Affiliations of authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (ETC, KES, HOA); Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen, Denmark (HH, MM); Department of Pathology and Cytology, Lund University Hospital, Lund, Sweden (MÅ); Department of Pathology and Cytology, Karolinska University Hospital, Stockholm Sweden (ET); Department of Haematology, Herlev Amtssygehus, University of Copenhagen, Herlev, Denmark (HEJ); Department of Oncology, Radiology and Clinical Immunology, University of Uppsala, Uppsala, Sweden, and Department of Oncology and Pathology, Karolinska University Hospital, Stockholm, Sweden (BG)
Correspondence to: Ellen Chang, ScD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden (e-mail: ellen.chang{at}meb.ki.se).
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Several studies (1524) have investigated the association between obesity and the risk of lymphoma. Most studies (1517,1921) have been limited by low numbers of case patients, and all but two studies (21,24) considered non-Hodgkin lymphoma as a single disease entity rather than analyzing its histopathologic subtypes. Five of the 10 studies of the association found a statistically significant positive association between obesity and lymphoma incidence (18,20,23,24) or mortality (22), whereas the rest detected no association (1517,19,21). Cerhan et al. (21) reported no overall association between anthropometric characteristics (including body mass index [BMI]) and risk of overall non-Hodgkin lymphoma, diffuse lymphoma, or follicular lymphoma. However, they detected a weak positive association between BMI and B-cell chronic lymphocytic leukemia and an inverse association between BMI and small lymphocytic lymphoma. In contrast, Skibola et al. (24) found that risks of non-Hodgkin lymphoma, diffuse large-cell lymphoma, and follicular lymphoma were positively associated with an overweight or obese status compared with a normal-weight status.
The results from these previous studies and the evident importance of rigorous histopathologic classification to allow assessment of subtype-specific associations emphasized the need for further examination of the association between obesity and risk of lymphoma. We have gathered the largest known population-based sample of malignant lymphoma cases that have been uniformly classified according to the current World Health Organization (WHO) classification of hematopoietic and lymphoid tumors (25). With these case patients and a comparable number of population-based control subjects, we conducted a casecontrol study to investigate whether BMI is associated with the development of various malignant lymphoma subtypes.
![]() |
PATIENTS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The Scandinavian Lymphoma Etiology (SCALE) study covered the population of Denmark and Sweden, including all residents between 18 and 74 years of age in Denmark from June 1, 2000, to August 30, 2002, and in Sweden from October 1, 1999, to April 15, 2002 (26). Danish participants in a regional pilot phase study beginning on November 1, 1999, were also included. All study participants were required to have sufficient knowledge of the Danish or Swedish language to answer questions in a telephone interview and to have no history of organ transplantation, of a positive test for human immunodeficiency virus (HIV), or of prior hematopoietic malignancy.
Case patients were defined as all patients with a first, incident, and morphologically verified diagnosis of non-Hodgkin lymphoma (International Classification of Diseases [ICD]-10 codes C82-C85, C88.0, C91.35, and C91.7), including chronic lymphocytic leukemia (ICD-10 code C91.1), or Hodgkin lymphoma (ICD-10 code C81) (27). In both countries, individuals with prevalent cases of Hodgkin lymphoma diagnosed in 1999 were also included. We identified patients with incident cases of these diseases through a rapid case ascertainment system organized for this study, consisting of a network of contact physicians from all clinical departments where malignant lymphomas are treated, for a total of 39 internal medicine, hematology, oncology, and clinical pathology departments in Denmark and 118 in Sweden. Continuous collaboration with the Danish National Pathology Registry and the six regional cancer registries in Sweden, both with an estimated coverage of approximately 100% (28) (personal communication, Inge Gram, Danish Pathology Registry), ensured complete reporting through the network.
Control subjects were randomly sampled from the entire Danish and Swedish populations by use of continuously updated, computerized population registers. We sampled a subset of control subjects every 6 months during the study period and frequency-matched them to the expected distribution of case patients with non-Hodgkin lymphoma in each country by age (in 10-year intervals) and sex.
