Caspase polymorphisms and genetic susceptibility to multiple myeloma

Multiple myeloma is a haematological malignency, characterized by clonal expansion of plasma cells. However, little is known about the cause of multiple myeloma. Cancer cells must avoid apoptosis to ensure unregulated tumour formation and growth. The highly conserved caspase cascade is essential to the regulation of the apoptotic pathway. To examine if five single nucleotide polymorphisms (SNPs) in four caspase genes [CASP3 Ex8-280 C > A (rs6948), CASP3 Ex8 + 567 T > C (rs1049216), CASP8 Ex14-271 A > T (rs13113), CASP9 Ex5 + 32 G > A (rs1052576), CASP10 Ex3-171 A > G (rs39001150)] alter multiple myeloma risk, we conducted a population-based case-control study of women (128 cases; 516 controls) in Connecticut. Compared to individuals with the TT genotype of CASP3 Ex8 + 567 T > C, subjects with the CC genotype had a five-fold decreased risk of multiple myeloma (odds ratio (OR)(CC) = 0.2, 95% confidence interval (CI) = 0.0-1.0). Further, individuals with the AG and AA genotypes of CASP9 Ex5 + 32 G > A also experienced a decreased risk of multiple myeloma (OR(AG) = 0.8, 95% CI = 0.5-1.3; OR(AA) = 0.5, 95% CI = 0.3-0.9; p-trend = 0.02). While no previous study has evaluated the association between caspase genes and multiple myeloma, studies have found associations with lung, breast, esophageal, gastric, colorectal and cervical cancers. Our parallel study of non-Hodgkin lymphoma, which utilized the same controls, found strong evidence that caspase genes play a key role in lymphogenesis. The protective associations observed in two key caspase genes suggest that genetic variation in CASP genes may play an important role in the aetiology of multiple myeloma.     

Case-control study of multiple myeloma and farming

A previous case-control study which utilised the occupational information available on the New Zealand Cancer Registry found an increased risk of multiple myeloma in agricultural workers consistent with previous findings in the United States. The findings are now presented for the second phase of the study which involved interviewing 76 cases of multiple myeloma (who had been included in the previous study) together with 315 controls with other types of cancer. The previous finding on an excess of farmers in the case group was confirmed by the interview data (odds ratio = 1.7, 95% confidence limits 1.0-2.9, P = 0.04). There were no significant differences between cases and controls regarding potential exposure to phenoxy herbicides or chlorophenols. There were also no significant differences regarding activities involving potential exposure to other agricultural chemicals, although the odds ratio for fencing work, which may involve exposure to arsenic and sodium pentachlorophenate, was 1.6 (95% confidence limits 0.9-2.7, P = 0.11). The odds ratios were significantly elevated for sheep farming (odds ratio = 1.9, 95% confidence limits 1.0-3.6, P = 0.04) and exposure to beef cattle (odds ratio = 1.7, 95% confidence limits 1.0-2.9, P = 0.05). The odds ratio was also elevated for persons reporting a history of hay fever (odds ratio = 1.9, 95% confidence limits 1.0-3.5, P = 0.05). Overall, these findings suggest that the search for the causes of elevated mortality in farmers from multiple myeloma should be directed to potential causes other than pesticide exposure.     

Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study

A population-based case-control study was conducted to evaluate risk of developing multiple myeloma (MM) associated with personal history of autoimmune diseases and occurrence of autoimmune and selected hematologic disorders in first-degree relatives. Data were obtained for all (n = 8,406) MM cases diagnosed in Sweden (1958-1998), with linkable relatives, 16,543 matched controls and first-degree relatives of cases (n = 22,490) and controls (n = 44,436). Odds ratios (ORs) were calculated to quantify the risk of MM in relation to personal/family history of 32 autoimmune disorders. Familial aggregation of malignancies was evaluated in a marginal survival model using relatives as the cohort. The risk for MM was significantly elevated among subjects with a personal history of pernicious anemia (OR = 3.27; 2.22-4.83) and individuals with a family history of systemic lupus erythematosus (OR = 2.66; 1.12-6.32). Compared with controls, relative risk (RR) of MM was significantly increased (RR = 1.67; 1.02-2.73) in relatives of cases, particularly relatives of probands aged > or =65 at diagnosis (RR = 2.50; 1.19-5.27). Risks were nearly 4-fold elevated among female relatives (RR = 3.97; 1.54-10.2) and among relatives of female probands (RR = 3.74; 1.58-8.83). MM cases had more cases of monoclonal gammopathy of undetermined significance (MGUS) among their relatives than controls, but the numbers were too small to be conclusive. There was generally no increase in risk of MM in probands whose relatives had hematologic malignancies other than MM. These findings do not support a strong association between personal/familial autoimmune diseases and MM. However, MM itself shows significant familial aggregation, implicating the etiologic importance of this type of hematological neoplasm and perhaps MGUS in germ line genes.     

