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PubMed2002

Early life factors in relation to breast cancer risk in postmenopausal women.

We evaluated the role of early life factors in a large, population-based, case-control study of breast cancer risk in postmenopausal women. Case women in Massachusetts, New Hampshire, and Wisconsin were ascertained through state cancer registries; control women were randomly selected from drivers license lists (50-65 years of age) or Medicare beneficiary lists (65-79 years of age). Information concerning factors of interest was obtained through structured telephone interviews. Overall, 83% of eligible cases and 78% of eligible controls participated, and data from more than 2900 women were available for this analysis. We observed a weak J-shaped relationship between birth weight and breast cancer risk; the increased risk was not statistically significant for either the lowest or the highest birth weight. Parental smoking during the pregnancy was not associated with risk of breast cancer in the adult daughter. Breast cancer risk increased significantly with father's education (P = 0.01). Risk also increased with greater age of the mother at the time of the subject's birth (P = 0.04). The subject's birth rank was inversely associated with risk (P = 0.03), as was the number of older sisters (P = 0.03), but the number of older brothers, number of younger siblings, sibship gender ratio, and total sibship size were unrelated to risk. Overall, our results are consistent with previous studies and suggest that these early life factors have a modest influence on breast cancer risk in postmenopausal women.

Aged↗
PubMed1992

The relation between multiple births and maternal risk of breast cancer.

Data from two case-control studies conducted in New York State during 1982-1986 were used to examine the relation between multiple births and the maternal risk of breast cancer. The cases were 2,561 women between 20 and 79 years of age with a diagnosis of primary breast cancer. Controls (n = 2,616) were selected from driver's license files and matched to cases by year of birth and county of residence. The odds ratio for any multiple birth was 0.94 (95% confidence interval (CI) 0.56-1.56) in women less than 55 years of age and 0.95 (95% CI 0.62-1.46) in women aged 55-79 years. A previous study had shown a multiple last birth to be protective against breast cancer in women less than 55 years of age (odds ratio (OR) = 0.60, 95% CI 0.43-0.85). A decreased risk of breast cancer was also observed for this age group in the present study, but the magnitude of the effect was not as strong and the confidence interval included unity (OR = 0.85, 95% CI 0.43-1.68). A logistic model that controlled for age at first pregnancy, number of live births, age, and county of residence increased the odds ratio to 0.97 for a multiple last birth. The current study does not support an association between multiple births and maternal risk of breast cancer.

Adult↗
PubMed2003

Weight and length at birth and risk of early-onset prostate cancer (United States).

OBJECTIVE: A case-control study was conducted to examine the association of weight and length at birth with early-onset prostate cancer. METHODS: Cases of prostate cancer diagnosed between 1988 and 1995 (n = 192) were identified through the Minnesota Cancer Surveillance System. Two separate control groups were selected using driver's license (DL) and birth certificate (BC) listings. RESULTS: Using the DL control group, an inverse association was observed between birth weight and prostate cancer risk; adjusted odds ratios (95% confidence intervals) for < or = 3000, 3001-3500, 3501-4000, and > 4000 g at birth were 1.0, 0.72 (0.40-1.28), 0.58 (0.31-1.10), and 0.49 (0.24-1.00). In analyses using the BC control group, adjusted odds ratios (95% CIs) for the aforementioned birth weight categories were 1.0, 1.18 (0.64-2.18), 0.80 (0.42-1.54), and 1.04 (0.48-2.26), respectively. For both control groups, adjusted odds ratios were somewhat elevated for the upper three categories of birth length, but all confidence intervals included the null value. CONCLUSIONS: These findings do not support the hypothesis that greater weight or length at birth increases risk of prostate cancer.

Adult↗
PubMed2006

Fra-1 a target for cancer prevention or intervention.

The transcription factor activator protein-1 (AP-1) has been implicated as a driver of carcinogenesis since its original characterization. Oncogenic transcription factors like AP-1 are becoming new targets for cancer intervention. Inhibitors of AP-1 have been shown to block tumor promotion, transformation, progression and invasion. The Fos related antigen-1 (Fra-1) is activated in multiple cancers and gene ablation can suppress the invasive phenotypes of many tumor cell lines. This review focuses on the regulation of fosl1 expression, stabilization and activation of the Fra-1 polypeptide and on Fra-1-mediated tumorigenesis.

Animals↗
PubMed2002

Marie Curie nurses: enabling patients with cancer to die at home.

Marie Curie Cancer Care established its nursing service in 1958; however, the service has had little formal evaluation. This study aimed to describe and evaluate the care provided by Marie Curie nurse, and in particular to determine whether patients in their care remained and died at home. Two existing data sets were used: data on all patients referred to the Marie Curie Nursing Services in 147 areas of England, Wales, Scotland and Northern Ireland for 26 months, and data on cancer death registrations in England. A request for a Marie Curie nurse was made for 26,632 patients, 97% of whom had cancer and 11% of whom lived alone. The amount of care provided varied enormously (<1 hour-2862 hours), although the vast majority of patients less than 300 hours of nursing care. Place of death was recorded for only half these patients; 94% died at home, 2.5% in a hospice, 2.3% in a hospital, 0.2% in a nursing home and 0.6% other. Home death was most often associated with patients receiving medication via a syringe driver, patients living with other people, patients with cancer, other than prostate cancer, shorter time between referral and death and younger age. The results lend support to the theory that the care given to patients in their homes by Marie Curie nurses facilitated home death for many patients. Services need to ensure that mechanisms are in place to achieve data collection. Rigorous prospective evaluation is needed in the future.

Data Collection↗
PubMed1983

Occupation and cancer of the lower urinary tract in Detroit.

The relationship between occupation and cancer of the lower urinary tract in Detroit was examined by means of a population-based case-control study conducted as part of the National Bladder Cancer Study. Three hundred three white male patients with transitional or squamous cell carcinoma of the lower urinary tract and 296 white male controls selected from the general population of the study area were interviewed to obtain lifetime occupational histories. Our findings suggested that truck drivers have a significant increased risk of lower urinary tract cancer [relative risk = 2.1; 95% confidence interval (Cl) = 1.4-4.4]. A significant trend in risk was apparent with increasing duration of employment as a truck driver (P = 0.004); the relative risk estimated for truck drivers employed at least 10 years was 5.5 (Cl = 1.8-17.3). Truck drivers with a history of operating vehicles with diesel engines experienced a significant elevated risk compared to non-truck drivers (relative risk = 11.9; Cl = 2.3-61.1), but whether the increased risk observed among truck drivers was attributable to diesel exposure could not be evaluated. Nonsignificant excess risks were also seen for tool and die makers as well as for workers in several other industries and occupations. Employment in the motor vehicle manufacturing industry was associated with no significant excess risk of lower urinary tract cancer (relative risk = 1.1; Cl = 0.8-1.5).

Adult↗
PubMed2001

[Epidemiology and costs of lung cancer in Germany].

OBJECTIVE: Lung cancer shows the leading incidence of all cancers among men in the developed world and an increasing incidence among women. We performed a cost of illness study that aimed to assess the economic burden of lung cancer in Germany and to identify the main cost drivers. METHODS: Costs were estimated for the year 1996. In a retrospective analysis we calculated direct and indirect costs based on secondary data from governmental institutions as well as from the pharmaceutical industry. We chose the cost perspective of sickness funds to estimate direct costs. The human capital approach was applied for the calculation of indirect costs. RESULTS: Total estimated costs were DM 8.31 billion per year. The indirect costs of DM 7.40 billion accounted for 89 % of total estimated costs. The most important cost driver of the indirect costs, early death, represented on its own DM 4.85 billion, according to 58 % of total estimated costs. Of the direct costs, 93 % were due to hospitalization, amounting to DM 0.85 billion. CONCLUSIONS: This cost of illness study concerning lung cancer illustrates the outstanding importance of the indirect costs, mostly due to early death, for total costs. Based on these findings and on the leading role of smoking in the etiology of lung cancer, we suggest that studies dealing with the net costs of smoking to society should include indirect costs.

Adult↗
PubMed2006

[Selected work-related health problems in drivers of public transport vehicles].

The literature data and our own studies show that in drivers of public transport vehicles, largely intensified work-related risk factors for arterial hypertension, ischemic heart disease, duodenal and gastric ulcer diseases and back pain syndrome are found. These involves occupational risk factors as well as classic ones, such as obesity, limited physical activity or tobacco smoking. Among occupational risk factors, stress induced by the responsibility for assuring public safety in heavy urban traffic, time pressure and contacts with passengers predominate. Other burdens observed in this occupational group include specific, partly forced, position of the body at work and the shift work system. Exposure to chemical agents present in exhaust gas may increase the incidence of cancer at some sites in this group of drivers. Multifaceted burdens occurring in this occupation may impair health, leading to temporary or permanent disability to work. Therefore, there is an urgent need to develop specific preventive programs addressed to this occupational group not only because of economic reasons, but mostly to increase public transport safety.

Automobile Driving↗
PubMed1991

Mortality among urban bus drivers.

Driving a bus in urban areas is considered to be a highly stressful occupation, one which also involves exposure to air pollutants generated by motor vehicles. In order to investigate the potential health hazards associated with this occupation, the causes of death of 376 New York City bus drivers were studied. Analyses of proportionate mortality found a significant excess due to ischaemic heart disease in drivers in both races combined (proportionate mortality ratio PMR = 1.23), and among the 58 non-white drivers (PMR = 1.72). A significantly elevated risk of death from mental, psychoneurotic and personality disorders (ICDA Ninth Revision 290-319, which includes alcoholism and narcotics abuse) was also found in the combined group (PMR = 2.66), and among the white drivers (PMR = 3.05). For all drivers, PMRs for all malignant neoplasms (PMR = 1.26) and for cancer of the oesophagus (PMR = 2.54) were significantly elevated. No cancer sites were found to be significantly elevated in the proportionate mortality analyses by race. These findings are consistent with the growing body of literature linking job strain with cardiovascular disease among bus drivers.

Aged↗
PubMed2000

Enhancement of tumor-specific immune response with plasmid DNA replicon vectors.

To enhance the immunogenicity of nucleic acid vaccines, we used plasmid DNA vectors that contained replicons derived from the prototype alphavirus, Sindbis, and another alphavirus, Semliki Forest virus. When transfected into cells or injected directly into animal muscle, these plasmids launch a self-replicating RNA vector (replicon) which in turn directs the expression of a model tumor antigen. Immunization with plasmid DNA replicons elicited immune responses at doses 100 to 1000-fold lower than conventional DNA plasmids and effectively treated mice bearing an experimental tumor expressing the model antigen. Significantly, replicon-based DNA plasmids did not produce a greater quantity of antigen; instead, antigen production differed qualitatively. Plasmid DNA replicons mediated antigen production that was homogeneous in all transfected cells and associated with the apoptotic death of the host cells. Because of their safety and efficacy, plasmid DNA replicons may be useful in the development of recombinant vaccines for infectious diseases and cancer.

Animals↗
PubMed2026

Early-onset colorectal cancer burden attributable to early-life obesity from 2000 to 2020 with projections to 2040.

PURPOSE: Early-onset colorectal cancer (age <50 years) incidence has increased globally since the 1990s for unknown reasons. Early-life exposure to established risk factors like adiposity is suspected to play a role, but the contribution to the rising disease burden remains unknown. This study quantified the potential impact of rising early-life obesity on early-onset colorectal cancer in Australia. METHODS: Population attributable fractions for early-onset colorectal cancer were derived from meta-analytic relative risks and obesity prevalence estimates in adolescents (10-19-year-olds), using body mass index data for 1990-2022 from the Noncommunicable Diseases Risk Factor Collaboration. Under age-specific carcinogenesis latency assumptions, we linked adolescent obesity prevalence estimates to colorectal cancer incidence across age groups (20-29, 30-39, and 40-49 years) using observed cancer incidence data from Australian cancer registries covering 2000-2019 and age-period-cohort modelling to generate scenario-based estimates of incidence and obesity-attributable cases through 2040. Trends in obesity-attributable colorectal cancer incidence were quantified using joinpoint regression. RESULTS: The proportion of early-onset colorectal cancers attributable to adolescent obesity across 1990-2022 rose from 2% to 6% in men and 1-3% in women (average annual change: 3-4%). Although absolute attributable incidence rates were low, they increased 2-20% per year, varying by period, age-dependent lag, and sex. Under the projection assumptions applied, scenario estimates suggest that adolescent obesity could account for an estimated 1465 early-onset cases by 2040. CONCLUSION: Early-life obesity is estimated to account for a growing yet minor fraction of early-onset colorectal cancers in Australia and is therefore unlikely to be a major driver of the rising disease incidence. These findings suggest that childhood obesity prevention programs may have only a small public health impact on early-onset colorectal cancer prevention. Therefore, it is imperative that other causal risk factors - especially early-life exposures - are identified to inform prevention strategies that stem the rising disease burden.

Obesity↗
PubMed2026

The potential clinical benefit of routine comprehensive genomic profiling in non-small cell lung cancer for the detection of prognostic co-mutations - A multicenter next generation sequencing study.

INTRODUCTION: Non-driver mutations such as TP53, STK11 and KEAP1 are clinically relevant in determining immunotherapy efficacy in patients with non-small cell lung cancer (NSCLC). The aim of this study is to determine the prevalence and clinical relevance of variations in TP53, STK11 and KEAP1 in patients in the analysis of NSCLC, using targeted next-generation sequencing. METHODS: This real-life prospective multicenter cohort study from July 2022 until October 2023 utilized samples of patients in the analysis of NSCLC. The samples were subjected to a targeted DNA NGS panel and, if indicated, RNA sequencing. The outcome of the molecular diagnostics was retrieved, including driver alterations and more in-depth analysis of TP53, STK11 and KEAP1. RESULTS: In 134 of the 437 samples an actionable genomic alteration (AGA) was detected. Of the remaining samples, 213 carried a mutation in either TP53, STK11 and/or KEAP1, while 90 harbored either variants of unknown significance (VUS) (16) or no variant (74). In-depth analysis showed 77 alterations of STK11, with 56 pathogenic and 21 VUS. Most STK11 variants were identified in exon 1, which is hypothesized to be correlated to an oncogenic isoform. Moreover, variants in KEAP1 were mostly VUS, with 48 VUS and 24 mutations. Lastly, 264 TP53 alterations, of which 249 pathogenic and 15 VUS, occurred, with an even spread in the DNA-binding domain. CONCLUSION: This study demonstrated the broad spectrum of variants in STK11, KEAP1 and TP53 in routine panel-based DNA NGS, with 70.3% of the samples without AGA showing a potential clinically relevant mutation in TP53, STK11 and/or KEAP1.

Humans↗
PubMed1986

Motor exhaust-related occupations and bladder cancer.

The relationship between employment in occupations with potential exposure to motor exhaust and bladder cancer risk was examined based on interviews conducted with 1909 white male bladder cancer patients and 3569 population controls during the National Bladder Cancer Study, a population-based, case-control study conducted in ten areas of the United States. Our findings indicated that males usually employed as truck drivers or deliverymen have a statistically significant, 50% increase in risk of bladder cancer. Overall, a statistically significant trend in risk with increasing duration of truck driving was observed. This trend was particularly consistent for drivers first employed at least 50 years prior to diagnosis. Of these, truck drivers employed 25 years or more experienced a 120% increase in risk. Elevations in risk were also suggested for taxicab and bus drivers. These findings, coupled with experimental evidence of the mutagenicity and possible carcinogenicity of motor exhaust emission particulates, suggest a role for motor exhaust exposure in human bladder carcinogenesis.

Adult↗
PubMed2005

Pigmentary characteristics and moles in relation to melanoma risk.

Although benign and atypical moles are considered key melanoma risk factors, previous studies of their influence were small and/or institution-based. We conducted a population-based case-control study in the state of New Hampshire. Individuals of ages 20-69 with an incident diagnosis of first primary cutaneous melanoma were ascertained through the New Hampshire State Cancer Registry. Controls were identified through New Hampshire driver's license lists and frequency-matched by age and gender to cases. We interviewed 423 eligible cases and 678 eligible controls. Host characteristics, including mole counts, were evaluated using logistic regression analyses. Our results showed that pigmentary factors, including eye color (OR = 1.57 for blue eyes compared to brown), hair color (OR = 1.85 for blonde/red hair color compared to brown/black), freckles before age 15 (OR = 2.39 for freckles present compared to absent) and sun sensitivity (OR = 2.25 for peeling sunburn followed by no tan or a light tan and 2.42 for sunburn followed by tan compared to tanning immediately), were related to melanoma risk; these associations held after adjustment for sun-related factors and for moles. In analyses confined to skin examination participants, the covariate-adjusted effects of benign and atypical moles were moderately strong. Compared to 0-4 benign moles, risk increased steadily for 5-14 moles (OR = 1.71), 15-24 moles (OR = 3.55) and >or= 25 moles (OR = 4.33). Risk also increased with the number of atypical moles; compared to none, the ORs for having 1, 2-3, or >or= 4 atypical moles were 2.08, 1.84 and 3.80, respectively. Although risk was highest for those with multiple benign and atypical moles, the interaction was not of statistical significance. Our findings, arising from the first population- and incidence-based study to evaluate atypical moles in relation to melanoma risk, confirm the importance of host susceptibility, represented by pigmentary factors and the tendency to develop benign or atypical moles, in the etiology of this disease.

Adult↗
PubMed1989

Design and performance of a high speed driver circuit for PIN diode switches used in microwave hyperthermia.

In many cancer treatment facilities where hyperthermia treatments are performed, there is a need to split a single channel microwave source into multiple, individually controllable channels. In the application reported here, microwave power is alternately switched between active and passive elements for each channel. The active element is either a microwave antenna inside a catheter in tumour tissue or a planar spiral applicator placed superficially, the total power to each channel being pulse width modulated from 1 to 99% of a 1 s duty cycle. The system is computer controlled and is capable of dividing and controlling power to 12 channels. PIN diode switch assemblies control the flow of power in each channel but they must be switched within a few microseconds to avoid failure at the high power levels used in the clinic. A high speed circuit was fabricated and tested to drive each PIN diode switch; the PIN diode switches are turned on in 1.5 microseconds and off in 3.0 microseconds, which meets the specifications for hot switching. The increase in speed over the former driver system is a factor of 5.1 for the on cycle and 1.5 x 10(5) for the off cycle and the maximum power tested in each channel was 80 W for 1 h at random duty cycles between 1 and 99%. The circuit was also tested with 40 W of power at duty cycles of 1, 50 and 99% for 1 h each; no failures or performance decrements were observed. The 12 channel circuit driver has been used for six months of clinical treatments without failure.

Equipment Design↗
PubMed2005

Occupational bladder cancer in New Zealand: a 1-year review of cases notified to the New Zealand Cancer Registry.

AIM: To identify which cases of adult bladder cancer notified to the New Zealand Cancer Registry in 2001 had a probable occupational cause. METHODS: Occupational Safety and Health (OSH), in conjunction with the Massey University Centre for Public Health Research, interviewed and obtained an occupational history for 210 (162 men, 48 women) cases. RESULTS: Of the 162 male cases (response rate 65%), 45 (28%) were considered to be 'probable' occupational cancers. Of the 48 female cases (response rate 76%), three cases (6%) were considered to be 'probable' occupational cancers. The largest occupational group for men was truck drivers, which made up 51% of probable cases. Other common groups were engineering and metal workers (18%), crop farmers/orchardists (7%), textile and leather workers (7%), painters/furniture finishers (7%), and plastics manufacturing workers (4%). The three female cases considered to be of occupational origin included two textile workers and one telephonist. CONCLUSIONS: The percentage of cases considered to be of occupational origin is similar to that reported in Europe and the United States, indicating that occupational cancer is a major occupational health problem in New Zealand as it is in other parts of the world.

Female↗
PubMed2026

Deletion of the MALAT1 RNA 3' end promotes transcript decay and inhibits proliferation in gastric and breast cancer cells.

The long non-coding RNA MALAT1 is a conserved oncogenic driver whose function relies on a 3' triple-helix motif. While its biochemistry is well-characterized in vitro, the endogenous requirement for this motif in regulating the stability of the transcript and other genes residing in its locus remains unclear. In this study, we employed a dual-sgRNA CRISPR-Cas9 approach to systematically excise triple-helix-forming sequences from the native MALAT1 locus in gastric (AGS) and breast (MCF7) cancer cells. Our findings demonstrate that the 3' end strongly contributes to MALAT1 stability. Perturbations ranging from genomic deletions to a single-base changes trigger transcript collapse and rapid exonucleolytic decay, while the biogenesis of the small RNA mascRNA (a byproduct of MALAT1, also involved in cancer) remains decoupled and unaffected. In cellulo, DMS probing reveals that edited transcripts retain structural complexity in the 3' region. Phenotypically, structural disruption of the 3' end significantly impairs proliferation of both cancer cellular models. These results identify the 3' triple-helix as a determinant of MALAT1 stability and provide endogenous validation for its role in the analyzed AGS and MCF7 cells.

Cancer↗
PubMed2005

Weight change and risk of endometrial cancer.

BACKGROUND: Obesity is an established risk factor for endometrial cancer. Less well understood is the role of weight gain and weight change in determining risk. METHODS: We analysed data from a population-based case-control study to evaluate the associations of body mass index (BMI), weight gain, and weight cycling with risk of endometrial cancer. Cases (n=740) under age 80 with a new diagnosis of endometrial cancer were identified from Wisconsin's cancer registry. Controls (n=2342) were randomly selected from driver's license lists and Medicare beneficiary files. Body size at three time points and other risk factor information were ascertained by interview in 1992-95. RESULTS: Endometrial cases were more likely than controls to be nulliparous, have early ages at menarche and late ages at menopause, be diabetic, smoke cigarettes, and use post-menopausal hormones. After adjustment for these factors, increasing BMI was associated with increased risk (P-trend<0.001); women in the top quartile of BMI (>29 kg/m2) had a 3-fold greater risk of endometrial cancer [95% confidence interval (95% CI) 2.4-4.2] compared with women in the lowest quartile (<23 kg/-m2). For each 5 kg weight gain, the odds ratio (OR) for endometrial cancer risk equalled 1.2 (95% CI 1.2-1.3). History of weight cycling modestly increased risk after adjustment for BMI and other factors (OR=1.3; 95% CI 1.0-1.6). In addition, women who reported sustained weight loss had a reduced risk of endometrial cancer (OR=0.7; 95% CI 0.6-0.9). CONCLUSIONS: These results suggest that weight gain and lack of weight stability are associated with risk of endometrial cancer.

Adult↗