Affiliations of authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (KES, AT, JA, HOA); Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (HH, MM, KR, LM); Department of Hematology, Odense University Hospital, Odense, Denmark (LM); Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden (JA); Department of Hematology, Rigshospitalet, Copenhagen, Denmark (MH); Department of Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden (APM); Department of Medicine, Hillerød Hospital, Hillerød, Denmark (BAJ); Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden (GR); Department of Medicine, Viborg Hospital, Viborg, Denmark (BBP); Department of Pathology, Akademiska Hospital, Uppsala, Sweden (CS); Department of Pathology and Oncology, Karolinska University Hospital, Stockholm, and Department of Oncology, Radiology and Clinical Immunology, Akademiska Hospital, Uppsala, Sweden (BG); Department of Epidemiology, Harvard University, Boston, MA (HOA)
Correspondence to: Karin Ekström Smedby, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden (e-mail: karin.ekstrom{at}meb.ki.se).
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Experimental studies in both humans and animals have shown that UV exposure induces systemic immune suppression (3,28,29). These findings add biologic credibility to the hypothesis of a link between UV exposure and lymphoma because immune suppression is the strongest known risk factor for this malignancy (30). Given the large public health implications of a causal association between UV light exposure and risk of malignant lymphomas, testing this hypothesis in analytic epidemiologic studies is warranted (21,31). To this end, we carried out a large population-based casecontrol study in Denmark and Sweden with detailed assessment of UV exposure in relation to all major lymphoma subtypes.
![]() |
SUBJECTS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The SCALE (Scandinavian lymphoma etiology) study base encompassed the entire population between the ages of 18 years and 74 years living in Denmark from June 1, 2000, through August 30, 2002, and in Sweden from October 1, 1999, through April 15, 2002. In Denmark, participants in a regional pilot phase study that started November 1, 1999, and gradually was expanded to national coverage were also included. The source population for the SCALE study was restricted to subjects with sufficient knowledge of the Danish or Swedish language to answer questions in a telephone interview and without a history of organ transplantation, human immunodeficiency virus infection, or other hematopoietic malignancy. Individuals with a first, newly diagnosed malignant lymphoma (non-Hodgkin lymphoma, including chronic lymphocytic leukemia [CLL], or Hodgkin lymphoma) according to the World Health Organization (WHO) classification (32) were eligible as case patients. The International Classification of Diseases, 10th Revision (ICD-10) codes used were C82C85, C88.0, C91.35, and C91.7 (non-Hodgkin lymphoma), C91.1 (CLL), and C81 (Hodgkin lymphoma). In both countries, because of the relatively low incidence of Hodgkin lymphoma, patients with prevalent Hodgkin lymphoma diagnosed in 1999 were also included.
We identified patients newly diagnosed with lymphoma through a rapid case ascertainment system set up separately for the purposes of the study in both Denmark and Sweden. A network of contact physicians was established with all hospital clinics in which malignant lymphomas are diagnosed and treated (internal medicine, hematology, oncology, and clinical pathology), involving a total of 39 departments in Denmark and 118 in Sweden. Continuous collaboration with the national pathology registry in Denmark and the six regional cancer registries in Sweden ensured complete reporting through the network. The estimated coverage of the Danish pathology register and the Swedish cancer registries is close to 100% (33) (Inge Gram, Danish pathology register, personal communication).
Control subjects were randomly sampled from continuously updated computerized population registers that encompass the entire Danish and Swedish populations. A subset of control subjects was sampled every 6 months during the study period and was frequency-matched within each country on the expected distribution of cases of non-Hodgkin lymphoma, by sex and age (in 10-year intervals). In addition, extra sampling of control subjects was performed in the youngest age groups to ensure at least a 1:1 matching ratio for patients with Hodgkin lymphoma in all age groups.
Classification of Case Patients
In Denmark, review of tumor material took place within the national lymphoma registry organization (LYFO) (34). In this registry, a random 10% sample of all incident cases in the country is reviewed continuously by a panel of expert hematopathologists. In addition, in all but 20% of the study patients in Denmark the diagnostic tumor specimens had been evaluated primarily by a LYFO-approved senior hematopathologist. In Sweden, samples from all case patients were histopathologically evaluated by one of six senior hematopathologists or cytologists and were classified according to the WHO classification (32). Altogether, 70% of all included Swedish patients were reviewed within the study, whereas the remaining 30% had been reviewed already in routine care by one of the six appointed experts. When there was disagreement about a sample, it was referred to a panel of hematopathologists for final evaluation. The original diagnostic slides could not be retrieved for 35 (1.5%) of Swedish patients included in the study. For these patients, the written results of the primary morphologic and immunohistochemical investigation were used for diagnostic evaluation.
