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Biomedical subjects

R E Tarone

Publications and source records attributed to R E Tarone.

At least 19 recordsLinked to original sources
PubMed2001

Recent trends in lung cancer mortality in the United States.

BACKGROUND: Previous age-period-cohort analyses of lung cancer incidence and mortality rates in the United States have demonstrated a decrease in risk by birth cohort through 1950, consistent with declining trends in smoking prevalence. This study was conducted to examine recent lung cancer trends, including trends among the cohorts born after 1950. METHODS: Lung cancer mortality rates from 1970 through 1997 for whites aged 24--83 years and for blacks aged 30--83 years were investigated. Using age--period--cohort analyses with 2-year age and 2-year calendar-period intervals, we examined changes in the slope of the trends in birth-cohort and calendar-period effects. All statistical tests are two-sided. RESULTS: There was an unexpected, statistically significant moderation in the rate of decrease of the birth-cohort trend in lung cancer mortality for whites born after 1950, with a corresponding smaller and statistically nonsignificant moderation for blacks. These data are consistent with smoking initiation rates: Rates of both cigarette and marijuana smoking initiation increased for children aged 12--17 years from 1965 through 1977. There was a statistically significant decrease in the slope of the calendar-period trend for lung cancer mortality in 1990 for both whites and blacks that was observed primarily in people 55 years of age and older. CONCLUSIONS AND IMPLICATIONS: The birth-cohort pattern of lung cancer mortality after 1950 appears to reflect the early impact of teenage cigarette smoking on lung cancer risk in people under the age of 45 years, although a contribution from marijuana smoking cannot be ruled out. This result provides additional support for increasing smoking cessation and prevention programs for teenagers. The calendar-period decrease in lung cancer mortality after 1990 may reflect the long-term benefits of reductions in tobacco carcinogens in cigarettes and increases in smoking cessation beginning around 1960.

Adult↗
PubMed2001

Cellular-telephone use and brain tumors.

BACKGROUND: Concern has arisen that the use of hand-held cellular telephones might cause brain tumors. If such a risk does exist, the matter would be of considerable public health importance, given the rapid increase worldwide in the use of these devices. METHODS: We examined the use of cellular telephones in a case-control study of intracranial tumors of the nervous system conducted between 1994 and 1998. We enrolled 782 patients through hospitals in Phoenix, Arizona; Boston; and Pittsburgh; 489 had histologically confirmed glioma, 197 had meningioma, and 96 had acoustic neuroma. The 799 controls were patients admitted to the same hospitals as the patients with brain tumors for a variety of nonmalignant conditions. RESULTS: As compared with never, or very rarely, having used a cellular telephone, the relative risks associated with a cumulative use of a cellular telephone for more than 100 hours were 0.9 for glioma (95 percent confidence interval, 0.5 to 1.6), 0.7 for meningioma (95 percent confidence interval, 0.3 to 1.7), 1.4 for acoustic neuroma (95 percent confidence interval, 0.6 to 3.5), and 1.0 for all types of tumors combined (95 percent confidence interval, 0.6 to 1.5). There was no evidence that the risks were higher among persons who used cellular telephones for 60 or more minutes per day or regularly for five or more years. Tumors did not occur disproportionately often on the side of head on which the telephone was typically used. CONCLUSIONS: These data do not support the hypothesis that the recent use of hand-held cellular telephones causes brain tumors, but they are not sufficient to evaluate the risks among long-term, heavy users and for potentially long induction periods.

Adult↗
PubMed2001

Static magnetic field measurements in residences in relation to resonance hypotheses of interactions between power-frequency magnetic fields and humans.

Bowman et al. used epidemiologic data to test a model in which subjects were classified as being "in-resonance" or "not-in-resonance" for 60-Hz magnetic-field exposures depending on single static magnetic-field measurements at the centers of their bedrooms. A second paper by Swanson concluded that a single static magnetic-field measurement is insufficient to meaningfully characterize a residential environment. The main objective of this study was to investigate exposure-related questions raised by these two papers in two U.S. data sets, one containing single spot measurements of static magnetic fields at two locations in homes located in eight states, and the other repeated spot measurements (seven times during the course of one year) of the static magnetic fields at the centers of bedrooms and family rooms and on the surfaces of beds in 51 single-family homes in two metropolitan areas. Using Bowman's criterion, bedrooms were first classified as being in-resonance or not-in-resonance based on the average of repeated measurements of the static magnetic field measured on the bed where the presumed important exposure actually occurred. Bedrooms were then classified a second time using single spot measurements taken at the centers of bedrooms, centers of family rooms, or on the surfaces of beds, as would be done in the typical epidemiologic study. The kappa statistics characterizing the degree of concordance between the first (on-bed averages) and second (spot measurements) methods of assessing resonance status were 0.44, 0.33, and 0.67, respectively. This level of misclassification could significantly affect the results of studies involving the determination of resonance status.

