© The Author 2008. Published by Oxford University Press.
The Utility of t(14;18) in Understanding Risk Factors for Non-Hodgkin Lymphoma
Affiliations of authors: Department of Preventive Medicine, Feinberg School of Medicine (BCHC) and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (BCHC); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD (QL, AB, SHZ); Munroe Meyer Institute for Genetics and Rehabilitation (BJD) and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE (BJD, DDW)
Correspondence to: Brian C.-H. Chiu, PhD, Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 North Lake Shore Drive, Suite 1102, Chicago, IL 60611 (e-mail: bchiu{at}northwestern.edu).
 |
ABSTRACT |
|---|
 Top Abstract IntroductionChromosomal AbnormalitiesIntegrating t(14;18) Status With...Risk Factors for t(14;18)...Lessons Learned and Future...FundingReferences |
|---|
Characteristic chromosomal abnormalities are associated with specific histological subtypes of non-Hodgkin lymphoma (NHL). The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in NHL, occurring in 70%–90% of cases of follicular lymphoma, 20%–30% of diffuse large B-cell lymphoma, and 5%–10% of other less common subtypes. The t(14;18)-positive NHL may represent a homogenous group and, consequently, increase etiologic specificity in epidemiological studies. Although the t(14;18) has important clinical ramifications, its etiologic significance remains to be determined. Two population-based, case–control studies addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. Both studies found that the association between pesticide exposures and risk of NHL was largely limited to t(14;18)-positive NHL cases. However, the findings regarding cigarette smoking, family history of hematopoietic cancer, and hair dye use were not entirely consistent. These results indicate that defining subgroups of NHL according to t(14;18) status may be useful for etiologic research, particularly for exposures that are genotoxic or may contribute to the development of NHL through pathways involving the t(14;18). Studies to further evaluate these associations and delineate the effects of various exposures in other genetically defined subgroups of NHL are warranted.
|
INTRODUCTION |
|---|
|
TopAbstractIntroductionChromosomal AbnormalitiesIntegrating t(14;18) Status With...Risk Factors for t(14;18)...Lessons Learned and Future...FundingReferences |
|---|
Non-Hodgkin lymphoma (NHL) includes many different subtypes with a variety of different molecular characteristics (1). The patterns of change in the incidence of NHL over the past 30 years vary across the different subtypes (2), suggesting differences in etiologic factors (3). NHL is presently classified according to the new World Health Organization (WHO) classification, which reflects the postulated cell lineage and stage of differentiation (1). However, many of the WHO-defined subtypes remain heterogeneous at the molecular level (4–6). Whether or not molecularly defined subgroups of NHL have etiologic significance is largely unknown. Two epidemiological studies (7–10) have addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. This paper describes the rationale for integrating molecular characteristics with epidemiological data, summarizes the findings from these two epidemiological studies, and suggests some lessons to be learned from the use of this novel approach.
|
Chromosomal Abnormalities |
|---|
|
TopAbstractIntroductionChromosomal AbnormalitiesIntegrating t(14;18) Status With...Risk Factors for t(14;18)...Lessons Learned and Future...FundingReferences |
|---|
NHL arises when reciprocal rearrangements of B-cell immunoglobulin or T-cell receptor genes occur with oncogenes within immature lymphoid cells in the bone marrow or more mature cells in the peripheral lymphoid organs (11,12). These chromosomal translocations often result in the overexpression of oncogenes and cause the cells to become malignant and proliferate in an uncontrolled manner (12). Characteristic chromosomal abnormalities are often associated with specific histological subtypes of NHL (13–15). These include the t(14;18)(q32;q21), t(2;18)(p11;q21), and t(18;22)(q21;q11) involving the BCL2 proto-oncogene in follicular lymphoma and diffuse large B-cell lymphoma; t(3;14)(q27;q32) and other translocations of 3q27 involving the BCL6 proto-oncogene in follicular lymphoma and diffuse large B-cell lymphoma; t(8;14)(q24;q32), t(2;8)(p11;q24), and t(8;22)(q24;q11) involving the C-MYC proto-oncogene in Burkitt’s lymphoma and diffuse large B-cell lymphoma; and the t(11;14)(q13;q32) involving the BCL1 proto-oncogene in mantle cell lymphoma (13,16). There is a convincing evidence suggesting that NHL can be subdivided on the basis of these nonrandom chromosomal translocations (17). However, the etiology of these translocations remains unknown.
