1–10, 11–20, 21–30, 31–
40, 41–60, 61–80, or 81) were solicited. We computed
cumulative lifetime exposure to cigarette smoking (packyears) on the basis of reported data on packs of cigarettes
smoked per day (midpoint of the categories listed above)
and years of smoking.
Alcohol consumption. Data on alcohol consumption
were solicited on the PLCO dietary history questionnaire
by first asking whether participants had consumed beer,
wine/wine coolers, or liquor during the preceding 12-month
period. If so, data on frequency and usual serving size
(small, medium, or large) were solicited for each beverage
type. Data on beer consumption were solicited separately
for the summer months versus the remainder of the year.
Serving sizes were defined for each beverage type as <1, 1–
3, or >3 12-ounce (355-mL) cans for beer; <5 ounces
(<148 mL) or <1 glass, 5–12 ounces (148–355 mL) or 2
glasses, or >12 ounces (>355 mL) or >2 glasses for wine or
wine coolers; and <1, 1–3, or >3 shots for liquor. Daily
alcohol consumption (grams of each beverage) was converted to number of drinks per week using standardized
sex- and beverage-specific gram equivalents for the usual
serving sizes (see Web Table 1, which is posted on the
Journal’s Web site (http://aje.oxfordjournals.org/)). Total
ethanol consumption (g/week) was calculated for each beverage type, defining 1 drink as a 12-ounce (355-mL) beer
containing 12.8 g of ethanol, a 4-ounce (118-ml) glass of
wine containing 11 g of ethanol, or a 1.5-ounce (44-mL)
serving of liquor containing 14 g of ethanol.
We analyzed the effect of alcohol consumption on NHL
risk according to total number of drinks per week and total
grams of ethanol consumed per week. We also evaluated
effects of specific alcoholic beverages by analyzing separately the numbers of drinks of beer, wine, and liquor consumed per week. Nondrinkers were defined as participants
who consumed less than 1 drink per month. Light drinkers
(<1 drink or <11.8 g of ethanol per week) were used as the
referent group for all categorical analyses.
Statistical analyses
Cox proportional hazards regression modeling was used to
estimate the risks of developing NHL overall and of the major
NHL subtypes (diffuse large B-cell lymphoma, follicular
lymphoma, CLL/SLL, and plasma cell neoplasms) associated
with anthropometric characteristics, smoking, and alcohol
consumption. When analyzing a single NHL subtype, other
subtypes were censored. Models were adjusted for age (continuous), race/ethnicity (non-Hispanic white vs. other/unknown), sex, and education (high school or less, post-high
school training or some college, and college graduation or
postgraduate study). Additional adjustment for several dietary factors (total energy intake (kcal/day); g/day of fat, meat,
Table 1. Distribution of Cases of Non-Hodgkin Lymphomaa
Identified During Follow-Up of 142,982 Participants in the Prostate,
Lung, Colorectal, and Ovarian Cancer Screening Trial, 1993–2006
Smoking and
Anthropometry
Analysis
All NHL cases
No.
%
Alcohol
Analysis
No.
%
1,264
100.0
700
100.0
Diffuse large B-cell lymphoma
215
17.0
127
18.1
Follicular lymphoma
162
12.8
72
10.3
CLL/SLL
382
30.2
218
31.1
Plasma cell neoplasms
243
19.2
144
20.6
Other NHL subtype
262
20.7
139
19.9
Abbreviations: CLL, chronic lymphocytic leukemia; NHL, nonHodgkin lymphoma; SLL, small lymphocytic lymphoma.
a
Lymphoid neoplasms were classified according the World Health
Organization-based system published by the International Lymphoma
Epidemiology Consortium (35).
and red meat; and pyramid servings/day of total fruit, citrus
fruit/melon/berries, other types of fruit, all vegetables, and
green vegetables), as well as mutual adjustment for the 3
lifestyle factors, did not materially (>10%) alter the results;
therefore, those factors were excluded from the final models.
To evaluate the consistency of the smoking risk estimates in
different demographic groups, we also conducted analyses
stratified by sex, age, and education.
The proportional hazards assumption was verified graphically for all independent variables. We conducted sensitivity analyses after excluding the first year of follow-up to
eliminate possible subclinical prevalent disease at baseline.
Tests for linear trend were conducted using continuous variables in the Cox regression models, including all participants for anthropometric characteristics, smokers only for
smoking exposure variables, and drinkers only for alcohol
consumption variables. All statistical tests were 2-sided.
All analyses were conducted using SAS, version 9.1.3
(SAS Institute, Cary, North Carolina).
RESULTS
During 1,201,074 person-years of follow-up (median, 8.8
years per person) accrued through December 31, 2006,
1,264 histologically confirmed cases of first primary NHL
were diagnosed among 70,905 women and 72,077 men
(age-adjusted incidence rate using 2000 US standard population: 16.6/100,000 person-years) (Table 1). The most common NHL subtype was CLL/SLL (30.2%), followed
by plasma cell neoplasms (19.2%), diffuse large B-cell
lymphoma (17.0%), and follicular lymphoma (12.8%). A
similar distribution was observed in the subset of cases
(n ¼ 700) available for the alcohol analysis. The median
age at diagnosis for all NHL cases was 64 years.
Risk was increased at older ages for NHL and the
NHL subtypes and was significantly higher among males
compared with females for NHL overall (hazard ratio (HR)
¼ 1.44, 95% confidence interval (CI): 1.28, 1.61) and for
all subtypes except follicular lymphoma (Table 2).