Within the study base and time period, 3740 case patients (83%) of all those diagnosed with malignant lymphoma participated; the remaining case patients did not participate because 7% had died, 4% were physically or mentally incapacitated, 5% refused to participate, and 1% had physicians who refused to let them participate. Participation among case patients with Hodgkin lymphoma (91%) was higher than that of case patients with non-Hodgkin lymphoma (81%). The median time between diagnosis and interview was 85 days (range = 0 days to 4.2 years, including that for case patients with prevalent Hodgkin lymphoma). In the same area and time, 3187 control subjects (71%) of all potential controls consented to participate in the study. All participants provided informed consent before the interview. This study was approved by all regional ethics committees in Denmark and in Sweden and by the U.S. National Institutes of Health, the Swedish Cancer Society, and Plan Denmark, the funding sources for this study.
Exposure Assessment
All study participants completed a telephone interview including questions on current height, normal adult weight, family background, smoking habits, sun exposure, medical history, family medical history, education, occupation, childhood environment, and other possible risk factors for lymphoma. A subset of about half of the participants from Sweden also completed a self-administered written food frequency questionnaire, assessing dietary habits.
BMI was calculated as weight (in kilograms) divided by height (in meters) squared. BMI status was then categorized according to WHO standards for adults (29) as follows: less than 18.5 kg/m2 was underweight, 18.524.9 kg/m2 was normal weight, 25.029.9 kg/m2 was overweight, 30.034.9 kg/m2 was obese, and 35.0 kg/m2 or more was highly and morbidly obese (referred to herein as highly obese). For analyses of the less common non-Hodgkin lymphoma subtypes and Hodgkin lymphoma, we combined the two upper categories into a single category (referred to as "obese") because of the small numbers of individuals in these groups. In analyses using the WHO cutoffs for BMI, we used individuals with a BMI of 18.524.9 kg/m2 (normal-weight status) as the reference group. In separate analyses, individuals with a BMI of 25.0 kg/m2 or more (overweight status) and those with a BMI of less than 25.0 kg/m2 (non-overweight status) were compared.
Because BMI was not evenly distributed in the population, with about half of case patients and control subjects falling in the normal range, BMI was also categorized into quartiles according to the following distribution among control subjects: less than 22.8 kg/m2 was quartile 1, 22.824.9 kg/m2 was quartile 2, 25.027.5 kg/m2 was quartile 3, and 27.6 kg/m2 or more was quartile 4. In the analyses using these categories, we used a BMI of less than 22.8 kg/m2 (quartile 1) as the reference group. BMI was additionally considered as a continuous variable.
We considered the following potential confounders: age (in 5-year categories, except for the category including ages 1824 years), sex, country of residence (Denmark or Sweden), smoking status (never, former, or current smokers of cigarettes daily for at least 1 year), history of autoimmune disease (yes or no), history of skin cancer (yes or no), family history of cancer (yes or no), history of blood transfusion (yes or no), outdoor occupation (yes or no), occupation involving regular exposure to pesticides (yes or no), education level (9 years or less, 1012 years, or 13 years or more), sunbathing habits 510 years ago (never, less than or equal to one time per week, two to three times per week, or four or more times per week), history of sunburns 510 years ago and during childhood (never, less than one per year, one per year, or two or more per year), sun or beach vacations abroad (never, one to five times, six to 20 times, or more than 20 times), solarium use (never, fewer than 10 times, 1049 times, or 50 times or more), and dietary consumption of certain foods and beverages including dairy products, fried red meat, and fruits and vegetables (quartiles of intake).
Histopathology
The histopathologic review of cases has been described in detail elsewhere (26). Briefly, review of tumor material from case patients in Denmark was performed within the Danish Lymphoma Group Registry (LYFO) (30), where specimens from 10% of all incident case patients in the country are continuously chosen at random and reviewed by expert hematopathologists. In all but 20% of our study's case patients, the diagnostic tumor specimens underwent primary evaluation by a LYFO-approved senior hematopathologist. The disease subtype of all case patients was subsequently classified according to the current WHO classification of hematopoietic and lymphoid tumors (25). As specified by the WHO classification system, we classified small lymphocytic lymphoma in the same subgroup as chronic lymphocytic leukemia (collectively referred to here as chronic lymphocytic leukemia).
