Use of hair colouring products and risk of multiple myeloma among US women.

OBJECTIVE: To evaluate the association between personal hair dye use and risk of multiple myeloma among women. METHODS: A population-based case-control study of 175 cases of multiple myeloma and 679 controls. Cases and controls were interviewed regarding the type and colour of hair colouring product used, age at first use, age use stopped, duration, and the frequency of use per year. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression to compare never users with four exposure groups: all users, ever semi-permanent dye users, ever permanent dye users and dark permanent dye users (most frequent use). RESULTS: No association was found between ever reporting hair colouring product use and myeloma risk among all users (OR 0.8; 95% CI 0.5 to 1.1), semi-permanent dye users (OR 0.7; 95% CI 0.4 to 1.2), permanent dye users (OR 0.8; 95% CI 0.5 to 1.1) or dark permanent dye users (OR 0.8; 95% CI 0.5 to 1.3). There were no significant associations among women who used hair dyes before 30 years of age, started use before 1980, had >or=240 lifetime applications, or had used dark permanent dye for 28 or more years. CONCLUSION: No evidence of an association between hair colouring product use and myeloma risk was found. However, given the conflicting body of literature on hair colouring product use and risk of multiple myeloma, this question should be further evaluated in larger studies or consortia, and in high risk groups.

Time period compared to birth cohort in Connecticut incidence rates for twenty-five malignant neoplasms.

Out of necessity and convenience many reports on population-based rates for cancer are limited to analyses by time period of diagnosis, and just how often cohort effects are important in cancer data has not been fully explored. To address this question, Connecticut cancer incidence rates for the years 1940-79 were fitted to the model: Log (incidence rate) = constant + age effect + period effect + birth cohort effect + error term. Data for each cancer site and sex were categorized into 10-year intervals by time period and age group. Significance testing for the curvilinear effects (which are estimable functions) of age (A), period (P), and cohort (C) in the 44 data sets led to no clear choice of model for three data sets; an APC model for 20, an AP model for 7, and an AC model for 14. These choices were corroborated by the RA2 index. Limitations in the interpretation of the results were enumerated. Presentation of population-based cancer rates by implicitly assuming an AP model is valuable (e.g., for studying age distribution in different regions or for age-adjustment in examining international variation or time trends). However, the assumption of an AP model may often be incorrect, as was shown to be the case for most of these 44 data sets. The implications for monitoring trends and generating etiologic hypotheses were discussed in light of the results for cutaneous malignant melanoma and cancers of the cervix, breast, ovary, lung, and bladder.

Oral contraceptive use and fibrocystic breast disease with special reference to its histopathology.

The relationship between use of oral contraceptives and fibrocystic breast disease was examined in a hospital-based case-control study undertaken in New Haven, Connecticut, from 1977 to 1979. Particular emphasis was placed on the extent of epithelial atypia and other histopathologic characteristics found in the biopsy specimens from the cases. Women who had ever used oral contraceptives were at a somewhat decreased risk for fibrocystic disease as a whole. Cases with high atypia and controls had similar patterns of oral contraceptive use, whereas cases with low and intermediate atypia had less oral contraceptive use than controls. Cases with intermediate atypia reported the lowest oral contraceptive use. Subjects with biopsy specimens exhibiting gross cysts, microscopic cysts, or papillomatosis were about 50% less likely to have used oral contraceptives than controls.

Exogenous estrogens and other factors in the epidemiology of breast cancer.

In a hospital-based case-control study of the epidemiology of breast cancer undertaken in Connecticut from 1977 to 1979, there was no evidence of an increase in risk for breast cancer among women who had used oral contraceptives or estrogen-replacement therapy. In fact, there was some suggestion of a decrease in risk for breast cancer with increasing length of use of oral contraceptives. Higher than average risks were found among women who had never give birth to a child, women with a late age at menopause, women, with an early age at menarche, women who had given birth to their first child at a relatively late age, women with previous benign breast disease, and women with a history of breast cancer in a sister or mother. Heavy women were at high risk for premenopausal breast cancer. The association between heaviness and postmenopausal breast cancer was strongest among women who had had their last menstrual period more than 5 years before the diagnosis of breast cancer.

Risk factors for fibrocystic breast disease and its histopathologic components.

The relationship between various sociodemographic, reproductive, and other factors to the occurrence of fibrocystic breast disease was evaluated in a case-control study undertaken at five Connecticut hospitals from 1979 to 1981. The study groups comprised 590 women with biopsy-proven fibrocystic breast disease and 1,018 women with other surgical conditions. Among the premenopausal women, multivariate analysis suggested that high socioeconomic status, Jewish religion, low parity, a history of benign breast disease, a history of breast cancer in the mother or a sister, and low Quetelet index were associated with increased odds ratios (OR) for fibrocystic breast disease. Similar analysis for the postmenopausal women revealed increased OR for women with high socioeconomic status, a late age at menopause, and a history of benign breast disease. Current smokers as well as those who had had a tubal sterilization had significantly reduced odds of fibrocystic disease. There was no convincing evidence of linear trends according to degree of epithelial atypia for any of the variables considered. Although some variation in the OR emerged in the analysis according to selected histologic components, the results provided little evidence that women with biopsy specimens exhibiting gross cysts, sclerosing adenosis, papillary hyperplasia, or papillomatosis showed epidemiologic similarities with breast cancer patients.

Differences in breast cancer risk factors according to the estrogen receptor level of the tumor.

One hundred and forty-eight postmenopausal breast cancer cases and 585 postmenopausal controls were included in an investigation of whether various risk factors for breast cancer are associated with the level of estrogen (E) receptor (ER) protein in the tumor. In an intracase analysis, the tumor ER level was positively associated with nulliparity, late age at first live birth, a history of benign breast disease, and having breast-fed at least 1 child and was negatively associated with previous use of E replacement therapy. A case-control analysis suggested that the first three variables, established risk factors for breast cancer, are associated with an increased risk for malignant breast tumors that are ER-positive but not for those that are ER-negative. This analysis did not provide a clear interpretation of the findings in the intracase comparisons with regard to prior breast-feeding and the use of E replacement therapy.

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies.

BACKGROUND: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors. METHODS: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided. RESULTS: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25-29.9 kg/m(2)); however, the risk was statistically nonsignificantly decreased among heavier women. CONCLUSIONS: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States.

Time trends of non-Hodgkin's lymphoma: are they real? What do they mean?

Factors that need to be considered in the analysis of time trends in disease incidence are age, year of diagnosis, and birth cohort. When these are included in a log-linear model, a nonidentifiability problem arises from the linear dependence among these three time factors so that only specified functions of the parameters can be unambiguously determined. One of these invariant functions is the drift or the sum of the period and cohort trend. Non-Hodgkin's lymphoma incidence rates from Connecticut for the period 1935-1989 were analyzed for males and females. In addition to an age effect, both period and cohort significantly improved the fit of the model. The estimated drift shows that there has been a 10.3% increase in risk every 5 years since 1965 for females and 9.2% for males. It is unlikely that a trend of this magnitude can be attributed entirely to data artifact.

Pulse pressure and risk for myocardial infarction and heart failure in the elderly.

OBJECTIVES: We sought to determine whether pulse pressure (PP), a measure of arterial stiffness, is an independent predictor of the incidence of coronary heart disease (CHD), congestive heart failure (CHF) and overall mortality among community-dwelling elderly. BACKGROUND: Current hypertension guidelines classify cardiovascular risk on the basis of elevated systolic blood pressure (SBP) or diastolic blood pressure (DBP) without considering their combined effects. Recent studies suggest that PP is a strong predictor of cardiovascular end points, but few data are available among community elderly. METHODS: The study sample included 2,152 individuals age > or =65 years, who were participants in the Established Populations for Epidemiologic Study of the Elderly program, free of CHD and CHF at baseline and still alive at one year after enrollment. Blood pressure was measured at baseline. Incidence of CHD, incidence of CHF and total mortality were monitored in the following 10 years. RESULTS: There were 328 incident CHD events, 224 incident CHF events and 1,046 persons who died of any cause. Pulse pressure showed a strong and linear relationship with each end point. After adjusting for demographics, comorbidity and CHD risk factors, a 10-mm Hg increment in PP was associated with a 12% increase in CHD risk (95% confidence interval [CI], 2% to 22%), a 14% increase in CHF risk (95% CI, 5% to 24%), and a 6% increase in overall mortality (95% CI, 0% to 12%). While SBP and mean arterial pressure (MAP) also showed positive associations with the end points, PP yielded the highest likelihood ratio chi-square. When PP was entered in the model in conjunction with other blood pressure parameters (SBP, DBP, MAP or hypertension stage, respectively), the association remained positive for PP but became negative for the other blood pressure variables. The effect of PP persisted after adjusting for current medication use and was present in normotensive individuals and individuals with isolated systolic hypertension but not in individuals with diastolic hypertension. CONCLUSIONS: Elevated PP is a powerful independent predictor of cardiovascular end points in the elderly.

A randomized controlled trial of auricular acupuncture for cocaine dependence.

BACKGROUND: Partly because of a lack of a conventional, effective treatment for cocaine addiction, auricular acupuncture is used to treat this disorder in numerous drug treatment facilities across the country for both primary cocaine-dependent and opiate-dependent populations. OBJECTIVE: To evaluate the effectiveness of auricular acupuncture for the treatment of cocaine addiction. METHODS: Eighty-two cocaine-dependent, methadone-maintained patients were randomly assigned to 1 of 3 conditions: auricular acupuncture, a needle-insertion control condition, or a no-needle relaxation control. Treatment sessions were provided 5 times weekly for 8 weeks. The primary outcome was cocaine use assessed by 3-times-weekly urine toxicology screens. RESULTS: Longitudinal analysis of the urine data for the intent-to-treat sample showed that patients assigned to acupuncture were significantly more likely to provide cocaine-negative urine samples relative to both the relaxation control (odds ratio, 3.41; 95% confidence interval, 1.33-8.72; P =. 01) and the needle-insertion control (odds ratio, 2.40; 95% confidence interval, 1.00-5.75; P =.05). CONCLUSIONS: Findings from the current study suggest that acupuncture shows promise for the treatment of cocaine dependence. Further investigation of this treatment modality appears to be warranted.

Longitudinal associations between asthma and general and abdominal weight status among Norwegian adolescents and young adults: the HUNT Study.

BACKGROUND: In adolescents the temporal directionality to the asthma and adiposity association remains unclear. Asthma may be a consequence of obesity; however, asthma may increase adiposity. OBJECTIVES: This study aimed to assess the associations between (i) baseline weight status and subsequent asthma and (ii) baseline asthma and subsequent weight status after 4 and 11 years of follow-up (N = 1543 and N = 1596, respectively) using data from three, sequentially enrolled population-based surveys of Norwegians aged 12-30 years from 1995 to 2008. METHODS: Weight status was defined as general (body mass index) or abdominal (waist circumference) underweight, normal weight, overweight or obesity. Self-report physician-diagnosed asthma defined asthma status. RESULTS: Over the longitudinal 11-year follow-up, baseline generally overweight or abdominally obese adolescents had increased risk of asthma. Likewise, baseline asthmatics had increased risk of general overweight or abdominal obesity. After sex stratification, these associations were stronger in males. Generally (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.32, 2.73) or abdominally (OR 1.66; 95% CI 1.13, 2.44) overweight males were at increased risk of asthma. Baseline asthmatic males were also at increased risk of general (OR 2.14; 95% CI 1.54, 2.98) and abdominal (OR 1.77; 95% CI 1.27, 2.47) overweight. CONCLUSIONS: Among Norwegian adolescents, a bidirectional association of asthma and adiposity was observed in males. Each baseline condition increased the risk of the other condition over time. No association was observed in females.

Smoking and drinking in relation to oral epithelial dysplasia.

Oral epithelial dysplasia (OED) is a histopathological diagnosis that is associated with an increased risk of oral cancer. The purpose of this case-control study was to measure the association between OED and the use of smoking tobacco and alcoholic beverages. Incident cases of OED (n = 127) were identified through two oral pathology laboratories. Controls, pair-matched 1:1 to cases on age (+/- 5 years), gender, appointment date (+/- 1 year), and surgeon, were identified through the office in which the respective case had been biopsied. Exposure information regarding smoking, drinking, and other potential risk factors was obtained through a standardized telephone interview. Conditional logistic regression was used to calculate measures of association and statistical significance. The odds ratio (OR) for current smoking adjusted for drinking, mouthwash use, denture status, and education was 4.1 (95% confidence interval, 2.1-7.9) relative to never/ex-smokers. The risk of OED increased with increasing levels of smoking and declined following smoking cessation, with ex-smokers of 15+ years demonstrating no excess risk relative to never smokers. Individuals drinking 7+ drinks/week, relative to less than that amount, had over twice the risk of OED (OR, 2.4; 95% confidence interval, 1.2-4.8) after controlling for smoking, mouthwash use, denture status, and education. Adjusted ORs tended to increase with increasing levels of alcohol intake. An exploratory analysis suggests that the joint effect of smoking and drinking may be more than additive as regards the risk of OED. The findings of this case-control study implicate smoking and drinking as important risk factors for OED.

Risk of female breast cancer associated with serum polychlorinated biphenyls and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene.

This case-control study was designed to investigate the relationship between polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene (DDE) and breast cancer risk in Connecticut. Cases were incident breast cancer patients who were either residents of Tolland County or who had a breast-related surgery at the Yale-New Haven Hospital in New Haven County. Controls were randomly selected from Tolland County residents or from patients who had newly diagnosed benign breast diseases or normal tissue at Yale-New Haven Hospital. A total of 475 cases and 502 controls had their serum samples analyzed for PCBs and DDE in 1995-1997. The age- and lipid-adjusted geometric mean serum level of DDE was comparable between the cases (460.1 ppb) and controls (456.2 ppb). The geometric mean serum level of PCBs was also comparable between cases (733.1 ppb) and controls (747.6 ppb). After adjustment for confounding factors, odds ratios of 0.96 (95% confidence interval, 0.67-1.36) for DDE and 0.95 (95% confidence interval, 0.68-1.32) for PCBs were observed when the third tertile was compared with the lowest. Further stratification by parity, lactation, and menopausal and estrogen receptor status also showed no significant association with serum levels of DDE or PCBs. The results by PCB congener groups also showed no major increased risk associated with any of the congener groups. Our study does not support the hypothesis that DDE and PCBs, as encountered through environmental exposure, increase the risk of female breast cancer.

Environmental exposure to hexachlorobenzene (HCB) and risk of female breast cancer in Connecticut.

Earlier studies have provided inconclusive results relating hexachlorobenzene (HCB), an organochlorine fungicide, to female breast cancer risk. The current study, with a total of 304 breast cancer cases and 186 controls recruited in Connecticut between 1994 and 1997, examined the association by directly comparing breast adipose tissue levels of HCB between incident breast cancer cases and noncancer controls. The cases and controls were patients who had breast biopsies or surgery at the Yale-New Haven Hospital (New Haven, CT) and histologically diagnosed either as breast cancer or benign breast disease. Information on major known or suspected risk factors for breast cancer was obtained through in-person interview by trained interviewers. No significant difference in mean breast adipose tissue levels of HCB was observed between breast cancer patients (21.0 ppb) and controls (19.1 ppb) in this large case-control study. The risk also did not vary significantly by menopausal status, estrogen or progesterone receptor status of the breast cancer cases, breast cancer histology, stage of diagnosis, or type of benign breast disease. Among parous women who reported ever breast feeding, an odds ratio (OR) of 0.5 [95% confidence interval (CI), 0.2-1.4] was observed when the highest quartile was compared with the lowest quartile. However, no association was observed among parous women who reported never breast feeding (OR = 0.7; 95% CI, 0.3-1.7 for the fourth quartile). For nulliparous women, the adjusted OR was 2.1 (95% CI, 0.5-8.8) for the third tertile when compared with the lowest based on few subjects. Therefore, our study does not support a positive association between environmental exposure to HCB and risk of breast cancer.

Time trend of female breast carcinoma in situ by race and histology in Connecticut, USA.

A rapid increase of female breast cancer has been reported in many areas of the world and the reasons are not fully understood. While some have attributed the increase to the increasing detection of early stage breast cancer through mammography screening, few studies have directly examined the time trend of in situ breast cancer specifically. This study included all incident cases of female breast carcinoma in situ reported to the Connecticut Tumor Registry between 1973 and 1992. The age-adjusted incidence rates and age-specific incidence rates were calculated by histology and by race. The age-adjusted incidence rates were standardised to the 1970 United States standard million population. The study found that the overall age-adjusted incidence rate of in situ breast cancer has increased dramatically, from 3.53/100000 in 1973-1975 to 17.51/100000 in 1991-1992. The increase was not uniform during the past two decades of cancer registration. In fact, most of the observed rise has occurred since the early 1980s. This increase was found in both Caucasians and Blacks. The results by histology indicate that the dramatic increase in carcinoma in situ is mostly attributable to an increase in ductal carcinoma in situ. The increase was also observed in all age groups 40 years and over. These results are consistent with the use pattern and the reported effect of mammography screening. Therefore, these results are qualitatively consistent with the idea that mammography screening is largely responsible for the recent upsurge in female breast cancer incidence in this population. The study also found that the age group 40-49 years in whites experienced a rapid increase in incidence that began in the same time period as the older age groups, but it has since levelled off. The potential impact of the highly publicized debate regarding the efficacy of mammography in this age group in recent years is discussed.

Use of hair colouring products and breast cancer risk: a case-control study in Connecticut.

This case-control study was designed to test the hypothesis that the risk of breast cancer varies by type and colour of the hair colouring products used. A total of 608 cases and 609 controls were included in the study. We found no increased risk associated with the overall use of hair dye products or exclusive use of permanent or temporary types of hair dye products. Among those who reported to have exclusively used semi-permanent types of hair colouring products, some of the ORs were elevated. However, none of the ORs related to age at first use, duration of use, total number of applications, and years since first use, was statistically significant. There was also no increased risk of breast cancer associated with exclusive use of dark or light hair colouring products, or use of mixed types or colours of hair dye products. We also found no increased risk of breast cancer associated with hair dye use based on an individual's reason for using a hair colouring product, such as to cover grey or to change natural hair colour. These data suggest that the use of hair colouring products does not have a major impact on the risk of breast cancer.

Prognostic indicators in diffuse large-cell (histiocytic) lymphoma.

Identification of prognostic groups among patients with diffuse large-cell (histiocytic) lymphoma (DHL) would help to select specific therapy for individual patients and allow comparisons among combination chemotherapy clinical trials. The Ann Arbor staging system is of limited value in predicting outcome in diffuse histiocytic lymphoma. Prognostic factors have been examined by various groups without a consensus of reliable prognostic indicators. This study was undertaken to examine the validity of a predictive model for response to treatment and survival in DHL. Eighty-six patients with the diagnosis of DHL treated with combination chemotherapy between the years 1976 and 1982 were examined for prognostic variables influencing response to treatment and survival. The variables examined included: age, sex, presence or absence of systemic symptoms, serum lactic dehydrogenase (LDH), sites of disease involvement, bulk of disease, prior therapy, stage of disease, according to the Ann Arbor classification, and pathological criteria, according to the Lukes Collins classification. Factors achieving a p-value in the 0 to 0.05 range with univariate analysis for predicting response were age and systemic symptoms. Factors significant for overall survival were age and bone marrow involvement. These factors have been found to influence survival in previous studies, but there has not been a consistency regarding the importance of these factors. Large numbers of patients must be examined for various factors in order to allow identification of prognostic groups among patients with DHL.

Indoor, outdoor, and regional summer and winter concentrations of PM10, PM2.5, SO4(2)-, H+, NH4+, NO3-, NH3, and nitrous acid in homes with and without kerosene space heaters.

Twenty-four-hour samples of PM10 (mass of particles with aerodynamic diameter < or = 10 microm), PM2.5, (mass of particles with aerodynamic diameter < or = 2.5 microm), particle strong acidity (H+), sulfate (SO42-), nitrate (NO3-), ammonia (NH3), nitrous acid (HONO), and sulfur dioxide were collected inside and outside of 281 homes during winter and summer periods. Measurements were also conducted during summer periods at a regional site. A total of 58 homes of nonsmokers were sampled during the summer periods and 223 homes were sampled during the winter periods. Seventy-four of the homes sampled during the winter reported the use of a kerosene heater. All homes sampled in the summer were located in southwest Virginia. All but 20 homes sampled in the winter were also located in southwest Virginia; the remainder of the homes were located in Connecticut. For homes without tobacco combustion, the regional air monitoring site (Vinton, VA) appeared to provide a reasonable estimate of concentrations of PM2.5 and SO42- during summer months outside and inside homes within the region, even when a substantial number of the homes used air conditioning. Average indoor/outdoor ratios for PM2.5 and SO42- during the summer period were 1.03 +/- 0.71 and 0.74 +/- 0.53, respectively. The indoor/outdoor mean ratio for sulfate suggests that on average approximately 75% of the fine aerosol indoors during the summer is associated with outdoor sources. Kerosene heater use during the winter months, in the absence of tobacco combustion, results in substantial increases in indoor concentrations of PM2.5, SO42-, and possibly H+, as compared to homes without kerosene heaters. During their use, we estimated that kerosene heaters added, on average, approximately 40 microg/m3 of PM2.5 and 15 microg/m3 of SO42- to background residential levels of 18 and 2 microg/m3, respectively. Results from using sulfuric acid-doped Teflon (E.I. Du Pont de Nemours & Co., Wilmington, DE) filters in homes with kerosene heaters suggest that acid particle concentrations may be substantially higher than those measured because of acid neutralization by ammonia. During the summer and winter periods indoor concentrations of ammonia are an order of magnitude higher indoors than outdoors and appear to result in lower indoor acid particle concentrations. Nitrous acid levels are higher indoors than outdoors during both winter and summer and are substantially higher in homes with unvented combustion sources.

Simultaneous interval estimates of the odds ratio in studies with two or more comparisons.

More than one odds ratio estimate will often arise from a single epidemiologic study. Examples of designs where this may occur include those where there is more than one case or control group, and investigations of several risk factors as part of the same study. Various methods for presenting multiple interval estimates are discussed, including: the naive method, the Bonferroni method, the Dunn method, the Scheffé method, and the Dunnett method. For rectangular regions the Dunnett method gives a region with the most appropriate confidence level, but this region contains a different set of odds ratio estimates than are implied by the usual significance tests. A confidence ellipse circumscribed by the Scheffé limits gives the best agreement with the significance tests. Each of these methods is illustrated with a numerical example.