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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Risks of cancer among a cohort of 23,935 men and women with osteoporosis.

Low hormone levels among persons with osteoporosis may decrease risk of some cancers. Other osteoporosis risk factors, such as smoking and alcohol consumption, however, may increase risk. As these deleterious factors are more often associated with osteoporosis diagnosed prior to age 70 years, cancer risk may be higher in these younger persons than in the general population. To examine this hypothesis, a cohort study of 23,935 persons with osteoporosis was conducted in Denmark. Patients hospitalized with osteoporosis between 1978 and 1993 were identified in the Danish Inpatient Register. Linkage to the Danish Cancer Registry identified all cancer outcomes through 2003. Standardized incidence ratios (SIR) and 95% confidence intervals (95%CI) were calculated to compare cancer incidence in the cohort with that in the general population. Persons diagnosed prior to age 70 years were at increased cancer risk (women: SIR = 1.11, 95%CI = 1.04-1.19; men: SIR = 1.31, 95%CI = 1.13-1.50) due, in part, to increased risks of cancers of the buccal cavity, esophagus, liver, pancreas and lung. Persons diagnosed at ages 70 and older were at decreased risk (women: SIR = 0.91, 95%CI = 0.87-0.96; men: SIR = 0.89, 0.77-1.01) due, in part, to decreased risks of breast, endometrial, colon, rectal and brain cancers in women and prostate cancer in men. These results suggest that risk factors associated with earlier onset osteoporosis may be associated with increased risk of cancer. Conversely, factors associated with later onset osteoporosis may be related to a decreased risk of cancer.

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.

Risk of cancer after blood transfusion from donors with subclinical cancer: a retrospective cohort study.

BACKGROUND: Although mechanisms for detection of short-term complications after blood transfusions are well developed, complications with delayed onset, notably transmission of chronic diseases such as cancer, have been difficult to assess. Our aim was to investigate the possible risk of cancer transmission from blood donors to recipients through blood transfusion. METHODS: We did a register-based retrospective cohort study of cancer incidence among patients who received blood from donors deemed to have a subclinical cancer at the time of donation. These precancerous donors were diagnosed with a cancer within 5 years of the donation. Data from all computerised blood bank registers in Sweden and Denmark gathered between 1968 and 2002 were merged into a common database. Demographic and medical data, including mortality and cancer incidence, were ascertained through linkages with nationwide, and essentially complete, population and health-care registers. The risk of cancer in exposed recipients relative to that in recipients who received blood from non-cancerous donors was estimated with multivariate Poisson regression, adjusting for potential confounding factors. FINDINGS: Of the 354 094 transfusion recipients eligible for this analysis, 12,012 (3%) were exposed to blood products from precancerous donors. There was no excess risk of cancer overall (adjusted relative risk 1.00, 95% CI 0.94-1.07) or in crude anatomical subsites among recipients of blood from precancerous donors compared with recipients of blood from non-cancerous donors. INTERPRETATION: Our data provide no evidence that blood transfusions from precancerous blood donors are associated with increased risk of cancer among recipients compared with transfusions from non-cancerous donors.

Risk of malignant disease among 1525 adult male US Veterans with Gaucher disease.

BACKGROUND: Some, but not all, reports suggest that patients with Gaucher disease are at increased risk of developing malignancies, particularly hematopoietic tumors. The aim of this study was to assess the pattern of Gaucher disease and subsequent malignancies among male veterans admitted to US Veterans Affairs hospitals. METHODS: Among 832 294 African American and 3 668 983 white male veterans with at least 1 hospital admission in US Veterans Affairs hospitals and up to 27 years of follow-up, we identified a total of 1525 patients with Gaucher disease; 11.7% were African Americans. We used Poisson regression methods for cohort data to estimate relative risks (RRs) and 95% confidence intervals (CIs) after adjusting for attained age and calendar year, race, number of hospital visits, and latency. RESULTS: When patients with Gaucher disease were compared with patients without Gaucher disease, the RR of any cancer was 0.91 (95% CI, 0.76-1.08 [n = 137]). When we stratified our analyses by race, risks were similar for whites (RR, 0.89; 95% CI, 0.74-1.07 [n = 120]) and African Americans (RR, 1.00; 95% CI, 0.61-1.64 [ n = 17]). Patients with Gaucher disease had an elevated risk for non-Hodgkin lymphoma (RR, 2.54; 95% CI, 1.32-4.88 [n = 9]), malignant melanoma (RR, 3.07; 95% CI, 1.28-7.38 [n = 5]), and pancreatic cancer (RR, 2.37; 95% CI, 1.13-4.98 [n = 7]). Among the remaining 19 cases involving defined solid tumors and 7 other hematologic malignancies, we found no statistical association with Gaucher disease. CONCLUSION: We found 2- to 3-fold risks of non-Hodgkin lymphoma, malignant melanoma, and pancreatic cancer in patients with Gaucher disease, but no significant association between Gaucher disease and cancer in general or with other specific malignancies such as multiple myeloma.

Acquired immune-related and inflammatory conditions and subsequent chronic lymphocytic leukaemia.