In Sweden, specimens from all case patients were histopathologically evaluated by a senior hematopathologist or cytologist and classified according to the WHO classification (25). Only 1.5% of original tumor slides were not retrieved and evaluated; for those 35 case patients, the results of the primary morphologic and immunohistochemical investigation were evaluated. Of the 3 740 case patients in the study, 3055 were classified as having non-Hodgkin lymphoma, 618 were classified as having Hodgkin lymphoma, and 67 were classified as having unspecified lymphoma.
Statistical Analysis
Differences in the distribution of BMI between case patients and control subjects were tested with two-sided t tests. Unconditional logistic regression analysis was used to estimate the associations of risk for overall non-Hodgkin lymphoma, non-Hodgkin lymphoma subtypes, and Hodgkin lymphoma with height, weight, and BMI, which were coded as indicator variables. All multivariable models were adjusted for age (with indicator variables for 5-year intervals), sex, and country. Other potential confounders were considered on the basis of prior knowledge of their being risk factors for malignant lymphoma or because their addition to the statistical model appreciably changed the estimates of association (31). Tests for linear trend were conducted with BMI coded as an ordinal variable with four or five levels, defined by the median values in each category or quartile. Estimates were stratified by age (younger than 60 years or 60 years or older for case patients with non-Hodgkin lymphoma; younger than 45 years or 45 years or older for case patients with Hodgkin lymphoma), sex, or smoking status. We evaluated heterogeneity of the stratified associations with a likelihood ratio test for the statistical significance of an interaction term between BMI and the potential modifier. Analyses were performed with the SAS System software, release 8.2 (SAS Institute, Cary, NC, 19992001). All statistical tests were two-sided.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
Further adjustment for other potential confounders, including smoking status, history of rheumatoid arthritis, history of skin cancer, family history of cancer, history of blood transfusion, outdoor occupation, occupation regularly involving pesticides, education level, sunbathing habits, sunburn history, sun vacations abroad, and solarium visits, had minimal effect on all estimates (less than a 10% change). Information on dietary habits was available for only a subset of 597 case patients with non-Hodgkin lymphoma and 467 control subjects in Sweden. In this group, the results adjusted for dietary intake of dairy products, fried red meat, and fruits and vegetables (all of which were statistically significantly associated with non-Hodgkin lymphoma risk; E. T. Chang, K. Ekström Smedby, S. M. Zhang, H. Hjalgrim, M. Melbye, Å. Öst, B. Glimelius, A. Wolk, H.-O. Adami, unpublished results) remained consistent with the overall findings. That is, we found no association between a high BMI and risk of overall non-Hodgkin lymphoma or most non-Hodgkin lymphoma subtypes, except for statistically non-significant associations between a high BMI and an increased risk of diffuse large B-cell lymphoma and a decreased risk of chronic lymphocytic leukemia (data not shown).
When we categorized BMI by quartiles, we found no association between high BMI and risk of non-Hodgkin lymphoma, most non-Hodgkin lymphoma subtypes, or Hodgkin lymphoma (Table 3). However, we found a statistically significant increased risk of diffuse large B-cell lymphoma for people in the highest BMI quartile (27.6 kg/m2 or more) compared with those in the lowest quartile (less than 22.8 kg/m2) (OR = 1.4, 95% CI = 1.1 to 1.7; Ptrend across all quartiles of BMI = .01). We found no association between the BMI quartile and the risk of mantle cell lymphoma (OR = 1.1, 95% CI = 0.6 to 1.8; Ptrend = .56) or of chronic lymphocytic leukemia (OR = 0.9, 95% CI = 0.7 to 1.1, Ptrend = .21), in contrast to the associations that we detected when we compared overweight status with normal-weight status. When we treated BMI as a continuous variable, we found that BMI was statistically significantly associated with only the risk of diffuse large B-cell lymphoma (for each 5 kg/m2 increase in BMI, OR = 1.1, 95% CI = 1.0 to 1.2; Ptrend = .01). Additional adjustment for possible confounders had negligible effect on all estimates of association (data not shown), and results in the dietary subset were consistent with the overall results.