Host Factors and Exposure Information
Information on host characteristics, history of sun and artificial UV exposure, history of skin cancer, and potential confounding factors was collected through a telephone interview that used a standardized and computer-aided questionnaire. The computer-based questionnaire allowed the interviewers to fill in the responses of the participants directly in the computer during the course of interview. The questionnaire computer program also included automatic feasibility checks of responses when applicable and guidance through question loops. All questions were identical in the two countries. We were unable to blind the interviewers to case or control status, but they were unaware of the specific hypothesis under study and were instructed to treat case patients and control subjects strictly the same. Most patients (82%) with incident lymphoma were interviewed within 6 months after the date of the diagnostic biopsy (median interval = 2.8 months; range = 040 months). Among the patients with prevalent Hodgkin lymphoma, the median time from biopsy to interview was 13 months (range = 150 months). The total number of questions asked varied from 93 to 345, depending on the number of "question loops" entered. The median duration of the interview was 25 minutes among case patients (range = 12121 minutes) and 26 minutes among the control subjects (range = 12106 minutes).
The questions concerning host factors and UV light exposures were adapted from a validated questionnaire that has previously been used in studies of sun-related behavior in individuals with dysplastic nevus syndrome (35). Recorded host characteristics included natural hair color (blond, red, red brown, light brown, medium brown, dark brown, or black), eye color (blue, blue/grey, blue/green, green, green/grey, brown, or black), and skin sensitivity to sun exposure (also referred to as skin type). Skin sensitivity was defined as the reaction of skin (without sunscreen protection) to the first sun exposure of the season. Four categories of skin sensitivity were used: type I, the skin always burns and never tans; type II, the skin often burns and is then lightly tanned; type III, the skin sometimes burns and then turns medium tanned; and type IV, the skin seldom burns and always tans deeply. Assessment of sun exposure included sunbathing frequency during summer in Denmark/Sweden 510 years before the interview and at age 20 years (seven categories, from never to six to seven times per week); frequency of sunburns 510 years before the interview, at age 20 years, and during childhood (five categories, from never to three times or more per year); lifetime history of sun vacations abroad (meaning vacation trips to southern latitudes with sunbathing as the main activity; six categories, from never to more than 20 times); and outdoor occupation lasting 1 year or more (ever/never). Questions about sunbathing and sunburns at age 20 years were asked only of people 40 years old or older.
We also assessed exposure to artificial UV radiation as use of solaria (sun beds) or sun lamps (ever/never, with questions about lifetime frequency, duration, and age of regular use for those who had ever used one or both). Since 1989, only sun beds of UV type 3 (i.e., with low emission of UV-A wavelengths and very low emission of UV-B wavelengths) have been permitted in the Nordic countries. Finally, we recorded history of skin cancer (ever/never), and, if positive, age at diagnosis of skin cancer. However, these self-reports did not allow us to reliably distinguish between the different histopathologic types of skin cancer: malignant melanoma and squamous cell and basal cell carcinoma. The study questionnaire also contained a wide range of questions about, for example, current height and normal weight (for calculation of body mass index), history of autoimmune disorders, medication use, blood transfusions, smoking, occupational exposure to pesticides and solvents, educational level, and family history of cancer (36).
The study was approved by all regional ethics committees in Denmark and Sweden. Verbal informed consent was obtained from each participant before the interview.
Statistical Analyses
We used unconditional logistic regression in both univariate and multivariable analyses. Results are presented as odds ratios (ORs) with 95 percent confidence intervals (CIs); the odds ratio was used as an approximation of relative risk. All analyses were adjusted for the matching factors age (in 5-year intervals), sex, and country. Potential confounders were considered on the basis of prior knowledge of risk factors for non-Hodgkin lymphoma (36) and on whether the addition of the covariates to the models changed estimates of relative risk.
The multivariable analyses of lymphoma risk according to host characteristics were mutually adjusted for all other host factors. In the analyses of the different measures of UV exposure, we adjusted for skin type. We further added occupational exposure to pesticides to the multivariable model in the analyses of outdoor occupation. In the analyses of skin cancer, multivariable models included skin type and lifetime number of sun vacations abroad. Overall, the multivariable adjustments changed only a few of the univariate estimates by no more than 10%, and most estimates remained unchanged. Therefore, only multivariable estimates are presented.