Adolescent↗
PubMed2001

Impact of age on hypermutation of immunoglobulin variable genes in humans.

Chronological aging is associated with an accumulation of DNA mutations that results in cancer formation. The effect of aging on spontaneous mutations in humans is difficult to study because mutations are infrequent in the overall genome and tumors are relatively rare. In contrast, somatic mutations in immunoglobulin variable genes are abundant and can be studied in peripheral blood lymphocytes. To determine if aging alters the frequency and pattern of hypermutation, we sequenced 331 cDNA clones with rearranged V(H)6 genes and compared 452 mutations from young humans to 570 mutations from old humans. There were more mutated clones in the young population compared to the old population. Among the mutated clones, the frequency, location, and types of substitutions were similar between the young and the old groups. However, the ratio of replacement-to-silent mutations was much higher in the complementarity-determining regions of heavy chains from old people, which indicates that their B cells had been selected by antigen. Among individuals, there was variability in the frequency of tandem mutations, which we have observed in mice defective for the PMS2 mismatch repair protein. Microsatellite variability in DNA, which is caused by impaired mismatch repair, was then measured, and there was a strong correlation between the frequency of tandem mutations and microsatellite alterations. The data suggest that individuals vary in their mismatch repair capacity, which can affect the mutational spectra in their antibodies.

Adult↗
PubMed2001

Third complementarity-determining region of mutated VH immunoglobulin genes contains shorter V, D, J, P, and N components than non-mutated genes.

The third complementarity-determining region (CDR3) of immunoglobulin variable genes for the heavy chain (VH) has been shown to be shorter in length in hypermutated antibodies than in non-hypermutated antibodies. To determine which components of CDR3 contribute to the shorter length, and if there is an effect of age on the length, we analysed 235 cDNA clones from human peripheral blood of VH6 genes rearranged to immunoglobulin M (IgM) constant genes. There was similar use of diversity (D) and joining (JH) gene segments between clones from young and old donors, and there was similar use of D segments among the mutated and non-mutated heavy chains. However, in the mutated heavy chains, there was increased use of shorter JH4 segments and decreased use of longer JH6 segments compared to the non-mutated proteins. The overall length of CDR3 did not change with age within the mutated and non-mutated categories, but was significantly shorter by three amino acids in the mutated clones compared to the non-mutated clones. Analyses of the individual components that comprise CDR3 indicated that they were all shorter in the mutated clones. Thus, there were more nucleotides deleted from the ends of VH, D, and JH gene segments, and fewer P and N nucleotides added. The results suggest that B cells bearing immunoglobulin receptors with shorter CDR3s have been selected for binding to antigen. A smaller CDR3 may allow room in the antibody binding pocket for antigen to interact with CDRs 1 and 2 as well, so that as the VDJ gene undergoes hypermutation, substitutions in all three CDRs can further contribute to the binding energy.

Adult↗
PubMed2001

Biomarker correlations of urinary 2,4-D levels in foresters: genomic instability and endocrine disruption.

Forest pesticide applicators constitute a unique pesticide use group. Aerial, mechanical-ground, and focal weed control by application of herbicides, in particular chlorophenoxy herbicides, yield diverse exposure scenarios. In the present work, we analyzed aberrations in G-banded chromosomes, reproductive hormone levels, and polymerase chain reaction-based V(D)J rearrangement frequencies in applicators whose exposures were mostly limited to chlorophenoxy herbicides. Data from appliers where chlorophenoxy use was less frequent were also examined. The biomarker outcome data were compared to urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) obtained at the time of maximum 2,4-D use. Further comparisons of outcome data were made to the total volume of herbicides applied during the entire pesticide-use season.Twenty-four applicators and 15 minimally exposed foresters (control) subjects were studied. Categorized by applicator method, men who used a hand-held, backpack sprayer in their applications showed the highest average level (453.6 ppb) of 2,4-D in urine. Serum luteinizing hormone (LH) values were correlated with urinary 2,4-D levels, but follicle-stimulating hormone and free and total testosterone were not. At the height of the application season; 6/7 backpack sprayers, 3/4 applicators who used multinozzle mechanical (boom) sprayers, 4/8 aerial applicators, and 2/5 skidder-radiarc (closed cab) appliers had two or more V(D)J region rearrangements per microgram of DNA. Only 5 of 15 minimally exposed (control) foresters had two or more rearrangements, and 3 of these 5 subjects demonstrated detectable levels of 2,4-D in the urine. Only 8/24 DNA samples obtained from the exposed group 10 months or more after their last chlorophenoxy use had two rearrangements per microgram of DNA, suggesting that the exposure-related effects observed were reversible and temporary. Although urinary 2,4-D levels were not correlated with chromosome aberration frequency, chromosome aberration frequencies were correlated with the total volume of herbicides applied, including products other than 2,4-D. In summary, herbicide applicators with high urinary levels of 2,4-D (backpack and boom spray applications) exhibited elevated LH levels. They also exhibited altered genomic stability as measured by V(D)J rearrangement frequency, which appears reversible months after peak exposure. Though highly detailed, the limited sample size warrants cautious interpretation of the data.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