|
Independent associations of height and weight with risk of lymphoma were evaluated separately. After adjusting for age, sex, and country, we found no association between either height or weight (categorized into quartiles) and the risk of non-Hodgkin or Hodgkin lymphoma overall or the risk of any major histopathologic subtype except for that of chronic lymphocytic leukemia (data not shown). We found that the risk of chronic lymphocytic leukemia was statistically significantly associated with the highest quartile of height (taller than 179 cm), compared with the lowest quartile (165 cm or shorter)(OR = 1.7, 95% CI = 1.2 to 2.4).
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Although we observed no statistically significant associations between obesity, as defined by the WHO, and risk of any form of lymphoma examined, we did detect borderline statistically significant associations between an overweight status and the risk of diffuse large B-cell lymphoma, mantle cell lymphoma, or chronic lymphocytic leukemia, and between a highly obese status and the risk of diffuse large B-cell lymphoma. When we categorized BMI into quartiles or treated it as a continuous variable, we found no association with the risk of non-Hodgkin lymphoma overall, but we did find a statistically significant positive association between high BMI and the risk of diffuse large B-cell lymphoma. The fact that the highest quartile of BMI was associated with risk of diffuse large B-cell lymphoma, but that obesity was not, most likely resulted from the low prevalence of obesity in the study population (only 11% among control subjects), which reduced the power to detect an association between an obese status and lymphoma risk. However, the fact that our findings varied slightly depending on the procedure used to categorize BMI emphasizes the fact that the marginal association with risk of diffuse large B-cell lymphoma was potentially spurious.
Previous findings of a positive association between an obese status and the risk of overall non-Hodgkin lymphoma in ahandful of studies (18,20,2224) may have been influenced by a possible positive association with risk of diffuse large B-cell lymphoma. This subtype generally accounts for more than 30% of all non-Hodgkin lymphoma, making it the most common subtype of non-Hodgkin lymphoma in various populations (3542). Overall survival of patients with diffuse large B-cell lymphoma (less than 50% after 5 years) is similar to or lower than that for other common subtypes of non-Hodgkin lymphoma, including follicular lymphoma and chronic lymphocytic leukemia (35,43). Therefore, it is possible that the findings of Calle et al. (22)that obesity was associated with increased risk of non-Hodgkin lymphoma mortalityalso reflected a high proportion of diffuse large B-cell lymphoma in the case population. Alternatively, it is possible that obesity contributes to lymphoma mortality but not to its incidence. If true, this association could have resulted in some selection bias among the case patients in our study if those who survived were leaner than those who died. Another difference between our study and previous investigations is that others have generally excluded chronic lymphocytic leukemialargely because no other study has classified non-Hodgkin lymphoma according to the current WHO system, which includes chronic lymphocytic leukemia as a non-Hodgkin lymphoma subtypefor which we did not detect a positive association with BMI. Although our finding of a positive association between high BMI status and the risk of diffuse large B-cell lymphoma agrees with that of Skibola et al. (24), they also detected a positive association between obesity and the risk of overall non-Hodgkin lymphoma or of follicular lymphoma, which we did not observe.
Our results are also consistent with several other studies detecting no association between BMI and non-Hodgkin lymphoma (1517,19,21). Although our results agree for the most part with those of Cerhan et al. (21), who reported no association between BMI and risk of non-Hodgkin lymphoma, of follicular lymphoma, or of diffuse lymphoma, we did not detect a marginal positive association with risk of chronic lymphocytic leukemia. If anything, the association between BMI and the risk of chronic lymphocytic leukemia that we detected was slightly inverse, driven mostly by an apparent positive association between height and the risk of chronic lymphocytic leukemia, which was not observed by Cerhan et al. However, that group distinguished chronic lymphocytic leukemia from small lymphocytic lymphoma, which we combined with chronic lymphocytic leukemia as specified by the WHO classification (25). If Cerhan et al. (21) had combined chronic lymphocytic leukemia with small lymphocytic lymphoma, for which they observed a statistically nonsignificant inverse association with BMI, they may also have obtained null results. In any case, the association of chronic lymphocytic leukemia with obesity in our study and in that of Cerhan et al. was weak at best. Our observation of a positive association between height and the risk of chronic lymphocytic leukemia needs to be confirmed in other study populations.
