Biomedical subjects

Wendy Cozen

Publications and source records attributed to Wendy Cozen.

At least 19 recordsLinked to original sources

PubMed2007

Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER case-control study.

We previously reported a lower risk of non-Hodgkin lymphoma (NHL) associated with high consumption of vitamin B6 and methionine, dietary determinants of one-carbon metabolism. Evidence has linked genetic variants involved in one-carbon metabolism to NHL. We investigated 30 polymorphisms in 18 genes for their main effect on NHL among 1141 incident cases and 949 population-based controls and examined gene-nutrient interactions in a subgroup of 386 cases and 319 controls who provided detailed food-frequency information. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for age, sex, and race. We observed a decreased risk of NHL over-all with BHMTEx8+453A>T and increased risk with CBS Ex13+41C>T, FPGS Ex15-263T>C, and SHMT1 Ex12+138C>T and Ex12+236C>T. Furthermore, significant gene-nutrient interactions limited the protective association comparing high versus low vitamin B6 to FPGS Ex15-263T>C CC (OR = 0.22; 95% CL = 0.10-0.52), MTHFS IVS2-1411T>G TT/TG (OR = 0.54; 95% CI = 0.36-0.81), and MTR Ex26-20A>G AA (OR = 0.55; 95% CI = 0.35-0.86) genotypes, and the protective association of methionine to FTHFD Ex10-40G>TGG (OR = 0.63; 95% CI = 0.44-0.91), MTHFR Ex8-62A>C CC (OR = 0.13; 95% CI = 0.04-0.39), and MTRR Ex5+136T>CTT (OR = 0.67; 95% CI = 0.47-0.97) genotypes. Warranting replication, our finding of gene-nutrient interactions in one-carbon metabolism supports their etiologic involvement in lymphomagenesis.

Adult↗

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

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

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

Polymorphism of Xeroderma Pigmentosum group G and the risk of lung cancer and squamous cell carcinomas of the oropharynx, larynx and esophagus.

We investigated the effects of XPG His1104Asp polymorphism (rs17655) on the risk of lung cancer and squamous cell carcinomas of the oropharynx, larynx and esophagus (SCCOLE). This population-based case-control study involves 611 new cases of lung cancer, 601 new cases of oropharyngeal, laryngeal and esophageal cancers, and 1,040 cancer-free controls. The XPG polymorphism was assayed by PCR-RFLP method for 497 lung cancer cases, 443 cases of oropharyngeal, laryngeal and esophageal cancers and 912 controls. Binary and polytomous unconditional logistic regression models were fitted to assess the main effects and the effect modifications between the polymorphism and environmental exposures. With the adjustment for potential confounders, the XPG Asp1104Asp genotype was inversely associated with lung cancer (odds ratio [OR] = 0.62, 95% confidence limits [CL] = 0.38, 1.0) and SCCOLE (OR = 0.47, 95% CL = 0.27, 0.82), with the combined His1104His and His1104Asp genotypes as the referent. With subjects having genotype Asp1104Asp and no tobacco smoking exposure as the common referent, the ORs on lung cancer were 13 (95% CL = 4.4, 37) for heavy tobacco smoking (>20 pack-years), 1.9 (95% CL = 0.78, 4.5) for having at least one copy of 1104His, and 23 (95% CL = 9.5, 56) for the joint effect, respectively. Compared to non-smokers with the Asp1104Asp genotype, the adjusted OR on SCCOLE for heavy smokers (>20 pack-years) having at least one copy of 1104His was 8.0 (95% CL = 2.7, 24). Similarly, compared to non-drinkers with the Asp1104Asp genotype, the adjusted OR on SCCOLE for heavy drinkers (> or =3 drinks/day) with at least one copy of 1104His was 10 (95% CL = 2.7, 38). In conclusion, our study suggests that the XPG Asp1104Asp genotype may be associated with decreased susceptibility to lung cancer and SCCOLE.

Adenocarcinoma↗

PubMed2006

Differential twin concordance for multiple sclerosis by latitude of birthplace.

OBJECTIVE: To address the inconsistency in the reported concordance of multiple sclerosis (MS) among twins by zygosity, sex, and latitude. METHODS: Four hundred eighteen medically documented monozygotic (MZ) and 380 same-sex dizygotic (DZ) pairs were ascertained from 1980 to 1992 and followed. The study population was representative of twins with multiple sclerosis. Twins from Canada and adjacent US states (at or above 41-42 degrees N) were considered "northern," and ancestry was dichotomized from descent from high-risk populations. Diagnosis before median age 29.3 years was considered "early." RESULTS: The MZ/DZ concordance ratio was 2.9 (95% confidence interval [CI], 1.0-8.9) among men and 2.6 (95% CI, 1.5-4.5) among women. The average age at northern diagnosis was independent of ancestry and 2 years earlier for both MZ (p < 0.02) and DZ (p < 0.01) patients. Among DZ twins, concordance was independent of all characteristics. Among MZ twins, concordance was 1.9 times (95% CI, 1.2-3.2) greater among northern twins, 1.9 (95% CI, 1.1-3.6) times greater among twins with high-risk ancestry, and 2.1 (95% CI, 1.2-3.6) times greater if diagnosis was early. Ancestry and early diagnosis made independent significant contributions to the differential concordance by latitude. INTERPRETATION: Multiple sclerosis is similarly heritable by sex, and the apparent variation in MZ concordance by latitude is influenced by environmental and genetic factors.