Immune-mediated pathways have been recognized to be of importance in the pathogenesis of chronic lymphocytic leukaemia (CLL). We assessed a broad variety of immune-related and inflammatory conditions and subsequent CLL development among 4 million adult male veterans admitted to VA hospitals. We identified 3,680 CLL cases with up to 27 years of follow-up. Using Poisson regression analyses restricted to immune-related or inflammatory conditions that occurred more than one year before CLL, we estimated relative risk (RR) and 95% confidence intervals for CLL risk. Elevated CLL risk was found among individuals with prior chronic sinusitis (RR = 1.27, 1.01-1.61). Pneumonia had a borderline (RR = 1.13, 1.00-1.27) association with CLL; the risk was further elevated (RR = 1.35, 1.07-1.72) for latency <5 years. Conversely, chronic non-rheumatic valvular heart disease was associated with 0.76-fold (0.58-0.99) decreased risk. Herpes zoster and simplex were associated with increased (RR = 1.98, 1.40-2.79) and borderline increased (RR = 1.69, 0.96-2.98) CLL risk. There was no general association between autoimmunity and CLL; however, autoimmune haemolytic anaemia was associated with 3.86-fold (1.93-7.74) elevated CLL risk. Individuals with chronic osteoarthritis and prostatitis had 1.14-fold (1.03-1.25) and 1.64-fold (1.14-2.37) elevated CLL risk. These association patterns suggest primary focus on infectious agents rather than autoantigens for future aetiologic CLL studies.

Respiratory tract infections in the pathway to multiple myeloma: a population-based study in Scandinavia.

Encounter with infectious antigens has been proposed to initiate the cascade of events associated with progression from premalignancy (monoclonal gammopathy of undetermined significance, MGUS) to multiple myeloma (MM). We conducted a population-based case-control study to evaluate risk of developing MM associated with a personal history of various respiratory tracts infections occurring >1 year prior to MM. Inpatient (1977-1997) and outpatient (1994-1997) diagnoses were obtained for all MM patients (n=4,476) diagnosed in Denmark (1977-1997) and 16,727 matched controls. A personal history of pneumonia was associated with a 1.6-fold (95%CI 1.3-2.0) increased risk of MM; the elevated risk was restricted to 1-4.99 years prior to the diagnosis of MM (OR=1.7,95%CI 1.3-2.2). Individuals with two and three or more previous episodes of pneumonia had a 1.7-fold (95%CI 1.0-3.0; p=0.05) and a 1.5-fold (95%CI 0.6-3.9) elevated MM risk, respectively. Pneumonia could be a trigger to the development of MM or a manifestation of immune disturbances in late-stage MGUS.

Allium vegetables and risk of prostate cancer: a population-based study.

Epidemiologic and laboratory studies suggest that allium vegetables and garlic constituents have antitumor effects. In a population-based, case-control study conducted in Shanghai, China, we investigated the association between intake of allium vegetables, including garlic, scallions, onions, chives, and leeks, and the risk of prostate cancer. We administered in-person interviews and collected information on 122 food items from 238 case subjects with incident, histologically confirmed prostate cancer and from 471 male population control subjects. Men in the highest of three intake categories of total allium vegetables (>10.0 g/day) had a statistically significantly lower risk (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.76; P(trend)<.001) of prostate cancer than those in the lowest category (<2.2 g/day). Similar comparisons between categories showed reductions in risk for men in the highest intake categories for garlic (OR = 0.47, 95% CI = 0.31 to 0.71; P(trend)<.001) and scallions (OR = 0.30, 95% CI = 0.18 to 0.51; P(trend)<.001). The reduced risk of prostate cancer associated with allium vegetables was independent of body size, intake of other foods, and total calorie intake and was more pronounced for men with localized than with advanced prostate cancer.

Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples.

The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL.

Causes of death in patients with celiac disease in a population-based Swedish cohort.

BACKGROUND: Patients with celiac disease have an increased risk of death from gastrointestinal malignancies and lymphomas, but little is known about mortality from other causes and few studies have assessed long-term outcomes. METHODS: Nationwide data on 10 032 Swedish patients hospitalized from January 1, 1964, through December 31, 1993, with celiac disease and surviving at least 12 months were linked with the national mortality register. Mortality risks were computed as standardized mortality ratios (SMRs), comparing mortality rates of patients with celiac disease with rates in the general Swedish population. RESULTS: A total of 828 patients with celiac disease died during the follow-up period (1965-1994). For all causes of death combined, mortality risks were significantly elevated: 2.0-fold (95% confidence interval [CI], 1.8-2.1) among all patients with celiac disease and 1.4-fold (95% CI, 1.2-1.6) among patients with celiac disease with no other discharge diagnoses at initial hospitalization. The overall SMR did not differ by sex or calendar year of initial hospitalization, whereas mortality risk in patients hospitalized with celiac disease before the age of 2 years was significantly lower by 60% (95% CI, 0.2-0.8) compared with the same age group of the general population. Mortality risks were elevated for a wide array of diseases, including non-Hodgkin lymphoma (SMR, 11.4), cancer of the small intestine (SMR, 17.3), autoimmune diseases (including rheumatoid arthritis [SMR, 7.3] and diffuse diseases of connective tissue [SMR, 17.0]), allergic disorders (such as asthma [SMR, 2.8]), inflammatory bowel diseases (including ulcerative colitis and Crohn disease [SMR, 70.9]), diabetes mellitus (SMR, 3.0), disorders of immune deficiency (SMR, 20.9), tuberculosis (SMR, 5.9), pneumonia (SMR, 2.9), and nephritis (SMR, 5.4). CONCLUSION: The elevated mortality risk for all causes of death combined reflected, for the most part, disorders characterized by immune dysfunction.