No biologic mechanisms have been proposed that could explain a potential association between high BMI and the risk of non-Hodgkin lymphoma or Hodgkin lymphoma. It is also unclear why high BMI should be associated with a higher risk of diffuse large B-cell lymphoma but not of overall non-Hodgkin lymphoma, other subtypes of non-Hodgkin lymphoma, or Hodgkin lymphoma; a possible explanation lies in the fact that the various forms of lymphoma are distinct disease entities (25) with presumably different etiologies. The positive association between obesity and endocrine-related malignancies might be explained by increased levels of endogenous hormones, including sex steroids, insulin, or insulin-like growth factor I (44,45), but a causative role of these hormones in lymphomagenesis has not been established (4648). From observations on laboratory animals fed calorie-restricted diets (49), body mass also appears to affect cell proliferation (50) and apoptosis (51). Moreover, obesity may impair immune function (52,53), which is critical to the development of non-Hodgkin lymphoma and Hodgkin lymphoma (1014).
Our findings should be interpreted in light of several limitations. BMI is a widely accepted and used index of weight adjusted for height, especially in population-based studies (29,54,55). However, the validity of BMI as a measure of an overweight or obese status varies among ethnic groups, which differ in weight distribution and body composition. Therefore, results from a Scandinavian population may not necessarily be applicable to other populations. We lacked a direct measure of general or central adiposity or lean body mass, any or all of which may be more relevant to lymphoma risk. Furthermore, we did not have data on weight change or weight cycling over time and, therefore, were unable to evaluate the association between time trends in weight and lymphoma risk.
Because the disease may have affected the current weight of case patients, we asked participants to report their normal or usual adult weight. It is possible, although unlikely, that there were systematic differences between case patients and control subjects in their recollection of normal weight. However, it is not clear whether having been diagnosed with lymphoma would cause case patients to remember their previous weight more or less accurately or as being higher or lower than it was. We compared the country-specific distributions of BMI among the control subjects with published data from the Danish (56) and Swedish (57) populations and found that the reported distributions were very similar to those in our study, suggesting a lack of systematic misclassification among the control subjects. However, grouping BMI into categories and quartiles may also have introduced a degree of misclassification, with unpredictable effects.
Other biases could also explain the results. Although enrollment rates were high among both case patients and control subjects, reasons for nonparticipation differed between the two groups, especially because the most common reason for nonparticipation among the case patients was death. Selection bias could have produced overestimates of the association between BMI and lymphoma risk if eligible, overweight control subjects were less likely to enroll in the study and/or if eligible, overweight lymphoma patients were more likely to survive or participate. Alternatively, selection bias could have resulted in underestimates if overweight control subjects were more likely to enroll and/or overweight patients were more likely to die or refuse to participate. The low prevalence of individuals with an obese or underweight status in our study population reduced our ability to assess the associations between very high or very low BMI with risk of lymphoma, especially with the less common subtypes of non-Hodgkin lymphoma, including T-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma. One explanation for the lack of association between high BMI and the risk of some lymphoma subtypes could, therefore, be lack of statistical power, especially given that the magnitude of any association appears to be low. However, it is unlikely that our observation of no association between high BMI and overall non-Hodgkin lymphoma risk was caused by lack of power, given the large number of case patients in our study. As in any observational study, confounding by unknown factors or residual confounding caused by imperfect exposure assessment cannot be ruled out.
Finally, the possible association between increased BMI and risk of diffuse large B-cell lymphoma could be accounted for by chance. This explanation has to be considered because many tests of association were performed on several non-Hodgkin lymphoma subtypes, so that a few statistically significant findings would be expected to arise by chance alone. However, if a BMI of 27.6 kg/m2 or more is in fact associated with a 40% increased risk of diffuse large B-cell lymphoma, as observed in our study, then a high BMI might account for a nontrivial proportion of diffuse large B-cell lymphoma, given the high prevalence of this level of BMI, especially in Western populations. Diffuse large B-cell lymphoma is generally the most common subtype of non-Hodgkin lymphoma worldwide (34).
