A case-control study of multiple myeloma in whites: chronic antigenic stimulation, occupation, and drug use

A hospital-based case-control study of multiple myeloma in whites (100 cases and 100 controls from seven Baltimore hospitals) was conducted to examine a number of postulated risk factors. Cases and controls were matched on age, sex, hospital, and year of diagnosis. Distributions by marital status and religious affiliation were found to be similar. Educational levels of cases were similar to controls except for postcollege schooling, where there was a slight excess of cases (6%) compared to controls (3%). No statistically significant associations were found between multiple myeloma and prior history of medical conditions believed to cause prolonged stimulation of the immune system including chronic bacterial infections [odds ratio (OR) = 0.8], autoimmune disorders (OR = 1.0), allergy-related disorders (OR = 1.0), or lymphoid tissue surgery (OR = 1.2). Statistically significant positive associations were found for occupational exposure to petroleum products (OR = 3.7; 1.3-10.3) and asbestos (OR = 3.5; 1.0-12.0). No increased risk was found for cigarette smoking or alcohol consumption or for employment in a variety of industries and occupations implicated in earlier studies. A significantly elevated risk was found for prior use of laxatives (OR = 3.5; 1.1-11.1), and elevated (OR greater than or equal to 1.8) but nonsignificant risks were found for use of other medications including diphenylhydantoin, phenobarbital, diazepam, propranolol, ibuprofen, and diet drugs and stimulants. These findings require clarification in larger, population-based studies.     

Autoimmune thrombocytopenia associated with the first cycle of fludarabine therapy in the treatment of relapsed non-Hodgkin's lymphoma

Fludarabine phosphate is a purine analogue now commonly used in the treatment of low-grade lymphoid malignancies. An increased incidence of autoimmune haemolytic anaemia is reported with the use of fludarabine for the treatment of chronic lymphocytic leukaemia (CLL). CLL already confers a high risk of autoimmune disorders and, although these are recognized in non-Hodgkiin's lymphoma (NHL), they are less common. Immune thrombocytopenia occurring in patients with CLL treated with fludarabine has been reported and we describe a further case in a patient with relapsed NHL. Possible mechanisms of the effect of fludarabine on autoimmune disorders are discussed.     

Leukemia,lymphoma, and multiple myeloma following selected medical conditions

The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.Ms Doody and Drs Linet, Pottern, Boice, and Fraumeni are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Glass is with the Kaiser Permanente Medical Care Program, Northwest Region, Portland, Oregon, USA. Dr Friedman is with the Kaiser Permanente Medical Care Program, Northern California Region, Oakland, California, USA. Address correspondence to Ms Doody, Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 408, Bethesda, MD 20892, USA. This research was supported in part by National Cancer Institute contracts NO1-CP-01047, NO1-CP-01054, NO1-CP-11009, NO1-CP-11037, NO1-CP-31035, and NO1-CP-61006.     

Chlamydial antibodies and risk of prostate cancer.

OBJECTIVE: We assessed the risk of prostate cancer by exposure to Chlamydia trachomatis. METHOD: Seven hundred thirty eight cases of prostate cancer and 2,271 matched controls were identified from three serum sample banks in Finland, Norway, and Sweden by linkage to the population based cancer registries. RESULTS: A statistically significant inverse association (odds ratio, 0.69; 95% confidence interval, 0.51-0.94) was found. It was consistent by different serotypes and there was a consistent dose-response relationship. CONCLUSION: C. trachomatis infection is not likely to increase the risk of prostate cancer. Whether the inverse relationship is true or due to difficulties in measuring the true exposure in prostatic tissue by serology, confounders or other sources of error remain open.     

Mucosa-associated lymphoid tissue (MALT) lymphoma combined with tuberculous enteritis at the same site in the jejunum.

Mucosa-associated lymphoid tissue (MALT) lymphoma is derived from the marginal zone B-cell compartment and can be found at a wide variety of extranodal sites, most frequently at the gastrointestinal site. Recent clinicopathologic studies suggest a relationship between MALT lymphoma and chronic inflammatory disorders, such as Helicobacter pylori infection in the stomach or autoimmune disorders, such as Sj?gren's syndrome in the salivary glands. Primary gastrointestinal MALT lymphomas most commonly arise in the stomach and less often in the small and large intestine. Recently we experienced a case who had MALT lymphoma combined with tuberculous enteritis at the same site (jejunum) confirmed by exploratory laparotomy. We suspect that there may be some relationship between MALT lymphoma and chronic inflammatory process of mycobacterial tuberculous enteritis.     

Food groups and risk of esophageal cancer in Chaoshan region of China: a high-risk area of esophageal cancer

The current study was designed to investigate the role of common foods in the etiology of esophageal cancer in the Chaoshan region of China. A large case-control study was conducted to investigate 1248 patients with squamous cell carcinoma of the esophagus and 1248 controls matched by sex, age, and hospitals. After adjusting for the effects of sex, age, occupation, areas of residence, income, alcohol intake, and cigarette usage, a strong association with a clear dose-response relationship was observed between the fermented fish sauce eaten weekly and esophageal cancer (P for trend less than 0.001). The results for pickles were similar to those for fermented fish sauce. A protective effect of fruits on esophageal cancer was observed, and this risk decreased (P for trend less than 0.001) as frequencies of fresh fruit intake increased. The risks from sowbelly and kipper were significantly higher in consumers than in nonconsumer, but the dose-response relationship was not statistically significant. No significant effects, however, were detected from vegetables, smoked foods, and so on. To the authors' knowledge, this is the first report on the relationship between fish juice and high risk of esophageal cancer in a population. Further epidemiological and experimental study are required to find a biological causal relationship between them.     

Allergic Disorders and the Risk of Childhood Acute Lymphoblastic Leukemia (United States)

Objectives: To test the hypothesis that childhood acute lymphoblastic leukemia (ALL) is associated with allergic disorders. Methods: We compared the histories of selected allergic disorders (asthma, hay fever, food or drug allergies, eczema, and hives) of 1842 cases of ALL with those of 1986 individually matched controls. The histories of the allergic disorders among siblings of cases and controls were also compared. Results: The combined history of any one or more of the five allergic disorders evaluated was associated with a significant reduced risk of ALL (adjusted OR = 0.7, 95% CI 0.6–0.8), as were hhistories of four specific allergic disorders (asthma, hay fever, food or drug allergies, and eczema). The combined history of any one or more of the five allergic disorders among any of the siblings of the study subjects also revealed a significantly inverse association (adjusted OR = 0.9, 95% CI 0.8–1.0). Conclusion: The results from this study, in agreement with most previous studies on adult cancer, suggest that allergic disorders may be associated with a reduced risk of childhood ALL.     

Childhood infectious diseases and risk of leukaemia in an adult population

Our study is aimed at investigating the association between common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing leukaemia in an adult population. A reanalysis of a large population‐based case–control study was carried out. Original data included 1,771 controls and 649 leukaemia cases from 11 Italian areas. To contain recall bias, the analysis was restricted to subjects directly interviewed and with a good quality interview (1,165 controls and 312 cases). Odds ratios (ORs) and their related 95% confidence intervals (95% CIs) were estimated by unconditional polychotomous logistic regression model adjusting for age, gender and occupational and lifestyle exposures. A protective effect of at least one infection (OR = 0.66, 95% CI: 0.45–0.97), measles (OR = 0.57, 95% CI: 0.39–0.82) and pertussis (OR = 0.66, 95% CI: 0.45–0.98) was observed for chronic lymphoid leukaemia (CLL). The number of infections was strongly inversely associated with the risk of CLL (p = 0.002, test for trend). With regard to the other types of leukaemia, only a protective effect of pertussis was observed for AML (OR = 0.52, 95% CI: 0.32–0.87). Our results pointed out a protective role of childhood infectious diseases on the risk of CLL in adults. Although a specific antioncogenic effect of some infectious disease, especially measles, cannot be ruled out, the observed decrease of risk with increasing number of infections suggests that a more general “hygiene hypothesis” could be the most likely explanation of the detected association. The protective role of pertussis remains to be elucidated.     

Tumors after radiotherapy for skin hemangioma in childhood. A case-control study

A case-control study was conducted to investigate the possible association between absorbed dose and cancer risk in a cohort of 14,647 individuals (33% males and 67% females) less than 18 months old and irradiated for skin hemangioma between 1920 and 1959. The cases consisted of 56 breast cancers (in 55 patients), 14 thyroid cancers, 16 brain tumors and 8 tumors of bone and soft tissues. Four controls were matched to each case. They were matched for sex, age at treatment, treatment modality and treatment year. Absorbed doses were categorized in three exposure groups, less than 0.1 Gy, 0.1-0.4 Gy, and greater than or equal to 0.5 Gy, and odds ratios (OR) were estimated with the lowest exposure group as reference. A statistically significant positive dose-response relationship was found for thyroid cancer (OR: 1.0; 4.8; 4.3) and for tumors of bone and soft tissues (OR: 1.0; 1.6; 19.5). For breast cancer and brain tumors no significant dose-response relationship could be found. The median absorbed dose in the tumor sites among the cases of thyroid cancer, tumors of bone and soft tissues, breast cancer and brain tumors was 0.2 Gy, 0.3 Gy, 0.03 Gy and 0.04 Gy respectively. The dose was probably too low to detect any dose-response relationship for breast cancer and brain tumors.     

Urinary infection,renal lithiasis and bladder cancer in Spain

A case-control study on bladder cancer was carried out in 12 hospitals located in 4 regions of Spain. The study included 497 cases and 530 population controls, matched by sex, age and residence. The present paper reports the results regarding the risk for bladder cancer in relation to history of infections and lithiasis of the urinary tract. Increased risk was found for infections starting 4 years or less before diagnosis (OR = 15.00; 95% CL; 6.07–51.66) but no statistically significant increase in risk was observed for infections starting 5 or more years before (OR = 1.44; 95% CL: 0.86–2.47). Our data suggest that the association of urinary infections with bladder cancer is probably not causal and is more likely to be a consequence of cancer, although a weak causal association cannot be excluded. A small but not statistically significant increase in risk was found to be associated with a history of renal lithiasis.     

Aberrant ribonucleotide pattern in lymphoid cells from patients with chronic lymphocytic leukaemia or non-Hodgkin lymphoma

The intracellular purine and pyrimidine ribonucleotide concentrations were determined in lymphoid cells from peripheral blood of 16 patients with chronic lymphocytic leukaemia (CLL) and from peripheral blood and/or lymphoid tissue of 18 patients with non-Hodgkin lymphoma (NHL). Compared to normal peripheral lymphocytes, the lymphoid cells from CLL patients contained lower, and those from NHL patients higher amounts of nucleotides. The lymphoid cells of NHL patients showed an imbalance in the nucleotide pool compared to either normal resting peripheral or proliferating tonsillar lymphocytes. The lymphoid cells of patients with CLL showed an imbalance only when compared to normal, resting peripheral lymphocytes. The abnormalities in the nucleotide pools involved decreased ratios of purine:pyrimidine, adenine:guanine and uracil:cytosine nucleotides. Lymphocytes from CLL and NHL patients contained increased amounts (relative and/or absolute) of UDP sugars, and NHL lymphocytes also showed a changed composition of the UDP sugars. Analysis of the ribonucleotides in the lymphoid cells provides useful information for the differential diagnosis of patients suspected of having CLL or NHL, and may be valuable for the design of new chemotherapeutic regimens.     

Autoimmunity in chronic lymphocytic leukemia

Opinion statement Chronic lymphocytic leukemia (CLL) is associated with the immune-mediated disorders autoimmune hemolytic anemia and immune thrombocytopenia. Initial treatment with corticosteroids is often successful in controlling these manifestations, but splenectomy should be considered if a rapid and complete response is not obtained. For those with persistent anemia or thrombocytopenia after splenectomy, treatment directed against the underlying CLL may be considered, although the use of purine analogues has also precipitated autoimmune hemolytic anemia. Pure red cell aplasia has been reported in CLL, and usually responds to immunosuppressive therapy.     

Family history of autoimmune thyroid disease and childhood acute leukemia.

The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.     

Risk factors for gliomas and meningiomas in males in Los Angeles County

Detailed job histories and information about other suspected risk factors were obtained during interviews with 272 men aged 25-69 with a primary brain tumor first diagnosed during 1980-1984 and with 272 individually matched neighbor controls. Separate analyses were conducted for the 202 glioma pairs and the 70 meningioma pairs. Meningioma, but not glioma, was related to having a serious head injury 20 or more years before diagnosis [odds ratio (OR) = 2.3; 95% confidence interval (CI) = 1.1-5.4], and a clear dose-response effect was observed relating meningioma risk to number of serious head injuries (P for trend = 0.01; OR for greater than or equal to 3 injuries = 6.2; CI = 1.2-31.7). Frequency of full-mouth dental X-ray examinations after age 25 related to both glioma (P for trend = 0.04) and meningioma risk (P for trend = 0.06). Glioma, but not meningioma risk, related to duration of prior employment in jobs likely to involve high exposure to electric and magnetic fields (P for trend = 0.05). This risk was greatest for astrocytoma (OR for employment in such jobs for greater than 5 years = 4.3; CI = 1.2-15.6). More glioma cases had worked in the rubber industry (discordant pairs 6/1) and more worked in hot processes using plastics (9/1). More meningioma cases had jobs that involved exposure to metal dusts and fumes (discordant pairs 13/5), and six of these cases and two controls worked as machinists. Finally, there was a protective effect among glioma pairs relating to frequency of use of vitamin C and other vitamin supplements (P for trend = 0.004); the OR for use at least twice a day was 0.4 (CI = 0.2-0.8).     

Relationship between ambient ultraviolet radiation and non‐Hodgkin lymphoma subtypes: A U.S. population‐based study of racial and ethnic groups

Associations between ultraviolet radiation (UVR) exposure and non‐Hodgkin lymphoma (NHL) have been inconsistent, but few studies have examined these associations for specific subtypes or across race/ethnicities. We evaluated the relationship between ambient UVR exposure and subtype‐specific NHL incidence for whites, Hispanics and blacks in the United States for years 2001–2010 (n = 187,778 cases). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quintiles using Poisson regression. Incidence was lower for the highest UVR quintile for chronic/small lymphocytic/leukemia (CLL/SLL) (IRR = 0.87, 95% CI: 0.77–0.97), mantle cell (IRR = 0.82, 95% CI: 0.69–0.97), lymphoplasmacytic (IRR = 0.58, 95% CI: 0.42–0.80), mucosa‐associated lymphoid tissue (MZLMALT) (IRR = 0.74, 95% CI: 0.60–0.90), follicular (FL) (IRR = 0.76, 95% CI: 0.68–0.86), diffuse large B‐cell (IRR = 0.84, 95% CI: 0.76–0.94;), peripheral T‐cell other (PTCL) (IRR = 0.76, 95% CI: 0.61–0.95) and PTCL not otherwise specified (PNOS) (IRR = 0.77, 95% CI: 0.61–0.98). Trends were significant for MZLMALT, FL, DLBCL, BNOS and PTCL, with FL and DLBCL still significant after Bonferroni correction. We found interaction by race/ethnicity for CLL/SLL, FL, Burkitt, PNOS and MF/SS, with CLL/SLL and FL still significant after Bonferroni correction. Some B‐cell lymphomas (CLL/SLL, FL and Burkitt) suggested significant inverse relationships in whites and Hispanics, but not in blacks. Some T‐cell lymphomas suggested the most reduced risk for the highest quintile of UVR among blacks (PNOS and MF/SS), though trends were not significant. These findings strengthen the case for an inverse association of UVR exposure, support modest heterogeneity between NHL subtypes and suggest some differences by race/ethnicity.     

Lymphoma of mucosa-associated lymphoid tissue in common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by reduced levels of all major immunoglobuline classes and recurrent c infections. The risk of non-Hodgkin's lymphoma (NHL) among patients with CVID was found to be increased in different studies. Mucosa-associated lymphoid tissue (MALT) lymphomas are a recently recognized sub-set of low-grade B-cell NHL composed of marginal zone-related cells. MALT lymphomas appear in the lymphoid tissues as a result of chronic inflammatory or autoimmune stimulation. This study briefly reviews previously published cases and reports a patient suffering from CVID with a history of chronic diarrhea and recurrent sinopulmonary infections. Despite treatment with intravenous immunoglobulin, chronic cough and wheezing progressed. Open lung biopsy showed a MALT lymphoma. Although a rare complication, pulmonary low grade B-cell lymphoma is a diagnosis that must be kept in mind in CVID patients with chronic pulmonary symptoms unresponsive to conventional therapies.     

Alcohol consumption and risk of leukemia: A multicenter case-control study

A population-based case-control study of 649 leukemia cases and 1771 controls carried out in 11 Italian areas, offered the opportunity to evaluate the relationship between alcohol consumption and leukemia risk. For all leukemias, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL), we found a non-significantly inverse association for moderate levels of total alcohol and wine intake, but increased risks at high levels, with, in most cases, significant trend effects (odd ratios (OR) for all leukemias in the lowest quartile of total alcohol consumption [0.1-9.0 g/day of ethanol] versus never-drinker = 0.73; 95% confidence intervals (95% CI) = 0.51-1.03; OR in the highest quartile [> 31.7 g/day] = 1.15; 95% CI = 0.82-1.63; p of the linear trend test = 0.007). For chronic myeloid leukemia (CML), we found a non-significantly positive association for all levels of total alcohol and wine intake, and a significant positive linear trend effect (p = 0.03) for wine intake (OR for 0.1-9.0 g/day of ethanol intake from wine = 1.34; 95% CI = 0.61-2.94; OR in the highest quartile of wine intake [> 27.7 g/day] = 2.13; 95% CI = 1.01-4.50). No consistent dose-response was detected analysing duration of alcohol consumption for any leukemia subtypes. In conclusion, even though our study did not show a clear association between alcohol intake and leukemia risk, some of the patterns of the risk estimates (a possible J-shaped dose-response curve between alcohol intake and ALL, AML, and CLL risks, and the positive association between alcohol and CML), may be suggestive.     

Family studies in acute leukaemia in childhood: a possible association with autoimmune disease.

Medical histories of themselves and their first-degree relatives were obtained from parents of 82 leukaemic children (54 acute lymphoblastic (ALL), 28 acute myeloblastic (AML)) and from control couples matched for age. The possibility of a primary familial immunological abnormality as an aetiological factor in childhood leukaemia was suggested by binding some infections significantly more frequently reported in parents than in controls, but more strongly supported by the finding of a significantly (P less than 0.02) increased prevalence of disorders associated with autoimmunity (but not of other conditions such as peptic ulceration, infective hepatitis, tuberculosis or malignancy) amongst members of ALL families compared to those of controls. Analogy with Down's syndrome and the strain of NZB mice, in which diminished T-cell function is associated with autoimmune disease and lymphoid neoplasia, is discussed. Varicella and herpes zoster occurred respectively in 2 ALL mothers during their pregnancies involving the patients and in none of the other 388 pregnancies here reported. This supports previous evidence that antenatal varicella infections may be of aetiological importance in some cases of ALL.     

Systemic Lupus Erythematosus and Chronic Lymphocytic Leukemia: Rare Coexistence in Three Patients, with Comments on Pathogenesis

We describe three patients with coexistent chronic lymphatic leukemia (CLL) and systemic lupus erythematosus (SLE). In two patients, the CLL was present before or coexistent with the SLE when the SLE was diagnosed, while in the third, the CLL developed 5 years after the diagnosis of SLE was first made. Although the association of autoimmune diseases and lymphoproliferative disorders is well established, only a few patients with coexistent CLL and concomitant SLE have been reported. The possible pathogenesis of this rare association is discussed.