A randomized clinical trial of 4-hydroxyphenylretinamide for high-grade squamous intraepithelial lesions of the cervix.

PURPOSE: Previous trials of topical trans-retinoic acid treatment of cervical intraepithelial neoplasia (CIN) grades 2 and 3 led to a statistically significant regression of CIN 2, but not CIN 3. We tested N-(4-hydroxyphenyl)retinamide (4-HPR), a promising oral retinoid that has been shown to induce apoptosis through nonretinoic receptor acid-mediated pathways, for its toxicity and efficacy against CIN 2/3. EXPERIMENTAL DESIGN: In a blinded randomized trial, 4-HPR at 200 mg/day for 6 months (with a 3-day/month drug holiday) was compared with placebo in patients with biopsy-proven CIN-2/3 [high-grade squamous intraepithelial lesions (HGSILs)]. Patients were treated with placebo or 4-HPR for 6 months, biopsied, and then followed for an additional 6 months. At the 12-month end point, they underwent either loop excision if a histological lesion was present or a biopsy from the original area of the lesion if no lesion was present. RESULTS: An interim analysis of blinded data showed a significantly worse prognosis at 12 months for one group. When the code was broken because of the poorer outcomes, we discovered that the 4-HPR treatment arm was performing more poorly than was the placebo at 6 and 12 months (25 versus 44% response rates at 6 months; 14 versus 50% at 12 months). Toxicity was not significant in either arm. CONCLUSIONS: 4-HPR at 200 mg/day with a 3-day/month drug holiday is not active compared with placebo in the treatment of HGSIL. Because 4-HPR is active in the laboratory, the lack of effect in our trial may indicate that higher doses are needed in patients to achieve comparable results.

Potential risk factors for undifferentiated connective tissue disease among women: implanted medical devices.

A case-control study was conducted among 205 women in Michigan and Ohio who were diagnosed with undifferentiated connective tissue disease (UCTD) to investigate the significance of self-reported past exposures to implanted silicone-containing or non-silicone-containing medical devices. The 205 UCTD cases were compared with 2,095 controls who were sampled by random digit dialing. When silicone-containing devices, including shunts and catheters, were analyzed collectively, a significant association was observed (odds ratio (OR) = 2.81, 95% confidence interval (CI): 1.34, 5.89). The odds ratio for exposure to breast implants was increased, but not significantly (OR = 2.22, 95% CI: 0.65, 7.57). Among the non-silicone-containing devices, artificial joints (OR = 5.01, 95% CI: 1.60, 15.71) and orthopedic metallic fixation devices (OR = 1.95, 95% CI: 1.05, 3.60) were associated with UCTD. The estimations of risk associated with implanted medical devices in UCTD cases were explored in a comparison with 660 scleroderma patients who were ascertained concurrently in Michigan and Ohio. In general, the associations that were observed with non-silicone-containing devices, and more specifically with the fixation devices, persisted in the comparison of UCTD cases with scleroderma patients. The studies conducted among populations in Michigan and Ohio are intended to stimulate new hypotheses, innovative approaches, and the fostering of understanding of the environmental determinants of autoimmune disease.

Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

The natural history of lower urinary tract symptoms in black American men: relationships with aging, prostate size, flow rate and bothersomeness.

