Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up.

Although preservation of the spleen following abdominal trauma and spleen-preserving surgical procedures have become gold standards, about 22,000 splenectomies are still conducted annually in the USA. Infections, mostly by encapsulated organisms, are the most well-known complications following splenectomy. Recently, thrombosis and cancer have become recognized as potential adverse outcomes post-splenectomy. Among more than 4 million hospitalized USA veterans, we assessed incidence and mortality due to infections, thromboembolism, and cancer including 8,149 cancer-free veterans who underwent splenectomy with a follow-up of up to 27 years. Relative risk estimates and 95% confidence intervals were calculated using time-dependent Poisson regression methods for cohort data. Splenectomized patients had an increased risk of being hospitalized for pneumonia, meningitis, and septicemia (rate ratios=1.9-3.4); deep venous thrombosis and pulmonary embolism (rate ratios=2.2); certain solid tumors: buccal, esophagus, liver, colon, pancreas, lung, and prostate (rate ratios =1.3-1.9); and hematologic malignancies: non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and any leukemia (rate ratios =1.8-6.0). They also had an increased risk of death due to pneumonia and septicemia (rate ratios =1.6-3.0); pulmonary embolism and coronary artery disease (rate ratios =1.4-4.5); any cancer: liver, pancreas, and lung cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, and any leukemia (rate ratios =1.3-4.7). Many of the observed risks were increased more than 10 years after splenectomy. Our results underscore the importance of vaccination, surveillance, and thromboprophylaxis after splenectomy.

Association between benign thyroid and endocrine disorders and subsequent risk of thyroid cancer among 4.5 million U.S. male veterans.

CONTEXT: Risk factors for thyroid cancer (TC) in males are poorly understood. OBJECTIVES, SETTING, AND PARTICIPANTS: Our aim was to evaluate the relationship between history of benign thyroid and endocrine disorders and risk of TC among 4.5 million male veterans admitted to U.S. Veterans Affairs hospitals between July 1, 1969, and September 30, 1996. DESIGN: We conducted a retrospective cohort study based on hospital discharge records with 1053 cases of TC. MAIN OUTCOME MEASURES: We estimated relative risks (RR) and computed 95% confidence intervals (CI) for TC using time-dependent Poisson regression models. To evaluate potential ascertainment bias and/or delayed diagnosis of TC, we also analyzed RR by time between diagnosis of benign disorder and TC (<5 or ≥ 5 yr). RESULTS: RR for TC were significantly elevated with many disorders and were often higher less than 5 yr compared with 5 yr or more before TC diagnosis. RR (95% CI) less than 5 yr/at least 5 yr were 67.9 (42.4-108.8)/28.9 (9.2-90.2) for thyroid adenoma, 77.8 (64.5-93.1)/25.9 (17.9-38.0) for nontoxic nodular goiter, 23.9 (13.8-41.3)/12.9 (4.8-34.4) for thyroiditis, 8.8 (6.9-11.3)/6.0 (3.8-9.6) for hypothyroidism, 6.4 (4.4-9.4)/ 2.0 (0.8-4.8) for thyrotoxicosis, and 1.2 (1.0-1.4)/1.1 (0.9-1.5) for diabetes. For some disorders, RR also significantly varied by attained age and race with younger patients and Blacks having higher RR than older patients and Whites. CONCLUSIONS: We found strong associations for a history of thyroid adenoma, nodular goiter, thyroiditis, or hypothyroidism with TC in males allowing for increased surveillance/delayed diagnosis and evidence that some of these associations are modified by age and race.

Fruit, vegetables, fibre and micronutrients and risk of US renal cell carcinoma.