Am J Epidemiol 2010;171:1270–1281
Am J Epidemiol 2010;171:1270–1281
Table 2. Risk of Non-Hodgkin Lymphoma Associated With Demographic Characteristics Among142,982 Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial,
1993–2006
Total Study Population
(N 5 142,982)
No.a
%
PersonYears
All NHL Cases
(n 5 1,264)
No.a
HRb
95% CI
DLBCL
(n 5 215)
No.a
HRb
95% CI
Follicular Lymphoma
(n 5 162)
No.a
HRb
95% CI
No.a
CLL/SLL
(n 5 382)
Plasma Cell Neoplasms
(n 5 243)
HRb
No.a
95% CI
HRb
95% CI
Age, years
59
47,730
33.4
381,539
265
1.00
Referent
34
1.00
Referent
52
1.00
Referent
85
1.00
Referent
52
1.00
Referent
60–64
44,140
30.9
386,517
391
1.42
1.21, 1.66
76
2.11
1.40, 3.17
44
0.84
0.56, 1.25
103
1.18
0.88, 1.58
70
1.24
0.87, 1.79
65–69
32,177
22.5
274,600
361
1.84
1.57, 2.16
59
2.30
1.50, 3.52
38
1.02
0.67, 1.55
122
1.97
1.49, 2.60
77
1.92
1.34, 2.74
70–74
18,935
13.2
155,093
244
2.24
1.88, 2.67
46
3.24
2.07, 5.06
28
1.35
0.85, 2.14
71
2.06
1.50, 2.83
43
1.91
1.27, 2.87
Female
70,905
49.6
599,308
517
1.00
Referent
86
1.00
Referent
74
1.00
Referent
163
1.00
Referent
100
1.00
Referent
Male
72,077
50.4
598,440
744
1.44
1.28, 1.61
129
1.49
1.13, 1.97
88
1.17
0.86, 1.61
218
1.33
1.08, 1.64
142
1.43
1.11, 1.85
126,220
88.3
1,061,788
1,151
1.00
Referent
202
1.00
Referent
156
1.00
Referent
361
1.00
Referent
201
1.00
Referent
16,762
11.7
135,961
110
0.74
0.61, 0.90
13
0.50
0.28, 0.87
6
0.30
0.13, 0.68
20
0.43
0.27, 0.67
41
1.58
1.13, 2.21
High school or less
43,335
30.4
359,303
398
1.00
Referent
72
1.00
Referent
49
1.00
Referent
123
1.00
Referent
83
1.00
Referent
Post-high school
training (not college)
or some college
48,981
34.4
409,519
403
0.91
0.79, 1.04
64
0.80
0.57, 1.12
49
0.87
0.59, 1.30
114
0.83
0.64, 1.07
78
0.86
0.63, 1.17
College graduation or
postgraduate study
50,282
35.3
428,927
460
0.96
0.84, 1.10
79
0.91
0.66, 1.25
64
1.07
0.73, 1.56
144
0.97
0.76, 1.24
81
0.83
0.61, 1.13
Sex
Race/ethnicity
White, non-Hispanic
Other/unknown
Education
Lifestyle and NHL in the PLCO Trial
Abbreviations: CI, confidence interval; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; NHL, non-Hodgkin lymphoma; SLL, small lymphocytic
lymphoma.
a
Numbers of cases may not sum to totals because of missing values for some independent variables.
b
Hazard ratio from a Cox proportional hazards regression model. All hazard ratios and 95% confidence intervals were adjusted for age (continuous, except where estimates for categorical
age are given), sex, race/ethnicity, and education.
1273
PersonYears of
Follow-up
All NHL Cases
(n 5 1,264)
No.a
HRb
95% CI
DLBCL
(n 5 215)
No.a
Follicular Lymphoma
(n 5 162)
HRb
95% CI
No.a
HRb
95% CI
CLL/SLL
(n 5 382)
No.a
Plasma Cell Neoplasms
(n 5 243)
HRb
95% CI
No.a
HRb
95% CI
c
WHO BMI at
age 20 years
89,607
72
0.84
0.66, 1.06
17
1.22
0.74, 2.02
10
0.85
0.45, 1.62
21
0.81
0.52, 1.26
12
0.71
0.40, 1.29
18.5–24.9
905,674
940
1.00
Referent
157
1.00
Referent
129
1.00
Referent
286
1.00
Referent
173
1.00
Referent
25–29.9
160,178
206
1.19
1.02, 1.38
35
1.19
0.82, 1.73
21
0.88
0.55, 1.41
63
1.20
0.91, 1.59
41
1.33
0.94, 1.88
21,718
23
1.09
0.72, 1.65
1
N/A
N/A
2
N/A
N/A
5
N/A
N/A
12
3.08
1.71, 5.54
<18.5
30
Ptrendd
0.230
<0.001
0.288
0.140
<0.001
Weighte at age
20 years, kg
Quartile 1
297,979
257
1.00
Referent
40
1.00
Referent
31
1.00
Referent
78
1.00
Referent
55
1.00
Referent
Quartile 2
225,541
232
1.14
0.95, 1.36
41
1.26
0.81, 1.95
24
0.92
0.54, 1.58
65
1.01
0.73, 1.41
43
1.09
0.73, 1.63
Quartile 3
357,725
392
1.37
1.17, 1.61
66
1.46
0.98, 2.17
62
1.58
1.02, 2.45
124
1.34
1.01, 1.79
58
1.06
0.73, 1.55
Quartile 4
305,482
370
1.49
1.27, 1.76
65
1.67