PURPOSE: Studies of lower urinary tract symptoms in men have been restricted to predominately white populations and these observations may not be generalized to black American men. A goal of the Flint Men's Health Study was to evaluate the prevalence of lower urinary tract symptoms in a community based sample of black American men. MATERIALS AND METHODS: We identified 721 eligible subjects after a 2-stage stratified sampling protocol of black American men residing in Flint, Michigan and an in-home interview. Of these men 364 (50%) completed the study protocol, including serum prostate specific antigen measurement, digital rectal examination, uroflowmetry and transrectal ultrasound. These men comprised our study group. Patients completed the American Urological Association (AUA) symptom and bothersomeness scores. Moderate to severe symptoms and impairment were defined as an AUA symptom score of greater than 7 and bothersomeness score of greater than 3, respectively. Data were stratified by 10-year age groups. RESULTS: Prostate volume increased, while the peak urinary flow rate decreased with increasing age (p <0.001). Total AUA symptom and bothersomeness scores were marginally associated with age (p = 0.08 and 0.01, respectively). Although only 8.2% of the men reported an enlarged prostate and 3% reported being on medical therapy for benign prostatic hyperplasia, moderate to severe lower urinary tract symptoms were reported by 39.6% and moderate to severe impairment was present in 35%. CONCLUSIONS: To our knowledge this is the first study to describe the prevalence of lower urinary tract symptoms and its associations with age, prostate size and peak flow rate in a black American population. A large proportion of the men in this study had from moderate to severe lower urinary tract symptoms, of whom many were undiagnosed and untreated. The AUA symptom score has the potential to identify these men and its validity in black Americans has now been established.

Surrogate endpoint biomarkers and their modulation in cervical chemoprevention trials.

BACKGROUND: Surrogate endpoint biomarkers (SEBs) are used as intermediate indicators of a reduction in cancer incidence in chemoprevention studies. SEBs should be expressed differentially in normal and high risk tissue; appear at a well defined stage of carcinogenesis; be studied with reasonable sensitivity, specificity, and accuracy; and be modulated in chemoprevention trials. The concept of SEBs may be useful in the trials of many new therapies. METHODS: The current review includes a comprehensive review of the literature. Many SEBs have been the subject of intense study and include quantitative histopathology and cytology, proliferation markers, regulation markers, differentiation markers, general genomic instability markers, and tissue maintenance markers. Because of the critical biologic and epidemiologic role of the human papillomavirus (HPV) in cervical carcinogenesis, the relation between these markers and HPV should be considered. In addition, biomarkers of HPV infection and its regression should be sought. RESULTS: Several chemoprevention trials have been published that have included the use of SEBs. The biomarkers that appear most promising in these clinical trials can be measured quantitatively and reproducibly: quantitative histology and cytology, proliferating cell nuclear antigen (PCNA), MIB-1, MPM-2, HPV viral load, epidermal growth factor receptor, polyamines, and ploidy. The markers that have been demonstrated to be modulated in chemoprevention trials in the literature are quantitative histology and cytology, PCNA, MPM-2, HPV viral load, and polyamines. CONCLUSIONS: The surrogate endpoint biomarkers of most interest in future research should correlate well with HPV infection, be modulated by several therapeutic agents, and have limited variability and ease in measurement.

Age-specific distribution of serum prostate-specific antigen in a community-based study of African-American men.

OBJECTIVES: Previous studies have observed higher age-specific serum prostate-specific antigen (PSA) values in African-American (AA) men without prostate cancer compared to white men, leading some to recommend race-specific PSA reference ranges for the early detection of prostate cancer. The primary objective of the Flint Men's Health Study was to determine age-specific PSA reference values in a community-based sample of AA men, aged 40 to 79 years. METHODS: A probability sample of 943 AA men was selected from households in Genesee County, Michigan. Men without a prior history of prostate cancer/surgery were invited to participate in a prostate cancer screening protocol, consisting of measurement of serum total PSA, free/total PSA ratio, and digital rectal examination. Sextant biopsies were recommended, based on total PSA greater than 4.0 ng/mL and/or an abnormal digital rectal examination. RESULTS: From the sample of 943 men, 732 were eligible, 432 had blood drawn for PSA testing, and 374 completed all phases of the clinical examination. The 95th percentile PSA values were estimated to range from 2.36 ng/mL for men in the fifth decade to 5.59 ng/mL for men in the eighth decade. The 95th percentile values for age-specific PSA were comparable to those observed in a similar study of white men in Olmsted County, Minnesota. The median and 5th percentile values for free/total PSA did not vary significantly across age. CONCLUSIONS: The minor differences in PSA reference ranges between AA and white men may not be of sufficient magnitude to recommend the use of race-specific PSA reference ranges for screening.