The association between renal cell cancer (RCC) and intake of fruit, vegetables and nutrients was examined in a population-based case-control study of 323 cases and 1827 controls; dietary intake was obtained using a mailed questionnaire. Cancer risks were estimated by OR and 95 % CI, adjusting for age, sex, smoking, obesity, hypertension, proxy status, alcohol consumption and dietary fat intake and energy. Intake of vegetables was associated with a decreased risk of RCC (OR 0·5; 95 % CI 0·3, 0·7; P trend = 0·002), (top compared to the bottom quartile of intake). When intake of individual nutrients was investigated, vegetable fibre intake was associated with decreased risks (OR 0·4; 95 % CI 0·2, 0·6; P < 0·001), but this was not the case with fruit fibre (OR 0·7; 95 % CI 0·4, 1·1) or grain fibre (OR 1·0; 95 % CI 0·6, 1·5). ß-Cryptoxanthin and lycopene were also associated with decreased risks, but when both were included in a mutually adjusted backwards stepwise regression model, only ß-cryptoxanthin remained significant (OR 0·5; 95 % CI 0·3, 0·8). When other micronutrients and types of fibre were investigated together, only vegetable fibre and ß-cryptoxanthin had significant trends (P < 0·01) (OR 0·6; 95 % CI 0·3, 0·9) (OR 0·5; 95 % CI 0·3, 0·9), respectively. These findings were stronger in those aged over 65 years (P interaction = 0·001). Among non-smokers, low intake of cruciferous vegetables and fruit fibre was also associated with increased risk of RCC (P interaction = 0·03); similar inverse associations were found for ß-cryptoxanthin, lycopene and vitamin C. When nutrients were mutually adjusted by backwards regression in these subgroups, only ß-cryptoxanthin remained associated with lower RCC risk. These findings deserve further investigation in ongoing prospective studies when sample size becomes sufficient.

Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans.

BACKGROUND: Autoimmunity is clearly linked with hematologic malignancies, but less is known about autoimmunity and alimentary tract cancer risk, despite the specific targeting of alimentary organs and tissues by several autoimmune diseases. The authors therefore conducted the first systematic evaluation of a broad range of specific autoimmune diseases and risk for subsequent alimentary tract cancer. METHODS: On the basis of 4,501,578 US male veterans, the authors identified 96,277 men who developed alimentary tract cancer during up to 26.2 years of follow-up. By using Poisson regression methods, the authors calculated relative risks (RRs) and 95% confidence intervals. RESULTS: A history of autoimmune disease with localized alimentary tract effects generally increased cancer risks in the organ(s) affected by the autoimmune disease, such as primary biliary cirrhosis and liver cancer (RR, 6.01; 95% confidence interval [CI], 4.76-7.57); pernicious anemia and stomach cancer (RR, 3.17; 95% CI, 2.47-4.07); and ulcerative colitis and small intestine, colon, and rectal cancers (RR, 2.53; 95% CI, 1.05-6.11; RR, 2.06; 95% CI, 1.70-2.48; and RR, 2.07; 95% CI, 1.62-2.64, respectively). In addition, a history of celiac disease, reactive arthritis (Reiter disease), and systemic sclerosis all were associated significantly with increased risk of esophageal cancer (RR, 1.86-2.86). Autoimmune diseases without localized alimentary tract effects generally were not associated with alimentary tract cancer risk, with the exception of decreased risk for multiple alimentary tract cancers associated with a history of multiple sclerosis. CONCLUSIONS: These findings support the importance of localized inflammation in alimentary tract carcinogenesis. Future research is needed to confirm the findings and improve understanding of underlying mechanisms by which autoimmune diseases contribute to alimentary tract carcinogenesis.

Concomitant and antecedent deep venous thrombosis and cancer survival in male US veterans.

Survival is reportedly worse in patients with cancer concurrently diagnosed with deep venous thrombosis. However, information on specific malignancies is limited. From a cohort study of male US veterans we identified incident cancer cases (n = 412,008) and compared survival patterns among those with versus without a history of deep venous thrombosis. Using Cox proportional hazard models, we estimated hazard ratios (HRs) and 95% confidence intervals as measures of the relative risk of dying. Individuals with (versus without) a concomitant deep venous thrombosis and cancer diagnosis had a higher risk of dying (HR = 1.38; 1.28-1.49). The most prominent excess mortality (HR = 1.29-2.55) was observed among patients diagnosed with deep venous thrombosis at the time of diagnosis of lung, gastric, prostate, bladder, or kidney cancer. Increased risk of dying was also found among cancer patients diagnosed with deep venous thrombosis 1 year (HR = 1.14; 1.07-1.22), 1-5 years (HR = 1.14; 1.10-1.19), and >5 years (HR = 1.27; 1.23-1.31) before cancer; this was true for most cancer sites (HR = 1.17-1.64). In summary, antecedent deep venous thrombosis confers a worse prognosis upon cancer patients. Advanced stage at diagnosis, treatment effects, lifestyle factors, and comorbidity could explain differences by cancer site and time frame between a prior deep venous thrombosis diagnosis and cancer outcome.

Risk of cancer in a large cohort of U.S. veterans with diabetes.

Prior studies of cancer risk among diabetic men have reported inconsistent findings. The aim of this study was to assess the risk of cancer among a large cohort (n = 4,501,578) of black and white U.S. veterans admitted to Veterans Affairs hospitals. The cancer risk among men with diabetes (n = 594,815) was compared to the risk among men without diabetes (n = 3,906,763). Poisson regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Overall, men with diabetes had a significantly lower risk of cancer (RR = 0.93, 95%CI = 0.93-0.94). Men with diabetes, however, had increased risks of cancers of the liver (RR = 1.95, 95%CI = 1.82-2.09), pancreas (RR = 1.50, 95%CI = 1.42-1.59), biliary tract (RR = 1.41, 95%CI = 1.22-1.62), colon (RR = 1.20, 95%CI = 1.16-1.25), rectum (RR = 1.12, 95%CI = 1.07-1.18), and kidney (RR = 1.09, 95%CI = 1.03-1.16), as well as leukemia (RR = 1.14, 95%CI = 1.08-1.21) and melanoma (RR = 1.13, 95%CI = 1.03-1.24). In contrast, men with diabetes had decreased risks of cancers of the prostate (RR = 0.89, 95%CI = 0.87-0.91), brain (RR = 0.91, 95% CI = 0.82-0.99), buccal cavity (RR = 0.85, 95%CI = 0.82-0.89), lung (RR = 0.79, 95%CI = 0.77-0.80), esophagus (RR = 0.77, 95%CI = 0.72-0.82), and larynx (RR = 0.76, 95%CI = 0.71-0.80). These findings indicate that black and white men with diabetes are at significantly lower risk of total cancer and of two of the most common cancers among U.S. males; lung and prostate cancers. These decreased risks were offset, however, by increased risks of cancer at several sites. Hyperinsulinemia may explain the increased risks of the digestive cancers, while lower testosterone levels, in the case of prostate cancer, and higher BMI, in the case of lung cancer, may explain the decreased risks of those tumors.

Racial differences in chronic immune stimulatory conditions and risk of non-Hodgkin's lymphoma in veterans from the United States.

PURPOSE: To examine underlying etiologic factors that may explain the racial disparity in non-Hodgkin's lymphoma (NHL) incidence patterns. PATIENTS AND METHODS: We assessed immune-related conditions and risk of developing NHL among more than 4 million hospitalized US veterans including 9,496 patients with NHL (7,999 white patients and 1,497 black patients) with up to 26 years of follow-up. We used time-dependent Poisson regression to estimate rate ratios (RRs) and 95% CIs for NHL risk among patients with a history of specific autoimmune diseases, infections, and allergies compared with patients without such history, adjusting for attained age, calendar year, race, number of hospital visits, and time between study entry and exit. RESULTS: Patients with infectious conditions had an increased risk of developing NHL (RR, 1.2; 95% CI, 1.1 to 1.2), particularly for gastrohepatic, genital, and systemic infectious conditions. Patients with autoimmune disease were generally more likely to develop NHL than patients without autoimmune disease, especially for conditions that typically present with detectable autoantibodies with systemic involvement (RR, 2.0; 95% CI, 1.8 to 2.2). Allergies were also associated with increased risk (RR, 1.4; 95% CI, 1.3 to 1.5). Although the risk of NHL was lower for blacks than whites (RR, 0.87; 95% CI, 0.82 to 0.92), blacks had a slightly higher risk of NHL associated with infections than whites (likelihood ratio test, P = .002) and a tendency toward higher risk associated with allergies (likelihood ratio test, P = .05). Risks associated with autoimmune conditions were similar by race (likelihood ratio test, P = .5). CONCLUSION: The observed difference in NHL risk by race supports a role for race-related differences in genes regulating immune/inflammatory response.

Etiologic factors for male breast cancer in the U.S. Veterans Affairs medical care system database.

The etiology of male breast cancer is largely unknown, reflecting its relative rarity. Although a number of previous studies have suggested relationships with a variety of medical conditions, the results have largely derived from case-control studies and may reflect recall biases. Within the large U.S. Veterans Affairs computerized medical care system database, we had the opportunity to access 26 million hospital discharge records over the period 1969-1996 and to relate various documented medical conditions to the risk of subsequent male breast cancer. This allowed us to calculate relative risks (RR) and 95% confidence intervals (CI) for male breast cancer associated with conditions occurring one or more years after initial hospitalization, adjusted for age, race, calendar year, duration of follow-up, and number of hospital visits. Among 4,501,578 men aged 18-100 years, a total of 642 cases of primary male breast cancer were identified (523 among whites, 119 among blacks). Medical conditions that were significantly related to risk were diabetes (RR 1.30, 95% CI 1.05-1.60), obesity (1.98, 1.55-2.54), orchitis/epididymitis (1.84, 1.10-3.08), Klinefelter syndrome (29.64, 12.26-71.68), and gynecomastia (5.86, 3.74-9.17). Additionally, among black patients, cholelithiasis emerged as a significant risk predictor (3.45, 1.59-7.47). Diseases that have previously been related to male breast cancer risk that were not supported by our study results included thyroid diseases, smoking-related conditions, liver cirrhosis, prostatic hyperplasia, and fractures. After adjustment for obesity, the association with diabetes disappeared, but that with gynecomastia persisted. In multivariate models that simultaneously considered all important medical predictors of risk, significant risks were seen for Klinefelter syndrome (16.83, 6.81-41.62), gynecomastia (5.08, 3.21-8.03), obesity (1.91, 1.50-2.44), and orchitis/epididymitis (1.80, 1.08-3.01). These results support previous speculations that male breast cancer is influenced not only by tissue at risk, but also by hormonal and inflammatory factors.

Low level alcohol intake, cigarette smoking and risk of breast cancer in Asian-American women.

Studies have shown that breast cancer incidence rates among Asian migrants to the United States approach US incidence rates over several generations, implicating potentially modifiable exposures such as moderate alcohol use that has been linked to excess breast cancer risk in other populations. The goal of this study was to investigate the effect of alcohol intake, primarily low levels, on breast cancer risk in Asian-American women and explore whether smoking and alcohol contributed to the breast cancer incidence rates observed among Asian migrants to the United States. Study subjects in this population-based case-control study included 597 incident cases of breast cancer of Chinese, Japanese, and Filipino ethnicity living in San Francisco-Oakland, Los Angeles, and Oahu, Hawaii, and 966 population controls frequency matched on age, ethnicity, and area of residence. The fraction of smokers and drinkers was significantly higher in women born in Western compared with Eastern countries. However, breast cancer risk was not significantly associated with smoking (odds ratio (OR) = 1.2, 95% confidence interval (95% CI) = 0.9-1.6) or alcohol drinking (OR = 0.9, 95% CI = 0.7-1.1) in this population of low consumers of alcohol (median intake among drinkers in grams per day was 0.48 for cases and 0.40 for controls). These data suggest that low alcohol intake is not related to increased breast cancer risk in Asian-American women and that neither alcohol nor cigarette use contributed to the elevated risks in Asian-American women associated with migration patterns and Westernization.

Flavonoid consumption and esophageal cancer among black and white men in the United States.

Flavonoids and proanthocyanidins are bioactive polyphenolic components of fruits and vegetables that may account for part of the protective effect of raw fruit and vegetable consumption in esophageal cancer. We studied the relationship between esophageal cancer and dietary proanthocyanidins, flavonoids and flavonoid subclasses (anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols and isoflavonoids) using recently developed USDA and Tufts flavonoid and proanthocyanidin databases. The study was a population-based, case-control analysis of 161 white men with esophageal adenocarcinoma (EAC), 114 white and 218 black men with esophageal squamous cell carcinoma (ESCC) and 678 white and 557 black male controls who lived in 3 areas of the United States. Neither total flavonoid nor proanthocyanidin intake was associated with EAC and ESCC in either white or black men. In white men, inverse associations were observed between anthocyanidin intake and EAC (4th vs. 1st quartile odds ratio [OR], 0.47, 95% confidence interval [CI], 0.24-0.91; p(trend) = 0.04) and between isoflavonoid intake and ESCC (4th vs. 1st quartile OR, 0.43, 95% CI, 0.20-0.93; p(trend) = 0.01). None of the associations remained significant after adjusting for dietary fiber, which is strongly correlated with flavonoid consumption. We conclude that total flavonoids and proanthocyanidins do not have strong protective effects in either EAC or ESCC. Some protective effects were evident in flavonoid subclasses and population subgroups. In white men, foods rich in anthocyanidins may have chemopreventive effects in EAC and those rich in isoflavonoids may do so in ESCC.

Genetics- and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/ Waldenström's macroglobulinemia.

There are emerging data to support a role for genetic and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia. In this article, we review our recently published, large, population-based studies using data from Sweden and from United States veterans and propose mechanisms and pathways underlying our observations. We also discuss future directions for new studies designed to increase our current knowledge and to define underlying biologic mechanisms of our findings. Finally, based on novel insights on this topic, we discuss clinical implications and provide perspective on the relevance of these data for patient counseling and clinical follow-up.

A cohort study of cancer among sarcoidosis patients.

Sarcoidosis is a chronic inflammatory condition that may increase the risk of cancer, but limited information is available on occurrence of cancer in these patients. We compared the incidence of cancer among 2,013 White and 3,755 Black male patients admitted to Veterans hospitals in the United States during 1969-1996 with a diagnosis of sarcoidosis, with that of 2,792,503 White and 662,204 Black nonsarcoidosis patients admitted to the same hospitals. Patients suffering from pulmonary and autoimmune diseases were excluded from the study, as was the first year of follow-up after first admission for sarcoidosis. A total of 241 malignant neoplasms were diagnosed in sarcoidosis patients [relative risk 0.99, 95% confidence interval (CI) 0.87-1.13]. The risks of rectal cancer (relative risk 2.12; 95% CI 1.27-3.52), colon cancer (relative risk 1.55; 95% CI 0.99-2.43) and kidney cancer (relative risk 1.84; 95% CI 1.02-3.33) were increased in sarcoidosis patients when compared with other Veterans hospital patients, whereas the risk of lung cancer was decreased (relative risk 0.60; 95% CI 0.42-0.85). The risk of kidney cancer remained elevated 10 years after first admission. Results were generally consistent among ethnic groups, although the increased risk of colon and kidney cancer was observed only in White patients. These results provide further evidence for an increased risk of specific cancers in patients with sarcoidosis, but do not support any additional increase in overall cancer risk.

Dietary fat and risk of renal cell carcinoma in the USA: a case-control study.

An increased risk of renal cell carcinoma (RCC) has been linked with obesity. However, there is limited information about the contribution of dietary fat and fat-related food groups to RCC risk. A population-based case-control study of 406 cases and 2434 controls aged 40-85 years was conducted in Iowa (1986-89). For 323 cases and 1820 controls from the present study, information on dietary intake from foods high in fat nutrients and other lifestyle factors was obtained using a mailed questionnaire. Cancer risks were estimated by OR and 95 % CI, adjusting for age, sex, smoking, obesity, hypertension, physical activity, alcohol and vegetable intake and tea and coffee consumption. In all nutrient analyses, energy density estimates were used. Dietary nutrient intake of animal fat, saturated fat, oleic acid and cholesterol was associated with an elevated risk of RCC (OR = 1.9, 95 % CI 1.3, 2.9, P trend < 0.001; OR = 2.6, 95 % CI 1.6, 4.0, P trend < 0.001; OR = 1.9, 95 % CI 1.2, 2.9, P trend = 0.01; OR = 1.9, 95 % CI 1.3, 2.8, P trend = 0.006, respectively, for the top quartile compared with the bottom quartile of intake). Increased risks were also associated with high-fat spreads, red and cured meats and dairy products (OR = 2.0, 95 % CI 1.4, 3.0, P trend = 0.001; OR = 1.7, 95 % CI 1.0, 2.2, P trend = 0.01; OR = 1.8, 95 % CI 1.2, 2.7, P trend = 0.02; OR = 1.6, 95 % CI 1.1, 2.3, P trend = 0.02, respectively). In both the food groups and nutrients, there was a significant dose-response with increased intake. Our data also indicated that the association of RCC with high-fat spreads may be stronger among individuals with hypertension. These findings deserve further investigation in prospective studies.

Prenatal and perinatal risk factors for neuroblastoma.

Neuroblastoma is a rare embryonal tumor of childhood for which risk factors are not well known. Using a nested case-control design, we investigated prenatal, perinatal and neonatal risk factors in detail by linking 245 pediatric neuroblastoma cases identified in the Swedish Cancer Register diagnosed in the year 1973-1995 with the Swedish Medical Birth Register. Five living controls per case were randomly selected from the birth registry, matched by gender and age. Increased risks were associated with maternal anemia during pregnancy (odds ratio (OR) = 2.95, 95% confidence interval (CI): 1.53, 5.69), neonatal respiratory distress (OR = 3.61, 95% CI: 1.41, 9.24) and low (below or equal to 7) 1-min Apgar score (OR = 2.23, 95% CI: 1.41, 3.52). Increased risks were limited to cases diagnosed before 1 year of age. Markers of prenatal, perinatal and neonatal distress may be associated with neuroblastoma in infancy, but not with diagnoses at 1 year or above.

Chronic immune stimulation and subsequent Waldenström macroglobulinemia.

BACKGROUND: Certain autoimmune and infectious conditions are associated with increased risks of subtypes of non-Hodgkin lymphoma. A few previous studies suggest that chronic inflammation may particularly elevate risk of the distinct non-Hodgkin lymphoma subtype Waldenström macroglobulinemia (WM). METHODS: We assessed WM risk in relation to a variety of chronic immune stimulatory conditions in 4 million US veterans. We identified 361 patients with WM with up to 27 years of follow-up. Using time-dependent Poisson regression, we estimated rate ratios (RRs) and 95% confidence intervals (CIs) for WM risk in relation to history of autoimmune diseases that typically have autoantibodies (with systemic or organ involvement) or do not have autoantibodies, infections, and allergies. All the models were adjusted for attained age, calendar year, race, number of hospital visits, and latency between study entry and exit. RESULTS: The age-standardized incidence of WM was 0.34 per 100,000 person-years. Risk of WM was elevated in individuals with any previous autoimmune condition (RR, 2.23; 95% CI, 1.68-2.97), autoantibodies with systemic involvement (2.50; 1.55-4.02), or autoantibodies with organ involvement (2.30; 1.57-3.37). Risks of WM were also increased with hepatitis (RR, 3.39; 95% CI, 1.38-8.30), human immunodeficiency virus (12.05; 2.83-51.46), and rickettsiosis (3.35; 1.38-8.14). CONCLUSIONS: In the largest investigation of WM risk factors to date, we found a 2- to 3-fold elevated risk of WM in persons with a personal history of autoimmune diseases with autoantibodies and notably elevated risks associated with hepatitis, human immunodeficiency virus, and rickettsiosis. These findings provide novel insights into the still unknown etiology of WM.

Survival patterns among lymphoma patients with a family history of lymphoma.

PURPOSE: Genetic factors are important in the etiology and pathogenesis of chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). Only a few small studies have assessed clinical characteristics and prognosis for familial patients, with inconsistent findings. METHODS: Using population-based registries from Sweden and Denmark, 7,749 patients with CLL, 7,476 patients with HL, and 25,801 patients with NHL with linkable first-degree relatives were identified. Kaplan-Meier curves were constructed to compare survival in patients with lymphoma with and without a family history of lymphoma. The risk of dying was assessed using adjusted Cox proportional hazard models. RESULTS: We found 85 patients with CLL (1.10%), 95 patients with HL (1.28%), and 206 patients with NHL (0.80%) with a family history of any lymphoma. Five-year mortality was similar for patients with CLL (hazard ratio [HR], 1.28; 95% CI, 0.95 to 1.72), HL (HR, 0.78; 95% CI, 0.49 to 1.25), and NHL (HR, 0.91; 95% CI, 0.74 to 1.12) versus without a family history of any lymphoma. Mortality was also similar for patients with versus without a family history of the same lymphoma. T-cell/anaplastic lymphoma patients with a family history of NHL had poorer outcome 5-years after diagnosis (HR, 5.38; 95% CI, 1.65 to 17.52). Results were similar for 10 years of follow-up. CONCLUSION: With the exception of T-cell/anaplastic lymphoma, survival patterns for patients with CLL, HL, and NHL with a family history of lymphoma were similar to those for sporadic patients, suggesting that most familial lymphomas do not have an altered clinical course. Our findings provide no evidence to modify therapeutic strategies for patients with CLL, HL, or NHL based solely on family history.

Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma.

Patients with multiple myeloma (MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT (crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively (crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P < .01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 (95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS (RR = 8.4; 95% CI, 5.7-12.2) and MM (RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM.

Blood transfusion, anesthesia, surgery and risk of non-Hodgkin lymphoma in a population-based case-control study.

The incidence of NHL has increased dramatically since at least the 1950s, and during this timeframe there has been a major increase in the use of blood transfusions, invasive surgical procedures and anesthesia, all of which can impact immune function. We evaluated these factors with NHL risk in a population-based study of 759 cases and 589 frequency-matched controls. Risk factor data were collected during in-person interviews. Unconditional logistic regression was used to estimate ORs and 95% CIs, adjusted for the matching factors. History of transfusion was associated with a 26% higher risk of NHL (95% CI 0.91-1.73), and the elevated risk was specific to transfusions first given 5-29 years before the reference date (OR = 1.69; 95% CI 1.08-2.62) and transfusions given for a medical condition (OR = 2.09; 95% CI 1.03-4.26). The total number of surgeries and dental procedures (OR = 1.53 for 26+ surgeries compared to 0-6; 95% CI 1.02-2.29) and to a lesser extent the total number of exposures to general or local/regional anesthesia (OR = 1.35 for 24+ times compared to 0-6; 95% CI 0.91-2.02) were positively associated with risk of NHL. Inclusion of transfusion and surgery or transfusion and anesthesia in the same model did not attenuate these associations. All results were broadly consistent for both DLBCL and follicular subtypes. Blood transfusions were associated with NHL risk, but appear to be a marker for underlying medical conditions. Multiple surgical procedures and/or repeated administration of anesthesia have not been previously reported to be associated with risk of NHL and these exposures warrant further evaluation.

Occupational physical activity and risk for cancer of the colon and rectum in Sweden among men and women by anatomic subsite.

Inverse association between physical activity and colon cancer is well established, at least in men. We investigated the association of occupational physical activity with subsite-specific colorectal cancer risk. On the basis of occupational titles from the Swedish nationwide censuses in 1960 and 1970, we defined a cohort of women and men with the same work-related physical demands in 1960 and 1970. Incidence of colon and rectum cancer during 1971-1989 was ascertained through linkages to the Cancer Register. Relative risks (RRs) were estimated through Poisson regression. The risk for colon cancer increased with decreasing occupational physical activity. RR among sedentary women and men was 1.2 and 1.3 (P for trend=0.08 and <0.001). For men, the risks for proximal and distal colon cancer increased by 20 and 40% (P for trend=0.005 and <0.001). Inactivity seemed to be particularly associated with descending colon cancer (RR =2.4, P for trend<0.001). In women, the inverse association with activity was concentrated to proximal parts of colon; RR for cancer in the proximal and transverse colon among sedentary women was 1.4 and 2.0 (P for trend <0.07 and <0.01). Cancer of the rectum was not associated with activity in either sex. We confirmed the well-known inverse relationship between activity and risk of colon cancer but not rectal cancer in both sexes. Data suggest that the physical activity-related variation in risk among women is greatest in the proximal and middle parts of the colon, whereas the corresponding peak in men seems to be more distal. Sex-specific anatomic and motility differences of the colon might contribute to this subsite difference.