In summary, our findings suggest that high BMI, including an overweight and obese status, does not play an important role in the development of overall non-Hodgkin lymphoma, most non-Hodgkin lymphoma subtypes, or Hodgkin lymphoma. We found an indication that high BMI may play a role in the development of diffuse large B-cell lymphoma. Given that our study was conducted in a fairly homogeneous population with a relatively low prevalence of obesity, our results may not be able to be generalized to other populations. However, because high BMI appears to be only a weak risk factor, if a factor at all, for a single subtype of non-Hodgkin lymphoma, the increasing incidence of overall non-Hodgkin lymphoma across recent decades is unlikely to be explained in large part by the global escalation of the prevalence of overweight and obese individuals.
![]() |
NOTES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
(1) Devesa SS, Fears T. Non-Hodgkin's lymphoma time trends: United States and international data. Cancer Res 1992;52:5432s40s.[Abstract]
(2) Rabkin CS, Devesa SS, Zahm SH, Gail MH. Increasing incidence of non-Hodgkin's lymphoma. Semin Hematol 1993;30:28696.[ISI][Medline]
(3) Cartwright R, Brincker H, Carli PM, Clayden D, Coebergh JW, Jack A, et al. The rise in incidence of lymphomas in Europe 19851992. Eur J Cancer 1999;35:62733.[CrossRef][ISI][Medline]
(4) Banks PM. Changes in diagnosis of non-Hodgkin's lymphomas over time. Cancer Res 1992;52:5453s5s.[Abstract]
(5) Hartge P, Devesa SS. Quantification of the impact of known risk factors on time trends in non-Hodgkin's lymphoma incidence. Cancer Res 1992;52: 5566s9s.[Abstract]
(6) Obrams GI, O'Conor G. The emerging epidemic of non-Hodgkin's lymphoma: current knowledge regarding etiological factors. Time trends and pathological classification: a summary. Cancer Res 1992;52:5570s.[Medline]
(7) Vose JM, Chiu BC, Cheson BD, Dancey J, Wright J. Update on epidemiology and therapeutics for non-Hodgkin's lymphoma. Hematol (Am Soc Hematol Educ Program) 2002:24162.
(8) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000;894:ixii, 1253.[Medline]
(9) Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: IncidenceSEER 9 Regs Public-Use, November 2003 Sub (19732001), released April 2004, based on the November 2003 submission. National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch; Released April 2004, based on the November 2003 submission. Available at: http://www.seer.cancer.gov.
(10) Filipovich AH, Mathur A, Kamat D, Shapiro RS. Primary immunodeficiencies: genetic risk factors for lymphoma. Cancer Res 1992;52:5465s7s.[Abstract]
(11) Hoover RN. Lymphoma risks in populations with altered immunitya search for mechanism. Cancer Res 1992;52:5477s8s.[Abstract]
(12) Levine AM. Lymphoma complicating immunodeficiency disorders. Ann Oncol 1994;5:2935.[CrossRef][ISI][Medline]
(13) Cimino G, Lo Coco F, Cartoni C, Gallerano T, Luciani M, Lopez M, et al. Immune-deficiency in Hodgkin's disease (HD): a study of patients and healthy relatives in families with multiple cases. Eur J Cancer Clin Oncol 1988;24:1595601.[CrossRef][ISI][Medline]
(14) Powles T, Bower M. HIV-associated Hodgkin's disease. Int J STD AIDS 2000;11:4924.[CrossRef][ISI][Medline]
(15) Franceschi S, Serraino D, Bidoli E, Talamini R, Tirelli U, Carbone A, et al. The epidemiology of non-Hodgkin's lymphoma in the north-east of Italy: a hospital-based case-control study. Leuk Res 1989;13:46572.[CrossRef][ISI][Medline]
(16) Møller H, Mellemgaard A, Lindvig K, Olsen JH. Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer 1994;30A:34450.[ISI][Medline]
(17) Tulinius H, Sigfusson N, Sigvaldason H, Bjarnadottir K, Tryggvadottir L. Risk factors for malignant diseases: a cohort study on a population of 22,946 Icelanders. Cancer Epidemiol Biomarkers Prev 1997;6:86373.[Abstract]
(18) Holly EA, Lele C, Bracci PM, McGrath MS. Case-control study of non-Hodgkin's lymphoma among women and heterosexual men in the San Francisco Bay Area, California. Am J Epidemiol 1999;150:37589.[Abstract]
(19) Zhang S, Hunter DJ, Rosner BA, Colditz GA, Fuchs CS, Speizer FE, et al. Dietary fat and protein in relation to risk of non-Hodgkin's lymphoma among women. J Natl Cancer Inst 1999;91:17518.