1.12, 2.50
45
1.32
0.83, 2.10
112
1.41
1.06, 1.89
84
1.80
1.27, 2.55
Ptrend
d
0.013
<0.001
0.182
0.033
<0.001
WHO baseline
BMI
8,295
9
1.23
0.64, 2.39
4
N/A
N/A
0
N/A
N/A
3
N/A
N/A
2
N/A
N/A
18.5–24.9
384,159
351
1.00
Referent
58
1.00
Referent
49
1.00
Referent
110
1.00
Referent
57
1.00
Referent
25–29.9
507,204
564
1.16
1.02, 1.33
87
1.07
0.76, 1.50
76
1.14
0.79, 1.65
169
1.12
0.88, 1.43
112
1.45
1.05, 2.01
30
279,347
321
1.32
1.13, 1.54
63
1.58
1.10, 2.27
36
1.03
0.67, 1.60
95
1.25
0.95, 1.65
66
1.69
1.18, 2.41
<18.5
Ptrendd
0.056
<0.01
0.465
0.746
<0.01
Baseline weighte,
kg
Am J Epidemiol 2010;171:1270–1281
Quartile 1
328,108
296
1.00
Referent
51
1.00
Referent
37
1.00
Referent
Quartile 2
283,105
288
1.15
0.98, 1.36
46
1.05
0.71, 1.57
44
1.32
0.85, 2.04
90
1.16
0.86, 1.55
51
1.26
0.85, 1.85
Quartile 3
299,518
353
1.35
1.16, 1.58
54
1.18
0.81, 1.74
45
1.27
0.82, 1.97
102
1.25
0.94, 1.67
79
1.88
1.32, 2.69
Quartile 4
278,182
318
1.40
1.19, 1.65
63
1.63
1.12, 2.37
36
1.14
0.72, 1.82
98
1.39
1.04, 1.86
59
1.59
1.09, 2.32
Ptrendd
<0.001
89
0.555
<0.01
1.00
Referent
52
0.215
1.00
Referent
<0.01
Baseline heightf,
cm
Quartile 1
260,243
263
1.00
Referent
38
1.00
Referent
32
1.00
Referent
84
1.00
Referent
55
1.00
Referent
Quartile 2
418,916
401
0.89
0.76, 1.04
62
0.92
0.61, 1.39
56
0.95
0.61, 1.48
116
0.77
0.58, 1.02
71
0.86
0.60, 1.24
Quartile 3
232,790
280
1.10
0.93, 1.31
53
1.40
0.91, 2.15
34
1.01
0.62, 1.66
78
0.91
0.66, 1.24
60
1.33
0.91, 1.95
Quartile 4
277,976
310
1.19
1.00, 1.40
59
1.56
1.03, 2.36
40
1.07
0.67, 1.71
102
1.14
0.85, 1.53
54
1.15
0.78, 1.69
Ptrendd
<0.01
<0.01
0.571
0.023
0.152
1274 Troy et al.
Table 3. Risk of Non-Hodgkin Lymphoma Associated With Anthropometric Risk Factors at Age 20 Years and Baseline Among 142,982 Participants in the Prostate, Lung, Colorectal, and
Ovarian Cancer Screening Trial, 1993–2006
Abbreviations: BMI, body mass index; CI, confidence interval; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; N/A, not applicable; NHL, nonHodgkin lymphoma; SLL, small lymphocytic lymphoma; WHO, World Health Organization.
a
Numbers of cases may not sum to totals because of missing values for some independent variables.
b
Hazard ratio from a Cox proportional hazards regression model. Hazard ratios were not calculated where the sample size was less than 5. Hazard ratios and 95% confidence intervals were
adjusted for age (continuous), sex, race/ethnicity, and education. Change in weight per 10 years was also adjusted for BMI at age 20 years (continuous). Mutual adjustment for smoking and
alcohol consumption did not alter risk estimates by more than 10%; therefore, these factors were excluded from the final models.
c
Weight (kg)/height (m)2.
d
Ptrend value from an adjusted test for trend performed using a Cox model and a continuous independent variable.
e
Quartiles of weight (kg) were defined separately for men and women, as follows. Weight at age 20 years: quartile 1—men, <64.2; women, <51.9; quartile 2—men, 64.2–72.7; women,
51.9–54.5; quartile 3—men, 72.8–79.5; women, 54.6–59.1; quartile 4—men, >79.5; women, >59.1. Baseline weight: quartile 1—men, <77.4; women, <61.5; quartile 2—men, 77.4–85.5;
women, 61.5–70.0; quartile 3—men, 85.6–95.5; women, 70.1–80.0; quartile 4—men, >95.5; women, >80.0.
f
Quartiles of baseline height (cm) were defined separately for men and women, as follows. Quartile 1—men, <172.8; women, <157.6; quartile 2—men, 172.8–177.8; women, 157.6–162.6;
quartile 3—men, 177.9–182.9; women, 162.7–167.6; quartile 4—men, >182.9; women, >167.6.
g
Change in weight per 10 years was calculated from age 20 years to baseline.
