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PubMed1999

Interactions of familial and hormonal risk factors for large bowel cancer in women.

BACKGROUND: Family history of colorectal cancer has been consistently associated with an increased personal risk of this disease. Since evidence suggests that hormones are related to colon cancer risk in women, the effect of family history on large bowel incidence may be modified according to endogenous and exogenous hormone levels. METHODS: We analysed data from a population-based case-control study of female colorectal cancer to evaluate family history and cancer risk. Cases (n = 702) were female residents of Wisconsin with a new diagnosis of colorectal cancer, identified through a statewide tumour registry. Controls (n = 2274) were randomly selected from lists of licensed drivers and from rosters of Medicare beneficiaries. All relative risks (RR) were adjusted for age, body mass index, smoking and alcohol history, education, and use of hormone replacement therapy. RESULTS: Compared with women who reported no history of cancer in a first degree relative, women with a family history had an RR of 2.07 (95% confidence interval [CI]: 1.60-2.68). Regardless of which parent was affected, risks were increased about twofold, while sibling history was associated with about a 50% increase in risk. Risk was greater if more than one family member was affected (RR 3.65, 95% CI: 1.81-7.37). The association between family history and risk was stronger for colon cancer than for rectal cancer. There were no indications that exogenous hormonal factors, notably hormone replacement use, modified these risks. There was a suggestion that high parity attenuated the risks associated with family history (P = 0.07). CONCLUSIONS: These results confirm that family history of colorectal cancer is associated with a doubling of risk for large bowel cancer in women; some histories were associated with greater risk. This relation was not substantially different among subgroups of women with varying exogenous and endogenous hormone exposures.

Aged↗

PubMed2025

Dynamic clustering of genomics cohorts beyond race, ethnicity-and ancestry.

BACKGROUND: Recent decades have witnessed a steady decrease in the use of race categories in genomic studies. While studies that still include race categories vary in goal and type, these categories already build on a history during which racial color lines have been enforced and adjusted in the service of social and political systems of power and disenfranchisement. For early modern classification systems, data collection was also considerably arbitrary and limited. Fixed, discrete classifications have limited the study of human genomic variation and disrupted widely spread genetic and phenotypic continuums across geographic scales. Relatedly, the use of broad and predefined classification schemes-e.g. continent-based-across traits can risk missing important trait-specific genomic signals. METHODS: To address these issues, we introduce a dynamic approach to clustering human genomics cohorts based on genomic variation in trait-specific loci and without using a set of predefined categories. We tested the approach on whole-exome sequencing datasets in ten cancer types and partitioned them based on germline variants in cancer-relevant genes that could confer cancer type-specific disease predisposition. RESULTS: Results demonstrate clustering patterns that transcend discrete continent-based categories across cancer types. Functional analysis based on cancer type-specific clusterings also captures the fundamental biological processes underlying cancer, differentiates between dynamic clusters on a functional level, and identifies novel potential drivers overlooked by a predefined continent-based clustering. CONCLUSIONS: Through a trait-based lens, the dynamic clustering approach reveals genomic patterns that transcend predefined classification categories. We propose that coupled with diverse data collection, new clustering approaches have the potential to draw a more complete portrait of genomic variation and to address, in parallel, technical and social aspects of its study.

Humans↗

PubMed2026

Cell Type-Resolved Causal Inference and Spatial Transcriptomic Integration Reveal Immune-Specific Genetic Drivers of Autoimmune and Malignant Thyroid Disease.