(20) Wolk A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 2001;12:1321.[CrossRef][ISI][Medline]
(21) Cerhan JR, Janney CA, Vachon CM, Habermann TM, Kay NE, Potter JD, et al. Anthropometric characteristics, physical activity, and risk of non-Hodgkin's lymphoma subtypes and B-cell chronic lymphocytic leukemia: a prospective study. Am J Epidemiol 2002;156:52735.
(22) Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003;348:162538.
(23) Pan SY, Johnson KC, Ugnat AM, Wen SW, Mao Y. Association of obesity and cancer risk in Canada. Am J Epidemiol 2004;159:25968.
(24) Skibola CF, Holly EA, Forrest MS, Hubbard A, Bracci PM, Skibola DR, et al. Body mass index, leptin and leptin receptor polymorphisms, and non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 2004; 13:77986.
(25) Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. WHO Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon (France): International Agency for Research on Cancer Press; 2001.
(26) Ekström Smedby K, Hjalgrim H, Melbye M, Torrång A, Rostgaard K, Munksgaard L, et al. Ultraviolet radiation exposure and risk of malignant lymphomas. J Natl Cancer Inst 2005;97:199209.
(27) International Statistical Classification of Diseases and Related Health Problems, 1989 Revision. Geneva: World Health Organization; 1992.
(28) Swedish Cancer Register. Cancer Incidence in Sweden 1998. Stockholm: Centre for Epidemiology; 2000.
(29) Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Org Tech Rep Ser 1995;854: 1452.
(30) d'Amore F, Christensen BE, Brincker H, Pedersen NT, Thorling K, Hastrup J, et al. Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group. Eur J Cancer 1991;27:12018.[ISI][Medline]
(31) Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol 1993;138:92336.[Abstract]
(32) MacMahon B. Epidemiology of Hodgkin's disease. Cancer Res 1966;26:1189201.[ISI][Medline]
(33) Gutensohn NM. Social class and age at diagnosis of Hodgkin's disease: new epidemiologic evidence for the "two-disease hypothesis." Cancer Treat Rep 1982;66:68995.[ISI][Medline]
(34) Alexander FE, McKinney PA, Williams J, Ricketts TJ, Cartwright RA. Epidemiological evidence for the "two-disease hypothesis" in Hodgkin's disease. Int J Epidemiol 1991;20:35461.[Abstract]
(35) A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997;89:390918.
(36) The World Health Organization classification of malignant lymphomas in Japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists. Pathol Int 2000;50:696702.[CrossRef][ISI][Medline]
(37) Naresh KN, Srinivas V, Soman CS. Distribution of various subtypes of non-Hodgkin's lymphoma in India: a study of 2773 lymphomas using R.E.A.L. and WHO Classifications. Ann Oncol 2000;11 (suppl 1) :637.
(38) Clarke CA, Glaser SL, Dorfman RF, Bracci PM, Eberle E, Holly EA. Expert review of non-Hodgkin's lymphomas in a population-based cancer registry: reliability of diagnosis and subtype classifications. Cancer Epidemiol Biomarkers Prev 2004;13:13843.
