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Biomedical subjects

R E Tarone

Publications and source records attributed to R E Tarone.

At least 73 records · Page 4Linked to original sources
PubMed1996

Pesticide appliers with mixed pesticide exposure: G-banded analysis and possible relationship to non-Hodgkin's lymphoma.

To further investigate the possible relationships between agricultural pesticide exposure and the increased risk of non-Hodgkin's Lymphoma among farm workers in the north central United States, we performed G-banded chromosome analyses of peripheral blood from workers classified according to primary types of pesticide exposure: herbicides (n = 20), insecticides (n = 18), fumigants (n = 23), and occupationally unexposed controls (n = 33). Significantly increased rearrangement frequencies were demonstrated in fumigant and insecticide appliers compared to control subjects. At certain chromosome bands there were significant excesses of breaks observed in pesticide appliers, but no breaks were observed in controls. Some of these bands contained genes with potential implications for cancer risk, including oncogenes and genes involved in tumor suppression and apoptosis. Of particular interest with regard to lymphoma risk were the excess rearrangement and breaks involving band 14q32 in fumigant appliers and the excess breaks involving band 18q21 in herbicide appliers; translocations linking 14q32 and 18q21 are the most common rearrangements observed in non-Hodgkin's lymphoma patients. The potential pathobiological relevance of these cytogenetic events warrants additional investigation at the molecular level.

Agricultural Workers' Diseases↗
PubMed1995

The excess of patients with advanced breast cancer in young women screened with mammography in the Canadian National Breast Screening Study.

BACKGROUND: An unexpected excess of patients with breast cancer with four or more positive lymph nodes was observed in mammographically screened women who were younger than the age of 50 years at enrollment into the Canadian National Breast Screening Study (NBSS). It has been suggested that this excess is consistent with prior screening trials evaluating mammography. METHODS: A quantitative evaluation of the distribution of patients with breast cancer with four or more positive lymph nodes in the NBSS was undertaken, and the percentages of patients with breast cancer who were at an advanced state at diagnosis in the NBSS and in previous randomized screening trials were compared. The validity of mortality analyses after eliminating advanced cases detected by physical examination at the initial screening visit is examined. RESULTS: The excess of patients with cancer with four or more positive lymph nodes in the 40-49-year mammography age group of the NBSS was statistically significant, even when expressed as a percentage of all invasive cancers diagnosed. Such an excess is inconsistent with published data on extent of disease at diagnosis from previous studies. Analysis of NBSS mortality data after eliminating advanced cases detected by physical examination at the initial visit should result in minimal, if any, bias. CONCLUSIONS: Mortality analyses eliminating advanced cases detected by physical examination at the initial screening visit may be less susceptible to bias caused by possible nonrandom allocation of study participants and should be considered in future evaluations of the NBSS cohort after longer follow-up periods and in meta-analyses that may include the NBSS in assessments of the efficacy of mammography.

Adult↗
PubMed1995

Recent cancer trends in the United States.

BACKGROUND: Cancer incidence rates have been reported to be increasing in the United States, although trends vary according to form of cancer. PURPOSE: We identify the cancers accounting for the rising incidence, quantify the changes that have occurred from the mid-1970s to the early 1990s, and contrast incidence and mortality trends to provide clues to the determinants of the temporal patterns. METHODS: Sex-, race-, and age-specific and age-adjusted incidence rates for the 5-year periods 1987-1991 versus 1975-1979 were calculated for 28 cancers among men and 30 cancers among women using data from the Surveillance, Epidemiology, and End Results (SEER) Program of cancer registration covering about 10% of the U.S. population. Similar rates were computed using national mortality data. Cancers were ranked according to the change in incidence rates over the two periods. RESULTS: Age-adjusted incidence rates for all cancers combined increased by 18.6% among males and 12.4% among females from 1975-1979 to 1987-1991, due largely to rising rates for prostate cancer among men and for breast and lung cancers among women. National mortality rates for all cancers combined rose less steeply, 3% and 6% among men and women, respectively, driven mostly by continuing increases in lung cancer mortality, while death rates for the majority of the cancers were steady or declining. Total cancer incidence rose at all ages, but with different tumors responsible for the increases at different ages: leukemia and brain/nervous system cancer among children; testicular cancer, nonmelanoma skin cancer (largely Kaposi's sarcoma), non-Hodgkin's lymphoma, and melanoma among young and middle-aged adults; and prostate, breast, and lung cancers among older individuals. In contrast, mortality rates for all cancers combined declined among both males and females under age 55 years, increasing only among older persons. CONCLUSIONS: Trends in cancer incidence and mortality differ. For most cancers, incidence rates are rising, while mortality rates are generally stable or declining. IMPLICATIONS: Much of the recent increase in cancer incidence can be explained by known factors. Improved detection appears to account for most of the increases in breast cancer among women and prostate cancer among men. On the other hand, cigarette smoking is the major determinant of the rise in lung cancer among women, acquired immunodeficiency syndrome has led to increases in non-Hodgkin's lymphoma and Kaposi's sarcoma among young and middle-aged men, and sunlight exposure patterns have affected the trends in melanoma. Some trends remain unexplained, however, and may reflect changing exposures to carcinogens yet to be identified and clarified.