Household solvent exposures and childhood acute lymphoblastic leukemia.

OBJECTIVES: This study explored the risk of childhood acute lymphoblastic leukemia (ALL) associated with participation by household members in hobbies or other home projects involving organic solvents. METHODS: Participants in this case-control study were 640 subjects with ALL and 640 matched controls. RESULTS: Childhood ALL was associated with frequent (> 4 times/month) exposure to model building (odds ratio [OR] = 1.9; 95% confidence interval [95% CI] = 0.7, 5.8) and artwork using solvents (OR = 4.1; 95% CI = 1.1, 15.1). We also found elevated risk (OR = 1.7; 95% CI = 1.1, 2.7) among children whose mothers lived in homes painted extensively (> 4 rooms) in the year before the children's birth. CONCLUSIONS: In this exploratory study, substantial participation by household members in some common household activities that involve organic solvents was associated with elevated risks of childhood ALL.

Child↗
PubMed2001

A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers.

RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 "c" allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

Adult↗
PubMed2000

The oxidative DNA lesion 8,5'-(S)-cyclo-2'-deoxyadenosine is repaired by the nucleotide excision repair pathway and blocks gene expression in mammalian cells.

Xeroderma pigmentosum (XP) patients with inherited defects in nucleotide excision repair (NER) are unable to excise from their DNA bulky photoproducts induced by UV radiation and therefore develop accelerated actinic damage, including cancer, on sun-exposed tissue. Some XP patients also develop a characteristic neurodegeneration believed to result from their inability to repair neuronal DNA damaged by endogenous metabolites since the harmful UV radiation in sunlight does not reach neurons. Free radicals, which are abundant in neurons, induce DNA lesions that, if unrepaired, might cause the XP neurodegeneration. Searching for such a lesion, we developed a synthesis for 8,5'-(S)-cyclo-2'-deoxyadenosine (cyclo-dA), a free radical-induced bulky lesion, and incorporated it into DNA to test its repair in mammalian cell extracts and living cells. Using extracts of normal and mutant Chinese hamster ovary (CHO) cells to test for NER and adult rat brain extracts to test for base excision repair, we found that cyclo-dA is repaired by NER and not by base excision repair. We measured host cell reactivation, which reflects a cell's capacity for NER, by transfecting CHO and XP cells with DNA constructs containing a single cyclo-dA or a cyclobutane thymine dimer at a specific site on the transcribed strand of a luciferase reporter gene. We found that, like the cyclobutane thymine dimer, cyclo-dA is a strong block to gene expression in CHO and human cells. Cyclo-dA was repaired extremely poorly in NER-deficient CHO cells and in cells from patients in XP complementation group A with neurodegeneration. Based on these findings, we propose that cyclo-dA is a candidate for an endogenous DNA lesion that might contribute to neurodegeneration in XP.

Adult↗
PubMed2000

Extremely low-frequency magnetic fields and childhood acute lymphoblastic leukemia: an exploratory analysis of alternative exposure metrics.

Data collected by the National Cancer Institute-Children's Cancer Group were utilized to explore various metrics of magnetic field levels and risk of acute lymphoblastic leukemia (ALL) in children. Cases were aged 0-14 years, were diagnosed with ALL during 1989-1993, were registered with the Children's Cancer Group, and resided in one home for at least 70 percent of the 5 years immediately prior to diagnosis. Controls were identified by using random digit dialing and met the same residential requirements. With 30-second ("spot") measurements and components of the 24-hour measurement obtained in the subject's bedroom, metrics evaluated included measures of central tendency, peak exposures, threshold values, and measures of short-term temporal variability. Measures of central tendency and the threshold measures showed good-to-high correlation, but these metrics correlated less well with the others. Small increases in risk (ranging from 1.02 to 1.69 for subjects in the highest exposure category) were associated with some measures of central tendency, but peak exposures, threshold values, measures of short-term variability, and spot measurements demonstrated little association with risk of childhood ALL. In general, risk estimates were slightly higher for the nighttime (10 p.m.-6 a.m.) interval than for the corresponding 24-hour period.