Interleukin-6-related genotypes, body mass index, and risk of multiple myeloma and plasmacytoma.

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.     

Hepatitis C virus and risk of non-Hodgkin lymphoma in British Columbia, Canada

We investigated Hepatitis C virus (HCV) seropositivity and the risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in British Columbia, Canada. Cases were aged 20-79, diagnosed between March 2000 and February 2004, and resident in greater Vancouver or Victoria. Cases with HIV or a prior transplant were excluded. Controls were chosen from the Client Registry of the British Columbia (BC) Ministry of Health, and were age/sex/region frequency matched to cases. Antibodies for HCV were measured in 795 cases and 697 control subjects. HCV seropositivity was 2.4% in cases and 0.7% in controls [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 0.9-7.4]. A significantly elevated risk was observed for B-cell lymphoma (OR = 2.9, 95%CI = 1.0-8.6). The highest risks were associated with diffuse large B-cell lymphoma (OR = 7.3, 95%CI = 2.1-25.0) and marginal zone lymphoma (OR = 6.1, 95%CI = 1.1-33.9). Our results provide further evidence that HCV infection contributes to NHL risk.     

Pancreatic cancer,animal protein and dietary fat in a population-based study,San Francisco Bay Area,California

Objective The associations between animal protein or fat and risk of pancreatic cancer have been reported previously with inconsistent results. A population-based case–control study of pancreatic cancer was conducted in the San Francisco Bay Area to examine these associations. Methods A semi-quantitative food-frequency questionnaire was administered to 532 cases and 1,701 controls between 1995 and 1999. Odds ratios (OR) and 95% confidence intervals (CI) were computed as estimates of the relative risk of pancreatic cancer. Results When comparing highest versus lowest levels of intake in multivariable adjusted models, positive associations were observed for several beef/lamb and individual animal protein items, including beef/lamb as a main dish (OR = 2.2, 95% CI: 1.0–4.5), regular hamburger (OR = 1.7, 95% CI: 1.2–2.4), whole eggs (OR = 1.6, 95% CI: 1.0–2.4), butter (OR = 2.4, 95% CI: 1.6–3.5), and total dairy not including butter (OR = 2.6, 95% CI: 1.8–3.7). Some high-fat/processed-meat products (i.e., sausage, salami, bacon), but not all (i.e., beef, pork, or poultry hot dogs), also were positively associated with risk. An inverse association was noted for greater chicken/turkey consumption (OR = 0.7, 95% CI: 0.5–1.0). The risk comparing the highest versus lowest quartiles for fats and cholesterol consumption were: total fat (OR = 1.6, 95% CI: 1.2–2.1); animal fat (OR = 1.9, 95% CI: 1.4–2.5); saturated fat (OR = 1.9, 95% CI: 1.4–2.6); monounsaturated fat (OR = 1.3, 95% CI: 1.0–1.8); and dietary cholesterol (OR = 1.5, 95% CI: 1.1–2.0, all p-trends ≤ 0.02). Conclusions These data provide some evidence that beef or lamb, eggs, dairy, fat, or cholesterol may increase the risk of pancreatic cancer.     

