Biomedical subjects

James R Cerhan

Publications and source records attributed to James R Cerhan.

At least 19 recordsLinked to original sources

PubMed2006

Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph).

A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% CI = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.

Case-Control Studies↗

PubMed2006

Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies.

Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in each study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident cases of colorectal cancer were diagnosed among 702,647 participants. The authors calculated study-specific multivariate relative risks and then combined them using a random-effects model. In general, intakes of specific carotenoids were not associated with colorectal cancer risk. The pooled multivariate relative risks of colorectal cancer comparing the highest quintile of intake with the lowest ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein + zeaxanthin intake was the result borderline statistically significant (95% confidence interval: 0.84, 1.00). The associations observed were generally similar across studies, for both sexes, and for colon cancer and rectal cancer. These pooled data did not suggest that carotenoids play an important role in the etiology of colorectal cancer.

Carotenoids↗

PubMed2006

Cellular telephones and non-Hodgkin lymphoma.

Dramatic increase in hand-held cellular telephone use since the 1980s and excess risk of lymphoproliferative malignancies associated with radio-frequency radiation (RFR) exposures in epidemiological and experimental studies motivated assessment of cellular telephones within a comprehensive US case-control investigation of non-Hodgkin lymphoma (NHL). A questionnaire ascertained cellular telephone use in 551 NHL cases and 462 frequency-matched population controls. Compared to persons who had never used cellular telephones, risks were not increased among individuals whose lifetime use was fewer than 10 (odds ratio (OR) = 0.9, 95% confidence intervals (CI): 0.6, 1.3), 10-100 (OR = 1.0, 95 % CI: 0.7, 1.5) or more than 100 times (e.g., regular users, OR = 0.9, 95% CI: 0.6, 1.4). Among regular users compared to those who had never used hand-held cellular telephones, risks of NHL were not significantly associated with minutes per week, duration, cumulative lifetime or year of first use, although NHL was non-significantly higher in men who used cellular telephones for more than 8 years. Little evidence linked use of cellular telephones with total, diffuse large B-cell lymphoma or follicular NHL. These findings must be interpreted in the context of less than 5% of the population reporting duration of use of 6 or more years or lifetime cumulative use of 200 or more hours.

Adult↗

PubMed2006

Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma.

Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P(trend) = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.

Adult↗

PubMed2006

Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes.

Chromosomal translocations, insertions, and deletions are common early events in non-Hodgkin lymphoma (NHL) carcinogenesis, and implicated in their formation are endogenous processes involved in antigen-receptor diversification, such as V(D)J recombination. DNA repair genes respond to the double- and single-strand breaks induced by these processes and may influence NHL etiology. We examined 34 genetic variants in 19 genes within or related to 5 DNA repair pathways among 1172 cases and 982 matched controls who participated in a population-based NHL study in Los Angeles, Seattle, Detroit, and Iowa from 1998 to 2000. Cases were more likely than controls to have the RAG1 820 R/R (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.4 to 5.0) than Lys/Lys genotypes, with evidence of a gene dosage effect (P trend < .001), and less likely to have the LIG4 (DNA ligase IV) 9 Ile/Ile (OR = 0.5; 95% CI = 0.3 to 0.9) than T/T genotype (P trend = .03) in the nonhomologous end joining (NHEJ)/V(D)J pathway. These NHEJ/V(D)J-related gene variants represent promising candidates for further studies of NHL etiology and require replication in other studies.

DNA Repair↗

PubMed2006

Clinically confirmed type 2 diabetes mellitus and colorectal cancer risk: a population-based, retrospective cohort study.

OBJECTIVES: Patients with type 2 diabetes mellitus (DM) may be at increased colorectal cancer (CRC) risk. However, existing data are inconsistent. We investigated CRC risks, overall and by anatomic subsite, within a population-based inception cohort of clinically confirmed type 2 DM subjects. METHODS: All residents of Rochester, Minnesota who first met standardized criteria for type 2 DM from 1970 to 1994 (997 men and 978 women) were identified and followed forward in time until emigration, death, or December 31, 1999. Incident CRC cases were identified by review of inpatient and outpatient medical records. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated to compare CRC incidence within the type 2 DM inception cohort with previously published rates for the Rochester general population. RESULTS: Over 19,158 person-years of follow-up, 51 incident CRC cases were identified within the type 2 DM cohort, while only 36.8 cases were expected (SIR = 1.39, 95% CI 1.03-1.82). Among men, type 2 DM was associated with increased overall (SIR = 1.67, 95% CI 1.16-2.33) and proximal (SIR = 1.96, 95% CI 1.16-3.10) CRC risks; distal CRC risk was also increased, but the point estimate was not statistically significant (SIR = 1.43, 95% CI 0.82-2.32). Among women, type 2 DM was not a risk factor for overall, proximal, or distal CRC (SIR = 1.03, 95% CI 0.60-1.66; SIR = 1.17, 95% CI 0.58-2.09; and SIR = 0.74, 95% CI 0.24-1.72, respectively). Within the type 2 DM cohort, current and former cigarette smokers were at higher CRC risk (SIR = 1.77, 95% CI 1.24-2.47) than never smokers (SIR = 0.99, 95% CI 0.57-1.61) and the interaction between type 2 DM and cigarette smoking status was statistically significant (p= 0.05). CONCLUSIONS: In this population-based, retrospective cohort study, clinically confirmed type 2 DM was associated with increased CRC risk, predominantly among men. Cigarette smoking appeared to positively modify DM-associated CRC risk, which to our knowledge has not been previously reported. These data suggest that further investigation of potential interactions between endogenous and exogenous factors involved in colorectal carcinogenesis may help to clarify the magnitude and extent of CRC risk experienced by persons with type 2 DM.

Chi-Square Distribution↗

PubMed2006

Cyclin D1 splice variant and risk for non-Hodgkin lymphoma.

To investigate the role of cell cycle gene variations in lymphomagenesis, we evaluated associations (odds ratios [OR] and 95% confidence intervals [CI]) in polymorphisms from seven candidate genes in 1,172 non-Hodgkin lymphoma (NHL) cases and 982 population-based controls. The cyclin D1 (CCND1) splice variant G870A (rs603965) increased NHL risk (OR(AA) = 1.4, 95% CI = 1.1-1.8, P-trend = 0.021), which was consistent for four B-cell subtypes. As CCND1 expression indicates poor NHL prognosis, our results, if true, would support its potentially dual importance in NHL etiology and survival.

Adult↗

PubMed2006

Asthma history, occupational exposure to pesticides and the risk of non-Hodgkin's lymphoma.

We previously reported that, although asthma did not increase the risk of non-Hodgkin's lymphoma (NHL), the risk from pesticide exposures was higher among asthmatics than that among nonasthmatics. To further evaluate this finding, we analyzed data from a population-based case-control study of NHL conducted in Iowa, Detroit, Los Angeles and Seattle. Cases (n = 668) diagnosed with NHL from 1998 to 2000 and controls (n = 543) randomly selected from the same geographical areas as that of the cases were included in this analysis. Odds ratios (OR) for the risk of NHL from potential occupational exposure to pesticides tended to be higher among asthmatics (OR = 1.7; 95% CI 0.3-9.1) when compared with that among nonasthmatics (OR = 0.9; 95% CI 0.6-1.5). The risks of NHL associated with pesticide exposure were also higher among asthmatics who had history of hospitalization (OR = 2.1; 95% CI 0.2-29.0) or daily medication for asthma (OR = infinite) than those among asthmatics who did not have such histories. Our results support the previous finding that the risk of NHL from pesticide exposure may be greater among asthmatics.

Adult↗

PubMed2006

Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma.

Evidence supporting the contribution of oxidative stress to key pathways in cancer, such as inflammation and DNA damage, continues to mount. We investigated variations within genes mediating oxidative stress to determine whether they alter risk for non-Hodgkin lymphoma (NHL). Thirteen single nucleotide polymorphisms (SNPs) from 10 oxidative stress genes (AKR1A1, AKR1C1, CYBA, GPX, MPO, NOS2A, NOS3, OGG1, PPARG and SOD2) were genotyped in 1172 NHL cases and 982 population-based controls from a USA multicenter case-control study. For NHL and five subtypes (diffuse large B-cell, follicular, marginal zone, small lymphocytic and T-cell), SNP associations were calculated. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for sex, age (<45, 45-64, 65+ years), race (white, black, other) and study site. Overall, the oxidative stress pathway was associated significantly with the B-cell NHL subtype, diffuse large B-cell lymphoma (DLBCL) (global P-value=0.003). Specifically, for nitric oxide synthase (NOS2A Ser608Leu, rs2297518) Leu/Leu homozygotes, there was a 2-fold risk increase for NHL (OR=2.2, 95% CI=1.1-4.4) (referent=Ser/Ser and Ser/Leu). This risk increase was consistent by cell lineage (B- and T-cell NHL) and pronounced for the two most common subtypes, diffuse large B-cell (OR=3.4, 95% CI=1.5-7.8) and follicular lymphoma (OR=2.6, 95% CI=1.0-6.8). In an analysis of manganese superoxide dismutase (SOD2 Val16Ala, rs1799725) Ala/Ala homozygotes, we observed moderately increased risks for B-cell lymphomas (OR=1.3, 95% CI=1.0-1.6; referent=Val/Val and Val/Ala) that was consistent across the B-cell subtypes. Genetic variations that result in an increased generation of reactive oxygen species appear to increase risk for NHL and its major subtypes, particularly DLBCL. Independent replication of our findings are warranted and further evaluation of oxidative stress in the context of inflammation, DNA repair and the induction of the NF-kappaB pathway may further reveal important clues for lymphomagenesis.

Adult↗

PubMed2006

Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders.

PURPOSE: Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease. PATIENTS AND METHODS: Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis. RESULTS: We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P = .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004). CONCLUSION: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.

Adult↗

PubMed2006

Ultraviolet radiation, dietary vitamin D, and risk of non-Hodgkin lymphoma (United States).

OBJECTIVE: Because of conflicting findings about the relationship between ultraviolet (UV) radiation and the risk of non-Hodgkin lymphoma (NHL), we evaluated the risk of several indicators related to UV, including two not previously studied: dietary vitamin D, and ambient UV levels by residential location. METHODS: As part of a case-control study conducted in four Surveillance, Epidemiology, and End Results (SEER) registries, we collected UV information from a self-administered questionnaire and computer-assisted personal interview with 551 NHL cases and 462 controls. We estimated the relative risk (RR) and 95% confidence intervals (CI) from unconditional logistic regression models. RESULTS: Eye color, a marker of host susceptibility to UV, showed a decreasing risk gradient for lightest eyes (0.47) compared to darkest. Relative risks were in the range of 0.73-0.78 for participants reporting more hours in the mid-day summer sun. Use of sunlamps or tanning booths was associated with decreased risk (RR = 0.88), as was estimated overall ambient UV (RR = 0.76 per 50 RB-units) overall. Vitamin D intake from diet and supplements was not related to risk. Results were thus consistent for the various indicators, although some estimated risks were not statistically significant. Effects were generally similar for diffuse large B-cell (DLBCL) and follicular lymphomas. CONCLUSION: These data suggest a slight protective effect of sunlight against NHL, and they agree with geographic patterns of NHL incidence observed in the US.

Adult↗

PubMed2006

Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers.

BACKGROUND & AIMS: Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment-insulin resistance (HOMA-IR) index. To date, few studies have directly examined serum insulin as an indicator of CRC risk, and none have reported associations on the basis of HOMA-IR. METHODS: We performed a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (n=29,133). Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects. HOMA-IR was derived as fasting insulin x fasting glucose/22.5. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models. RESULTS: Median (interquartile range) values for serum insulin, glucose, and HOMA-IR were 4.1 (2.9-7.2) mIU/L, 101 (94-108) mg/dL, and 0.99 (0.69-1.98) for case subjects and 4.1 (2.7-6.1) mIU/L, 99 (93-107) mg/dL, and 1.02 (0.69-1.53) for non-case subjects, respectively. On the basis of comparison of the highest versus lowest quartiles for each biomarker, insulin (HR, 1.84; 95% CI, 1.03-3.30) and HOMA-IR (HR, 1.85; 95% CI, 1.06-3.24) were significantly associated with incident CRC, whereas glucose was marginally associated with incident CRC (HR, 1.70; 95% CI, 0.92-3.13) in age-adjusted risk models. However, trends across biomarker quartiles were somewhat inconsistent (P trend=.12, .04, and .12, respectively), and multivariable adjustment generally attenuated the observed risk estimates. CONCLUSIONS: Data from this prospective study of male smokers provide limited support for hyperinsulinemia, hyperglycemia, and/or insulin resistance as CRC risk factors.

Aged↗

PubMed2006

Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium.

BACKGROUND: Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). METHODS: We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. FINDINGS: The tumour necrosis factor (TNF) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083). INTERPRETATION: Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.

Case-Control Studies↗

PubMed2006

Vegetables, fruit, and antioxidant-related nutrients and risk of non-Hodgkin lymphoma: a National Cancer Institute-Surveillance, Epidemiology, and End Results population-based case-control study.

BACKGROUND: Factors related to DNA damage and altered immunologic responses, such as reactive oxygen species production, are associated with the risk of non-Hodgkin lymphoma (NHL). OBJECTIVE: The aim was to evaluate NHL risk with intakes of vegetables, fruit, and nutrients involved in antioxidant activities. DESIGN: Incident case subjects aged 20-74 y were identified between 1998 and 2000 from a National Cancer Institute-sponsored study by using four Surveillance, Epidemiology, and End Results registries. Control subjects, who were selected by random dialing (< 65 y) and from Medicare files (> or = 65 y), were matched to cases by age, center, race, and sex. Of 1321 case and 1057 control subjects who enrolled, dietary data were collected on a subset (466 cases and 391 controls). Carotenoid intakes were estimated by using updated values from the US Department of Agriculture nutrient databases. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs. RESULTS: NHL risk was inversely associated with higher number of weekly servings of all vegetables (multivariable OR for highest compared with lowest quartile: 0.58; 95% CI: 0.35, 0.95; P for trend = 0.04), green leafy vegetables (OR: 0.59; 95% CI: 0.36, 0.96; P for trend = 0.01), and cruciferous vegetables (OR: 0.62; 95% CI: 0.39, 1.00; P for trend = 0.05) and with higher daily intakes of lutein and zeaxanthin (OR: 0.54; 95% CI: 0.32, 0.91; P for trend = 0.06) and zinc (OR: 0.58; 95% CI: 0.36, 0.91; P for trend = 0.02). An effect modification by exercise and NHL subtype was observed with some food groups and nutrients. CONCLUSION: Higher intakes of vegetables, lutein and zeaxanthin, and zinc are associated with a lower NHL risk.

Adult↗

PubMed2006

Risk of non-Hodgkin lymphoma and nitrate and nitrite from drinking water and diet.

INTRODUCTION: Nitrate and nitrite are precursors in the in vivo formation of N-nitroso compounds, potent animal carcinogens. METHODS: We conducted a population-based case-control study of non-Hodgkin lymphoma (NHL) in 1998 to 2000 in Iowa, Detroit, Seattle, and Los Angeles. Because nitrate levels were elevated in many drinking water supplies in Iowa, but not in the other study centers, we evaluated water nitrate levels and risk of NHL in Iowa only. Monitoring data for public supplies were linked to water source histories from 1960 onward. Nitrate was measured at interview homes with private wells. We limited most analyses to those with nitrate estimates for > 70% of their person-years since 1960 (181 cases, 142 controls). For those in the diet arm of the study (458 cases, 383 controls from 4 centers) and for Iowa participants in both the diet and drinking water analyses, we estimated dietary nitrate and nitrite intake using a 117-item food-frequency questionnaire that included foods high in nitrate and nitrite. Odds ratios and 95% confidence intervals were calculated using logistic regression, adjusting for the study matching factors, education, and caloric intake (diet analyses only). RESULTS: We found no overall association with the highest quartile of average drinking water nitrate (> 2.90 mg/L nitrate-N: odds ratios = 1.2; 95% confidence interval = 0.6-2.2) or with years > or = 5 mg/L (10+ years: 1.4; 0.7-2.9). We observed no evidence of an interaction between drinking water nitrate exposure and either vitamin C or red meat intake, an inhibitor and precursor, respectively, of N-nitroso compound formation. Among those in the diet arm, dietary nitrate was inversely associated with risk of NHL (highest quartile: 0.54; 0.34-0.86). Dietary nitrite intake was associated with increasing risk (highest quartile: 3.1; 1.7-5.5) largely due to intakes of bread and cereal sources of nitrite. CONCLUSION: Average drinking water nitrate levels below 3 mg/L were not associated with NHL risk. Our study had limited power to evaluate higher levels that deserve further study.

Aged↗

PubMed2006

Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma.

Animal studies suggest that lymphomagenesis can be induced by exposure to carcinogenic aromatic and heterocyclic amines found in diet, cigarette smoke and the environment, but human epidemiologic investigations of these exogenous exposures have yielded conflicting results. As part of our evaluation of the role of aromatic and heterocyclic amines, which are metabolized by N-acetyltransferase (NAT) enzymes, in the etiology of non-Hodgkin lymphoma (NHL), we examined NHL risk in relation to genetic variation in NAT1 and NAT2 and exposure to cigarette smoke and dietary heterocyclic amines and mutagens. We genotyped 10 common single nucleotide polymorphisms (SNPs) in NAT1 and NAT2 among 1136 cases and 922 controls from a population-based case-control study in four geographical areas of the USA. Relative risk of NHL for NAT1 and NAT2 genotypes, NAT2 acetylation phenotype, and exposure to cigarette smoke and dietary heterocyclic amines and mutagens was estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from unconditional logistic regression models. We observed increased risk of NHL among individuals with the NAT1*10/*10 genotype compared with individuals with other NAT1 genotypes (OR = 1.60, 95% CI = 1.04-2.46, P = 0.03). We also observed increased NHL risk in a dose-dependent model among NAT2 intermediate- and rapid-acetylators compared with slow-acetylators, although only the trend was statistically significant (intermediate: OR = 1.18, 95% CI = 0.97-1.44, P = 0.1; rapid: OR = 1.43, 95% CI = 0.97-2.14, P = 0.07; P for linear trend = 0.03). Compared with non-smokers, NHL risk estimates for current cigarette smoking were increased only among NAT2 intermediate/rapid-acetylators (OR = 2.44, 95% CI = 1.15-5.20, P = 0.02). Our data provide evidence that NAT1 and NAT2 genotypes are associated with NHL risk and support a contributory role for carcinogenic aromatic and/or heterocyclic amines in the multi-factorial etiology of NHL.

Adult↗

PubMed2006

Metabolic gene variants and risk of non-Hodgkin's lymphoma.

Genes involved in metabolism of environmental chemical exposures exhibit sequence variability that may mediate the risk of non-Hodgkin's lymphoma. We evaluated associations between non-Hodgkin's lymphoma and 15 variants in AHR, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2E1, GSTP1, GSTM3, EPHX1, NQO1, and PON1. Cases were identified from four Surveillance, Epidemiology, and End Results registries in the United States, and population-based controls were identified through random-digit dialing and Medicare eligibility files. Metabolic gene variants were characterized for the 1,172 (89% of total) cases and 982 (93%) controls who provided biological samples for genotyping. Subjects who were heterozygous or homozygous for the cytochrome P450 gene variant CYP1B1 V432L G allele were at slightly greater risk of non-Hodgkin's lymphoma [odds ratio (OR), 1.27; 95% confidence interval (95% CI), 0.97-1.65]; these results were consistent across B-cell lymphoma subtypes and among both non-Hispanic White and Black subjects, although not statistically significant. The CYP2E1 -1054T allele was associated with decreased risk of non-Hodgkin's lymphoma (CT and TT genotypes combined OR, 0.59; 95% CI, 0.37-0.93), and this pattern was observed among all histologic subtypes. The numbers of cases of particular subtypes were rather small for stable estimates, but we noted that the PON1 L55M AA allele, associated with slightly increased risk of non-Hodgkin's lymphoma (variant homozygotes OR, 1.36; 95% CI, 0.96-1.95), was most strongly associated with follicular non-Hodgkin's lymphoma and T-cell lymphoma, with ORs for variant homozygotes of 2.12 and 2.93, respectively. There was no overall association with non-Hodgkin's lymphoma for the other gene variants we examined. The modest effects we observed may reflect the context of exposures within the general population represented in our study.

Adult↗

PubMed2006

No association between 25-hydroxyvitamin D and mammographic density.

There is increasing evidence that vitamin D may protect against breast cancer. Some studies have suggested that dietary and supplemental vitamin D is associated with reduced mammographic density, which is highly associated with breast cancer risk, although this evidence is not entirely consistent. We investigated a possible association between circulating 25-hydroxyvitamin D (25OHD), the best indicator of vitamin D status, and quantitative mammographic density in the Minnesota Breast Cancer Family Study. Mean values of mammographic density (both percent and area densities) and circulating levels of 25OHD were compared across categories of covariates using ANOVA. Models were adjusted for age and body mass index, as well as other covariates, and also stratified by dietary calcium intake, menopause, and season. Serum, mammographic density, and questionnaire data were available from 487 women [133 premenopausal and 354 postmenopausal; mean age, 56.4 years (range, 27-85 years)] without breast cancer, and for 73%, the blood was drawn within 1 year of their mammogram. No evidence was found for an association between 25OHD and either percent density or total dense area. There was also no evidence for any association when the data were stratified by season of sample (winter and summer) or menopause. However, both percent density and dense area were lowest among those in the highest vitamin D quartile with calcium intake above the median. Unlike some previous reports, vitamin D does not seem to be related to mammographic density in this cohort.

Adult↗