Adolescent↗
PubMed2000

Alternate ranging methods for cancer mortality maps.

BACKGROUND: Mapping techniques can highlight the spatial or temporal variations in rates of cancer mortality. In mapping geographic patterns of cancer mortality, spatial units are grouped into categories defined by specified rate ranges, and then the units in each category are assigned a particular color in the map. We examined the consequences of using different ranging methods when comparing maps over several time intervals. METHODS: Maps of mortality rates for cancers of the breast, lung (including the lung, trachea, bronchus, and pleura), and cervix uteri in the United States by county or state economic area are created for different time intervals between 1950 and 1994. Two ranging methods are employed: 1) Ranges are defined for individual time interval by the deciles of rates in that interval (ranging within intervals), and 2) constant ranges for all time intervals are defined by the deciles of rates for the entire 45-year period from 1950 through 1994 (ranging across intervals). The time intervals from 1950 through 1969 and from 1970 through 1994 were chosen to accommodate the availability of detailed county-level population estimates specifically for blacks starting in 1970. RESULTS: The ranging method has little impact on maps for breast cancer mortality, which changed little over time. For lung cancer, which increased over time, and cervix uteri cancer, which decreased over time, ranging within time intervals shows the geographic variability but does not convey the temporal trends. Trends are evident when ranging across time intervals is employed; however, geographic variability is partially obscured by the predominance of spatial units in the highest rate categories in the recent time intervals for lung cancer and in the early time intervals for cervix uteri cancer. CONCLUSIONS: Ranging within time intervals displays geographic patterns and changes in geographic patterns, regardless of time trends in rates. Ranging across time intervals shows temporal changes in rates but with some loss of information about geographic variability.

Breast Neoplasms↗
PubMed2000

Are children living near high-voltage power lines at increased risk of acute lymphoblastic leukemia?

In the National Cancer Institute/Children's Cancer Group case-control study of childhood acute lymphoblastic leukemia (1989-1993), living in a home with a high-voltage wire code was not associated with disease risk. To further investigate risk near power lines, the authors analyzed distance to transmission and three-phase primary distribution lines within 40 m of homes and created an exposure index of distance and strength of multiple power lines (408 case-control pairs). Neither distance nor exposure index was related to risk of childhood acute lymphoblastic leukemia, although both were associated with in-home magnetic field measurements. Residence near high-voltage lines did not increase risk.

Adolescent↗
PubMed2000

Children's exposure to magnetic fields produced by U.S. television sets used for viewing programs and playing video games.

Two epidemiologic studies have reported increased risk of childhood leukemia associated with the length of time children watched television (TV) programs or played video games connected to TV sets. To evaluate magnetic field exposures resulting from these activities, the static, ELF, and VLF magnetic fields produced by 72 TV sets used by children to watch TV programs and 34 TV sets used to play video games were characterized in a field study conducted in Washington DC and its Maryland suburbs. The resulting TV-specific magnetic field data were combined with information collected through questionnaires to estimate the magnetic field exposure levels associated with TV watching and video game playing. The geometric means of the ELF and VLF exposure levels so calculated were 0.0091 and 0.0016 microT, respectively, for children watching TV programs and 0.023 and 0.0038 microT, respectively, for children playing video games. Geometric means of ambient ELF and VLF levels with TV sets turned off were 0.10 and 0.0027 microT, respectively. Summed over the ELF frequency range (6-3066 Hz), the exposure levels were small compared to ambient levels. However, in restricted ELF frequency ranges (120 Hz and 606-3066 Hz) and in the VLF band, TV exposure levels were comparable to or larger than normal ambient levels. Even so, the strengths of the 120 Hz or 606-3066 Hz components of TV fields were small relative to the overall ambient levels. Consequently, our results provide little support for a linkage between childhood leukemia and exposure to the ELF magnetic fields produced by TV sets. Our results do suggest that any future research on possible health effects of magnetic fields from television sets might focus on the VLF electric and magnetic fields produced by TV sets because of their enhanced ability relative to ELF fields to induce electric currents.

Adolescent↗
PubMed2000

Increased lymphocyte replicative index following 2,4-dichlorophenoxyacetic acid herbicide exposure.

OBJECTIVE: Evaluate peripheral blood lymphocyte proliferation (replicative index:RI) and micronuclei frequency (MF) among 2,4-D herbicide applicators. METHODS: Twelve applicators spraying only 2,4-D provided a blood and urine specimen upon enrollment, several urine samples during the spraying season, and a blood specimen at the study's end. Nine controls provided blood and urine specimens upon enrollment and at the study's end. Gas chromatography/tandem mass spectroscopy determined urinary 2,4-D levels and standard in-vitro assays determined RI and MF scores. Applicator RI and MF were compared before and after spraying and with controls. RESULTS: Applicators contributed 45 urine specimens with concentrations ranging from 1.0 to 1700 (microg 2,4-D/g creatinine/L urine) that logarithmically (In) increased as spraying time increased. Applicator RI increased after spraying (p = 0.016), independent of tobacco and alcohol use, and demonstrated a weak dose-response with increasing urinary 2,4-D levels (p = 0.15). Among 2,4-D applicators, pre-exposure complete blood counts and lymphocyte immunophenotypes were not significantly different from post-exposure measurements. CONCLUSION: Urinary 2,4-D concentration, an exposure biomarker, may be associated with lymphocyte replicative index, a cell proliferation biomarker.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2000

Chromosome analysis of workers occupationally exposed to radiation at the Sellafield nuclear facility.

PURPOSE: To investigate the relationship between stable chromosome aberration frequency in peripheral blood lymphocytes and occupational cumulative radiation exposure. MATERIALS AND METHODS: Cytogenetic analysis using G-banding was performed on peripheral blood lymphocyte cultures from 104 workers from the British Nuclear Fuels PLC facility at Sellafield, UK. The study group comprised 61 men with lifetime cumulative doses > 500 mSv, 39 men with minimal exposure (i.e. < 50 mSv) who formed a control group and 4 men with intermediate doses. RESULTS: The slope of the dose-response, adjusted for smoking status, for translocations and insertions was 0.55+/-0.31 x 10(-2)/cell/Sv. Consideration of chromosome breakpoints for all aberrations combined in the radiation workers revealed an excess in the C group chromosomes and a deficit in the F group chromosomes with breakpoints being concentrated in the terminal regions whereas the distribution in the control group did not deviate from expectation. CONCLUSIONS: The dose-response was not significantly different from the parallel FISH analysis (Tucker et al. 1997) and confirms that chronic radiation exposure appears to be substantially less effective at inducing stable chromosome aberrations in comparison with acute exposure.

Adult↗
PubMed2000

A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism.

We found a common biallelic polymorphism (PAT) in the xeroderma pigmentosum complementation group C (XPC) DNA repair gene consisting of an insertion of 83 bases of A and T [poly(AT)] and a 5 base deletion within intron 9. We developed a PCR assay to resolve the XPC PAT+ and PAT- alleles and found that the PAT+ allele frequency was 0.44 in 156 cancer-free donors from the Johns Hopkins School of Public Health, 0.41 in 263 cancer-free donors from the Baltimore Longitudinal Study of Aging and 0.36 in samples from 216 unselected donors from NIH. We also found a single nucleotide polymorphism in exon 15 of the XPC gene (A2920C, Lys939-->Gln) that creates a new enzyme restriction site. This XPC exon 15 single nucleotide polymorphism occurred at a frequency of 0.38 in 98 NIH donors and is in linkage disequilibrium with the PAT locus. We developed an allele-specific complementation assay utilizing post-UV host cell reactivation to assess DNA repair capacity of polymorphic alleles. We found similar DNA repair with XPC 2920A and XPC 2920C. These common polymorphisms in the XPC DNA repair gene may be useful for molecular epidemiological studies of cancer susceptibility.

Adolescent↗
PubMed2000

Implications of stage-specific survival rates in assessing recent declines in prostate cancer mortality rates.

It has been noted that the most important evidence for a benefit of early detection of prostate cancer using prostate-specific antigen (PSA) testing would be a decline in prostate cancer mortality rates to levels below those existing before diagnostic use of PSA testing. We document a decrease in U.S. prostate cancer mortality rates in white men less than 85 years of age to levels below those existing in 1986, the year use of PSA testing was approved. In fact, for men 60-79 years of age, prostate cancer mortality rates were lower in 1997 than in any year since 1950. Although it has been argued that the decrease in prostate cancer mortality rates began too soon to be explained by PSA testing, stage-specific survival rates indicate that a rapid decrease in mortality may be explained by the large number of high-grade prostate cancers detected before metastasis. If recent decreases in U.S. prostate cancer mortality rates are due to early detection using PSA testing, randomized clinical trials investigating PSA testing will show early evidence of a mortality benefit.

Age Distribution↗