Pre-natal and peri-natal exposures and risk of testicular germ-cell cancer

The present case-control study was undertaken to investigate the association between exposure to maternal hormones and risk of testicular germ-cell cancer by histologic subgroups. Cases were males, aged 16 to 59 years, diagnosed with testicular germ-cell cancer in Ontario between 1987 and 1989. Histologic review was performed on all eligible cases for the purpose of categorizing cases as seminoma or non-seminoma (the latter classified 2 ways, with and without tumors containing seminoma). Risk factor data were collected on 502 cases, 346 case mothers, 975 age-matched controls, and 522 control mothers. Exogenous hormone exposure was associated with elevated risk (OR = 4.9, 95% CI 1.7-13.9). Several additional risk factors were associated with risk of testicular cancer: bleeding and threatened miscarriage (OR = 0.6, 95% CI 0.3-1.0), maternal cigarette smoking (12+ cigarettes/day OR = 0.6, 95% CI 0. 4-1.0). pre-term birth (OR = 1.6, 95% CI 1.0-2.5), and treatment for undescended testicle (OR = 8.0, 95% CI 3.2-20.0). First births were associated with elevated risk (OR = 1.7, 95% CI 1.0-2.8) among mothers below the age of 24 years at conception. There was little evidence that risk factors differed by histologic subgroup. We found evidence that exposure to maternal hormones, particularly estrogens, is associated with testicular germ-cell cancer risk. Not only does exposure to elevated levels (exogenous hormone use, pre-term birth, and first births among young mothers) increase risk but also exposure to relatively lower levels (heavy cigarette consumption and, perhaps, bleeding and threatened miscarriage) may decrease cancer risk.     

A case-control study of aplastic anemia

A case-control interview study of aplastic anemia was conducted to evaluate suspected risk factors. Cases (N = 59) newly diagnosed during 1975-82 at 25 Baltimore area hospitals were compared with 59 individually matched (on age, sex and race) controls selected by random digit dialing. The average educational level was less for cases than controls. The major job-related findings were a significant excess for occupational exposure to paint (OR = 6.1; 95% C.I. = 1.2-29.7), further substantiated by a positive dose-response relationship, although painters were not at excess risk. An increased risk of occupational exposure to viruses (OR = 9.0; 95% C.I. = 0.8-105.6) was noted. Additional evidence implicating viral factors included a significant association with prior history of hepatitis (OR = 9.0; 95% C.I. = 1.0, 84.2) and an elevated risk for pre-diagnostic receipt of blood transfusions (OR = 7.1; 95% C.I. = 0.7-68.4). Risks were not increased for other occupational, residential, personal, or medical treatment exposures or for other viral infections, medical conditions, smoking or alcohol consumption prior to diagnosis. Because of the small number of subjects studied and the multiple comparisons examined, these findings should be interpreted cautiously and confirmation should be undertaken in larger, population-based studies.     

Hormonal factors and risk of ovarian germ cell cancer in young women

No previous controlled studies of ovarian germ cell tumours have been reported; however the tumour is similar to germ cell testicular cancer in terms of histology, age-specific incidence rates (i.e. highest rates in young adulthood), and secular trends of increasing incidence. The investigation was designed to determine if maternal hormonal factors which have been found to increase the risk of testis cancer in male offspring are also risk factors for the ovarian tumour. The analysis is based on 73 cases diagnosed before age 35 and 138 age-race matched controls. The cases were identified by tumour registries in Los Angeles (1972-84) and Seattle (1974-84) and controls were selected from friends and/or neighbourhood residents. Interviews were conducted on the telephone with mothers of cases and controls. The primary finding was that mother's use of exogenous hormones (including the hormonal pregnancy test, DES or other supportive hormones, and inadvertant use of oral contraceptives after conception) increased risk (Odds ratio, OR = 3.60, 95% CL = 1.2-13.1). Other maternal factors associated with elevated risk were high pre-pregnancy body mass (OR = 2.7, 95% CL = 1.0-7.6), more rapid achievement of regular menstruation after menarche (OR = 1.8, 95% CL = 0.9-3.8), and age at index pregnancy under 20 (OR = 2.8, 95% CL = 1.0-10.7). In conclusion, these results support findings from testis cancer studies regarding a hormonal aetiology for germ cell tumours, and a mechanism by which oestrogen may affect the germ cells is proposed.     

Hormonal contraceptive use, pregnancy and parity, and the risk of cervical intraepithelial neoplasia 3 among oncogenic HPV DNA-positive women with equivocal or mildly abnormal cytology

Oral contraceptive (OC) use, hormonal contraceptive use and multiparity are potential risk factors for cervical precancer, cervical intraepithelial neoplasia 3 (CIN3), but a limited number of studies have adequately accounted for possible confounding effect of oncogenic human papillomavirus (HPV) infection. To examine the relationships of these factors with CIN3, we conducted an analysis of women (n = 5,060) with minimally abnormal Pap smears who were enrolled in the ASCUS and LSIL Triage Study (ALTS), a clinical trial to evaluate management strategies. Cervical specimens collected at enrollment were tested for HPV DNA using 2 methods. Multivariate logistics regression models were used to assess associations (odds ratio [OR] with 95% confidence intervals [CI]) of the potential risk factors (e.g., OC use and parity) with testing oncogenic HPV positive among controls (相似文献   

Childhood Hodgkin's lymphoma, non-Hodgkin's lymphoma and factors related to the immune system: the Escale Study (SFCE)

The study investigated the role of factors considered related to the early stimulation of the immune system in the aetiology of childhood lymphoma. The national registry-based case-control study, Escale, was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Data from 128 cases of Hodgkin's lymphoma (HL) aged 5-14 years, 164 cases of non-Hodgkin's lymphoma (NHL) aged 2-14 years and 1,312 controls were analyzed. Negative associations were observed between HL and day care attendance [OR = 0.5 (0.2-1.2)] and between HL and repeated early common infections among non-breastfed children [OR = 0.3 (.2-0.7), p = 0.003] [OR for breastfed children: 1.0 (.5-2.1)], but not for the other factors investigated. Negative associations were observed between NHL and birth order 3 or more [OR = 0.7 (0.4-1.1)], prolonged breastfeeding [OR = 0.5 (0.3-1.0)], regular contact with farm animals [OR = 0.5 (0.3-1.0)], frequent farm visits in early life [OR = 0.6 (0.4-1.1)] and history of asthma [OR = 0.6 (0.3-1.1)]. In conclusion, the results partly support the hypothesis that an abnormal maturation of the immune system may play a role in childhood HL or NHL, and call for further investigations.     

Multiple myeloma and family history of cancer among blacks and whites in the U.S.

BACKGROUND: In the U.S., the incidence rate of multiple myeloma is more than twice as high for blacks as for whites, but the etiology of this malignancy is not well understood. METHODS: A population-based case-control interview study of 565 subjects (361 white, 204 black) with multiple myeloma and 2104 controls (1150 white, 954 black) living in 3 areas of the U.S. offered the opportunity to explore whether family history, of cancer contributes to the risk of multiple myeloma and explains the racial disparity in risk. RESULTS: For both races combined, the risk of multiple myeloma was significantly elevated for subjects who reported that a first-degree relative had multiple myeloma (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.2-12.0). Increased risk was also associated with a family history of any hematolymphoproliferative (HLP) cancer (OR = 1.7, 95% CI = 1.0-2.8), especially in a sibling (OR = 2.3, 95% CI = 1.1-4.5). The risk associated with familial occurrence of HLP cancer was higher for blacks than for whites, but the difference between the ORs was not statistically significant. CONCLUSIONS: These data are consistent with previous studies that indicate a familial risk of multiple myeloma, but they explain little of the race-related difference in incidence rates.     

Sexual behaviour, STDs and risks for prostate cancer

A population-based case-control study was carried out among 981 men (479 black, 502 white) with pathologically confirmed prostate cancer and 1315 controls (594 black, 721 white). In-person interviews elicited information on sexual behaviour and other potential risk factors for prostate cancer. Blood was drawn for serologic studies in a subset of the cases (n = 276) and controls (n = 295). Prostate cancer risk was increased among men who reported a history of gonorrhoea or syphilis (odds ratio (OR) = 1.6; 95% confidence internal (CI) 1.2-2.1) or showed serological evidence of syphilis (MHA-TP) (OR = 1.8; 95% CI 1.0-3.5). Patterns of risk for gonorrhoea and syphilis were similar for blacks (OR = 1.7; 95% CI 1.2-2.2) and whites (OR = 1.6; 95% CI 0.8-3.2). Risks increased with increasing occurrences of gonorrhoea, rising to OR = 3.3 (95% CI 1.4-7.8) among subjects with three or more events (Ptrend = 0.0005). Frequent sexual encounters with prostitutes and failure to use condoms were also associated with increased risk. Syphilis, gonorrhoea, sex with prostitutes and unprotected sexual intercourse may be indicators of contact with a sexually transmissible factor that increases the risk of prostate cancer.     

Medical history and the risk of multiple myeloma

The relationship between various diseases and immunisations and the risk of multiple myeloma was analysed using data from a hospital-based case-control study conducted in Northern Italy on 117 patients with multiple myeloma and 477 controls. Associations were observed for clinical history of scarlet fever (relative risk, RR = 2.0; 95% confidence interval, CI = 1.1-3.9), tuberculosis (RR = 2.3%; 95% CI = 0.9-5.7) and BCG immunisation (RR = 3.0; 95% CI = 1.4-6.4). The relative risk was 1.8 (95% CI = 0.9-3.5) for episodes of Herpes zoster infection, but most of the excess cases occurred within 10 years of diagnosis, suggesting that this might have been an early manifestation of the disease. No association emerged for common childhood viral infections or any other immunisation practice. When various classes of infectious or inflammatory diseases were grouped together according to their aetiology, there was a significant positive association with chronic bacterial illnesses (RR = 1.8; 95% CI = 1.1-2.8), and the relative risk estimates increased with the number of bacterial diseases. The trend in risk with number of diseases was significant (chi 21 = 4.5, P = 0.03). A negative association was found between allergic conditions and risk of multiple myeloma (RR = 0.6; 95% CI = 0.3-1.0).     

Adult dietary intake and prostate cancer risk in Utah: a case-control study with special emphasis on aggressive tumors

A population-based case-control study in Utah of 358 cases diagnosed with prostate cancer between 1984 and 1985, and 679 controls categorically matched by age and county of residence, were interviewed to investigate the association between dietary intake of energy (kcal), fat, protein, vitamin A, beta-carotene, vitamin C, zinc, cadmium, selenium, and prostate cancer. Dietary data were ascertained using a quantitative food-frequency questionnaire. Data were analyzed separately by age (45-67, 68-74) and by tumor aggressiveness. The most significant associations were seen for older males and aggressive tumors. Dietary fat was the strongest risk factor for these males, with an odds ratio (OR) of 2.9 (95 percent confidence interval [CI] 1.0-8.4) for total fat; OR = 2.2 (CI = 0.7-6.6) for saturated fat; OR = 3.6 (CI = 1.3-9.7) for monounsaturated fat; and OR = 2.7 (CI = 1.1-6.8) for polyunsaturated fat. Protein and carbohydrates had positive but nonsignificant associations. Energy intake had an OR of 2.5 (CI = 1.0-6.5). In these older men, no effects were seen for dietary cholesterol, body mass, or physical activity. There was little association between prostate cancer and dietary intake of zinc, cadmium, selenium, vitamin C, and beta-carotene. Total vitamin A had a slight positive association with all prostate cancer (OR = 1.6, CI = 0.9-2.4), but not with aggressive tumors. No associations were found in younger males, with the exception of physical activity which showed active males to be at an increased but nonsignificant risk for aggressive tumors (OR = 2.0, CI = 0.8-5.2) and beta-carotene which showed a nonsignificant protective effect (OR = 0.6, CI = 0.3-1.6). The findings suggest that dietary intake, especially fats, may increase risk of aggressive prostate tumors in older males.     

Meningioma and schwannoma risk in adults in relation to family history of cancer

Relatively little is known about factors that contribute to the development of meningioma and vestibular schwannoma, two intracranial nervous system tumors. We evaluated the risk of these tumors in relation to family history of malignant or benign tumors. Incident cases of meningioma (n = 197) or schwannoma (n = 96) were identified at three U. S. referral hospitals between June 1994 and August 1998. Controls (n = 799) admitted to the same hospitals for nonmalignant conditions were matched to cases on age, sex, race/ethnicity, hospital, and proximity of residence to hospital. We found that risk of meningioma was increased among persons reporting a family history of a benign brain tumor (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.0-21.0; n = 5) or melanoma (OR, 4.2; 95% CI, 1.2-15.0; n 5). A family history of breast cancer was associated with an elevated meningioma risk among participants aged 18 to 49 years (OR, 3.9; 95% CI, 1.4-11.0; n = 8) but a reduced risk among older respondents (OR, 0.2; 95% CI, 0.1-0.7; n = 3). Family history of cancer did not differ between schwannoma cases and controls, although the statistical power to detect associations was limited. Some relative risk estimates were based on a small number of observations and may have arisen by chance. Inheritance of predisposing genes, shared environmental factors, or both within families with a history of benign brain tumors, melanoma, or possibly breast cancer may be related to altered meningioma risk.     

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.     

A population-based case-control study of thyroid cancer

A population-based case-control interview study of thyroid cancer (159 cases and 285 controls) was conducted in Connecticut. Prior radiotherapy to the head or neck was reported by 12% of the cases and 4% of the controls [odds ratio (OR) = 2.8; 95% confidence interval = 1.2-6.9]. Risk was inversely related to age at irradiation and was highest among children exposed under age 10. Few persons born after 1945 received prior radiotherapy, consistent with the declining use of radiation to treat benign conditions in the 1950's. Among females the radiogenic risk appeared to be potentiated by the number of subsequent live-births. Other significant risk factors included a history of benign thyroid nodules (OR = 33) or goiter (OR = 5.6). Miscarriage and multiparity increased risk but only among women who developed thyroid cancer before age 35 years. Consumption of shellfish (a rich source of iodine) seemed to increase the risk of follicular thyroid cancer, whereas consumption of goitrogen-containing vegetables appeared to reduce risk of total thyroid cancer, possibly because of their cruciferous nature. A significantly low risk was observed among persons of English descent, whereas Italian ancestry appeared to increase risk. No significant associations were found with a number of suspected risk factors: diagnostic x-rays, radioactive isotope scans, occupational radiation exposure, tonsillectomy, Jewish ethnicity, alcohol intake, cigarette smoking, oral contraceptives, lactation suppressants, menopausal estrogens, most other common medications, and water source. New associations were suggested for obesity among females (OR = 1.5), surgically treated benign breast disease (OR = 1.6), use of spironolactone (OR = 4.3) or vitamin D supplements (OR = 1.8), and a family history of thyroid cancer (OR = 5.2). About 9% of the incident thyroid cancers could be attributed to prior head and neck irradiation, 4% to goiter, and 17% to thyroid nodular disease, leaving the etiology of most thyroid cancers yet to be explained.     

Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas

Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis coli-beta-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G(1) to S-phase cell cycle transition, promoting cell proliferation. A recently described codon 242, exon 4, G to A single nucleotide polymorphism (A870G) produces a longer half-life cyclin D1. To investigate whether CCND1 genotype influences risk for colorectal adenoma, we genotyped CCND1 by PCR/RFLP on 161 incident sporadic adenoma cases and 213 controls ages 30-74 years in a North Carolina colonoscopy-based case-control study. At least one polymorphic A allele was found in 68% of cases and 60% of controls. Having an A allele was associated with increased risk for adenoma: the age- and sex-adjusted odds ratio (OR) was 1.5 [95% confidence interval (CI) 1.0-2.4], a finding that was stronger for those whose adenomas were multiple (OR 2.9, 95% CI 1.4-6.0), larger (>or=1 cm; OR 2.4, 95% CI 1.2-4.8), had moderate to severe dysplasia (OR 2.1, 95% CI 1.1-3.8), or were in the right side of the colon (OR 3.6, 95% CI 1.3-10.0). Joint risk factor multivariate analyses revealed stronger positive associations among those who were older (>57 years; OR 2.8, 95% CI 1.4-5.5), male (OR 2.8, 95% CI 1.3-5.7), currently smoked (OR 2.7, 95% CI 1.3-5.7), or currently drank alcohol (OR 2.2, 95% CI 1.2-4.2) if they had an A allele and stronger inverse associations among those who used nonsteroidal anti-inflammatory drugs (OR 0.4, 95% CI 0.2-0.9) or had higher calcium intakes (OR 0.4, 95% CI 0.2-0.9) if they had no A allele. These data support the hypothesis that the CCND1 A870G polymorphism may increase risk for colorectal neoplasms.     

Birth order, allergies and lymphoma risk: results of the European collaborative research project Epilymph

Lymphomas are a heterogeneous group of malignancies of the immune system. Recent studies suggest that immunological conditions which are modulated by lifestyle-dependent environmental determinants might affect lymphoma risk. We used data from Epilymph, a European multi-centric case-control study with 2,480 cases and 2,540 controls, to analyse the relationship between lifestyle-dependent immunological determinants and risk of lymphomas. We found an inverse relationship between risk of lymphoma and allergies, mainly respiratory (OR=0.86, CI=0.89-1.01) and food allergies (OR=0.67, CI=0.52-0.85), a slightly elevated lymphoma risk for first-born children (OR=1.17, CI=0.99-1.39) and only children (OR=1.10, CI=0.86-1.39). The inverse relationship between atopic disorders and risk of lymphomas is consistent with earlier observations. Our findings on birth order and lymphoma increase the inconsistency of findings across studies and suggest a critical reappraisal of potential underlying mechanisms.