Because of the small numbers of subjects in the upper two categories of the variables concerning sunbathing, sunburns at different ages, and use of solaria and sun lamps, we combined these categories. For the same reason, in the analyses of sunbathing we combined three intermediate categories into one category, in the analyses of sun vacations abroad we combined four intermediate categories into two categories, and in the analyses of solaria and sun lamps we combined two intermediate categories into one. In analyses of host characteristics, subjects with red brown, light brown, and medium brown hair were combined in one category. With respect to eye color, categories of brown and black color were combined into the referent category, and the colors blue/grey, grey, green, blue/green, and green/brown were combined into an intermediate category.
Statistical significance of independent variables and interaction effects were tested by the likelihood ratio test. We tested for trend across categories of some variables by assigning equally spaced values (e.g., 1, 2, 3, and 4) to the categories and treating them as continuous variables in the logistic regression analysis. All significance tests were two-sided.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
Hair color was not statistically significantly associated with risk of malignant lymphomas (Table 2). Grey, green, or mixed eye color was associated with a statistically significant slightly increased risk of non-Hodgkin lymphoma compared with brown or black color (OR = 1.3, 95% CI = 1.1 to 1.5, Table 2). There were no statistically significant associations between blue eye color and risk of any malignant lymphoma types. A U-shaped negative association between skin sensitivity to sun and lymphoma risk was observed for both non-Hodgkin and Hodgkin lymphoma. Subjects whose skin often burns on the first seasonal exposure to the sun (type II) consistently had the lowest relative risk compared with subjects whose skin seldom burns (type IV). For subjects with even more sensitive skin (type I), the risk estimates were higher, approaching unity.
|
Increasing frequency of sunbathing during summer in Denmark/Sweden and increasing numbers of sun vacations abroad were both associated with a decreasing risk of non-Hodgkin lymphoma (Table 3). Individuals with a history of sunbathing four times a week or more (both during the period 510 years before interview and at age 20 years) or a lifetime total of 20 or more sun vacations abroad had approximately 30% lower risks of all non-Hodgkin lymphomas than individuals without such sunbathing or vacation histories; these risk reductions were statistically significant, as were the negative trends (all Ptrend.001). We observed reductions in risk of Hodgkin lymphoma of the same magnitude, but these estimates were based on smaller numbers and were not statistically significant. Similar results were observed for all non-Hodgkin lymphoma subtypes as for non-Hodgkin lymphoma overall, although the data for T-cell lymphomas were less consistent and less precise. Frequent use of solaria or sun lamps was associated with a 20% reduced risk of non-Hodgkin lymphoma of borderline statistical significance and with a statistically significant risk reduction of 30% of Hodgkin lymphoma. Ever having an outdoor occupation for 1 year or more was associated with a slightly increased risk of non-Hodgkin lymphoma (OR = 1.2, 95% CI = 1.0 to 1.3) compared with never having worked outdoors, but this association was weakened (OR = 1.1, 95% CI = 1.0 to 1.2, Table 3) after additional adjustment for occupational exposure to pesticides.
|
Sunburns
An increasing annual frequency of sunburns during all time periods assessed was clearly inversely associated with risk of all non-Hodgkin lymphomas (Ptrend.003) (Table 4). The association was most pronounced for exposure at 20 years of age; individuals in the highest category of sunburn frequency (twice a year or more) at that age experienced a statistically significant 40% decrease in their risk of non-Hodgkin lymphoma compared with those who had no sunburns (OR = 0.6, 95% CI = 0.5 to 0.8, Ptrend<.001). There was little variation in associations among non-Hodgkin lymphoma subtypes, although the associations appeared slightly stronger for diffuse large B-cell and follicular lymphomas (Table 4). Mutual adjustment for all other measures of UV exposure for subjects at least 40 years old resulted in no association for the period 510 years before interview (data not shown).
|
We found no statistically significant interactions between any UV exposure variable and age, sex, or skin type. Interactions between sunburns and country were of borderline statistical significance, with risks of non-Hodgkin lymphoma being lower in Sweden than in Denmark for sunburns 510 years before interview (P for heterogeneity = .05) and at age 20 years (P for heterogeneity = .007) but not for sunburns in childhood (P for heterogeneity = .26). Importantly, however, protective associations were seen in both countries. For all other UV exposure variables, there was no effect variation by country.