Age Distribution↗
PubMed1995

Colorectal cancer trends by race and anatomic subsites, 1975 to 1991.

OBJECTIVES: To determine whether colorectal cancer rates among black men and women show the abrupt declines seen in whites since the mid-1980s and to determine how the cancer trends vary by anatomic subsites. DATA SOURCES: Mortality data from the National Center for Health Statistics, Hyattsville, Md, and incidence and survival data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, Bethesda, Md. MAIN OUTCOME MEASURES: Trends in incidence, survival, and mortality rates. RESULTS: For white men and women, cancer incidence rates declined for the right colon, left colon, and rectum after 1985. Stage-specific incidence rates for white men and women for each subsite had generally similar patterns. Distant-disease incidence rates declined beginning in the late 1970s, whereas regional-disease rates increased until the early to mid-1980s and then declined. An exception is the right colon in men, for which the incidence rates of distant disease did not decline, although the regional-disease pattern was similar to other sites. For blacks, colorectal cancer incidence rates changed little in the 1980s for men or women. In particular, there were no significant declines in the cancer incidence rates of the colorectum or of subsites after 1985. Black colorectal cancer mortality trends showed gender and age differences. Black men had significantly increasing colorectal cancer mortality rates from 1975 through 1992, but the increase after 1985 was observed only in men 65 years of age and older. The colorectal cancer mortality rates did not increase overall in black women in the 1980s, but the mortality rates increased slightly in women 65 years of age and older while declining in women younger than 65 years. CONCLUSIONS: For whites, the trends in colorectal cancer rates by anatomic subsite support the contention that early-detection procedures, such as sigmoidoscopy and colonoscopy, are contributing to the declines in incidence and mortality rates since 1985. The absence in blacks of significant declines in colorectal incidence or mortality rates since 1985 suggests the need for a greater emphasis on early-detection programs in the black community, particularly for elderly blacks.

Black People↗
PubMed1995

On the association between canine malignant lymphoma and opportunity for exposure to 2,4-dichlorophenoxyacetic acid.

In response to criticisms raised regarding a case-control study of canine malignant lymphoma, the results of several ancillary analyses are reported. The case-control study demonstrated a significant association between risk for canine malignant lymphoma and the opportunity for exposure to 2,4-dichlorophenoxyacetic acid herbicides. It is demonstrated that risk estimates do not vary by type of control group (i.e., tumor control or nontumor control group), by method of response (i.e., self-administered or telephone interview), or by geographic area. Questions related to the potential for referral bias, supposed inconsistencies in subject responses regarding frequency of herbicide use, and ambiguities regarding exposure classification are also examined.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1995

G2 phase repair of X-ray-induced chromosomal DNA damage in trichothiodystrophy cells.

The repair of X-ray-induced DNA damage during G2 cell-cycle phase has been examined in lines of skin fibroblasts from three patients with trichothiodystrophy (TTD), one with apparently normal and two with defective nucleotide excision repair (NER). These responses are compared with those of five lines from clinically normal controls, lines from xeroderma pigmentosum (XP), Cockayne syndrome (CS), Down syndrome (DS), and ataxia telangiectasia (AT) patients. Chromosomal DNA repair was measured as the chromatid aberration frequency (CAF) or total number of chromatid breaks and long gaps per 100 metaphase cells, determined 0.5-1.5 h after X-irradiation (53 rad). Chromatid breaks and gaps (as defined herein) represent unrepaired DNA strand breaks. Only one of the TTD lines, TTD 1BR, showed an abnormally high CAF. This line was shown subsequently to be of a different complementation group, representing a new nucleotide excision repair gene. An abnormally high CAF was also observed, as reported previously, in XP-C, AT and DS but not in CS skin fibroblasts. In addition, cell lines were examined for DNA incision activity by an indirect method in which chromatid aberrations were enumerated with or without ara-C, an inhibitor of repair synthesis, added after X-irradiation. All TTD lines had abnormally low incision activity.

Abnormalities, Multiple↗
PubMed1995

A cohort study of the effects of Vietnam service on testicular pathology of U.S. military working dogs.

Using histopathologic diagnoses made on necropsy material from 3,024 military working dogs (MWDs) who died from 1968 to 1973, we analyzed the effect of military service in the Republic of Vietnam on testicular pathology. Among 1,048 MWDs that died in Vietnam and had no reported developmental risk factors for testicular disease, significant excesses of testicular hemorrhage, epididymitis/orchitis, sperm granuloma, testicular degeneration, and seminoma were evident. Among 126 MWDs with prior Vietnam service who died at other duty stations outside Vietnam from 1968 to 1973, significant excesses of testicular degeneration and seminoma were likewise evident. Among 136 MWDs with prior Vietnam service that later died from 1974 to 1980, seminoma continued to be diagnosed in significant excess. In each instance, the odds ratio for the association between Vietnam service and seminoma was 2.0 or greater. Analysis of ever service by Corps Tactical Zones showed significant excesses of seminoma with each Corps area of service compared to Vietnam-era MWDs, but risk was highest in I Corps, particularly at Da Nang Port and Da Nang Air Base. This finding with respect to I Corps is consistent with certain human studies in Vietnam veterans and points to the need for further investigation of possible environmental exposures, particularly those associated to a greater extent with service in I Corps.

Animals↗
PubMed1994

Temporal patterns in colorectal cancer incidence, survival, and mortality from 1950 through 1990.

BACKGROUND: Colorectal cancer mortality rates among U.S. white males remained relatively constant from 1950 through 1984 but declined sharply from 1985 through 1990. Those for U.S. white females decreased consistently from 1950 through 1984, with an acceleration of the decline from 1985 through 1990. PURPOSE: A study was planned to investigate patterns in incidence, survival, and mortality rates over time in order to examine possible reasons for the gender difference in mortality trends and for the decrease in the slope of the mortality trends for both males and females in the late 1980s. METHODS: Incidence and survival data from the Connecticut Cancer Registry were examined to investigate the gender differences in mortality rates from 1950 through 1984. Incidence and survival data from the Surveillance, Epidemiology, and End Results (SEER) Program were investigated to examine reasons for the abrupt downturn in mortality rates for both white males and white females beginning around 1985. RESULTS: During the period 1950 through 1984, the colorectal cancer incidence rates in Connecticut increased for males and declined slightly for females. Survival rates were similar for both sexes, increasing on average over 1% per year for both females and males from 1950 through 1984. Examination of SEER data from 1975 through 1990 revealed that for both males and females there were 1) declines in overall incidence and mortality rates beginning in the mid-1980s, 2) steady declines in distant disease incidence rates since 1975, 3) increases in regional disease incidence rates until the early 1980s followed by declines in the late 1980s, and 4) increases in local disease incidence rates until the mid-1980s followed by declines in the late 1980s. Age-period-cohort analyses of mortality rates indicated a statistically significant moderation of colorectal cancer risk with both advancing birth cohorts and recent calendar periods. CONCLUSIONS: The gender differences in colorectal cancer mortality rate trends observed from 1950 through 1984 are due to differences in incidence rate trends between males and females. Declining colorectal mortality rates in the late 1980s for males and females appear to reflect improved early detection. The peaking and subsequent decline of stage-specific incidence rates at later years for successively lower stage indicate sequential stage shifts as cancers are detected increasingly earlier over time. The increased use of sigmoidoscopy and fecal occult blood tests (triggering colonoscopy) appears to have played an important role in reducing colorectal cancer mortality. Improvements in birth cohort trends in risk for colorectal cancer for each sex suggest that lifestyle changes may have also contributed to the steady reductions in colorectal cancer mortality.

Adult↗
PubMed1994

Involution and the etiology of breast cancer.

Because of the recognized relationship between aging and the development of cancer, the authors have proposed that the rate and extent of involution may be important factors in the etiology of breast cancer. They further have examined existing epidemiologic and histopathologic data to evaluate the possible association between abnormal involution and breast cancer risk. Evidence for the association is largely circumstantial, because studies have not been designed specifically to evaluate the relationship between the process of involution and breast cancer. Until studies are performed to compare histopathologically the extent of involution in breast cancer patients and age-matched controls, the role of involution in the etiology of breast cancer will remain uncertain.

Adult↗
PubMed1994

Association of deficient DNA repair during G2 phase with progression from benign to malignant state in a line of human skin keratinocytes transfected with ras oncogene.

Human skin keratinocytes after malignant neoplastic transformation by infection with Kirsten murine sarcoma virus (KiMSV) or transfection with pSV2 ras (containing an activated c-Ha-ras oncogene) showed a DNA repair deficiency(ies). The repair deficiency was manifest as an abnormally high frequency of chromatid breaks and gaps persisting after X-ray-induced DNA damage inflicted during the G2 phase of the cell cycle. Non-tumorigenic control cells at that time were clearly repair-efficient. By analyzing benign and malignant tumorigenic HaCaT-ras clones, we could exclude ras p21 oncoprotein expression as the causal mechanism for repair deficiency, since both clone types expressed similar levels of the mutated protein and only the malignant tumorigenic cells showed repair deficiency. The results suggest that mutated p21 ras provided the human keratinocytes with a growth advantage in vivo (benign tumor growth), but acquisition of repair deficiency is required for progression from benign to malignant state.

Animals↗
PubMed1994

A potential laboratory test for dysplastic nevus syndrome: ultraviolet hypermutability of a shuttle vector plasmid.

The diagnosis of the melanoma-prone disorder dysplastic nevus syndrome (DNS) is based currently on a combination of clinical and histopathologic examinations of patients. To develop a potential laboratory test for DNS, we utilized the observation that an ultraviolet light (UV)-treated mutagenesis plasmid shuttle vector has an abnormally increased frequency of mutations after transfection into lymphoblastoid cells from a patient with familial DNS. pSP189 (containing the bacterial suppressor tRNA gene supF as a marker for mutations and a gene for ampicillin resistance for selection) was treated with UV and transfected into familial DNS, xeroderma pigmentosum complementation group A (XP-A), and normal lymphoblastoid cells by electroporation or diethylaminoethyl (DEAE) dextran. Untreated plasmid pZ189K (containing a gene for kanamycin resistance) was co-transfected as an internal standard to reduce the variability of plasmid survival measurements. After 2 d, plasmids were extracted, used to transform an indicator strain of Escherichia coli, and assayed on plates containing ampicillin or kanamycin. Counting light blue or white colonies (containing mutated supF in the plasmid) and blue colonies (with wild type supF) permitted measurement of the plasmid survival and mutation frequency. Transfection by electroporation or DEAE dextran resulted in abnormally reduced survival of UV-treated plasmid after passage through the XP-A but normal survival in the three DNS lines. Transfection of UV-treated plasmid by DEAE dextran yielded a greater hypermutability with the familial DNS lines than by electroporation. These results suggest that pSP189 UV hypermutability with normal UV survival using DEAE dextran transfection may form the basis of a potential laboratory assay for familial DNS.

Diagnostic Tests, Routine↗
PubMed1994

U.S. military working dogs with Vietnam service: definition and characteristics of the cohort.

We verified and corrected inaccuracies in descriptive profile information on military working dogs (MWDs) that died from 1965 to 1980 and were reported in the Armed Forces Institute of Pathology Registry of Veterinary Pathology. Using other available military records, we determined which dogs served in Vietnam. Identified were 3,895 MWDs with a unique identity tattoo that served in Vietnam, of which 2,389 served exclusively with U.S. military forces and died in Vietnam. Another 479 Vietnam veteran MWDs completed their service elsewhere. This overall effort resulted in signalment corrections, generally age at death, in 21% of the Registry MWD accessions during the study period. The improved definition and characterization of the Vietnam cohort will lead to greater precision in epidemiologic investigations of the health effects from the Vietnam experience in U.S. military working dogs.

Animals↗
PubMed1994

Chromosome aberrations in lymphocytes from women irradiated for benign and malignant gynecological disease.

Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow (8 Gy vs 0.7 Gy, respectively). High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received.

Aged↗
PubMed1993

X-ray-induced chromatid damage in cells from Down syndrome and Alzheimer disease patients in relation to DNA repair and cancer proneness.

Frequencies of chromatid aberrations in response to G2-phase x-irradiation were compared in PHA-stimulated blood lymphocytes from healthy control subjects, Down syndrome (DS) patients, and Alzheimer disease (AD) patients. In cells arrested with Colcemid immediately (0-30 min) after x-irradiation, DS, AD, and control cells showed similar high frequencies of chromatid breaks and gaps, representing unrepaired DNA strand breaks. Frequencies had decreased in AD and control cells arrested 30-90 min after irradiation. However, DS cells had two- to three-fold higher frequencies than AD or control cells. This result indicates deficient repair of the DNA damage in DS cells. Similar responses were obtained with lymphocytes from four of seven DS parents tested and with skin fibroblasts from DS patients compared to age-matched controls. Addition of 1-beta-D-arabinofuranosylcytosine (ara-C), an inhibitor of the repair polymerase, after x-irradiation during G2 phase increased the frequencies of chromatid breaks and gaps in lymphocytes from control and AD donors significantly more than in those from DS patients. This result indicates a deficiency in DS cells in incision at sites of x-ray-induced damage. Thus DS, like other cancer-prone genetic disorders, has a G2-phase DNA repair deficiency in strand break repair and also a second DNA repair deficiency in incision activity.

Adult↗
PubMed1993

X-ray-induced chromatid damage in relation to DNA repair and cancer incidence in family members.

The cytogenetic response to G2-phase X-irradiation was examined in phytohemagglutinin-stimulated peripheral-blood lymphocytes from 69 individuals, a few of whom were cancer patients. The cancer patients had not received radiation or chemotherapy. The responses of cells arrested by Colcemid 30 to 90 min after X-irradiation (58R) could be divided into 2 distinct categories: 51 individuals had aberration frequencies typical of normal individuals in previous studies, while 18 others had a 2- to 3-fold higher frequency of chromatid breaks and gaps. Because chromatid breaks and gaps result from unrepaired DNA strand breaks, the first category may represent an efficient DNA repair phenotype, while the second may represent a deficient repair phenotype. The individuals with the deficient G2 response reported having first- and second-degree relatives with a 3.6- and 2.2-fold higher mean frequency of cancer, respectively. The present results, together with those from earlier studies of families with a genetic disorder predisposing to cancer, suggest that this deficient cytogenetic response to G2 phase X-irradiation is associated with a high risk of cancer.

Adolescent↗
PubMed1993

On the possible role of involution in the natural history of breast cancer.

Although the importance of the relationship between age and cancer incidence rates is recognized universally, little attention seems to have been paid to the relationship between the physiologic aging process in the breast and breast cancer risk. The natural history of breast cancer was examined in the context of involution of the breast, and it was proposed that the rate and extent of involution might be important determinants of breast cancer risk. It was concluded that additional studies to characterize the process of involution better histopathologically and to examine the associations between the rate and extent of involution and breast cancer risk are warranted.

Adult↗
PubMed1993

Gene-specific DNA repair in xeroderma pigmentosum complementation groups A, C, D, and F. Relation to cellular survival and clinical features.

We have examined the gene- and strand-specific DNA repair of UV-induced cyclobutane pyrimidine dimers in fibroblasts from normal individuals and from patients with the DNA repair-deficient disorder xeroderma pigmentosum (XP). Cells were studied from XP complementation groups A, C, D, and F. DNA repair was assessed in the essential, active gene, dihydrofolate reductase (DHFR), in the active c-myc protooncogene, and in the transcriptionally inactive delta-globin gene. In addition, repair was studied in the individual strands of the DHFR gene in normal and group C cells. In the two strains of group C cells, we find preferential DNA repair of the DHFR gene and a strand bias of the repair with more repair in the transcribed strand. This is in general accordance with previously published reports (Venema, J., van Hoffen, A., Natarajan, A.T., van Zeeland, A.A., and Mullenders, L.H.F. (1990) Nucleic Acids Res. 18, 443-448; Venema, J., van Hoffen, A., and Mullenders, L.H.F. (1991) Mol. Cell. Biol. 11, 4128-4134), but we now find that there is more repair in the nontranscribed strand and less in the transcribed strand than what has been observed previously. In XP group A and D strains, we find little or no gene-specific DNA repair. In cells from an individual in XP complementation group F, we find less repair of dimers in the active gene than what has been observed for the overall genome. We have also measured the colony-forming ability of the strains after treatment with UV and find that this measure of survival does not correlate with the level of gene-specific repair of dimers. Thus, XP group F represents a novel repair phenotype with little or no gene-specific repair of dimers, but with relatively high UV resistance. We also evaluate the XP patients' clinical features in relation to gene-specific repair of dimers.

Adult↗