Adult↗

PubMed2006

Risk patterns of multiple myeloma in Los Angeles County, 1972-1999 (United States).

OBJECTIVE: To describe the risk patterns of multiple myeloma in Los Angeles County (LAC). METHODS: Incident multiple myeloma cases diagnosed from 1972 to 1999 were ascertained by the population-based cancer registry for LAC. Average annual age-specific and age-adjusted incidence rates (AAIR), standardized to the 2000 US census age distribution, were calculated using age-, race-, sex- and socioeconomic status (SES)-specific denominators estimated for all years from US census data for 1970, 1980 and 1990. Odds ratios (ORs) for risk by birthplace and religion were estimated using multivariate logistic regression, comparing multiple myeloma patients with other cancer patients. RESULTS: All groups experienced increasing incidence with age; African-Americans experienced the steepest increase which began a decade earlier compared to other groups. Overall incidence rates were 50% higher among males (n = 4,692) than females (n = 4,343) (p < 0.05). AAIRs were highest for African-Americans, followed by Spanish-surnamed whites (SSW), non-Spanish-surnamed whites (NSSW), Filipinos and other Asian groups. Among African-Americans, incidence rates increased with increasing SES. US-born SSW had 14% lower risk compared to non-US born SSW (OR = 0.86, 95% confidence interval [CI] = 0.74-0.99]. Jews had an 11% higher risk compared to Protestants (OR = 1.11; 95% CI = 0.99-1.24). CONCLUSION: Risk patterns suggest a role for both environmental and genetic factors.

Adolescent↗

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

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

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

Residential insecticide use and risk of non-Hodgkin's lymphoma.

Previous studies have linked non-Hodgkin's lymphoma (NHL) with occupational exposure to insecticides, but residential use is largely unexplored. In this population-based case-control study, we examined NHL risk and use of insecticides in the home and garden. We identified NHL cases, uninfected with HIV, diagnosed between 1998 and 2000 among women and men ages 20 to 74 years in Iowa and the metropolitan areas of Los Angeles, Detroit, and Seattle. Controls were selected using random digit dialing or Medicare files. Computer-assisted personal interviews (1,321 cases and 1,057 controls) elicited data on insecticide use at each home occupied since 1970. Insecticide levels were measured in dust taken from used vacuum cleaner bags (682 cases and 513 controls). We previously reported a positive association with dichlorodiphenyldichloroethylene levels in carpet dust residues. Here, we focus on insecticides that were commonly used after 1970, the time period covered by our questionnaire. People whose homes were treated for termites had elevated NHL risk (odds ratio, 1.3; 95% confidence interval, 1.0-1.6). Risk was modestly, although not significantly, elevated in all but one study center and in all sexes and races. The elevation in risk was restricted to people whose homes were treated before the 1988 chlordane ban. There was a significant trend of increasing risk with increasing levels of alpha-chlordane residues in dust (P(trend) = 0.04) and a marginally significant trend for gamma-chlordane (P(trend) = 0.06). We found no evidence of associations for insects overall, for specific types of insects other than termites, or for elevated residues of other insecticides. We concluded that chlordane treatment of homes for termites may increase residents' NHL risk.

Adult↗

PubMed2006

Gender differences in determinants of smoking initiation and persistence in California twins.

OBJECTIVE: To determine the effects of genetic versus environmental influences on smoking initiation (SI) and smoking persistence (SP). METHODS: Native California twins (32,359 pairs), who completed a questionnaire in 1992 or 1998 to 2001, were studied. Standard epidemiologic and genetic analyses were conducted using multiple logistic regression and biometric models to determine factors related to smoking phenotype. RESULTS: The strongest influence on SI was having a co-twin who ever smoked; the adjusted odds ratio was 9.7 [95% confidence limits (CL), 8.8-10.6] among monozygotic twins and 5.7 (95% CL, 5.2-6.2) among dizygotic like-sex pairs. The risk of SP was also increased if the co-twin currently smoked [adjusted odds ratios, 3.5 (95% CL, 3.0-4.1) for monozygotic twins and 2.3 (95% CL, 2.0-2.7) for like-sex dizygotic pairs]. The proportions of variance due to genetic effects, shared environment, and individual environment for SI were 31.6% (24.2-39.1), 47.5% (41.1-53.7), and 20.9% (18.8-23.1) for females, and 71.2% (66.7-75.4), 12.0% (8.7-15.7), and 16.7% (15.0-18.7) for males. For SP, estimates were identical by gender: 54.6% (43.6-65.5), 8.6% (0-17.1), and 36.8% (32.9-40.9). Modification of SI by closeness between twins was found, but little difference was seen for SP by closeness, birth cohort, or age. CONCLUSIONS: Gender differences in the pattern of genetic and environmental determinants of SI indicate that gender-specific approaches may be needed for smoking prevention efforts. Modification of genetic effects by closeness between twins and birth cohort suggests that environmental interventions could reduce a heritable propensity to smoke. However, the apparently heritable tendency to continue smoking is unaffected by gender, age, birth cohort, or closeness between twins.

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↗