Skin Cancer
A self-reported previous diagnosis of skin cancer was associated with a statistically significantly twofold increased risk of non-Hodgkin lymphoma (OR=2.1, 95% CI = 1.6 to 2.9). When we excluded skin cancers diagnosed within 1 year before lymphoma diagnosis among the case patients (and 1 year before interview for the control subjects), to avoid reversed causality, the relative risks did not change appreciably for either non-Hodgkin or Hodgkin lymphoma (Table 5). When non-Hodgkin lymphomas were stratified by subtype, the risk of T-cell lymphoma was increased fourfold in people with a history of skin cancer, whereas we found no association between skin cancer and diffuse large B-cell lymphoma. In analyses stratified according to time between diagnosis of skin cancer and of malignant lymphomas (Table 5), the relative risks were highest within the first 5 years after the diagnosis of skin cancer. With an interval of more than 5 years, the risk estimates for all non-Hodgkin lymphomas, CLL, and follicular lymphoma approached unity, whereas the risks of T-cell lymphoma and Hodgkin lymphoma remained statistically significantly increased. Multivariable adjustment for skin type and total number of sun vacations abroad increased a few risk estimates slightly. Further adjustment for other measures of UV exposure, smoking, educational level, occupational exposure to pesticides, autoimmune disorders, family history of cancer, and history of blood transfusions did not change the results (data not shown). There was no statistically significant interaction between history of skin cancer and sex, age, or country. In exploratory analyses (data not shown), high levels of UV exposure were generally positively associated with history of skin cancer, as expected.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We also observed an approximately twofold increased risk of both non-Hodgkin and Hodgkin lymphoma associated with a self-reported history of skin cancer. This finding is consistent with those of numerous registry-based cohort studies, in which a history of skin cancer has been associated with 1.5- to 3-fold increased risks of non-Hodgkin lymphoma, including CLL. These previous observations pertained not only to squamous cell skin cancer (4,6,10,12,15) but also to basal cell carcinoma (57,13) and malignant melanoma (4,6,8,9,11). In addition, several studies have observed two- to ninefold increased risks for skin cancer associated with a diagnosis of non-Hodgkin lymphoma (4,6,8,9,14). Data on risk of Hodgkin lymphoma after skin cancer are scarce, but nonstatistically significant twofold increased risks have been reported (3,5, 10, 12). In these earlier reports, proposed explanations for the observed association between skin cancer and lymphomas include shared etiologic factors such as chronic immune suppression resulting from genetic or environmental factors, in particular UV exposure. A link between the two groups of malignancies might also arise spuriously because of closer surveillance and thereby higher detection rate of a second primary malignancy.
Geographic and temporal correlations between incidence of skin cancer and non-Hodgkin lymphoma (2,16) support a relationship between the two malignancies but do not convey any information about the mechanism(s). Other ecologic studies of latitude and/or estimated UV-B radiation levels and incidence or mortality from non-Hodgkin lymphoma have shown either positive (1618), negative (19,2123), or no correlations (20). Not only are these results far from clear, but ecologic studies are also often difficult to interpret due to the lack of individual-level information on exposure and possible confounders. Moreover, studies on occupational exposure to UV light and risk of non-Hodgkin lymphoma mostly provide evidence of no association (26,27,38) or of weak positive (24) or weak negative associations (25). However, because none of these studies had data on recreational sun exposure, a potentially large exposure misclassification might have biased the results.
Given the indirect nature of almost all previously published evidence for a possible relationship between UV exposure and risk of malignant lymphomas, the strength of our study lies in the detailed and individual assessment of this exposure. Other strengths include the population-based design, the complete and rapid case ascertainment, and the thorough and uniform classification of malignant lymphomas. Moreover, the large study size permitted us to analyze relative risks of major non-Hodgkin lymphoma subtypes and of Hodgkin lymphoma.
One limitation of the study is the nonparticipation rate (17% versus 29% among eligible case patients and control subjects, respectively), which could have introduced selection bias. However, it is not likely that nonparticipation would be differently linked to UV exposure among case patients nd control subjects. Another possible bias in a casecontrol study design is differential recollection of exposure between case patients and control subjects (i.e., recall bias). However, there are presently no firmly established or widely known associations between UV exposure and malignant lymphoma. Therefore, it is unlikely that patients would have been influenced to link their disease to UV exposure or, further, that they would have systematically underreported their exposureeven more so at age 20 years than 510 years before interviewin such a way that a true positive association became convincingly inverse. Given the limitations of self-reported data on past exposures and the challenging task of capturing all aspects of UV exposure, it is more likely that our study suffers to some extent from imprecise exposure assessment, which is likely to affect case patients and control subjects equally. Such nondifferential exposure misclassification generally attenuates any true differences between case patients and control subjects, biasing the results toward no association, i.e., causing associations to be underestimated.