One of the most common chromosomal abnormalities in NHL is the t(14;18)(q32;q21), which occurs in 70%–90% of cases of follicular lymphoma, 20%–30% of diffuse large B-cell lymphoma, and 5%–10% of other less common subtypes (1,13,15). The t(14;18) joins the BCL2 gene on chromosome 18 to the immunoglobulin heavy chain gene on chromosome 14, leading to an inhibition of programmed cell death through BCL2 overexpression and, consequently, prolonged survival of the affected B cells (17). The t(14;18) has important clinical ramifications. Patients with germinal center B cell–like diffuse large B-cell lymphoma, which is typically associated with the t(14;18)(q32;q21) and BCL2 overexpression, have better survival than patients of activated B cell–like diffuse large B-cell lymphoma, which lack the t(14;18)(q32;q21) (18,19). Recently, two epidemiological studies have explored whether defining subgroups of NHL according to presence or absence of the t(14;18) also has etiologic significance (7–10).
|
Integrating t(14;18) Status With Epidemiological Data |
|---|
|
TopAbstractIntroductionChromosomal AbnormalitiesIntegrating t(14;18) Status With...Risk Factors for t(14;18)...Lessons Learned and Future...FundingReferences |
|---|
The first study was conducted by Schroeder et al. (9,10) using a population-based, case–control study conducted in Iowa and Minnesota between 1981 and 1983 as the data source. The parent study included 622 cases and 1245 controls and was limited to men. Tumor blocks were retrieved for 248 of the 622 cases (40%) in the parent case–control study. The presence of the t(14;18) was determined by a polymerase chain reaction (PCR) method that detected translocations involving the major break point region in chromosome 18, and 182 of the 248 blocks (73%) were successfully assayed. In total, 37% (68) of these cases were t(14;18) positive and 114 were t(14;18) negative.
The second study was conducted by Chiu et al. (7,8) using a population-based, case–control study conducted in Nebraska between 1983 and 1986 as the epidemiological data source. The parent case–control study included 385 cases and 1432 controls and included both men and women. Tumor blocks were obtained for 175 of the 385 cases (45.5%) in the parent study. Fluorescence in situ hybridization (FISH) analysis was used to determine the t(14;18). FISH analysis was successfully conducted on 172 of the 175 cases (98.3%). In total, 37% (64) of the cases were t(14;18) positive and 62% (108) were t(14;18) negative. The prevalence of t(14;18)-positive NHL was comparable in these two studies (7–10).
Risk factors evaluated in these two epidemiological studies include agricultural activities and exposures, cigarette smoking, hair dye use, and a family history of hematopoietic cancer. These risk factors have been associated with a higher risk of NHL (3,20–30). In some studies, these risk factors were not associated, or only weakly associated with risk of NHL overall, but were specifically associated with risk of follicular lymphoma, diffuse large B-cell lymphoma, or chronic lymphocytic leukemia and small lymphocytic lymphoma (21–23,25,28–31). There is also evidence that these risk factors may be associated with development of t(14;18). Farmers who are exposed to pesticides have an increased prevalence of the t(14;18) during the high pesticide use period (32), and the use of pesticides was more common among t(14;18)-positive individuals (33–35). One study found that the frequency of BCL2 translocations was 3.6-fold higher in heavy smokers than in nonsmokers (36). In that study, greater smoking was associated with a higher frequency of the t(14;18). Thus, Schroeder et al. (9,10) and Chiu et al. (7,8) proposed that defining subtypes of NHL according to t(14;18) status may increase the etiologic specificity relative to all NHL combined, and allow risk factors to be better identified because cases with t(14;18) may be more closely related etiologically than NHL cases as a whole.
|
Risk Factors for t(14;18)-defined Subgroups of NHL |
|---|
|
TopAbstractIntroductionChromosomal AbnormalitiesIntegrating t(14;18) Status With...Risk Factors for t(14;18)...Lessons Learned and Future...FundingReferences |
|---|
Agricultural Activities
Studies in Iowa/Minnesota and Nebraska both found a consistent pattern of greater risk for t(14;18)-positive NHL than t(14;18)-negative associated with agricultural exposures (8,9). In the Iowa/Minnesota study (9), t(14;18)-positive NHL was associated with farming (odds ratio [OR] = 1.4; 95% confidence interval [CI] = 0.9 to 2.3) and exposures to fungicides (OR = 1.8; 95% CI = 0.9 to 3.6) as well as a few specific pesticides, including dieldrin (OR = 3.7; 95% CI = 1.9 to 7.0), lindane (OR = 2.3; 95% CI = 1.3 to 3.9), toxaphene (OR = 3.0; 95% CI = 1.5 to 6.1), and atrazine (OR = 1.7, 95% CI = 1.0 to 2.8), whereas there were no such associations with t(14;18)-negative NHL. In the Nebraska study (8), the risk of t(14;18)-positive NHL was significantly elevated among farmers who used animal insecticides (OR = 2.6; 95% CI = 1.0 to 6.9), crop insecticides (OR = 3.0; 95% CI = 1.1 to 8.2), herbicides (OR = 2.9; 95% CI = 1.1 to 7.9), and fumigants (OR = 5.0; 95% CI = 1.7 to 14.5), compared with farmers who never used pesticides. None of these categories of pesticides were associated with t(14;18)-negative NHL. Consistent with the findings of Schroeder et al. (9), Chiu et al. (8) also found that the risk of t(14;18)-positive NHL was elevated among farmers using dieldrin (OR = 2.4; 95% CI = 0.8 to 7.9), toxaphene (OR = 3.2; 95% CI = 0.8 to 12.5), and lindane (OR = 3.5; 95% CI = 1.4 to 8.4), compared with nonfarmers. In addition, the risk of t(14;18)-positive NHL associated with insecticides and herbicides increased with longer duration of use. The Iowa/Minnesota study (9) used nonfarmers and farmers without exposures as the referent group, whereas the Nebraska study (8) used farmers who never used pesticides as the referent group. When the same definition for the referent group was applied to the Nebraska data, the researchers found that the ORs for t(14;18)-positive NHL became smaller but remained statistically significant, whereas the ORs for t(14;18)-negative NHL were essentially unchanged.
Cigarette Smoking
The results on tobacco product use from the Iowa/Minnesota (10) and Nebraska (7) studies are not entirely consistent. In the Iowa/Minnesota study in men (10), cigarette smoking was not associated with either t(14;18)-positive NHL (OR = 1.3; 95% CI = 0.8 to 2.2) or t(14;18)-negative NHL (OR = 1.0; 95% CI = 0.7 to 1.4). The Nebraska study (7) also found no association between cigarette smoking and risk of either t(14;18)-positive or t(14;18)-negative NHL among men. However, among women, there was a positive association between cigarette smoking and risk of t(14;18)-negative NHL (OR = 1.7; 95% CI = 0.9 to 3.4 for ex-smokers and OR = 2.1; 95% CI = 1.1 to 4.4 for current smokers compared with never smokers) (7). The risk increased with longer duration of use (OR = 2.1 for having smoked >30 years; 95% CI = 1.1 to 4.1) and early initiation (OR = 2.2 for starting smoking at <20 years of age; 95% CI = 1.1 to 4.4).
Family History of Hematopoietic Cancer
In the Iowa/Minnesota study (10), a family history of hematopoietic cancer among first-degree relatives was associated with t(14;18)-negative NHL (OR = 2.4; 95% CI = 1.4 to 3.9), but not t(14;18)-positive NHL (OR = 1.3; 95% CI = 0.5 to 3.3). In the Nebraska study (7), in both men and women, a positive family history of hematopoietic cancer among first-degree relatives was nonsignificantly associated with an approximately twofold higher risk of both t(14;18)-positive NHL and t(14;18)-negative NHL compared with those with no family history of hematopoietic cancer. The point estimates changed little when analyses combined men and women (OR = 2.1 for t(14;18)-positive NHL, 95% CI = 0.8 to 5.2; OR = 1.9 for t(14;18)-negative NHL, 95% CI = 1.0 to 3.8).
Hair Dye Use
In the Iowa/Minnesota study (10), hair dye use was associated with both t(14;18)-positive NHL (OR = 1.8; 95% CI = 0.9 to 3.7) and t(14;18)-negative NHL (OR = 2.1; 95% CI = 1.3 to 3.4) among men. In contrast, in the Nebraska study (7), hair dye use was not associated with either t(14;18)-positive NHL or t(14;18)-negative NHL among men or women. However, the use of permanent dyes was associated with a nonsignificant increased risk of t(14;18)-negative NHL among Nebraska women (OR = 1.4; 95% CI = 0.7 to 2.7).
|
Lessons Learned and Future Directions |
|---|
|
TopAbstractIntroductionChromosomal AbnormalitiesIntegrating t(14;18) Status With...Risk Factors for t(14;18)...Lessons Learned and Future...FundingReferences |
|---|
In a recent editorial, Potter (37) suggested that "it is essential to work toward a better molecular classification of disease, particularly of cancer, rather than continue to rely extensively on histopathology." The recent studies by Schroeder et al. (9,10) and Chiu et al. (7,8) represent the first epidemiological studies of NHL that have defined subgroups of NHL molecularly to investigate risk factors for NHL. Both studies found that the association between pesticide exposure and risk of NHL was limited to t(14;18)-positive NHL cases. In addition, both studies reported no association between smoking and risk of either t(14;18)-defined subtypes of NHL among men. However, there is discrepancy for familial cancer and hair dye use. Because the sample sizes are not large in these two studies, these differences could be just chance variation. The Iowa/Minnesota study (9,10) was limited to men, whereas the Nebraska study (7,8) included both men and women. It is possible that the distributions of risk factors vary between the two study populations. Furthermore, whereas the prevalence of t(14;18)-positive NHL is similar between the two studies (ie, 37% in both studies) (7–10), misclassification of t(14;18) status may be possible in the Iowa/Minnesota study in which PCR was used, a process that may miss certain t(14;18) break points (38). Nevertheless, the consistent findings for pesticides argue against a significant role that these explanations may play in the discrepancy. Alternatively, findings from these two studies (7–10) suggest that defining subgroups of NHL according to t(14;18) status may be a useful approach for etiologic research only if an exposure involves the development of NHL through a t(14;18) pathway. Specific chromosomal translocations have not been convincingly linked to hair dye use (39) or reported as a feature of familial lymphoma (40). In contrast, a high frequency of the t(14;18) in healthy subjects has been associated with pesticides (32,34), smoking (36,41), organic pollutants such as polychlorinated byphenyls or dioxins (41), hepatitis C virus infection (42), and ultraviolet levels (41,43). Analytic epidemiological studies evaluating the association of these exposures with NHL risk might benefit particularly from defining subgroups of NHL according to t(14;18) status.
The findings on cigarette smoking from the Iowa/Minnesota and Nebraska studies (7,10) are not entirely consistent. Whereas both studies found no association between smoking and either t(14;18)-positive or t(14;18)-negative NHL among men, the Nebraska study reported a positive association between cigarette smoking and risk of t(14;18)-negative NHL among women. Because cigarette smoking has been linked to a higher risk of follicular lymphoma (23–25,44) and diffuse large B-cell lymphoma (26), the two major subtypes that exhibit t(14;18), one might expect a positive association between cigarette smoking and t(14;18)-positive NHL. Again, these may be chance findings due to small sample size. Alternatively, it is possible that smoking-associated risk varies according to chromosomal abnormalities. A study of acute myeloid leukemia found that smoking was positively associated with the t(8;21)(q22;q22) subgroup, but inversely associated with the t(15;17)(q22;q12) subgroup (45). In NHL, it could be that smoking is associated with chromosomal abnormalities other than the t(14;18). Future studies with larger sample size to assess this possibility are warranted.
It remains to be determined whether or not defining NHL subgroups by t(14;18) status is more specific than classifying NHL by histological subtypes for etiologic research. In the Nebraska study (7,8), the researchers also compared ORs for t(14;18)-positive NHL vs t(14;18)-negative NHL using multivariate polytomous logistic regression where the dependent variable was treated as a three-level variable (ie, t(14;18)-positive NHL, t(14;18)-negative NHL, and controls), and the logit estimator always compared t(14;18)-defined NHL subtypes with controls. The researchers found that the associations of pesticides and cigarette smoking (women only) differed significantly between t(14;18)-positive NHL and t(14;18)-negative NHL (P difference < .05) (7,8). In contrast, the associations with a family history of hematopoietic cancer and hair dye use were similar between t(14;18)-positive and t(14;18)-negative NHL (7). The researchers also classified the 175 cases in the Nebraska study from whom tumor blocks were available according to the new WHO classification (1). They found that neither agricultural pesticide use, smoking, nor hair dye use were associated with follicular NHL or diffuse large B-cell NHL, and that a positive family history of hematopoietic cancer was associated with follicular NHL but not diffuse large B-cell NHL. These findings are not entirely consistent with those observed using the molecular cytogenetic approach in which pesticide use was associated with t(14;18)-positive NHL but not t(14;18)-negative NHL, smoking was associated with t(14;18)-negative NHL but not t(14;18)-positive NHL among women, and a family history of hematopoietic cancer was associated with t(14;18)-positive and t(14;18)-negative NHL in both men and women. Together, these findings suggest that defining subsets of NHL by t(14;18) status may add additional information to etiologic research. Unfortunately, the sample size in the Nebraska study is not large enough for additional comparisons (ie, ORs between t(14;18)-defined subgroups within follicular lymphoma as well as ORs between t(14;18)-defined subgroups within diffuse large B-cell lymphoma), which might be the most appropriate way of evaluating whether defining NHL according to t(14;18) status is more specific than classifying NHL by histological subtypes.
The presence of the t(14;18) is not sufficient for the development of NHL because it occurs in healthy individuals at a frequency of 10%–50%, a range that may be partially dependent on the PCR technology used (15). The causes of the t(14;18) remain largely unknown, although random events and environmental genotoxins such as chemicals or ionizing radiation have been reported (12). Findings from these two epidemiological studies (7–10) suggest that pesticides contribute to the development of NHL through pathways involving the t(14;18). However, it remains unclear whether pesticides caused the t(14;18) or provide a second or later hit in lymphoid cells with the t(14;18), that ultimately leads to the occurrence of NHL. Nevertheless, observations from these two epidemiological studies provide clues for additional research regarding potential exposures that may be important in the long-term evolution of t(14;18)-positive cells.
The two studies reviewed in this paper represent the first epidemiological studies of NHL that have defined subgroups of NHL molecularly to investigate risk factors for NHL. The findings from these studies are intriguing and suggest that molecular classification of NHL according to t(14;18) status is useful for etiologic research, particularly for exposures that involve the development of NHL through a t(14;18) pathway. Future epidemiological studies that investigate other chromosomal abnormalities, in addition to the t(14;18), are also warranted since t(14;18)-negative NHL remains a molecularly heterogeneous group. Integrating genetic and epidemiological data may provide additional new insights concerning the pathogenesis of NHL. In addition, studies with repeated measures of exposures and chromosomal abnormalities are needed to delineate the effects of various exposures in molecularly defined subgroups of NHL.
|
Funding |
|---|
|
TopAbstractIntroductionChromosomal AbnormalitiesIntegrating t(14;18) Status With...Risk Factors for t(14;18)...Lessons Learned and Future...FundingReferences |
|---|
This research was supported by grants CA94770, CA132153, and CA100555 from the National Cancer Institute (NCI) and, in part, by the Intramural Research Program of the National Institutes of Health (Division of Cancer Epidemiology and Genetics of the NCI).
|
REFERENCES |
|---|
|
TopAbstractIntroductionChromosomal AbnormalitiesIntegrating t(14;18) Status With...Risk Factors for t(14;18)...Lessons Learned and Future...FundingReferences |
|---|
1. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissues (2001) Lyon, France: IARC Press.
2. Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood (2006) 107(1):265–276.
3. Chiu BC, Weisenburger DD. An update of the epidemiology of non-Hodgkin's lymphoma. Clin Lymphoma (2003) 4(3):161–168.[Web of Science][Medline]
4. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature (2000) 403(6769):503–511.[CrossRef][Web of Science][Medline]
5. de Jong D. Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors. J Clin Oncol (2005) 23(26):6358–6363.
6. Lossos IS. Molecular pathogenesis of diffuse large B-cell lymphoma. J Clin Oncol (2005) 23(26):6351–6357.
7. Chiu BC, Dave BJ, Blair A, et al. Cigarette smoking, familial hematopoietic cancer, hair dye use, and risk of t(14;18)-defined subtypes of non-Hodgkin's lymphoma. Am J Epidemiol (2007) 165(6):652–659.
8. Chiu BC, Dave BJ, Blair A, Gapstur SM, Zahm SH, Weisenburger DD. Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma. Blood (2006) 108(4):1363–1369.
9. Schroeder JC, Olshan AF, Baric R, et al. Agricultural risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma. Epidemiology (2001) 12(6):701–709.[CrossRef][Web of Science][Medline]
10. Schroeder JC, Olshan AF, Dent RB, et al. A case-control study of tobacco use and other non-occupational risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma (United States). Cancer Causes and Control (2002) 13(2):159–168.[CrossRef][Web of Science][Medline]
11. Magrath IT. Introduction: concepts and controversies in lymphoid neoplasia. In: The Non-Hodgkin's Lymphoma—Magrath IT, ed. (1997) 2nd ed. New York, NY: Oxford University Press. 3–46.
12. Weisenburger DD. Pathological classification of non-Hodgkin's lymphoma for epidemiological studies. Cancer Res. (1992) 52((suppl)):5456s–5464s.
13. Vega F, Medeiros LJ. Chromosomal translocations involved in non-Hodgkin lymphomas. Arch Pathol Lab Med (2003) 127(9):1148–1160.[Web of Science][Medline]
14. Aplan PD. Causes of oncogenic chromosomal translocation. Trends Genet. (2006) 22(1):46–55.[CrossRef][Web of Science][Medline]
15. Janz S, Potter M, Rabkin CS. Lymphoma- and leukemia-associated chromosomal translocations in healthy individuals. Genes Chromosomes Cancer (2003) 36(3):211–223.[CrossRef][Web of Science][Medline]
16. Hartge P, Wang SS, Bracci PM, Devesa SS, Holly EA. Non-Hodgkin lymphoma. In: Cancer Epidemiology and Prevention—Schottenfeld D, Fraumeni JFJ, eds. (2006) 3rd ed. New York, NY: Oxford University Press. 898–918.
17. Mitelman F. Recurrent chromosome aberrations in cancer. Mutat Res. (2000) 462(2-3):247–253.[CrossRef][Web of Science][Medline]
18. Staudt LM. Molecular diagnosis of the hematologic cancers. N Engl J Med (2003) 348(18):1777–1785.
19. Huang JZ, Sanger WG, Greiner TC, et al. The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood (2002) 99(7):2285–2290.
20. Zahm S, Ward MH, Blair A. Pesticides and cancer. In: Human Health Effects of Pesticides—Keifer MC, ed. (1997) Philadelphia, PA: Hanley & Belfus, Inc. 269–289.
21. Chiu BC, Weisenburger DD, Zahm SH, et al. Agricultural pesticide use, familial cancer, and risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev (2004) 13(4):525–531.
22. Wang SS, Slager SL, Brennan P, et al. Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph). Blood (2007) 109(8):3479–3488.
23. Morton LM, Hartge P, Holford TR, et al. Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph). Cancer Epidemiol Biomarkers Prev (2005) 14(4):925–933.
24. Morton LM, Holford TR, Leaderer B, et al. Cigarette smoking and risk of non-Hodgkin lymphoma subtypes among women. Br J Cancer (2003) 89(11):2087–2092.[CrossRef][Web of Science][Medline]
25. Stagnaro E, Tumino R, Parodi S, et al. Non-Hodgkin's lymphoma and type of tobacco smoke. Cancer Epidemiol Biomarkers Prev (2004) 13(3):431–437.
26. Talamini R, Polesel J, Montella M, et al. Smoking and non-Hodgkin lymphoma: case-control study in Italy. Int J Cancer (2005) 115(4):606–610.[CrossRef][Web of Science][Medline]
27. Schollkopf C, Smedby KE, Hjalgrim H, et al. Cigarette smoking and risk of non-Hodgkin's lymphoma—a population-based case-control study. Cancer Epidemiol Biomarkers Prev (2005) 14(7):1791–1796.
28. Altieri A, Bermejo JL, Hemminki K. Familial risk for non-Hodgkin lymphoma and other lymphoproliferative malignancies by histopathologic subtype: the Swedish Family-Cancer Database. Blood (2005) 106(2):668–672.
29. Chang ET, Smedby KE, Hjalgrim H, et al. Family history of hematopoietic malignancy and risk of lymphoma. J Natl Cancer Inst (2005) 97(19):1466–1474.
30. Chatterjee N, Hartge P, Cerhan JR, et al. Risk of non-Hodgkin's lymphoma and family history of lymphatic, hematologic, and other cancers. Cancer Epidemiol Biomarkers Prev (2004) 13(9):1415–1421.
31. Zahm SH, Weisenburger DD, Babbitt PA, et al. A case-control study of non-Hodgkin's lymphoma and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska. Epidemiology (1990) 1(5):349–356.[Medline]
32. Roulland S, Lebailly P, Lecluse Y, Briand M, Pottier D, Gauduchon P. Characterization of the t(14;18) BCL2-IGH translocation in farmers occupationally exposed to pesticides. Cancer Res. (2004) 64(6):2264–2269.
33. Garry VF, Tarone RE, Long L, Griffith J, Kelly JT, Burroughs B. Pesticide appliers with mixed pesticide exposure: G-banded analysis and possible relationship to non-Hodgkin's lymphoma. Cancer Epidemiol Biomarkers Prev (1996) 5(1):11–16.[Abstract]
34. Garry VF, Danzl TJ, Tarone R, et al. Chromosome rearrangements in fumigant appliers: possible relationship to non-Hodgkin's lymphoma risk. Cancer Epidemiol Biomarkers Prev (1992) 1(4):287–291.
35. Figgs LW, Holland NT, Rothman N, et al. Increased lymphocyte replicative index following 2,4-dichlorophenoxyacetic acid herbicide exposure. Cancer Causes Control (2000) 11(4):373–380.[CrossRef][Web of Science][Medline]
36. Bell DA, Liu Y, Cortopassi GA. Occurrence of bcl-2 oncogene translocation with increased frequency in the peripheral blood of heavy smokers. J Natl Cancer Inst (1995) 87(3):223–224.
37. Potter JD. Toward the last cohort. Cancer Epidemiol Biomarkers Prev (2004) 13(6):895–897.
38. Liu J, Johnson RM, Traweek ST. Rearrangement of the BCL-2 gene in follicular lymphoma. Detection by PCR in both fresh and fixed tissue samples. Diagn Mol Pathol (1993) 2(4):241–247.[Web of Science][Medline]
39. Hofer H, Bornatowicz N, Reindl E. Analysis of human chromosomes after repeated hair dyeing. Food Chem Toxicol (1983) 21(6):785–789.[CrossRef][Web of Science][Medline]
40. Segel GB, Lichtman MA. Familial (inherited) leukemia, lymphoma, and myeloma: an overview. Blood Cells Mol Dis (2004) 32(1):246–261.[CrossRef][Web of Science][Medline]
41. Baccarelli A, Hirt C, Pesatori AC, et al. t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy. Carcinogenesis (2006) 27(10):2001–2007.
42. Zignego AL, Ferri C, Giannelli F, et al. Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas. Ann Intern Med (2002) 137(7):571–580.
43. Bentham G, Wolfreys AM, Liu Y, et al. Frequencies of hprt(-) mutations and bcl-2 translocations in circulating human lymphocytes are correlated with United Kingdom sunlight records. Mutagenesis (1999) 14(6):527–532.
44. Herrinton LJ, Friedman GD. Cigarette smoking and risk of non-Hodgkin's lymphoma subtypes. Cancer Epidemiol Biomarkers Prev (1998) 7(1):25–28.[Abstract]
45. Moorman AV, Roman E, Cartwright RA, Morgan GJ. Smoking and the risk of acute myeloid leukaemia in cytogenetic subgroups. Br J Cancer (2002) 86(1):60–62.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. M. Evens and B. C.-H. Chiu The Challenges of Epidemiologic Research in Non-Hodgkin Lymphoma JAMA, November 5, 2008; 300(17): 2059 - 2061. [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Rabkin and S. Janz Overview of Mechanisms and Consequences of Chromosomal Translocation J Natl Cancer Inst Monographs, July 1, 2008; 2008(39): 1 - 1. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||