BACKGROUND: Thyroid diseases, including autoimmune thyroid disease (AITD) and thyroid cancer, are characterized by immune dysregulation, yet the cell type-specific genetic mechanisms underlying these conditions remain poorly understood. Most genome-wide association studies (GWAS) have relied on bulk tissue expression quantitative trait loci (eQTL), which cannot resolve the heterogeneity of immune cell populations. METHODS: We performed two-sample Mendelian randomization (MR) analyses using single-cell cis-eQTLs from 14 immune cell subtypes (OneK1K cohort) as instrumental variables against GWAS summary statistics for four thyroid outcomes: autoimmune hyperthyroidism, autoimmune hypothyroidism, thyroid cancer and autoimmune thyroiditis. Causal associations were validated through Bayesian colocalization, phenome-wide association analysis (PheWAS) and multi-layered transcriptomic validation encompassing spatial transcriptomics of AITD tissue (GSE248205), bulk RNA-seq of thyroid cancer (GSE3678) and single-cell RNA-seq of thyroid tumours (GSE250521). gsMap spatial LD score regression was applied to map disease heritability onto spatial tissue architecture. RESULTS: We identified six Bonferroni-significant causal gene-cell type pairs for autoimmune hyperthyroidism, including protective effects of ABHD16A in naïve/immature B cells (OR = 0.440), HIST1H3H in CD8 NC T cells (OR = 0.324), HMGN4 in NK recruiting cells (OR = 0.556) and ZKSCAN4 in CD8 S100B T cells (OR = 0.427), with five pairs showing strong colocalization (PP.H4 ≥ 86%). Three pairs reached significance for autoimmune hypothyroidism, including a risk association of HLA-F in CD4 NC T cells (OR = 1.139). For autoimmune thyroiditis, FAM134B/RETREG1 showed consistent suggestive protective associations across both CD4 and CD8 NC T cells (PP.H4 ≥ 90% for both), suggesting a possible involvement of ER phagy regulation in thyroiditis susceptibility. Thyroid cancer showed a suggestive association with HLA-G in classical monocytes (OR = 1.899, PP.H4 = 53%). Spatial transcriptomic validation demonstrated progressive immune infiltration from control tissue to Graves' disease to Hashimoto's thyroiditis (7.7%-15.7%, 46.1%-54.1%, respectively) and strong spatial correlation between target gene expression and corresponding cell type enrichment (e.g., plasma cell-HLA-DQB1: r = 0.491, p < 10-300). HLA-G was independently validated in thyroid cancer bulk (log2fc = 0.542, p = 9.51 × 10-3, AUC = 0.857) and single-cell datasets. PheWAS revealed no significant associations detected for the core candidates. gsMap identified significant enrichment of autoimmune hypothyroidism heritability in gastrointestinal tract, adrenal gland and adipose tissue (all Bonferroni p < 0.002). CONCLUSIONS: This study establishes a multi-scale analytical framework integrating cell type-resolved genetic inference with spatial tissue validation, revealing distinct immunogenetic architectures underlying autoimmune versus malignant thyroid disease. Protective genetic programs in autoimmune hyperthyroidism converge on chromatin remodelling (HIST1H3H, HMGN4, ZKSCAN4) and lipid metabolism (ABHD16A) across lymphocyte subsets, whereas thyroid cancer risk involves immune escape mediated by HLA-G in myeloid cells. The ER-phagy receptor RETREG1 represents a candidate pathway warranting further investigation in autoimmune thyroiditis. These findings provide genetically supported, cell type-specific therapeutic targets and demonstrate a generalizable strategy for dissecting the immune-mediated mechanisms of complex thyroid diseases.

Mendelian randomization↗

PubMed2003

Early life risk factors in cancer: the relation of birth weight to adult obesity.

The intrauterine environment appears to play a role in the development of adult diseases, including several prominent cancers. Our study aims to characterize the relationship between birth weight, a measure of the intrauterine environment, and adult obesity. A population-based sample of women aged 50-79, living in the states of Massachusetts, New Hampshire or Wisconsin, were randomly selected from lists of licensed drivers and Medicare beneficiaries to participate as controls in a case-control study of breast cancer. Information on birth weight, adult height and adult weight were collected through structured telephone interviews from 1992-1995. Our analysis was based on 1,850 interviews. A U-shaped relationship between birth weight and adult BMI was observed. Median adult BMI for the birth weight categories (in kilograms) <2.3, 2.3<2.5, 2.5<3.2, 3.2<3.9, 3.9<4.5 and > or =4.5 were 26.6, 24.4, 25.1, 25.5, 25.4 and 26.6 kg/m respectively. Compared to women 2.5<3.2 kg at birth, women in highest birth weight category (> or =4.5 kg) had an odds ratio of 1.99 (95% CI 1.13-3.48) of being obese (> or =30 kg/m(2)) as adults. The odds ratio for women in the <2.3 kg birth weight category was 1.67 (95% CI 1.01-2.76). These data suggest that both low and high birth weights are associated with higher adult BMI and support the hypothesis that fetal experience may influence adult obesity with potential consequences for risk of several major cancers.

Aged↗

PubMed2026

Subtype-specific clinical significance of RRM1 and RRM2 expression in non-small cell lung cancer: a TCGA-based analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), exhibits significant molecular heterogeneity. Ribonucleotide reductase (RNR), composed of RRM1 and RRM2, is essential for DNA synthesis and repair, but its subtype-specific clinical significance in NSCLC remains unclear. OBJECTIVE: To investigate the clinical and prognostic significance of RRM1 and RRM2 expression in NSCLC, with a focus on subtype-specific differences between LUAD and LUSC. METHODS: We analyzed RNA expression and clinical data from 980 NSCLC patients in The Cancer Genome Atlas (TCGA). Associations with clinicopathologic characteristics, overall survival, and oncogenic driver alterations were assessed. RESULTS: In LUAD, high RRM2 expression was significantly associated with advanced pathologic stage (p = 0.004), nodal involvement (p = 0.005), higher T stage (p = 0.030), and gender (p = 0.046). In LUSC, RRM2 was associated with age (p = 0.008), pathologic stage (p = 0.006), and N stage (p = 0.001). RRM1 showed no significant associations with stage-related parameters in either subtype. Correlation analyses revealed modest associations between RRM1 and multiple oncogenic drivers, whereas RRM2 showed stronger subtype-specific correlations, particularly with KRAS/BRAF in LUAD and CDKN2A/SOX2 in LUSC. Kaplan-Meier analysis demonstrated that high expression of both RRM1 and RRM2 was associated with poorer overall survival in LUAD, but not in LUSC. However, neither marker remained significant after adjustment for clinicopathological variables in multivariate analysis. CONCLUSION: RRM2 is associated with tumor progression in both NSCLC subtypes, while the prognostic associations of RRM1 and RRM2 are confined to LUAD. Although neither marker demonstrated independent prognostic significance in multivariate analysis, the findings support subtype-dependent roles of RNR components and highlight the potential biological and therapeutic relevance of nucleotide metabolism pathways in LUAD.

Carcinoma, Non-Small-Cell Lung↗

PubMed2026

Integrating single-cell transcriptomics to construct an oncogene-driven prognostic model and elucidate metabolic-immune crosstalk in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, its progression and treatment heterogeneity are mainly influenced by driver gene and tumor micro-environment (TME) interactions. Nevertheless, the mechanisms of this process at the single-cell level remain unclear. This study integrated TCGA and multi-center single-cell transcriptome data to identify a 575 genes HCC-specific core set, developing a single-cell "oncogene scoring" system to quantify individual carcinogenic activity. This score is significantly elevated in malignant and proliferative T cells and is closely associated with metabolic reprogramming, aberrant cell‒cell communication, and immunosuppressive phenotypes. Based on these characteristics, we constructed a machine learning-based Random Survival Forest (RSF) prognostic model validated in multiple independent cohorts, which classifies patients into distinct risk subtypes. The high-risk group exhibits genomic instability, increased tumor stemness, and immune evasion, while the low-risk group was more sensitive to drugs such as sorafenib. This study highlights the potential pathways by which high oncogenic activity is associated with HCC progression, suggesting a profound link with single-cell metabolic‒immune crosstalk. The constructed RSF model offers a promising computational framework for risk stratification and provides hypothesis-generating insights that may inform future personalized treatment strategies for HCC patients.

Hepatocellular carcinoma↗

PubMed2005

Sirolimus: its role in nephrology.

Sirolimus (Rapamycin, Wyeth Pharmaceuticals Australia Pty Ltd, Baulkham Hills, NSW, Australia) (SRL) has received increasing attention as an immunosuppressant in renal and other solid organ transplantation. Sirolimus is the first marketed agent in a new class of drugs with a novel mechanism of action. Sirolimus binds, like tacrolimus, to a member of the FK binding protein (FKBP) family. The SRL/FKBP complex binds to the protein kinase mTOR. Binding to mTOR blocks activation of signal transduction pathways causing arrest of the cell cycle in the G1 phase. It is now known that mTOR is a central regulator of cell growth and proliferation. The immunosuppressive properties of SRL are due primarily to blockade of interleukin-2 (IL-2)-induced proliferation of T cells. There is still much to be learnt about how best to use the drug. The key advantage over the current choice of immunosuppressive agents is the ability to preserve renal function and pathology while producing excellent rejection-free, graft survival rates. Thus, SRL may find its pivotal role as a calcineurin inhibitors replacement in patients whose grafts are affected by chronic allograft nephropathy. A second major driver for use may prove to be the impact of SRL on cancer incidence and prognosis. Studies still need to be performed to evaluate the best timing for commencement of SRL and the optimal dosage to minimize side-effects.

Animals↗

PubMedDate not supplied

Evaluating technology for acquisition.

Cancer care consumes approximately 8% to 9% of all healthcare spending. The use of technology plays a key role in cancer, with both diagnostic and treatment implications, and technology is a large driver of healthcare spending. Understanding the role of technology and its integration in care may contribute to appropriate selection and utilization of technology, better decision making as to priorities in acquisition, and clinical cost efficiency.

Capital Expenditures↗

PubMed1976

Cancer in the offspring of fathers in hydrocarbon-related occupations.

A case-control study has been conducted to see whether a hydrocarbon-related occupation of the father at the time of conception constitutes a risk factor for malignant disease in the offspring. The series comprised 852 cancer cases from the Finnish Cancer Registry and 852 controls matched for date of birth and domicile. The father's occupation for both the cases and controls was ascertained from the records of antenatal clinics. No significant associations were found between the commonest types of childhood cancer and hydrocarbon-related occupations--that is, motor-vehicle mechanics, machinists, miners, painters, and motor-vehicle drivers. Risk ratio 2 was excluded from most of the 95% confidence intervals for children under 15 years of age. The results do not support the hypothesis that there is an excess risk of cancer in the children of fathers in hydrocarbon-related occupations.

Adolescent↗

PubMed2026

Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.

For the past decades, chemotherapy constituted the therapeutic foundation in advanced or metastatic pancreatic cancer. Despite significant advances in the molecular understanding, translation into tangible patient benefit has remained modest. Until recently, mutant KRAS, the dominant oncogenic driver, was considered undruggable, and only a small subgroup of patients potentially benefited from targeted therapies. With the emergence of KRAS inhibitors, most patients with pancreatic cancer in theory qualify for targeted therapeutics. Final results from the RASolute 302 trial showed clinically meaningful activity of RAS inhibition in patients with metastatic pancreatic cancer and paved the way for approval. Ongoing preclinical and coclinical studies have documented both intrinsic and acquired mechanisms of resistance to KRAS inhibition. Given the cellular plasticity seen in pancreatic cancer, the identification and anticipation of resistance mechanisms will be critical to exploit emerging therapeutic vulnerabilities through novel combination strategies. In view of the increasing number of trials and the growing body of evidence for targeted therapies, pancreatic cancer is entering a transitional phase in which precision oncology strategies must be redefined beyond rare molecular subgroups. In this review, we will briefly revisit targeted therapeutic approaches in pancreatic cancer to then discuss the clinical implications of genomic and transcriptomic heterogeneity in KRAS-mutant and KRAS wild-type disease. We will outline how our expanding biological insights into pancreatic cancer could inform combination and sequential therapeutic approaches.

Humans↗

PubMed1996

Variation in female breast cancer risk by occupation.

Data from a population-based case control study were used to estimate occupation-specific relative risks for female breast cancer, adjusted for established breast cancer risk factors. Breast cancer cases under age 75 were identified from tumor registries in four states. Controls were randomly selected from driver's license and Medicare beneficiary lists. Information on usual occupation and risk factors was obtained by telephone interview. Odds ratios from logistic regression adjusted for age, state, body mass index, benign breast disease, family history of breast cancer, menopausal status, age at menarche, parity, age of first birth, lactation history, education, and alcohol consumption were calculated for each of 26 occupational groups. Complete occupational information was obtained for 6,835 cases and 9,453 controls. Of 26 occupational groups, only "administrative support occupations" had a statistically significantly increased risk of breast cancer (OR = 1.15, 95% CI 1.06-1.24). In these data, no specific occupational group had an unusual risk of breast cancer. Increased risks reported elsewhere for nurses and teachers were not corroborated.

Administrative Personnel↗

PubMed2026

Landscape of genetic alterations affecting cancer genes in primary and advanced malignant phyllodes tumours.

BACKGROUND: Malignant phyllodes tumours (MPT) are aggressive breast fibroepithelial neoplasms. Their rarity has limited their genetic characterization, and associations with genetic ancestry and progression drivers remain poorly understood. Prior studies suggest two evolutionary pathways according to MED12 mutational status. We sought to determine the repertoire of somatic genetic alterations in cancer genes in primary versus metastatic/recurrent MPTs, and according to MED12 mutational status and genetic ancestry. MATERIALS AND METHODS: We analysed the paired tumour-normal targeting sequencing data (up to 505 cancer-related genes) of 31 MPTs (primary, n = 20; metastatic/recurrent, n = 11). RESULTS: Metastatic/recurrent MPTs harboured a numerically higher frequency of genetic alterations in CDKN2A/2B (55% vs. 25%). Moreover, analysis of an MPT case with paired primary and metastatic samples revealed a CDKN2A/2B homozygous deletion restricted to the metastatic sample, suggesting a role for CDKN2A/2B in progression. Compared with MED12-wild type MPTs, MED12-mutant MPTs had higher tumour mutation burden (P = 0.002), frequency of TERT promoter (82% vs. 35%; P = 0.02) and RB1 mutations (45% vs. 5%; P = 0.01). Genetic alterations in the PI3K pathway, including PIK3CA and PTEN, were only present in MED12-wild type MPTs, and absent in MED12-mutant cases (15% vs. 0%; P > 0.05). Furthermore, genetic alterations in EGFR were restricted to MPTs from patients of European genetic ancestry and absent in those of Asian ancestry (43% vs. 0%; P > 0.05). CONCLUSIONS: Taken together, the repertoire of genetic alterations in primary and metastatic/recurrent MPTs shows overlap, and CDKN2A/2B homozygous deletions may play a role in progression. Additionally, molecular profiles of MPTs may vary according to genetic ancestry and MED12 mutational status.

Humans↗

PubMed1983

Lung cancer and occupation in Alameda County: a death certificate case-control study.

A case-control comparison of lung cancer deaths versus deaths from all other cancers occurring in Alameda County, California, between 1958 and 1962 was conducted to investigate possible associations between lung cancer and occupation. Age-adjusted, sex-specific analyses indicated that a history of work in certain industries and occupations was associated with an increased risk of lung cancer. Among males, a significant positive association was found for glass, metal, furniture, professional and photographic equipment, rubber, leather and plastic manufacturing; water and air transportation; auto repair services; and construction. Specific occupations associated with a significant positive risk for males were: electricians, aircraft mechanics, painters, plasterers, machine operators, construction workers, bus and truck drivers, and guards and nightwatchmen. Among females, beauticians had a significantly high risk associated with lung cancer. These results were consistent with other studies of lung cancer related to occupation.

Adult↗

PubMed2026

Age and sex: dual drivers remodeling the anti-tumor immune microenvironment and shaping personalized immuno-oncology.

Despite breakthrough advancements in cancer immunotherapy, significant inter-individual heterogeneity in clinical outcomes persists, bringing the regulatory roles of intrinsic host biological variables into sharp focus. Accumulating fundamental and clinical evidence indicates that age and sex play crucial roles in determining tumor susceptibility, disease progression, and the remodeling of the anti-tumor immune microenvironment. This review systematically delineates the profound impacts of the dual dimensions of age and sex on anti-tumor immune responses and immune evasion mechanisms. In the dimension of age, this article outlines the progressive functional decline of T/B lymphocytes and innate immune subsets driven by immunosenescence, and emphatically reveals how inflammaging and its associated senescence-associated secretory phenotype (SASP) orchestrate the formation of an immunosuppressive tumor microenvironment. In the dimension of sex, we deeply explore four core mechanisms comprising sex chromosome genomics (e.g., escape from X-chromosome inactivation and loss of Y chromosome), sex hormone networks, microenvironmental metabolic reprogramming, and the host gut microbiome, elucidating the molecular basis driving the disparities in innate and adaptive immunity between males and females. In summary, thoroughly deciphering the complex immune regulatory networks driven by age and sex not only helps elucidate the disparities in efficacy and toxicity observed in patients undergoing immune checkpoint inhibitors, but also provides crucial theoretical foundations and translational insights for the future development of "age-tailored" and "sex-specific" strategies in personalized immuno-oncology.

Humans↗

PubMed2026

Genomic instability, postoperative recurrence and therapeutic vulnerabilities in resectable non‑small cell lung cancer (Review).

Resectable non‑small cell lung cancer (NSCLC) is managed largely according to anatomical stage, pathological risk and actionable driver alterations, yet these factors do not fully explain postoperative recurrence. Genomic instability may contribute to recurrence by promoting clonal diversification, intratumoral heterogeneity, occult dissemination, persistence of residual tumor cells, and immune escape. In the present review, chromosomal instability (CIN), copy‑number complexity, whole‑genome doubling, DNA repair defects, replication stress, and extrachromosomal DNA (ecDNA) were critically evaluated using a three‑axis translational framework encompassing biological consequences, potential clinical roles, and strength of evidence. Current evidence suggests that clonal diversity and copy‑number complexity have the clearest near‑term prognostic rationale. By contrast, CIN and whole‑genome doubling are supported more strongly by evolutionary and mechanistic rather than prospective clinical evidence. Defects in DNA repair, replication stress, and ecDNA represent potential therapeutic vulnerabilities, but their clinical relevance remains to be established. To date, no treatment‑predictive biomarkers based on genomic instability have been identified for resectable NSCLC. Direct clinical evidence linking any specific genomic instability feature to the presence or longitudinal dynamics of postoperative molecular residual disease (MRD) remains limited. Postoperative circulating tumor DNA‑defined MRD provides prognostic information more directly related to residual disease but remains assay‑dependent and should not be considered a genomic‑instability phenotype. Therefore, features of genomic instability should remain investigational and should not replace established clinical, pathological, or molecular decision‑making. Their near‑term value lies in refining biological risk models and generating testable hypotheses for biomarker‑defined perioperative trials.

Humans↗

PubMed2026

Kinesins in Cancer Drug Resistance: Mechanisms, Therapeutic Targeting, and Translational Potential.

Drug resistance in cancer remains a major barrier to durable therapeutic benefits and limits the effectiveness of chemotherapy, targeted therapy, and combination treatment in multiple malignancies. Increasing evidence indicates that specific kinesin superfamily proteins contribute to tumor adaptation and therapeutic response in a context-dependent manner through their roles in mitotic regulation, intracellular transport, and stress-response pathways. Aberrant expression of multiple kinesin family members has been documented across diverse cancers and is frequently associated with aggressive clinicopathological features, poor prognosis, and resistance to treatment. However, expression alterations alone do not establish functional dependency, and mechanistic validation is required to distinguish true resistance drivers from adaptive tumor states. In this review, we summarize the classification, biological functions, and abnormal expression patterns of kinesins in cancer; discuss the major mechanisms through which they contribute to drug resistance; and examine strategies for targeting kinesins, including natural-product-derived direct inhibitors, small-molecule inhibitor development, rational combination approaches, and structure-guided and computational optimization strategies. We also evaluate the biomarker potential of kinesin dysregulation and the value of advanced preclinical models for mechanistic and translational investigations. Finally, we highlight the major challenges that hinder clinical translation, including target specificity, compensatory resistance, insufficient biomarker validation, and tumor heterogeneity. Future progress will require integration of functional genomics, multiomics profiling, and mechanism-guided therapeutic strategies to determine when kinesin inhibition represents a clinically actionable approach for resistant malignancies.

biomarker potential↗

PubMed2002

Chromosomal damage in peripheral blood lymphocytes of traffic policemen and taxi drivers exposed to urban air pollution.

Urban air contains a diversity of chemical compounds, some of which are genotoxins. An increased risk of cancer has also been reported in occupations with heavy exposure to traffic-related pollution. The aim of this study was to assess the cytogenetic effects of urban air pollution by analyzing the chromosomal aberration (CA) frequencies in lymphocytes and to estimate the polycyclic aromatic hydrocarbons (PAHs) exposure by measuring urinary 1-hydroxypyrene (1-OHP) levels. A total of 15 traffic policemen and 17 taxi drivers working in the city of Ankara were the exposed groups and 23 healthy men working in the office departments were the control group. The overall mean +/- S.D. values of 1-OHP excretions of traffic policemen, taxi drivers and control subjects were 0.59 +/- 0.40 micromol/mol creatinine, 0.32 +/- 0.25 micromol/mol creatinine and 0.57 +/- 0.36 micromol/mol creatinine, respectively. Urinary 1-OHP levels of non-smoking policemen were significantly greater than those of nonsmoking control subjects (p < 0.05). The overall mean +/- S.D. values for CA frequencies (%) from policemen, taxi drivers and control group were 1.29 +/- 1.59, 1.81 +/- 1.79, and 0.26 +/- 0.73, respectively. There was a significantly greater frequency of CAs in exposed groups relative to the matched control population (p < 0.05; p < 0.01). Age, sex and smoking habits have not influenced the cytogenetic end-point in this study. Our results demonstrate that occupational exposure to urban air pollutants leads to a significant induction of cytogenetic damage in peripheral lymphocytes of traffic policemen and taxi drivers.

Adult↗

PubMed2003

History of antibiotic use and risk of non-Hodgkin's lymphoma (NHL).

A population-based, incidence case-control study was conducted among women in upstate New York to determine whether histories of certain infections and antibiotic use are associated with risk of non-Hodgkin's lymphoma (NHL). Our study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver's license records. Information about use of common medications including antibiotics, history of selected infectious diseases and potential confounding variables was obtained by telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model. There was a progressive increase in risk of NHL with increasing frequency and duration of systemic antibiotic use, as assessed over the period of 2-20 years before the interview. The ORs for the highest exposure categories, >/=36 episodes and >/=366 days of use, were 2.56 (95% CI 1.33-4.94) and 2.66 (95% CI 1.35-5.27), respectively. These associations were primarily due to antibiotic use against respiratory infections and dental conditions. Moreover, the association with frequency of antibiotic use for respiratory infections was pronounced for marginal zone B-cell lymphoma and for respiratory tract lymphoma. Analyses by class of antibiotics did not suggest that a general cytotoxic effect of antibiotics was responsible for these increased risks. Although recall bias and selection bias remain potential concerns in our study, the results are generally consistent with the hypothesis that persistent infection/inflammation predisposes individuals to the development of NHL. However, a direct role of antibiotics in NHL induction has not been ruled out.

Adult↗