We cannot exclude the possibility that our results were influenced by residual confounding of unknown etiologic factors related to UV exposure or were due to chance. However, adjustment for a number of known and suspected risk factors for malignant lymphomas had little or no impact on the risk estimates. Although there is a possibility that some of the statistically significant associations arose by chance (especially given that multiple comparisons were carried out), the consistency of the results across UV exposure variables and the highly statistically significant inverse doseresponse relationships indicate that chance alone is unlikely to explain our findings. The similarity of results between Denmark and Sweden and between the sexes and the independence of the associations from skin type further decrease the possibility that our findings would have arisen as a result of bias or chance. The fact that inverse associations were observed for all skin types may further imply that our findings are generalizable beyond a Scandinavian population. In contrast with the rest of the findings, we observed no associations with ever having an outdoor occupation. This could be due to de facto low levels of UV light exposure associated with outdoor occupation, insufficiently detailed information about job history, or residual confounding.
Subtypes of lymphatic malignancies show considerable heterogeneity with respect to clinical behavior, histopathology, and molecular biology (32). There is increasing awareness that etiologic factors might also differ between subtypes (31,39). Interestingly, risk factors for some uncommon lymphoma types are well established, for example, Epstein-Barr virus for Burkitt's lymphoma and non-Hodgkin lymphoma in strongly immunosuppressed individuals, Helicobacter pylori for gastric lymphoma, and human herpes virus 8 for pleural effusion lymphomas. Much less is known about risk factors for more common non-Hodgkin lymphoma subtypes. Most consistently, a number of autoimmune and chronic inflammatory disorders have been positively associated with non-Hodgkin lymphoma (40). There is also evidence of a degree of familiar clustering (40). Hence, although primary and acquired suppression of cell-mediated immunity are the most well-known risk factors for non-Hodgkin lymphoma, lymphomagenesis also appears to involve immune stimulation and/or dysfunction, driven by exogenous as well as endogenous factors.
It is unclear whether our data indicate that UV-induced systemic immune modulation, which involves alterations of T-cell subsets (CD4+, CD8+, and natural killer cells) (28), can confer a reduced risk of non-Hodgkin lymphoma (or perhaps only B-cell lymphoma), rather than a risk increase as previously believed (13,31). However, because systemic immune effects by UV radiation appear to be modulated by skin type (28), this mechanism would be consistent with our finding of an association between skin type and lymphoma risk. Another possible biologic mechanism by which UV exposure could inhibit lymphomagenesis is photo-initiation of vitamin D production by UV-B radiation (22,41). Vitamin D deficiency may have a role in the development of several common cancers, including cancers of the prostate, colon, breast, and ovary (41). The active vitamin D hormone calcitriol (1,25-dihydroxyvitamin D3) promotes differentiation and has an antiproliferative effect on a variety of cell lines, including those derived from the hematopoietic system (42). Treatment with alpha-calcidiol, which is metabolized to calcitriol, has also been shown to produce tumor regression in follicular low-grade lymphomas (42). It has been proposed that this action is enhanced through a modulation of CD4+ T cells (42). An increase in skin pigmentation is also known to be associated with diminished cutaneous production of cholecalciferol (vitamin D3) after UV exposure (41).
In light of our finding that UV exposure is inversely associated with the risk of non-Hodgkin lymphoma, the link between malignant lymphomas and skin cancer is intriguing. Decreasing relative risks of non-Hodgkin lymphoma with increasing time from diagnosis of skin cancer, both in previous reports (4,9,10) and in this study, may indicate shared predisposing factors, such as acquired dysfunction of the cellular immune system or of DNA repair. This possibility is indirectly supported by observations that skin cancer is associated with poor prognosis in patients with second cancers (non-Hodgkin lymphoma and breast, prostate, colon, and lung cancer) (43,44). Moreover, skin cancer patients appear to be at increased risk, not only of non-Hodgkin lymphoma but also of carcinomas of the upper aerodigestive tract, breast, kidney, lung, and brain (5,1012,45). Our results further indicate that different subtypes of malignant lymphoma may have different associations with skin cancer.
To conclude, our data do not support the a priori hypothesis that UV exposure is associated with an increased risk of malignant lymphomas. Rather, the results suggest an inverse association between UV light exposure and non-Hodgkin lymphoma risk. However, before this association can be considered causal we need further confirmatory data from other epidemiologic studies and, ideally, a better understanding of possible biologic mechanisms.
![]() |
APPENDIX |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Contact doctors in Sweden: M. Adriansson, J. Ahlgren, T. Ahlgren, D. Almqvist, J. Alsenhed, P-O. Andersson, D. Aronson, U. Bandmann, S. Bergström, A. Bjurman, B. Boeryd, L. Bohlin, P. Boiesen, U. Bolsöy, H. Bäck, R. Cameron, K. Carlson, M. Carlsson, G. Carlstedt, A. Danielsson, F. Dejby, F. Dommanget, A. Dybjer, T. Däldborg, M. Eckerrot, T. Edekling, M. Ehinger, A-M. Ekelund, T. Ekman, A. Elmhorn-Rosenborg, T. End, L. Engqvist, M. Eriksson, D. Fors, T. Frazer, S. Fredén, C. Gestblom, I. Glifberg, B. Goine, B. Gollvik, G. Greim, A. Gummeson, E. Haapaniemi, J. Habberstad, H. Hagberg, S. Hansen, U. Hansson, L. Hardell, S. Hasselblom, O. Hasslow, R. Hast, G. Havel, M. Hedenus, A. Heikkilä, I. Henke, S. Herbertsson, E. Hesse-Sundin, M. Hjort, E. Holm, J. Häggström, E. Härnby, I. Idvall, B. Jacobsson, S. Jacobsson, I. Jarlsfelt, B. Johansson, J-E. Johansson, P. Johansson, K. Karlsson, M. Karlsson, E. Kimby, R-M. Kristoffersson, T. Kunze, N. Kuric, K. Landys, O. Lannemyr, P. Lannes, B. Larsson, K. Larsson, G. Larsson, B. Lauri, G. Lilja, A. Lindblom, A. Lindgren, L. Lundgren-Eriksson, K. Lundkvist, M. Luthman, L. Malmberg, J. Matusik, N. Mauritzson, L. Mellbom, L. Mikaelsson, Z. Nezadalova, G. Nilsson, I. Nilsson, R. Nilsson, S-B. Nilsson, B. Norberg, M. Nordström, G. Nyberg, A. Othzén, P-G. Persson, U. Petersson, H. Renvall, B. Ridell, G. Roupe, J. Ryde, A. Rådlund, J. Samuelsson, T. Samuelsson, B. Sander, M. Sandhall, R. Schnell, M. Sender, L. Skoog, L. Skoog, U. Stjernberg, M. Strandberg, G. Strömblad, H. Strömblad, B. Strömdahl, H. Stålhammar, G. Sundström, A. Svensson, E. Svensson, P. Svensson, A. Sverrisdottir, A. Swedin, G. Tallroth, L. Tennvall-Nittby, K. Tholin, B. Thulé, U. Tidefelt, I. Timberg, L. Timberg, T. Tot, H. Tove, O. Tullgren, B. Uggla, J. Vaktnäs, E. Vancea, L. Vavica, J. Väärt, T. Wahlin, T. Wallin, K. Wallman, J. Wallvik, C. Wedelin, L. Westin, J. Wågermark, E. Ösby.
![]() |
NOTES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We are deeply indebted to Charlotte Appel in Denmark and Leila Nyrén in Sweden for coordination of the fieldwork, to cytologist Edneia Tani and pathologists Måns Åkerman and Åke Öst for extensive review of tumor material, to Yvonne Brandberg for invaluable help with the UV light exposure questions, and to Kirsten Ehlers at the LYFO secretariat. Furthermore, this study could not have been performed without the kind help and positive attitude of all contact doctors and nurses throughout Denmark and Sweden (see names listed in Appendix).
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
(1) Zheng T, Mayne ST, Boyle P, Holford TR, Liu WL, Flannery J. Epidemiology of non-Hodgkin lymphoma in Connecticut. 19351988. Cancer 1992;70:8409.[ISI][Medline]
(2) Cartwright R, McNally R, Staines A. The increasing incidence of non-Hodgkin's lymphoma (NHL): the possible role of sunlight. Leuk Lymphoma 1994;14:38794.[ISI][Medline]
(3) Melbye M, Adami HO, Hjalgrim H, Glimelius B. Ultraviolet light and non-Hodgkin's lymphoma. Acta Oncol 1996;35:6557.[ISI][Medline]
(4) Adami J, Frisch M, Yuen J, Glimelius B, Melbye M. Evidence of an association between non-Hodgkin's lymphoma and skin cancer. BMJ 1995;310:14915.
(5) Frisch M, Hjalgrim H, Olsen JH, Melbye M. Risk for subsequent cancer after diagnosis of basal-cell carcinoma. A population-based, epidemiologic study. Ann Intern Med 1996;125:81521.
(6) Levi F, Randimbison L, Te VC, La Vecchia C. Non-Hodgkin's lymphomas, chronic lymphocytic leukaemias and skin cancers. Br J Cancer 1996;74:184750.[ISI][Medline]
(7) Friedman GD, Tekawa IS. Association of basal cell skin cancers with other cancers (United States). Cancer Causes Control 2000;11:8917.[ISI][Medline]
(8) Goggins WB, Finkelstein DM, Tsao H. Evidence for an association between cutaneous melanoma and non-Hodgkin lymphoma. Cancer 2001;91:87480.[CrossRef][ISI][Medline]
(9) McKenna DB, Doherty VR, McLaren KM, Hunter JA. Malignant melanoma and lymphoproliferative malignancy: is there a shared aetiology? Br J Dermatol 2000;143:1713.[CrossRef][ISI][Medline]
(10) Frisch M, Melbye M. New primary cancers after squamous cell skin cancer. Am J Epidemiol 1995;141:91622.[Abstract]
(11) Swerdlow AJ, Storm HH, Sasieni PD. Risks of second primary malignancy in patients with cutaneous and ocular melanoma in Denmark, 19431989. Int J Cancer 1995;61:7739.[ISI][Medline]
(12) Levi F, Randimbison L, La Vecchia C, Erler G, Te VC. Incidence of invasive cancers following squamous cell skin cancer. Am J Epidemiol 1997;146:7349.[Abstract]
(13) Levi F, La Vecchia C, Te VC, Randimbison L, Erler G. Incidence of invasive cancers following basal cell skin cancer. Am J Epidemiol 1998;147:7226.[Abstract]
(14) Dong C, Hemminki K. Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 19581996: a search for common mechanisms. Br J Cancer 2001;85:9971005.[CrossRef][ISI][Medline]
(15) Hemminki K, Jiang Y, Steineck G. Skin cancer and non-Hodgkin's lymphoma as second malignancies. markers of impaired immune function? Eur J Cancer 2003;39:2239.[CrossRef][ISI][Medline]
(16) McMichael AJ, Giles GG. Have increases in solar ultraviolet exposure contributed to the rise in incidence of non-Hodgkin's lymphoma? Br J Cancer 1996;73:94550.[ISI][Medline]
(17) Bentham G. Association between incidence of non-Hodgkin's lymphoma and solar ultraviolet radiation in England and Wales. BMJ 1996;312:112831.
(18) Langford IH, Bentham G, McDonald AL. Mortality from non-Hodgkin lymphoma and UV exposure in the European community. Health Place 1998;4:35564.[CrossRef][Medline]
(19) Hartge P, Devesa SS, Grauman D, Fears TR, Fraumeni JF Jr. Non-Hodgkin's lymphoma and sunlight. J Natl Cancer Inst 1996;88:298300.
(20) Newton R. Solar ultraviolet radiation is not a major cause of primary cutaneous non-Hodgkin's lymphoma. BMJ 1997;314:14834.
(21) Grant WB. Ecologic studies of solar UV-B radiation and cancer mortality rates. Recent Results Cancer Res 2003;164:3717.[Medline]
(22) Hu S, Ma F, Collado-Mesa F, Kirsner RS. Ultraviolet radiation and incidence of non-Hodgkin's lymphoma among Hispanics in the United States. Cancer Epidemiol Biomarkers Prev 2004;13:5964.
(23) Grant WB. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer 2002;94:186775.[CrossRef][ISI][Medline]
(24) Hakansson N, Floderus B, Gustavsson P, Feychting M, Hallin N. Occupational sunlight exposure and cancer incidence among Swedish construction workers. Epidemiology 2001;12:5527.[CrossRef][ISI][Medline]
(25) Freedman DM, Zahm SH, Dosemeci M. Residential and occupational exposure to sunlight and mortality from non-Hodgkin's lymphoma: composite (threefold) case-control study. BMJ 1997;314:14515.