Potential selection bias in a community-based study of PSA levels in African-American men.

The first phase of the Flint Men's Health Study (FMHS) in Michigan was a community-based epidemiologic study of prostate cancer and benign prostatic hyperplasia (BPH) in African-Americans aged 40 to 79 years. An objective of the FMHS was to determine age-specified prostate specific antigen (PSA) reference ranges in a random population sample of African-American men without clinically evident prostate cancer. The FMHS study protocol included an initial in-home epidemiologic interview followed by PSA testing and a urologic examination of eligible subjects. Since the participation rate in the PSA phase of the study was under 60%, it was important to determine whether selectivity in participation biased the FMHS results for age-specific PSA distributions. Logistic regression analyses were used to investigate selectivity in the sample of subjects who participated in the PSA testing and urologic examination. Younger men, with current urologic symptoms, and with a family history of prostate cancer were more likely to participate in the PSA testing and urologic examination. Linear regression analysis indicated that greater participation by African-American men without clinically evident prostate cancer but with obstructive or irritative lower urinary tract symptoms or a family history of prostate cancer did not bias the estimated age-specific reference ranges for total PSA concentrations and free-to-total PSA ratios.

Chromosomal aberrations and hprt mutant frequencies in long-term American thorotrast survivors.

PURPOSE: Patients injected with thorotrast, a radiologic contrast medium used from the 1920s to early 1950s, received chronic internal exposure to thorium-232, an alpha-emitter. Epidemiologic studies have observed markedly elevated risks of death from hepatic and hematologic cancers and extensive chromosomal damage among these patients. Few investigations have correlated multiple measures of genetic damage to determine whether these have independent induction kinetics. The distribution of chromosomal aberrations (CA) and mutant frequencies (MF) at the hypoxanthine phosphoribosyltransferase (hprt) locus was evaluated in eight long-term thorotrast survivors (mean exposure time=47.4 years) and five individuals who received a nonradioactive contrast medium during the same era. MATERIALS AND METHODS: Peripheral blood lymphocytes were harvested from whole blood, CA were scored in 500 complete metaphases and a clonal assay was used to determine hprt MF. Symmetrical aberrations were not evaluated. Differences in frequencies and correlations between endpoints were assessed using nonparametric methods. RESULTS: Thorotrast-exposed individuals differed from the comparison group in total number of multicentrics and centric and acentric rings (per 500 cells [median, mean +/- sd]: 11, 18.3+/-23.1 vs 2, 2.4+/-1.1, p =0.04). There was no difference between the groups on hprt MF (12.6, 15.9+/-13.5 vs 16.6, 14.0+/-8.8[ x 10(-6)]; p= 1.0). Among the exposed, hprt MF was moderately correlated with the frequency of asymmetrical chromosomal aberrations, although the association was not statistically significant. CONCLUSION: Noting the limitations of small samples, long-term thorotrast survivors were observed to be at an increased risk for genetic damage.

Screening for squamous intraepithelial lesions with fluorescence spectroscopy.

OBJECTIVE: To evaluate the accuracy of fluorescence spectroscopy in screening for squamous intraepithelial lesions (SILs) and to compare its performance with that of Papanicolaou smear screening, colposcopy, cervicoscopy, cervicography, and human papillomavirus (HPV) testing. DATA SOURCES: Receiver operating characteristic (ROC) curve analysis was used to analyze performance by fluorescence spectroscopy (primary data) and other methods (secondary data). METHODS OF STUDY SELECTION: In our search, 275 articles were identified in MEDLINE (1966-1996). Articles were included if the investigators had studied a population in whom low disease prevalence was expected; used either Papanicolaou smear screening and colposcopy or colposcopically directed biopsy as a standard against which the screening technique was measured, and included enough data for recalculation of reported sensitivities and specificities. TABULATION, INTEGRATION, AND RESULTS: Receiver operating characteristic curves for fluorescence spectroscopy were calculated using a Bayesian algorithm, and ROC curves for the other screening methods were constructed using metaanalytic techniques. Areas under the ROC curves and Q points were calculated. Screening colposcopy had the highest area under the curve (0.95), followed by screening cervicography (0.90), HPV testing (0.88), cervicoscopy (0.85), fluorescence spectroscopy (0.76), and Papanicolaou smear screening (0.70). CONCLUSION: In terms of screening for SILs, fluorescence spectroscopy performed better than the standard technique, Papanicolaou smear screening, and less well than screening colposcopy, cervicography, HPV testing, and cervicoscopy. The promise of this research technique warrants further investigation.

Trends in prostatectomy for benign prostatic hyperplasia among black and white men in the United States: 1980 to 1994.

OBJECTIVES: To estimate the annual rate of discharge for prostatectomy for benign prostatic hyperplasia (BPH) in black and white men from 1980 to 1994 using the National Hospital Discharge Survey. METHODS: Overall and race-, age-, and year-specific utilization rates were estimated for the civilian population in the United States. Length of stay was calculated for each discharge, and the results were plotted over time. An expected number of discharges based on the rates observed in 1980 was estimated to determine the impact of decreased prostatectomy rates on the number of procedures that would have been expected in this aging population. RESULTS: Discharge rates for whites were within a narrow range (233.2 to 274.5 per 100,000) from 1980 through 1990 and then displayed a monotonic decline after 1991 to 131.3 per 100,000 in 1994. Rates for blacks were 10% to 24% lower from 1980 to 1991; the decline in discharge rates began in 1993 for blacks, and by 1994 the racial gap had closed. Length of stay decreased throughout the period but length of stay averaged 30% longer for blacks throughout. On the basis of the observed rates of 1980, there were more than 140,000 fewer prostatectomies performed for BPH in 1994 than would have been expected owing to the aging of the population. CONCLUSIONS: These data demonstrate that the black/white differences in prostatectomy for BPH that were observed in the 1980s have disappeared in recent years. Furthermore, rates have declined dramatically in all age- and race-specific groups. Further work is needed to determine whether this convergence in discharge rates is due to equalization of access to medical care or to differences in utilization of alternative therapies.

Diet and risk for breast cancer recurrence and survival.

Dietary factors may influence the risk for breast cancer and also the prognosis following diagnosis and treatment. The aim of this study was to assess whether self-reported prediagnosis diet or other patient factors associated with breast cancer incidence were predictive of recurrence and survival. Patients (n = 149) diagnosed with primary breast cancer between 1989 and 1991 were followed for five or more years. Total energy (hazard ratio (HR) = 1.58, 95%, confidence interval (CI) = 1.05, 2.38) as well as total (HR = 1.46, 95% CI = 1.05, 2.01), saturated (HR = 1.79, 95% CI = 1.05, 3.04), and monounsaturated (HR = 1.65, 95% CI = 1.09, 2.49) fat intakes were associated with increased risk, and energy-adjusted bread and cereal consumption (HR = 0.55, 95% CI = 0.33, 0.93) with decreased risk of recurrence. Both total energy (HR = 1.58, 95% CI = 1.03, 2.43) and polyunsaturated fat (HR = 1.84, 95% CI = 1.09, 3.13) intakes were associated with an increased risk of death. All associations between dietary fat and recurrence and survival attenuated following energy adjustment. Oral contraceptive use (HR = 1.28, 95% CI = 1.03, 1.60), lymph node positive status (HR = 2.36, 95% CI = 1.01, 5.49), and tumor stage (HR = 2.22, 95% CI = 1.02, 4.81) were associated with increased risk of recurrence. Tumor stage (HR = 4.96, 95% CI = 1.86, 13.23), lymph node positive status (HR = 3.31, 95% CI = 1.38, 7.95), and estrogen receptor negative status (HR = 2.46, 95% CI = 1.02, 5.94) were associated with increased risk, and arm muscle circumference (HR = 0.27, 95% CI = 0.09, 0.86) and mammographic utilization (HR = 0.77, 95% CI = 0.61, 0.98) with decreased risk of death. Higher levels of energy, fat intakes, and selected patient characteristics (particularly disease stage and anthropometric indicators of adiposity) appear to increase risk of recurrence and/or shortened survival following the diagnosis of breast cancer.

Petroleum distillate solvents as risk factors for undifferentiated connective tissue disease (UCTD).

Occupational solvent exposure may increase the risk of connective tissue disease (CTD). The objective of this case-control study was to investigate the relation between undifferentiated connective tissue disease (UCTD) and solvent exposure in Michigan and Ohio. Women were considered to have UCTD if they did not meet the American College of Rheumatology classification criteria for any CTD but had at least two documented signs, symptoms, or laboratory abnormalities suggestive of a CTD. Detailed information on solvent exposure was ascertained from 205 cases, diagnosed between 1980 and 1992, and 2,095 population-based controls. Age-adjusted odds ratios (OR) and 95 percent confidence intervals (CI) were calculated for all exposures. Among 16 self-reported occupational activities with potential solvent exposure, furniture refinishing (OR = 9.73, 95 percent CI 1.48-63.90), perfume, cosmetic, or drug manufacturing (OR = 7.71, 95 percent CI 2.24-26.56), rubber product manufacturing (OR = 4.70, 95 percent CI 1.75-12.61), work in a medical diagnostic or pathology laboratory (OR = 4.52, 95 percent CI 2.27-8.97), and painting or paint manufacturing (OR = 2.87, 95 percent CI 1.06-7.76) were significantly associated with UCTD. After expert review of self-reported exposure to ten specific solvents, paint thinners or removers (OR = 2.73, 95 percent CI 1.80-4.16) and mineral spirits (OR = 1.81, 95 percent CI 1.09-3.02) were associated with UCTD. These results suggest that exposure to petroleum distillates increases the risk of developing UCTD.

Cancer of the corpus uteri in white and black women in Michigan, 1985-1994: an analysis of trends in incidence and mortality and their relation to histologic subtype and stage.

BACKGROUND: Cancer of the corpus uteri occurs more commonly among white women in the U.S., yet survival is poorer for black women. This study examined whether this trend has changed and also examined the relation of age and histologic subtype to differences in stage. METHODS: This retrospective cohort study assessed incidence trends, mortality trends, and the relation of age and histologic subtype to stage for 12,079 incident cases and 2325 deaths registered between 1985 and 1994 in Michigan. Rate ratios compared incidence and mortality. Odds ratios quantified the contribution of age and histologic subtype to differences in risk for advanced stage, using Mantel-Haenszel univariate techniques and multivariate logistic regression. RESULTS: The overall incidence rate was 21.99 per 100,000, and the overall mortality rate was 3.82 per 100,000. Black women had a 40% lower risk (rate ratio [RR] =0.60) of developing cancer of the corpus uteri but had a 54% greater risk (RR=1.54) of dying from cancer of the corpus uteri. Black women were at greater risk of being diagnosed with either sarcoma or more aggressive adenocarcinoma. However, after adjustment for age and histologic subtype, black women still had an increased risk for advanced stage disease (2.63, 95% confidence interval=2.19-3.16). CONCLUSIONS: The disparity between white and black women persists in incidence and mortality trends for cancer of the corpus uteri. The greater frequency of more aggressive histologic subtypes experienced by black women accounts for only 10% of their excess risk for more advanced stage disease.

Colposcopy for the diagnosis of squamous intraepithelial lesions: a meta-analysis.

OBJECTIVE: To quantify by meta-analysis the performance of colposcopy to set a standard against which new technologies can be compared. DATA SOURCES: MEDLINE was searched for articles on colposcopy for diagnosis of squamous intraepithelial lesions (SIL). The search selected articles from 1960 to 1996 combining the key word "colposcopy" with key words "diagnosis," "positive predictive value," "negative predictive value," "likelihood ratio," and "receiver operating characteristic (ROC) curve." METHODS OF STUDY SELECTION: Articles were selected if the authors studied a population of patients with abnormal screening Papanicolaou smears and presented raw data showing for each cervical lesion type the number of patients judged positive and negative by colposcopic impression versus the standard of colposcopic biopsy results. Nine of 86 studies met these criteria. TABULATION, INTEGRATION, AND RESULTS: Biopsies had been categorized as normal, atypia, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, carcinoma in situ, and invasive cancer; we recalculated performance measures using the Bethesda system. Overall sensitivity, specificity, likelihood ratios, ROC curves, and the corresponding areas under the curves were calculated. The average weighted sensitivity of diagnostic colposcopy for the threshold normal compared with all cervix abnormalities (atypia, low-grade SIL, high-grade SIL, cancer) was 96% and the average weighted specificity 48%. For the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer, average weighted sensitivity was 85% and average weighted specificity 69%. Likelihood ratios generated small but important changes in probability for distinguishing normal cervix and low-grade SIL from high-grade SIL and cancer. Areas under the ROC curve were 0.80 for the threshold normal cervix compared with all abnormalities and 0.82 for the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer. CONCLUSION: Colposcopy compares favorably with other medical diagnostic tests in terms of sensitivity, specificity, and area under the ROC curve. New diagnostic methods for the cervix can be compared with colposcopy using these quantified values.

A two-step intervention of increase mammography among women aged 65 and older.

OBJECTIVES: This study evaluated a two-step intervention for mammography screening among older women. METHODS: Four hundred and sixty women, identified from physician practices, were randomized to a control or a two-step intervention (physician letter and peer counseling call) group. Women in the intervention group who obtained a mammogram received a grocery coupon. RESULTS: Over the 12 months of the study, more women in the intervention group than in the control group obtained mammograms (38% vs 16%). The most dramatic difference was in the higher odds that women in the intervention group would obtain a mammogram within 2 months (odds ratio = 10.5). CONCLUSIONS: The intervention significantly increased screening mammography. Future efforts must be multifaceted and incorporate the unique concerns of older women.

Risk of multiple primary cancers in prostate cancer patients in the Detroit metropolitan area: a retrospective cohort study.

BACKGROUND: Patterns of excess risk for second primary cancers (SPC) in prostate cancer patients have been observed for urinary bladder, other sites in the urinary tract, and hematolymphopoietic tissues in several, but not all, previously reported cohort studies. METHODS: The risk of SPC was evaluated in 9,794 Detroit metropolitan-area men originally diagnosed with carcinoma of the prostate during 1973-1982. The cohort was assembled using Detroit Surveillance, Epidemiology, and End Results (SEER) Registry data and followed until December 31, 1993. RESULTS: The observed number of SPC of all sites was similar to the expected number in the cohort. A significant excess of invasive SPC of the urinary bladder [Standardized incidence ratio (SIR) = 1.57; 95% CI, 1.34-1.83] was observed in this cohort, but after excluding the first 2 months after prostate cancer diagnosis, the excess (SIR = 1.06) was no longer statistically significant. The cumulative proportion of patients with prostate cancer who developed bladder cancer during a follow-up interval of 20 years was 5.5% (95% CI, 4.1-6.9%). The patients who received first-course radiation treatment were observed to be at increased risk for bladder SPC (all stages; SIR = 1.49; 95% CI, 1.07-2.02) when compared to the Detroit-area male population. CONCLUSIONS: These results underscore the importance of continuing medical surveillance for urinary bladder second primary cancers in patients with prostate cancer, but are reassuring in that the magnitude of relative and absolute risks does not suggest deterring adverse effects of radiation treatment or intrinsic risks for neoplasms in other organs or tissues.

A case-control study of self-reported exposures to pesticides and pancreas cancer in southeastern Michigan.

A case-control study of pancreas cancer in residents, aged 30-79 years, of 18 counties in southeastern Michigan was conducted to investigate the risks of exposure to DDT and related materials in the general population. Sixty-six people with cytologically diagnosed pancreas cancer were identified using 7 participating hospitals in metropolitan Detroit and Ann Arbor. One hundred and thirty-one controls were frequency-matched to the cases on age, sex, ethicity and county of residence by random-digit dialing. All study participants were administered a questionnaire to assess life-time exposure to pesticides from both environmental and occupational sources, family history of cancer, past medical history, smoking history and demographic information. A statistically significant increased risk was found for self-reported exposure to ethylan (1,1-dichloro-2,2-bis(4-methoxyphenyl) ethane). Increased odds ratios were observed for self-reported exposures to chloropropylate and DDT, as well as for the summary group of organochlorine pesticides which included all of these materials, though these associations were not significant.

Racial differences in scleroderma among women in Michigan.

OBJECTIVE: To examine racial differences in disease onset, extent, manifestations, and survival among women with scleroderma. METHODS: A retrospective cohort study of women with scleroderma, diagnosed in Michigan between 1980 and 1991, was conducted. Clinical, laboratory, and demographic data were abstracted from the patients' medical records. RESULTS: A total of 514 women with scleroderma were identified: 117 (23%) were black and 397 (77%) were white. Among black women, the mean age at diagnosis was lower (44.5 years versus 51.5 years; P < 0.001) and diffuse disease was more common (49.6% versus 24.9%; P < 0.001) than among white women. The overall incidence of scleroderma was 14.1 per million per year: 22.5 per million per year in black women versus 12.8 per million per year in white women (P < 0.001). Pericarditis (P = 0.009), pulmonary hypertension (P < 0.001), pleural effusions (P = 0.01), myositis (P = 0.02), and an erythrocyte sedimentation rate >40 mm/hour (P < 0.001) were more frequent among black women, while white women were more likely to have digital infarctions (P < 0.001). Survival at 7 years from diagnosis was 72.5% among black women and 77.6% among white women. Age-adjusted survival was significantly reduced among black women (P = 0.033), most likely because of increased diffuse involvement. Survival among those with renal or pulmonary involvement was also significantly reduced. CONCLUSION: Black women with scleroderma were significantly more likely than white women to develop diffuse disease, be diagnosed at a younger age, have a higher incidence of inflammatory features, and have a worse age-adjusted survival rate.

Cumulative risk of second primary cancers in women with index primary cancers of uterine cervix and incidence of lower anogenital tract cancers, Michigan, 1985-1992.

A retrospective cohort study of women with cancers of the lower anogenital tract was derived from the Michigan Tumor Registry records for the years 1985-1992. Incidence rates of invasive cervical, vulvar, vaginal and anal cancers were analyzed with respect to age, race, year of diagnosis, stage at diagnosis, and histopathology. The incidence of metachronous primary cancers following initial primaries of the cervix was also investigated. Anogenital cancers constituted about 4% of all cancers in Michigan women between 1985 and 1992. Age-adjusted incidence rates per 100,000 women per year for each site were found to be as follows: 10.1 (cervix), 1.9 (vulva), 1.0 (vagina), and 0.6 (anus). The incidence rates of women in the United States for cancers in the anogenital region were higher in blacks than in whites, with the exception of vulvar cancer. U.S. blacks were more likely to develop squamous cell carcinomas, but less likely to develop adenocarcinomas of the cervix and vagina when compared to whites. Over the 5- to 8-year follow-up period, 6.5% of the women with index cases of cervical cancer developed second primary cancers. This represented a 40% increase in the risk of incident primary cancers compared to the risk in the general population of Michigan women. The significant occurrence of second primaries of the vagina following index primaries of the cervix suggests a shared etiology, such as infection with human papillomavirus. The incidences of cancers related to smoking, including cancers of the urinary bladder, lung/bronchus, and lower anogenital tract were also increased.