1.02, 2.36
0.216
0.946
0.946
0.114
0.153
Ptrendd
1.00, 2.20
1.55
42
210,479
Gain of >6 kg
192
1.15
0.96, 1.39
37
1.41
0.91, 2.18
29
1.16
0.71, 1.90
49
0.88
0.62, 1.26
1.48
0.98, 2.00
1.40
1.00, 1.79
51
1.03
1.34
91
114
0.74, 1.70
0.46, 1.30
0.77
1.12
52
23
0.88, 1.97
0.78, 1.63
1.13
1.32
46
66
0.98, 1.32
1.11, 1.54
1.30
1.14
235,519
Gain of 4.1–6 kg
387
357,600
Gain of 2.1–4 kg
273
0.78, 1.35
78
Referent
1.00
1.00
16
Referent
1.00
1.00
26
97
Referent
0.97, 3.05
1.72
1.00
40
18
0.35, 1.39
Referent
1.00
0.70
10
53
Referent
0.85, 1.37
1.08
1.00
305
90
77,634
301,501
Loss
Change in weight
per 10 yearsg
Gain of 0–2 kg
0.64, 1.56
52
0.56, 1.78
Lifestyle and NHL in the PLCO Trial
Am J Epidemiol 2010;171:1270–1281
1275
Nonwhite race/ethnicity was associated with lower risk of
NHL overall (HR ¼ 0.74, 95% CI: 0.61, 0.90) and for all
subtypes except plasma cell neoplasms (HR ¼ 1.58, 95%
CI: 1.13, 2.21). Socioeconomic status, as measured by education, was not associated with NHL overall or any NHL
subtype. Risk estimates for these demographic characteristics did not change appreciably after exclusion of the first
year of follow-up (data not shown).
Anthropometric factors
Analysis of men and women combined showed increasing body mass index at baseline to be positively associated
with NHL overall (Ptrend < 0.01) (Table 3), with an elevated risk for overweight (body mass index 25–29.9; HR ¼
1.16, 95% CI: 1.02, 1.33) and obesity (body mass index
30; HR ¼ 1.32, 95% CI: 1.13, 1.54) as compared with
normal weight (body mass index 18.5–24.9). Weight at
baseline was associated with NHL (Ptrend < 0.001), with
increased risk in the third (HR ¼ 1.35, 95% CI: 1.16, 1.58)
and fourth (HR ¼ 1.40, 95% CI: 1.19, 1.65) quartiles as
compared with the first, and height was positively associated with NHL risk (Ptrend < 0.01). Between age 20 years
and baseline, 33.8% of participants remained in the same
body mass index category, 2.0% moved into a lower category, and 64.3% moved into a higher category. Lifetime
weight change (Table 3 and Web Tables 2–4) was moderately associated with risk of NHL overall (gain of 4.1–6 kg
every 10 years: HR ¼ 1.30, 95% CI: 1.11, 1.54), although
no linear trend was detected. Similar results were observed
for weight change from age 20 years to age 50 years and
from age 50 years to baseline (data not shown). In analyses
by NHL subtype, risk estimates for all anthropometric
measures were generally higher for diffuse large B-cell
lymphoma and plasma cell neoplasms than for follicular
lymphoma and CLL/SLL. Anthropometric characteristics
at ages 20 and 50 years (Table 3 and Web Table 5) showed
similar effects on the risk of NHL and its subtypes compared with baseline, with neither body mass index nor
weight emerging as the dominant influence on risk. Analyses by sex (Web Tables 2 and 3) showed that greater
height was a risk factor only in men (top quartile vs. bottom: for men, HR ¼ 1.46, 95% CI: 1.13, 1.88; for women,
HR ¼ 1.00, 95% CI: 0.79, 1.25; P for difference ¼ 0.04).
Risk estimates for body mass index and weight at each
age were also slightly higher among men than among
women, but these differences were not significant (Web
Tables 2 and 3).
Results were similar after exclusion of the first year of
follow-up (data not shown), and anthropometric characteristics were consistent in the PLCO cohort during the study
period, with 69.8% of participants reporting the same World
Health Organization category of body mass index upon
reassessment that they reported at baseline.
Smoking
Risk of NHL overall and most NHL subtypes was not
associated with cigarette smoking as measured by current
All NHL Cases
(n 5 1,264)
DLBCL
(n 5 215)
Follicular Lymphoma
(n 5 162)
PersonYears of
Follow-up
No.a
HRb
Never smoker
565,061
603
1.00
Referent
102
1.00
Referent
94
Ever smoker
632,523
657
0.94
0.84, 1.05
113
0.96
0.73, 1.26
67
95% CI
No.a
HRb
95% CI
No.a
HRb
CLL/SLL
(n 5 382)
95% CI
No.a
HRb
1.00
Referent
174
0.62
0.45, 0.85
207
Plasma Cell Neoplasms
(n 5 243)
95% CI
No.a
HRb
1.00
Referent
120
1.00
Referent
1.05
0.85, 1.29
122
0.87
0.67, 1.13
95% CI
Smoking status
Current smoker
117,745
105
0.90
0.73, 1.11
13
0.68
0.38, 1.23
14
0.74
0.42, 1.31
39
1.20
0.84, 1.71
14
0.58
0.33, 1.01
Former smoker
514,778
552
0.95
0.84, 1.06
100
1.01
0.76, 1.34
53
0.59
0.42, 0.83
168
1.02
0.82, 1.27
108
0.93
0.71, 1.21
1–10
126,203
116
0.88
0.72, 1.08
23
1.06
0.67, 1.67
12
0.57
0.31, 1.05
33
0.89
0.61, 1.29
21
0.78
0.49, 1.25
11–20
130,832
136
0.95
0.79, 1.15
18
0.76
0.46, 1.25
18
0.81
0.48, 1.34
43
1.06
0.75, 1.48
29
1.01
0.67, 1.52
21–30
130,146
147
1.00
0.83, 1.20
25
1.02
0.65, 1.58
13
0.57
0.32, 1.02
47
1.12
0.81, 1.55
28
0.96
0.63, 1.45
>30
117,283
148
1.01
0.84, 1.21
34
1.35
0.91, 2.01
9
0.42
0.21, 0.84
43
1.01
0.72, 1.42
28
0.98
0.65, 1.50
Years since quitting
smoking (former
smokers)
Ptrendc
0.338
0.154
0.374
0.604
0.637
Age at starting
smoking, years
Never smoker
565,061
603
1.00
Referent
102
1.00
Referent
94
1.00
Referent
174
1.00
Referent
120
1.00
Referent
1–16
203,795
213
0.95
0.81, 1.12
34
0.90
0.60, 1.35
24
0.67
0.42, 1.07
64
1.02
0.76, 1.37
45
1.01
0.71, 1.44
17–18
181,612
205
1.01
0.86, 1.19
39
1.14
0.78, 1.66
15
0.47
0.27, 0.82
74
1.29
0.98, 1.71
36
0.90
0.62, 1.32
19–20
113,558
109
0.88
0.71, 1.08
17
0.81
0.49, 1.36
11
0.57
0.31, 1.07
30
0.85
0.58, 1.26
20
0.81
0.50, 1.30
>20
128,806
126
0.89
0.73, 1.07
23
0.96
0.61, 1.51
17
0.80
0.47, 1.34
37
0.92
0.65, 1.32
21
0.72
0.45, 1.15
Ptrendc
0.235
0.385
0.318
0.297
<0.01
Years of having
smoked
Never smoker
565,061
603
1.00
Referent
102
1.00
Referent
94
1.00
Referent
174
1.00
Referent
120
1.00
Referent
Am J Epidemiol 2010;171:1270–1281
1–15
151,253
152
0.94
0.79, 1.13
34
1.27
0.86, 1.88
13
0.50
0.28, 0.90
41
0.89
0.63, 1.26
29
0.92
0.61, 1.38
16–30
196,641
215
0.97
0.83, 1.14
39
1.05
0.72, 1.52
23
0.68
0.43, 1.07
70
1.12
0.85, 1.49
41
0.93
0.65, 1.34
31–40
149,646
152
0.97
0.81, 1.17
20
0.77
0.48, 1.25
19
0.77
0.46, 1.26
48
1.09
0.79, 1.50
23
0.73
0.46, 1.15
>40
121,355
129
0.88
0.72, 1.06
20
0.79
0.49, 1.29
11
0.52
0.28, 0.97
44
1.07
0.76, 1.50
27
0.90
0.59, 1.38
Ptrend
c
0.493
0.026
0.365
0.846
0.730
Packs of cigarettes
smoked per day
Never smoker
565,061
603
1.00
Referent
102
1.00
Referent
94
1.00
Referent
174
1.00
Referent
120
1.00
Referent
0.25
163,413
156
0.93
0.78, 1.11
27
0.98
0.64, 1.50
14
0.55
0.32, 0.97
51
1.09
0.80, 1.49
32
0.90
0.61, 1.33
0.75
230,910
229
0.88
0.76, 1.03
36
0.82
0.56, 1.21
20
0.50
0.31, 0.82
81
1.11
0.85, 1.45
42
0.81
0.56, 1.15
1.25
125,391
144
1.02
0.84, 1.22
29
1.21
0.79, 1.85
21
0.94
0.58, 1.52
41
1.02
0.72, 1.44
23
0.83
0.53, 1.32
1.75
111,386
128
0.99
0.81, 1.21
21
0.96
0.59, 1.55
12
0.59
0.32, 1.09
34
0.93
0.64, 1.35
25
1.00
0.64, 1.56
Ptrendc
0.420
0.964
0.627
0.472
0.741
1276 Troy et al.
Table 4. Risk of Non-Hodgkin Lymphoma Associated With Smoking Behavior Among 142,982 Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 1993–
2006
Abbreviations: CI, confidence interval; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; NHL, non-Hodgkin lymphoma; SLL, small lymphocytic
lymphoma.
a
Numbers of cases may not sum to totals because of missing values for some independent variables.
b
Hazard ratio from a Cox proportional hazards regression model. All hazard ratios and 95% confidence intervals were adjusted for age (continuous), sex, race/ethnicity, and education.
Mutual adjustment for anthropometric characteristics and alcohol consumption did not alter risk estimates by more than 10%; therefore, these factors were excluded from the final models.
c
Ptrend value from an adjusted test for trend (among smokers only) performed using a Cox model and a continuous independent variable.
0.62, 1.40
0.619
0.93
31
0.64, 1.25
0.565
0.89
44
0.37, 1.07
0.949
0.63
17
0.54, 1.33
0.169
0.85
25
0.80, 1.14
0.891
0.95
165
148,440
>39.75
Ptrendc
0.76, 1.59
0.41, 1.03
0.65
1.10
39
22
0.88, 1.62
0.78, 1.46
1.07
1.19
53
57
0.38, 1.07
0.44, 1.21
0.64
0.73
19
17
0.88, 1.88
0.57, 1.37
0.88
1.29
38
22.5–39.75
25
0.83, 1.17
0.79, 1.12
0.99
0.94
173
158
156,415
151,920
8.75–22.4
Referent
1.00
0.82
28
120
Referent
0.76, 1.43
1.04
49
1.00
174
Referent
0.28, 0.89
0.50
1.00
94
13
0.58, 1.41
Referent
1.00
0.91
25
0.91
152
161,046
<8.75
102
Referent
0.76, 1.09
1.00
603
565,061
Never smoker
Pack-years of smoking
0.55, 1.25
Lifestyle and NHL in the PLCO Trial
Am J Epidemiol 2010;171:1270–1281
1277
smoking status, years since quitting smoking, age at starting
smoking, duration, intensity (packs/day), and cumulative
lifetime smoking (pack-years), and no significant trends
were observed for any of these measures of smoking behavior (Table 4). Cigarette smoking was inversely associated
with follicular lymphoma (ever smoking vs. never smoking:
HR ¼ 0.62, 95% CI: 0.45, 0.85), but there was no clear
pattern by intensity, duration, or cumulative lifetime exposure. The inverse association between smoking and follicular lymphoma persisted in analyses stratified by sex, age
category, and level of education and after controlling for
body mass index, drinking status, total number of drinks
per week, grams of ethanol consumed per week, and several
dietary factors (data not shown).
Results were similar after exclusion of the first year of
follow-up (data not shown), and smoking behavior remained
consistent in the PLCO cohort over time, with 92.7% of
participants reporting the same smoking status upon reassessment that they reported at baseline.
Alcohol consumption
Among subjects who completed the dietary history questionnaire, 700 NHL cases were diagnosed during 596,280
person-years of follow-up (median, 6.4 years per person)
(Table 5). Alcohol consumption was not significantly associated with the risk of NHL overall in the PLCO cohort as
measured by total number of drinks per week or grams of
ethanol consumed per week. Analysis of NHL subtypes
showed a significant inverse association between alcohol
consumption and diffuse large B-cell lymphoma as measured by total number of drinks per week (Ptrend ¼ 0.016)
and grams of ethanol consumed per week (Ptrend ¼ 0.017).
However, risk of diffuse large B-cell lymphoma was not
elevated among nondrinkers in comparison with light
drinkers, and estimates were based on a small number of
cases. Risk estimates for NHL overall and NHL subtypes
did not vary according to alcoholic beverage type or sex.
Results were similar after controlling for smoking status and
dietary risk factors and after excluding the first year of
follow-up (data not shown).
DISCUSSION
In this large, population-based prospective cohort study
of older adults, enlarged body size, as measured by body
mass index, height, and weight, was associated with elevated risk of NHL, with height being a risk factor only in
men. Smoking was not related to NHL overall but was inversely associated with follicular lymphoma, and alcohol
consumption was unrelated to NHL risk.
Our study adds to existing evidence suggesting that increased body mass index is modestly associated with elevated NHL risk (9–18). Our observation of increased risk of
NHL with greater height also agrees with prior reports (13,
14, 18, 23, 28, 36). Anthropometry-related risk of NHL is
not consistent in the literature, however. Several prior studies have shown no association of body mass index (19–23)
or height (12, 19) with NHL, and to our knowledge only 1
Am J Epidemiol 2010;171:1270–1281
Total alcohol
consumption,
drinks/week
Nondrinker
<1
1–3
4–13
14
Ptrendc
Beer consumption,
drinks/week
Nondrinker
<1
1–2
3
Ptrendc
Wine consumption,
drinks/week
Nondrinker
<1
1–2
3
Ptrendc
Liquor consumption,
drinks/week
Nondrinker
<1
1–2
3
Ptrendc
Total ethanol
consumption,
g/week
Nondrinker
2.9–11.8
11.9–37.3
37.4–123.9
>123.9
Ptrendc
All NHL Cases
(n 5 700)
PersonYears of
Follow-up
No.a
HRb
197,180
103,394
124,768
107,635
62,167
228
119
161
121
68
0.96
1.00
1.08
0.88
0.84
0.187
197,180
276,440
55,750
65,774
DLBCL
(n 5 127)
95% CI
No.a
0.77, 1.19
Referent
0.85, 1.37
0.68, 1.14
0.62, 1.14
41
26
28
25
7
0.78
1.00
0.84
0.79
0.37
0.016
228
323
69
77
0.96
0.81, 1.14
1.00
Referent
0.94
0.72, 1.22
0.89
0.69, 1.15
0.247
197,180
234,031
76,335
87,599
228
279
101
89
197,180
306,107
33,698
58,160
197,180
98,911
100,947
99,109
98,999
No.a
0.47, 1.27
Referent
0.49, 1.43
0.45, 1.39
0.16, 0.87
22
14
21
8
7
0.83
1.00
1.16
0.48
0.71
0.302
0.42, 1.62
Referent
0.59, 2.30
0.20, 1.17
0.28, 1.79
74
31
51
37
24
1.21
1.00
1.30
1.03
1.13
0.272
41
65
11
10
0.86
0.58, 1.27
1.00
Referent
0.69
0.36, 1.33
0.54
0.28, 1.07
0.077
22
35
7
8
0.92
1.00
0.90
0.90
0.553
0.54, 1.58
Referent
0.39, 2.07
0.40, 1.99
0.99
0.83, 1.18
1.00
Referent
1.14
0.91, 1.44
0.88
0.69, 1.12
0.304
41
50
23
13
1.00
0.66, 1.53
1.00
Referent
1.47
0.89, 2.42
0.72
0.39, 1.34
0.232
22
31
7
12
0.88
1.00
0.67
0.96
0.513
228
355
46
68
0.98
0.83, 1.16
1.00
Referent
1.09
0.80, 1.49
0.89
0.69, 1.16
0.455
41
69
6
11
0.90
0.61, 1.34
1.00
Referent
0.70
0.30, 1.62
0.70
0.37, 1.32
0.219
22
40
4
6
228
113
133
105
118
0.96
1.00
1.11
0.86
0.92
0.199
41
25
27
14
20
0.77
1.00
1.00
0.50
0.66
0.017
22
14
14
13
9
0.47, 1.26
Referent
0.58, 1.72
0.26, 0.96
0.36, 1.21
HRb
CLL/SLL
(n 5 218)
95% CI
0.77, 1.21
Referent
0.86, 1.43
0.66, 1.12
0.71, 1.20
HRb
Follicular Lymphoma
(n 5 72)
95% CI
No.a
0.79, 1.84
Referent
0.83, 2.04
0.64, 1.68
0.66, 1.95
44
28
32
27
12
0.77
1.00
0.96
0.92
0.71
0.068
74
96
22
25
1.07
0.79, 1.46
1.00
Referent
1.00
0.62, 1.61
0.98
0.62, 1.55
0.462
44
73
11
15
0.77
0.53, 1.13
1.00
Referent
0.72
0.38, 1.37
0.81
0.46, 1.44
0.441
0.51, 1.54
Referent
0.29, 1.52
0.49, 1.90
74
87
26
30
1.05
0.77, 1.44
1.00
Referent
0.95
0.61, 1.47
0.95
0.62, 1.45
0.693
44
61
23
15
0.81
0.54, 1.20
1.00
Referent
1.20
0.74, 1.94
0.70
0.39, 1.24
0.138
0.90
1.00
N/A
0.71
0.395
0.53, 1.52
Referent
N/A
0.30, 1.69
74
109
17
17
1.06
0.78, 1.42
1.00
Referent
1.29
0.77, 2.15
0.71
0.43, 1.19
0.058
44
71
10
18
0.88
1.00
1.28
1.29
<0.01
0.60, 1.28
Referent
0.66, 2.50
0.77, 2.18
0.79
1.00
0.92
0.84
0.55
0.295
0.40, 1.54
Referent
0.44, 1.94
0.39, 1.80
0.24, 1.30
74
29
41
36
37
1.23
1.00
1.32
1.14
1.12
0.239
44
26
26
22
25
0.79
1.00
1.00
0.85
0.96
0.043
0.48, 1.28
Referent
0.58, 1.73
0.48, 1.51
0.55, 1.68
95% CI
No.a
HRb
Plasma Cell Neoplasms
(n 5 144)
0.80, 1.90
Referent
0.82, 2.13
0.70, 1.87
0.68, 1.84
HRb
95% CI
0.48, 1.23
Referent
0.58, 1.61
0.54, 1.57
0.36, 1.41
Abbreviations: CI, confidence interval; CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; N/A, not applicable; NHL, non-Hodgkin lymphoma; SLL, small lymphocytic
lymphoma.
a
Numbers of cases may not sum to totals because of missing values for some independent variables.
b
Hazard ratio from a Cox proportional hazards regression model. All hazard ratios and 95% confidence intervals were adjusted for age (continuous), sex, race/ethnicity, and education. Hazard ratios were not
calculated where the sample size was less than 5. Mutual adjustment for anthropometric characteristics and smoking did not alter risk estimates by more than 10%; therefore, these factors were excluded from the final
models.
c
Ptrend value from an adjusted test for trend performed using a Cox model and a continuous independent variable. Ptrend was calculated among drinkers only for total drinks per week and among only drinkers of each
type of beverage for beer, wine, and liquor.
1278 Troy et al.
Table 5. Risk of Non-Hodgkin Lymphoma Associated With Alcohol Consumption Among 142,982 Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, 1993–
2006
Lifestyle and NHL in the PLCO Trial
other study has shown increased risk of NHL associated
with higher weight (18). Results of our sex-specific analyses
of body mass index and NHL risk were consistent with those
of prior studies, showing slightly higher risk among men
than among women (17), although our male-specific height
finding contradicts the strong height-related risk detected in
a large all-female cohort (18). Our nonsignificant findings
for lifetime weight change were similar to those reported
previously (14, 23). Results of our analyses by NHL subtype
were consistent with those of prior studies, with somewhat
higher risks for diffuse large B-cell lymphoma and plasma
cell neoplasms as compared with CLL/SLL and follicular
lymphoma (12–15, 21).
Several plausible mechanisms exist through which enlarged body size might increase NHL risk. Greater height
may be an indicator of childhood nutrition patterns that
could indirectly affect NHL risk—for example, by altering
the likelihood of childhood infection (37). Alternatively,
elevated body mass index and weight may be markers for
certain dietary patterns, insulin resistance, inflammation,
and lower levels of physical activity that may influence
cancer risk (38). Future studies of anthropometric factors
and NHL would benefit from assessing these parameters
in conjunction with weight and height.
Our observation that smoking was unrelated to the risk of
NHL overall is consistent with prior case-control (7) and
cohort (24–28) studies. The inverse association we noted
between smoking and follicular lymphoma was unexpected,
however. Case-control (7) and some cohort (24, 25) studies
have shown smoking to be associated with an increased risk
of follicular lymphoma, although at least 1 cohort study
showed no association between smoking and follicular lymphoma (26) and 1 found an inverse association (28) similar
to our observation in the PLCO Trial. Our failure to detect
a dose-response with intensity, duration, or cumulative lifetime exposure to cigarette smoking suggests confounding
rather than a true protective association. However, the inverse association we observed between smoking and follicular lymphoma persisted after we accounted for alcohol,
body mass index, and dietary factors that might lower the
risk of NHL or its subtypes. Other sources of confounding
that we were unable to control for may include immunitymodulating comorbid conditions, such as atopy, that have
been shown to be protective against follicular lymphoma
(39). Although it is likely that the inverse association between follicular lymphoma and smoking was due to chance
or unmeasured confounding, the subtype specificity and the
consistency with another study of older US adults (28) suggests that additional research in prospective studies is
warranted.
We did not observe any significant association between
total alcohol consumption and risk of NHL overall in the
PLCO cohort, nor did we observe any association between
beverage type and NHL risk, even after controlling for
smoking status and dietary factors. Because of the unusually
large number of nondrinkers in the PLCO cohort, we were
able to separate nondrinkers (<1 drink/month) from light
drinkers (<1 drink/week). Under the hypothesis that alcohol
is inversely associated with NHL risk, we expected to observe increased risk among nondrinkers as compared with
Am J Epidemiol 2010;171:1270–1281
1279
light drinkers and progressively decreasing risk as consumption increased. Although our risk estimates were generally
less than 1 for participants who consumed the highest
amounts of alcohol, we did not observe any significant associations for NHL overall, and the inverse association we
observed for diffuse large B-cell lymphoma was based on
few cases. Our overall null results cannot rule out the hypothesis that the inverse association observed in casecontrol studies (8) is part of a prodrome in which patients
reduce or eliminate alcohol consumption prior to diagnosis.
However, several other large cohorts with similar levels of
alcohol consumption have shown an inverse association between alcohol and NHL risk (28–30). In addition, high
levels of alcohol consumption (300 g/week) were associated with significantly decreased risk of NHL in a Japanese
cohort (31). However, similar to our observation in the
PLCO Trial, risk among nondrinkers in the Japanese cohort
was not elevated relative to light drinkers. Decreased risk of
NHL associated with alcohol consumption is supported by
evidence that alcohol modulates the immune system (40)
and retards the growth of malignant lymphoid cells via inhibition of the mammalian target of rapamycin (mTOR)
(41). In light of such evidence, in future studies of alcohol
use and NHL risk, investigators should combine data on
drinking behavior with biologic measures of exposure that
may affect alcohol-related NHL risk.
The strengths of our study include its prospective design;
the availability of a large number of histologically confirmed incident cases, which enabled us to analyze risks
by NHL subtype; data on anthropometric factors at different
ages; our ability to examine nondrinkers versus light
drinkers; the length of follow-up; the consistency of anthropometric and smoking exposures in the PLCO cohort over
time; and the similarity of NHL risk patterns in the PLCO
cohort with the broader population of white, non-Hispanic
US adults. However, our failure to observe a dominant effect
of body mass index, height, or weight may have been due to
underestimation of body size in self-reports, which could
have attenuated risk estimates (42). Our findings of decreased risk of follicular lymphoma among smokers and
no association between NHL and alcohol consumption
may have resulted from residual confounding. In addition,
we performed many statistical tests, and thus some findings
could have been due to chance; and we did not have data on
some potential confounders such as physical activity.
In summary, anthropometric factors were modestly associated with increased risk of NHL in the PLCO cohort and
were slightly stronger predictors of risk in men than in
women; no clear association was observed between smoking and NHL; and alcohol consumption appeared unrelated
to NHL. Our data support previous studies suggesting that
body mass index is associated with NHL risk. Future studies
of anthropometric factors and NHL that incorporate measurement of biomarkers are essential to help elucidate potential causal mechanisms. The protective effect of smoking
on follicular lymphoma has been observed previously but
may have been due to residual confounding, so additional
prospective studies are warranted to clarify the association
between smoking and follicular lymphoma. Finally, although our findings for alcohol consumption argue against
1280 Troy et al.
a biologic association with NHL risk, future laboratory research into the action of alcohol on the immune system may
identify genetic or other biologic risk factors that could be
measured in epidemiologic investigations of alcohol use and
NHL risk.
ACKNOWLEDGMENTS
Author affiliations: Department of Epidemiology and
Biostatistics, School of Public Health and Health Services,
George Washington University, Washington, DC (Jesse
Troy); Division of Cancer Epidemiology and Genetics,
National Cancer Institute, Bethesda, Maryland (Patricia
Hartge, Lindsay M. Morton); University of Pittsburgh
Cancer Institute, Pittsburgh, Pennsylvania (Joel L.
Weissfeld); Department of Medicine, Medical School,
University of Minnesota, Minneapolis, Minnesota (Martin
M. Oken); Alvin J. Siteman Cancer Center, School of Medicine, Washington University, St. Louis, Missouri (Graham
A. Colditz); and Westat, Inc., Rockville, Maryland (Leah E.
Mechanic).
This work was supported by the Intramural Program
of the National Cancer Institute, National Institutes of
Health. The Prostate, Lung, Colorectal, and Ovarian
(PLCO) Cancer Screening Trial (ClinicalTrials.gov identifier: NCT00002540) is supported by individual contracts
from the National Cancer Institute to each of the 10 screening centers and the coordinating center.
The authors thank Drs. Christine Berg, Richard Hayes,
and Philip Prorok (National Cancer Institute); the PLCO
Screening Center investigators and staff of the PLCO
Cancer Screening Trial; and Thomas Riley, Jerome Mabie,
and Sally Shaul of Information Management Services, Inc.
(Silver Spring, Maryland).
A modified version of the abstract from this article was
accepted for a poster presentation at the University of
Pittsburgh Cancer Institute Scientific Retreat, scheduled
for July 17–18, 2010, in Pittsburgh, Pennsylvania.
Conflict of interest: none declared.
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