(39) Turner JJ, Hughes AM, Kricker A, Milliken S, Grulich A, Kaldor J, et al. Use of the WHO lymphoma classification in a population-based epidemiological study. Ann Oncol 2004;15:6317.
(40) Ko YH, Kim CW, Park CS, Jang HK, Lee SS, Kim SH, et al. REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma. Cancer 1998;83: 80612.[CrossRef][ISI][Medline]
(41) Sukpanichnant S. Analysis of 1983 cases of malignant lymphoma in Thailand according to the World Health Organization classification. Hum Pathol 2004;35:22430.[CrossRef][ISI][Medline]
(42) Jakic-Razumovic J, Aurer I. The World Health Organization classification of lymphomas. Croat Med J 2002;43:52734.[ISI][Medline]
(43) Diebold J, Anderson JR, Armitage JO, Connors JM, Maclennan KA, Muller-Hermelink HK, et al. Diffuse large B-cell lymphoma: a clinicopathologic analysis of 444 cases classified according to the updated Kiel classification. Leuk Lymphoma 2002;43:97104.[CrossRef][ISI][Medline]
(44) Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk. Lancet Oncol 2002;3:56574.[CrossRef][ISI][Medline]
(45) Vainio H, Bianchini F, editors. Weight control and physical activity. IARC Handbooks of Cancer Prevention, Vol 6: weight control and physical activity. Lyon (France): International Agency for Research on Cancer Press; 2002.
(46) Nelson RA, Levine AM, Bernstein L. Reproductive factors and risk of intermediate- or high-grade B-cell non-Hodgkin's lymphoma in women. J Clin Oncol 2001;19:13817.
(47) Beiderbeck AB, Holly EA, Sturkenboom MC, Coebergh JW, Stricker BH, Leufkens HG. No increased risk of non-Hodgkin's lymphoma with steroids, estrogens and psychotropics (Netherlands). Cancer Causes Control 2003;14:63944.[CrossRef][ISI][Medline]
(48) Cerhan JR, Vachon CM, Habermann TM, Ansell SM, Witzig TE, Kurtin PJ, et al. Hormone replacement therapy and risk of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Cancer Epidemiol Biomarkers Prev 2002;11:146671.
(49) Hursting SD, Lavigne JA, Berrigan D, Perkins SN, Barrett JC. Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. Annu Rev Med 2003;54:13152.[CrossRef][Medline]
(50) Lok E, Nera EA, Iverson F, Scott F, So Y, Clayson DB. Dietary restriction, cell proliferation and carcinogenesis: a preliminary study. Cancer Lett 1988;38:24955.[CrossRef][ISI][Medline]
(51) Poetschke HL, Klug DB, Perkins SN, Wang TT, Richie ER, Hursting SD. Effects of calorie restriction on thymocyte growth, death and maturation. Carcinogenesis 2000;21:195964.
(52) Marti A, Marcos A, Martinez JA. Obesity and immune function relationships. Obes Rev 2001;2:13140.[CrossRef][Medline]
(53) Lamas O, Marti A, Martinez JA. Obesity and immunocompetence. Eur J Clin Nutr 2002;56 (suppl 3) :S425.[Medline]
(54) Kuczmarski RJ, Carroll MD, Flegal KM, Troiano RP. Varying body mass index cutoff points to describe overweight prevalence among U.S. adults: NHANES III (1988 to 1994). Obes Res 1997;5:5428.[Abstract]
(55) Willett WC. Nutritional epidemiology. 2nd ed. New York (NY): Oxford University Press; 1998.
(56) Kjøller M, Rasmussen NK, editors. Health and morbidity in Denmark 2000 and the development since 1987. Copenhagen (Denmark): National Institute of Public Health; 2002.
(57) Rasmussen F, Tynelius P, Kark M. Importance of smoking habits for longitudinal and age-matched changes in body mass index: a cohort study of Swedish men and women. Prev Med 2003;37:19.[CrossRef][ISI][Medline]
Manuscript received June 7, 2004; revised November 8, 2004; accepted November 23, 2004.
This article has been cited by other articles in HighWire Press-hosted journals:
Correspondence about this Article
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |