Geographic boundaries in breast,lung and colorectal cancers in relation to exposure to air toxics in Long Island,New York

Background  

This two-part study employs several statistical techniques to evaluate the geographic distribution of breast cancer in females and colorectal and lung cancers in males and females in Nassau, Queens, and Suffolk counties, New York, USA. In this second paper, we compare patterns in standardized morbidity ratios (SMR values), calculated from New York State Department of Health (NYSDOH) data, to geographic patterns in overall predicted risk (OPR) from air toxics using exposures estimated in the USEPA National Air Toxics Assessment database.     

Cigarette smoking and risk of bladder, pancreas, kidney, and colorectal cancers in Iowa

PURPOSE: Although there are numerous reports on the effects of cigarette smoking and cancer, they have infrequently compared risks at more than one cancer site after multivariate adjustment. We analyzed data from a population-based case-control study that included five anatomic sites to evaluate the association between cigarette smoking and each cancer site and to rank the associations by site. METHODS: Study respondents included 1452 bladder, 406 kidney, 376 pancreatic, 685 colon, and 655 rectal cancer cases, as well as 2434 population controls. A self-administered questionnaire was used to collect information on cigarette smoking and other potential confounders including occupation, drinking water source, and dietary practices. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), after adjustment for age, total energy intake, and other site- and sex-specific confounders. RESULTS: In both sexes, cigarette smoking (ever vs. never) was associated with risk of bladder cancer (OR = 2.5; 95% CI, 2.0-3.1 for males; OR = 2.7; 2.0-3.6 for females) and pancreatic cancer (OR = 1.8; 1.2-2.8 for males; OR = 2.1; 1.4-3.1 for females). Cigarette smoking also increased the risk of kidney cancer among males (OR = 1.8; 1.3-2.7), and to a lesser degree, among females (OR = 1.2; 0.8-1.8). No association was found for colon or rectal cancer in either sex. CONCLUSIONS: Cigarette smoking increased the risk of bladder, kidney, and pancreatic cancer in men and women. The rankings of multivariate-adjusted ORs from highest to lowest were bladder, pancreas, kidney, and colorectum, with little difference between men and women.     

Environmental exposure to polychlorinated biphenyls and breast cancer risk

Breast cancer is a major public health problem in the United States and in most industrialized countries. Although epidemiologic studies have identified a number of established risk factors for this disease, these factors explain only a small proportion of breast cancer incidence. Environmental exposure has been implicated in breast cancer etiology because of the vast geographic variation in breast cancer incidence rates across countries and regions within countries. Further, the steady increase in breast cancer rates over the past decades points to a potential role of environmental exposure in its development. One suspected environmental factor is the polychlorinated biphenyls (PCBs), which were manufactured commercially for a variety of industrial applications from the 1930s until the 1970s. PCBs have been associated with estrogenic, tumor promoting, and immunosuppressive activities, all of which are relevant in the development of breast cancer. The purpose of this review is to summarize the growing body of epidemiological evidence on the association between environmental PCB exposure and breast cancer risk. Three major types of study design have been used to investigate such a relation: clinic-based case-control studies, retrospective case-control studies, and nested case-control studies. Although findings from clinic-based case-control studies tend to point to an adverse effect of high PCB body burden on risk, the results from the more methodologically sound retrospective and nested studies do not provide strong support for a role of PCBs in breast cancer development. The association between PCB exposure and risk among racially and genetically susceptible subgroups may warrant further investigation. Methodological challenges in the design and analysis of epidemiologic studies on PCBs and breast cancer risk are discussed.     

2006-2017年中国女性乳腺癌和生殖系统癌症发病趋势分析

目的 评估2006-2017年不同年龄和地区女性乳腺癌和生殖系统癌症的发病趋势。方法 结合发病率、人口数计算全国分地区、分年龄的女性乳腺癌、外阴癌、阴道癌、宫颈癌、子宫体癌及卵巢癌的发病数及平均诊断年龄。通过世界标准人口进行标化。采用Joinpoint 4.5.0.1软件计算平均年变化百分比（AAPC）。结果 2006-2017年,6种癌症的合计年龄标化发病率（ASIR）从39.48/10万上升至51.11/10万（AAPC=2.24%,95%CI：1.59%~2.89%）。这一上升趋势在农村地区更加显著（AAPC=4.65%,95%CI：3.67%~5.64%）,而城市地区未见明显上升（AAPC=0.15%,95%CI：-0.26%~0.56%）。除子宫体癌外,其他5种癌症发病均呈上升趋势。宫颈癌的ASIR在城市和农村地区上升趋势相近。乳腺癌、阴道癌和外阴癌的ASIR在城市地区无明显上升趋势,而在农村地区明显上升。卵巢癌的ASIR在城市地区呈下降趋势,而在农村地区则呈上升趋势。从发病年龄上看,除子宫体癌外,所有女性癌症平均诊断年龄均呈上升趋势。通过世界标准人口标化后,仅在宫颈癌和阴道癌中观察到标化平均诊断年龄的上升,从49.11岁和55.15岁分别上升至52.13岁和58.81岁。结论 2006-2017年,女性癌症标化发病率总体呈上升趋势,且农村地区上升趋势高于城市地区。同时,农村居民的医疗资源可及性需进一步提升,保证医疗保健服务和早诊早治,从而弥合女性癌症城乡差距。     

Low-dose bioactivity of xenoestrogens in animals: fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice

The hormonal activity of natural estrogens is influenced by the degree to which they bind to serum proteins. In the pregnant female and in the fetus, greater than 99% of estradiol may be bound by serum binding proteins. Therefore, even though total serum levels of estradiol appear very high in fetuses, we have found that in rodent fetuses, there is a very low free concentration of estradiol (0.2 pg/ml). Naturally occurring variation in fetal serum estradiol predicts differences in numerous postnatal traits, including prostate size. In addition, when this low level of free estradiol was experimentally increased from 0.2 to 0.3 pg/ml during the last third of fetal life, treated male mice showed an increase in adult prostate weight. Fetal exposure to low doses of xenobiotic estrogens by feeding to pregnant females, including the compounds methoxychlor (20 and 2000 micrograms/kg body weight), DES (0.02 to 2 micrograms/kg body weight) and bisphenol A (2 and 20 micrograms/kg body weight), also led to increased prostate weight in adulthood. In contrast, fetal doses of natural estradiol and DES above the physiological range of estrogenic activity, and within a toxicological dose range, led to the opposite outcome, a reduction in subsequent adult prostate weight. This indicates that it may be impossible to assess endocrine-disrupting activities in response to low doses within a physiological range of activity by using high, toxic doses of xenoestrogens in testing procedures. We have developed approaches in vitro to predict the potential estrogenic bioactivity of compounds in the physiologically relevant range in animals and humans. We address the following factors in predicting the final observed endocrine-disrupting effect in the animal: (1) the intrinsic estrogenic activity of a given molecule, (2) the effective free concentration determined by how the molecule is carried in serum, (3) partitioning between aqueous and lipid compartments in body and cell lipids, and (4) absorption and metabolism relative to the route of exposure. The studies and strategies we describe are important in developing criteria for a tiered testing system for the detection of estrogenic chemicals as well as endocrine-disrupting chemicals with different modes of action.     

Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans

After briefly discussing human exposure to phthalates—diesters of 1,2-benzenedicarboxylic acid (phthalic acid)—this article first presents recent findings from the Study for Future Families, a multi-center pregnancy study in which the human analogue of the phthalate syndrome was first identified. This is one of an increasing number of studies that have investigated human endpoints in relation to environmental exposure to these ubiquitous compounds. This literature, which includes a range of human health endpoints following prenatal, neonatal, childhood, and adult exposures, is then summarized. At least one significant association has been reported for urinary metabolites of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BzBP), diethyl phthlate (DEP), and di-isononyl phthalate (DINP) and for three of the urinary metabolites of di(2-ethylhexyl) phthalate (DEHP). Many of the findings reported in humans—most of which have been in males—are consistent with the anti-androgenic action that has been demonstrated for several phthalates. Replication of the results described here and further mechanistic studies are needed to strengthen links between phthalates and adverse health outcomes.     

Environmental estrogens: roles in male reproductive tract problems and in breast cancer

It has been hypothesized that endocrine disruptors and particularly synthetic estrogenic environmental contaminants (xenoestrogens) are etiologic factors in the global decrease of sperm counts and other problems of the male reproductive tract, including cryptorchidism, hypospadias, and testicular cancer. Xenoestrogens might also be linked to an increased incidence of breast cancer in women. These hypotheses have stimulated research addressing the current incidence rates and time-dependent changes in these human health problems, and the results do not support the hypotheses. With the exception of testicular cancer, the evidence does not indicate that sperm counts and other male reproductive tract problems are increasing, and correlations with xenoestrogen exposure have not been made. Moreover, initial observations that the level of certain organochlorine pollutants is higher in breast cancer patients vs. controls have not been duplicated in more recent studies. The results do not preclude an environmental eitology to some of these health problems or to susceptible subpopulations, and these areas require further research and critical scrutiny.     

P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers.

In this paper we describe a statistical analysis of the European Molecular Library p53 mutation database comparing p53 mutations occurring in breast, colorectal, liver, lung, and ovarian cancers. The analyses show that mutation hot spots vary by cancer and that base pair changes and predicted amino acid changes in the gene product vary by cancer and by codon. The analyses use relative frequencies and epidemiologic measures of effect (prevalence ratios) not applied previously to these data. The five cancers in the database with the largest sample sizes were breast (418), colorectal (398), liver (341), non-small cell lung (313), and ovarian cancers (251), for a total of 1,721 reports of p53 mutations. The five cancers varied considerably in the distribution of mutations over sites, with different hot spots in each cancer. At the six most frequently reported codon sites, we compared base pair and amino acid changes by type of cancer. The comparison of base pair changes indicated a predominance of particular base pair changes at a codon (for example, C-->T and G-->A changes at Codon 248) and their association with specific cancers (C-->T changes with colorectal cancer and G-->A changes with both colorectal and breast cancers at codon 248). Comparing predicted amino acid changes by codon and cancer was also intriguing, as in codons 175 and 273, where arginine to cysteine and arginine to histidine changes were frequent in breast, colorectal, and ovarian cancers. Variations in p53 mutational distributions by cancer may be explained by different exposures to carcinogens or by organ-specific clonal selection. Further research may be stimulated by this analysis.     

母乳和配方奶粉中的环境化学品:暴露和风险评估影响

近年来,人类健康风险评估方法不断发展和进步,以更准确地评估与儿童期暴露相关的风险。然而,预测婴儿暴露于母乳和配方奶粉中的环境化学物质的风险仍然具有挑战性。该研究的目的是汇编有关婴儿暴露于母乳和配方奶粉中的环境化学品的现有信息,阐述在风险评估的背景下描述婴儿暴露和潜在健康风险的方法,并确定根据此类暴露和健康风险信息改进风险分析所需的研究。该研究回顾了有关母乳和配方奶粉中环境化学物质含量的最新文献,重点是来自美国的数据。然后,选择了三个实例出版物,利用母乳或配方奶粉的化学浓度和估计母乳或配方奶粉的摄入量来量化婴儿的暴露。通过与现有健康风险基准进行比较,确定这些膳食暴露可能带来的健康风险特征。该研究确定了这一方法需要改进的领域,以便更好地描述这一关键暴露途径对婴儿健康的潜在风险。母乳和配方奶粉中化学物质的测定对于评估早期膳食暴露于环境化学物质的风险是不可或缺的。风险评估也可以通过调查婴儿期化学品暴露对已知活跃且易受干扰的发育过程的影响的研究,以及分析特定于婴儿生命阶段的暴露-反应数据来进行。所有这些领域都存在重要的数据差距。该研究发现,为确定婴儿在母乳和婴儿配方奶粉中暴露于环境化学物质的特征,并改进对这两种食品中发现的化学物质的风险评估,需要进行更好的设计研究。     

Metsovo lung: pleural calcification and restrictive lung function in northwestern Greece. Environmental exposure to mineral fiber as etiology

Pleural calcifications are described in 122 of 268 (45.5%) inhabitants of four villages (Metsovo, Anilio, Milea, and Votonosi) in a small area of northwestern Greece (total population about 5000). All affected individuals are of one ethnic group, Vlachi. Calcifications were not noted in any of the 103 persons in the control group made up of 73 non-Vlachi inhabitants from the same and neighboring villages and 30 Vlachi from distant villages. The calcifications were seen in both sexes, equally, and their frequently increased with age, from 28.6% between 30 and 39 years to 81.0% in individuals over 70 years of age. When plaque development was extensive, a small restrictive pulmonary function defect was noted. Because of its prevalence in the Metsovo area we call this clinical pattern Metsovo lung. The identification of tremolite, related amphibole fibers, and traces of chrysotile fiber in settled dusts and soil specimens and of identical fibers in tissue specimens obtained at lung biopsy from 8 people with plaques supports the hypothesis that abestiform minerals are the agents responsible for these disease processes. Further, reports of the occurrence of mesothelioma and benign pleural effusions in inhabitants in the Metsovo area, along with the striking similarities to disease patterns observed in the Karain area of Turkey, add further weight to the hypothesis that mineral fiber(s) in the environment of the four villages are agent(s) in the etiology of Metsovo lung.     

雌激素相关基因及生殖因素对乳腺癌协同作用

目的研究CYP1A1 MspⅠ，ERα PvuⅡ，ERα XbaⅠ基因多态性与生殖、生育因素在乳腺癌发生中的协同作用。方法本研究样本来自1999年1月-2001年4月，在上海市进行的以人群为基础的乳腺癌病例对照研究。采用PCR-限制性酶切长度多态性法（PIER—RFLP）对282例乳腺癌病例和298例口腔黏膜细胞对照标本进行3个候选基因位点的检测，拟合Logistic回归模型，估计基因多态与生殖、生育因素对乳腺癌协同作用OR值和95％CI，并采用Rothman方法对基因一环境的协同作用进行估计。结果良性乳腺疾病史与CYPIA1 MspⅠ多态存在正相加协同作用。与基准组比较，OR为5．66（95％CI=3．28-9．76），协同作用指数S=2．05，协同作用归因比AP=0．42，经检验差异有统计学意义（P〈0．05）。未发现其他生殖、生育因素与3个基因位点有显著的协同作用。结论良性乳腺疾病史与CYP1A1 MspⅠ基因之间存在增加乳腺危险的协同作用。     

Smoking, occupational exposure to rubber, and lung cancer

A cohort of 1624 employees (957 men, 667 women) in a rubber factory in Shanghai have been followed up since 1972 and their 12 year mortality experience is presented. The relative risk of lung cancer for smokers was 8.5 for men and 11.4 for women and for rubber workers exposed to curing agents or talc powder 3.2 for men and 4.6 for women.     

Cadmium levels in the lung,liver, kidney cortex,and urine samples from Australians without occupational exposure to metals

The authors undertook this study to assess levels of cadmium exposure in the general population. Samples of lung, liver, and kidney were obtained from 61 cadavers (43 males, 18 females; 2-89 yr of age, mean age = 38.5 yr) who died from accidental causes and who were subject to postmortem examinations at the John Tonge Centre for Forensic Sciences, Queensland Health Scientific Services, Brisbane, Australia, in 1997 and 1998. Samples of bladder urine were also obtained from 22 cadavers. Tissue and urine samples were analyzed for cadmium, zinc, and copper with inductively coupled plasm (ICP) mass spectrometry. The overall mean values for cadmium in the lung, liver, and kidney cortex samples were 0.13, 0.95, and 15.45 microg/gm wet tissue weight. The average renal cadmium level in subjects with high lung-cadmium levels (n = 13) was 6 microg/gm wet tissue weight higher than that of similarly aged subjects who had medium lung-cadmium levels (n = 30). In females, the average level of cadmium in the liver was 74% greater than in males, and the average liver cadmium in females with high lung-cadmium levels was 100% higher than in males in the same age range who had the same high lung-cadmium levels. Renal cadmium accumulation tended to be greater in females than in males who were in the same age range and who had similar lung-cadmium levels, a result that suggested that there was a higher absorption rate of cadmium in females. The mean value for a urinary cadmium excretion of 2.30 microg/gm creatinine was found in a subset of samples that had a mean age of 39 yr and a renal cortex cadmium concentration of 18.6 microg/gm wet tissue weight. Urinary cadmium excretion rates were correlated more strongly with lung and kidney cadmium content than with age or liver cadmium levels. The results suggest that urinary cadmium excretion may be increased in smokers and could provide some estimate of body cadmium burdens in future Australian epidemiological studies.     

Concurrent exposure to lead,manganese, and cadmium and their distribution to various brain regions,liver, kidney,and testis of growing rats

Growing rats were exposed to 5 mg/L Pb,ad libitum in drinking water, and administered low or high doses of Mn and Cd intraperitoneal (i.p.) for 30 days. Some groups of animals were also administered combinations of Pb + Mn and Pb + Cd in an identical manner. Analysis of Pb, Mn, and Cd in tissue samples showed the expected dose-dependent accumulation when the metal was administered singly. However, combined treatment produced different types of metal shift in different tissues. Enhanced accumulation of all three metals in the brain, Mn in liver, Pb in kidney and Cd in testis and kidney after combined exposure may make target organs vulnerable to the toxic effects of metals, even when encountered at low concentrations. Further, the decreased levels of blood Pb after combined treatment with Cd or Mn suggests that the significance of blood Pb level as a diagnostic aid for Pb toxicity in coexposed conditions may not be of much value. Changes in the metallic distribution within the tissues after coexposure may be the result of a competition between the administered metals for common binding sites.     

A clinical and immunologic study to assess risk of TMA-induced lung disease as related to exposure

The objective of this study was to determine whether there are trimellitic anhydride (TMA) exposure levels that are very unlikely to cause immunologically mediated respiratory disease. A 3-year clinical and immunologic survey study of 286 employees was conducted at a facility that manufactures TMA. Each employee was assigned an exposure classification from 1 (highest) to 5 (lowest). Of the 28 individuals in exposure class 1, 8 (29%) developed disease; of the 57 class 2 employees, 2 (4%) developed disease; of the 79 class 3 employees, 4 (5%) developed disease. Of the 98 class 4 employees and the 24 class 5 employees, none developed disease. Inasmuch as individuals in class 4 and 5 (TMA exposure < 0.002 mg/m3) are at low risk of developing disease due to TMA, it appears that they do not warrant routine inclusion in surveillance studies.     

Smoking, occupational exposure to rubber, and lung cancer.

A cohort of 1624 employees (957 men, 667 women) in a rubber factory in Shanghai have been followed up since 1972 and their 12 year mortality experience is presented. The relative risk of lung cancer for smokers was 8.5 for men and 11.4 for women and for rubber workers exposed to curing agents or talc powder 3.2 for men and 4.6 for women.     

Low dose exposure to cadmium and its health effects (2). Life-cycle related diseases and reproductive toxicity

We have reviewed earlier studies on the possible involvement of cadmium in life-cycle related diseases and the reproductive toxicity of Cd including environmental disrupting actions. Experimental studies have suggested that Cd may be involved in the aggravation of life-cycle related diseases and the occurrence of reproductive toxicity. On the other hand, epidemiological studies did not necessarily support the experimental observations. Thus, we conclude that it is necessary to investigate further to determine whether Cd is responsible for the aggravation of life-cycle related diseases or has the capability to act as an environmental endocrine disrupter in humans.