(26) Adami J, Gridley G, Nyren O, Dosemeci M, Linet M, Glimelius B, et al. Sunlight and non-Hodgkin's lymphoma: a population-based cohort study in Sweden. Int J Cancer 1999;80:6415.[CrossRef][ISI][Medline]
(27) van Wijngaarden E, Savitz DA. Occupational sunlight exposure and mortality from non-Hodgkin lymphoma among electric utility workers. J Occup Environ Med 2001;43:54853.[ISI][Medline]
(28) Norval M. Effects of solar radiation on the human immune system. J Photochem Photobiol B 2001;63:2840.[CrossRef][ISI][Medline]
(29) Garssen J, van der Molen R, de Klerk A, Norval M, van Loveren H. Effects of UV irradiation on skin and nonskin-associated herpes simplex virus infections in rats. Photochem Photobiol 2000;72:64551.[CrossRef][ISI][Medline]
(30) Evans LS, Hancock BW. Non-Hodgkin lymphoma. Lancet 2003;362:13946.[CrossRef][ISI][Medline]
(31) Zheng T, Owens PH. Sunlight and non-Hodgkin's lymphoma. Int J Cancer 2000;87:8846.[CrossRef][ISI][Medline]
(32) Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of hematopoietic and lymphoid tissues. Lyon (France): IARC Press; 2001.
(33) Mattsson B, Wallgren A. Completeness of the Swedish Cancer Register. Non-notified cancer cases recorded on death certificates in 1978. Acta Radiol Oncol 1984;23:30513.[ISI][Medline]
(34) 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]
(35) Brandberg Y, Sjoden PO, Rosdahl I. Assessment of sun-related behaviour in individuals with dysplastic naevus syndrome: a comparison between diary recordings and questionnaire responses. Melanoma Res 1997;7:34751.[ISI][Medline]
(36) Melbye M, Trichopoulos, D. Non-Hodgkin's lymphomas. In: Adami HO, Hunter, D, Trichopoulos, D, editors. Textbook of cancer epidemiology. 1st ed. New York (NY): Oxford University Press; 2002. p. 53549.
(37) Hughes AM, Armstrong BK, Vajdic CM, Turner J, Grulich AE, Fritschi L, et al. Sun exposure may protect against non-Hodgkin lymphoma: a case-control study. Int J Cancer 2004;112:865871.[CrossRef][ISI][Medline]
(38) Newton R, Roman E, Fear N, Carpenter L. Non-Hodgkin's lymphoma and solar ultraviolet radiation. Data are inconsistent. BMJ 1996;313:298.
(39) Chiu BC, Weisenburger DD. An update of the epidemiology of non-Hodgkin's lymphoma. Clin Lymphoma 2003;4:1618.[ISI][Medline]
(40) Baris D, Zahm SH. Epidemiology of lymphomas. Curr Opin Oncol 2000;12:38394.[CrossRef][ISI][Medline]
(41) Holick MF. Vitamin D: a millenium perspective. J Cell Biochem 2003;88:296307.[CrossRef][ISI][Medline]
(42) Hickish T, Cunningham D, Colston K, Millar BC, Sandle J, Mackay AG, et al. The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma. Br J Cancer 1993;68:66872.[ISI][Medline]
(43) Askling J, Sorensen P, Ekbom A, Frisch M, Melbye M, Glimelius B, et al. Is history of squamous-cell skin cancer a marker of poor prognosis in patients with cancer? Ann Intern Med 1999;131:6559.
(44) Hjalgrim H, Frisch M, Storm HH, Glimelius B, Pedersen JB, Melbye M. Non-melanoma skin cancer may be a marker of poor prognosis in patients with non-Hodgkin's lymphoma. Int J Cancer 2000;85:63942.[CrossRef][ISI][Medline]
(45) Kahn HS, Tatham LM, Patel AV, Thun MJ, Heath CW Jr. Increased cancer mortality following a history of nonmelanoma skin cancer. JAMA 1998;280:9102.
Manuscript received June 23, 2004; revised November 15, 2004; accepted November 26, 2004.
This article has been cited by other articles in HighWire Press-hosted journals:
Editorial about this Article
Related Memo to the Media
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |