Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 65-year-old woman of normal weight, hospitalized because of pleuritis, was found to have chronic renal failure (creatinine clearance 20 ml/min). Renal biopsy (light and electron-microscopy) revealed nodular glomerulosclerosis (Kimmerstiel-Wilson disease), described as a diabetes-specific renal change. Fundoscopy discovered bilateral proliferative retinopathy as seen in diabetes. But oral and intravenous glucose tolerance tests were normal, excluding a manifest diabetic metabolic disorder. No other cause of the glomerulosclerosis (such as amyloidosis or multiple myeloma) was found. The patient had been overweight for a time when younger, reversed by dieting. It is suggested that the "diabetic" changes in the kidneys and eyes without diabetes could be the result of a transitory disorder of glucose tolerance during the period of obesity.
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PMID:["Diabetic" proliferative retinopathy and nodular glomerulosclerosis without diabetes mellitus]. 319 24

An exploratory study was conducted of common clinical conditions as predictors of subsequent cancer in 143,574 outpatients of a health maintenance organization (in California, USA). An association was noted between obesity, diagnosed in 14,388 patients, and the subsequent development of multiple myeloma (MM) in up to 21 years (33 cases observed, 21.3 expected based on the experience of the entire cohort; standardized morbidity ratio = 1.55, 95 percent confidence interval [CI] = 1.06-2.17). This association was evaluated further in a second cohort of 163,561 multiphasic-checkup examinees followed up for as many as 24 years. Body mass index (BMI) at entry examination was associated positively with the incidence of MM in White men (e.g., relative risk [RR] = 1.07, CI = 1.01-1.15 per unit increase in BMI; and RR = 1.68, CI = 0.75-3.78, comparing the highest with lowest quartile). This association was absent in White women, partially confirmed in Black men and women (BMI quartiles two, three, and four showed higher risk than quartile one), and not explained by the presence of diabetes mellitus. The association was reduced or absent with BMI based on reported greatest adult-weight, and in White women was inverse with BMI based on reported lowest adult-weight. Among subjects with more than one checkup, increased risk was associated directly with weight loss among White men and associated inversely with weight gain among Black women. These findings suggest that body build or nutritional status may be involved in the development of MM by mechanisms that are presently unknown.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Obesity and multiple myeloma. 799 70

Bone localisations of amyloidosis are rare, usually diffuse and associated with myeloma. We report the case of a patient with massive obesity complicated by diabetes, hypertension, sleep apnea and liver steatosis, who complained of rapidly worsening bilateral polyradiculalgia of the lower limbs. After sufficient weight loss made nuclear magnetic resonance imaging feasible, a spinal tumour was visualised on the 5th lumbar vertebra, extending to soft tissues. Total excision was performed, and pathological studies revealed an amyloid bone tumour with no evidence of myeloma.
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PMID:Bone amyloidoma in a diabetic patient with morbid obesity. 1049 96

Multiple myeloma is an uncommon disease, with approximately 12,000 cases per year diagnosed in America. Blacks have had at least double the risk of being diagnosed with myeloma, and have had twice the mortality rate from the disease compared to whites. Research of the origins of this difference has yielded both insight and controversy. Obesity is likely a risk factor for myeloma, in both blacks and whites. Obesity is more prevalent in the black population, and this may help explain some of the increased incidence of myeloma. Also, genetic factors such as HLA antigens and family history seem to be important in explaining the differential risk of myeloma. Exposure to immunological challenges, especially urinary tract infections in black men, seems important in explaining some of the excess risk in blacks. Factors such as socioeconomic status, dietary preferences, vitamin intake, alcohol and tobacco use, either lack a consensus finding, or may not play a role in explaining the increased myeloma morbidity and mortality in blacks.
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PMID:Myeloma and race: a review of the literature. 1271 40

We used the nation-wide Swedish Family-Cancer Database to analyse cancer risks in men who had had children with more than one woman. Cancer cases were retrieved from the Swedish Cancer Registry from years 1961-1998. A total of 2.9 million men and 298,134 cancer cases were covered. For men having children with two, three or more women, increasing risk trends were shown for upper aerodigestive tract, lung, urinary bladder and oesophageal cancers. Decreasing trends were observed for tumours of the colon, skin (squamous cell and melanoma), nervous system and endocrine glands and against myeloma and non-Hodgkin's lymphoma. The present results indicated that men who had had children with multiple women showed an excess of smoking- and alcohol consumption-related cancers. The decreased risks for colon cancer, non-Hodgkin's lymphoma and melanoma were possibly related to lifestyle factors connected with economic deprivation, less obesity and physical fitness. These ill-defined protected factors may be a challenge to epidemiological studies.
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PMID:Cancer risks in men who had children with different partners from the Swedish Family-Cancer Database. 1451 98

The authors conducted a population-based, case-control study of 21,022 incident cases of 19 types of cancer and 5,039 controls aged 20-76 years during 1994-1997 to examine the association between obesity and the risks of various cancers. Compared with people with a body mass index of less than 25 kg/m(2), obese (body mass index of > or = 30 kg/m(2)) men and women had an increased risk of overall cancer (multivariable adjusted odds ratio = 1.34, 95% confidence interval (CI): 1.22, 1.48), non-Hodgkin's lymphoma (odds ratio = 1.46, 95% CI: 1.24, 1.72), leukemia (odds ratio = 1.61, 95% CI: 1.32, 1.96), multiple myeloma (odds ratio = 2.06, 95% CI: 1.46, 2.89), and cancers of the kidney (odds ratio = 2.74, 95% CI: 2.30, 3.25), colon (odds ratio = 1.93, 95% CI: 1.61, 2.31), rectum (odds ratio = 1.65, 95% CI: 1.36, 2.00), pancreas (odds ratio = 1.51, 95% CI: 1.19, 1.92), breast (in postmenopausal women) (odds ratio = 1.66, 95% CI: 1.33, 2.06), ovary (odds ratio = 1.95, 95% CI: 1.44, 2.64), and prostate (odds ratio = 1.27, 95% CI: 1.09, 1.47). Overall, excess body mass accounted for 7.7% of all cancers in Canada-9.7% in men and 5.9% in women. This study provides further evidence that obesity increases the risk of overall cancer, non-Hodgkin's lymphoma, leukemia, multiple myeloma, and cancers of the kidney, colon, rectum, breast (in postmenopausal women), pancreas, ovary, and prostate.
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PMID:Association of obesity and cancer risk in Canada. 1474 86

Interleukin-6 (IL-6) and C-reactive protein (CRP, a surrogate marker for IL-6) are important in monoclonal gammopathy of undetermined significance (MGUS) and myeloma. Smoking and obesity may elevate CRP levels, while statins decrease CRP levels. A case-control study in 200 MGUS patients found that statin use, smoking history and obesity do not affect MGUS progression.
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PMID:Effect of statins, smoking and obesity on progression of monoclonal gammopathy of undetermined significance: a case-control study. 1513 36

Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n = 112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions -174, -572, and -597; one variable number of tandem repeats (-373 A(n)T(n)); and one SNP in the IL-6 receptor (IL-6ralpha) gene at position -358. The variant allele of the IL-6 promoter SNP -572 was associated with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 0.7-4.7] or population controls (OR, 2.4; 95% CI, 1.2-4.7). The -373 9A/9A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI >or= 30 kg/m(2)) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of <25 kg/m(2). These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms.
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PMID:Interleukin-6-related genotypes, body mass index, and risk of multiple myeloma and plasmacytoma. 1711 59

Multiple myeloma, a neoplasm of plasma cells, accounts for approximately approximately 15% of lymphatohematopoietic cancers (LHC) and 2% of all cancers in the US. Incidence rates increase with age, particularly after age 40, and are higher in men, particularly African American men. The etiology is unknown with no established lifestyle, occupational or environmental risk factors. Although several factors have been implicated as potentially etiologic, findings are inconsistent. We reviewed epidemiologic studies that evaluated lifestyle, dietary, occupational and environmental factors; immune function, family history and genetic factors; and the hypothesized precursor, monoclonal gammopathies of undetermined significance (MGUS). Because multiple myeloma is an uncommon disease, etiologic assessments can be difficult because of small numbers of cases in occupational cohort studies, and few subjects reporting exposure to specific agents in case-control studies. Elevated risks have been reported consistently among persons with a positive family history of LHC. A few studies have reported a relationship between obesity and multiple myeloma, and this may be a promising area of research. Factors underlying higher incidence rates of multiple myeloma in African Americans are not understood. The progression from MGUS to multiple myeloma has been reported in several studies; however, there are no established risk factors for MGUS. To improve our understanding of the causes of multiple myeloma, future research efforts should seek the causes of MGUS. More research is also needed on the genetic factors of multiple myeloma, given the strong familial clustering of the disease.
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PMID:Multiple myeloma: a review of the epidemiologic literature. 1740 20

Guggulsterone is a plant polyphenol traditionally used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, possibly through an anti-inflammatory mechanism. Whether this steroid has any role in cancer is not known. In this study, we found that guggulsterone inhibits the proliferation of wide variety of human tumor cell types including leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma, breast carcinoma, and ovarian carcinoma. Guggulsterone also inhibited the proliferation of drug-resistant cancer cells (e.g., gleevac-resistant leukemia, dexamethasone-resistant multiple myeloma, and doxorubicin-resistant breast cancer cells). Guggulsterone suppressed the proliferation of cells through inhibition of DNA synthesis, producing cell cycle arrest in S-phase, and this arrest correlated with a decrease in the levels of cyclin D1 and cdc2 and a concomitant increase in the levels of cyclin-dependent kinase inhibitor p21 and p27. Guggulsterone-induced apoptosis as indicated by increase in the number of Annexin V- and TUNEL-positive cells, through the downregulation of anti-apoptototic products. The apoptosis induced by guggulsterone was also indicated by the activation of caspase-8, bid cleavage, cytochrome c release, caspase-9 activation, caspase-3 activation, and PARP cleavage. The apoptotic effects of guggulsterone were preceded by activation of JNK and downregulation of Akt activity. JNK was needed for guggulsterone-induced apoptosis, inasmuch as inhibition of JNK by pharmacological inhibitors or by genetic deletion of MKK4 (activator of JNK) abolished the activity. Overall, our results indicate that guggulsterone can inhibit cell proliferation and induce apoptosis through the activation of JNK, suppression of Akt, and downregulation of antiapoptotic protein expression.
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PMID:Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. 1747 22


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