Metabolic syndrome as a late effect of childhood hematopoietic stem cell transplantation - A thorough statistical evaluation of putative risk factors.

BACKGROUND: Metabolic syndrome (MetS) is frequent among survivors of childhood hematopoietic stem-cell transplantation (HSCT), but assessment of risk factors is challenged by survivor and participation bias in long-term follow-up studies. METHODS: A cohort of 395 pediatric patients transplanted between 1980 and 2018 was investigated. MetS was assessed at follow-up between December 2018 and March 2020. Two composite outcomes ((a) combining MetS and death, (b) combining MetS, death, and nonparticipation) were considered to address the risk of selection bias. RESULTS: Among 234 survivors invited to the follow-up, 96 individuals (median age 27 years) participated. MetS prevalence was 30% among participants. The only significant HSCT risk factor was a variable combining HSCT indication and conditioning with total-body irradiation (TBI) (p = .0011). Compared to acute leukemias (AL) treated with high-grade TBI (8-12 Gy), a lower MetS prevalence was seen for nonmalignant diseases treated with no/low-grade TBI (0-4.5 Gy) (OR = 0.04, 95% confidence interval (CI): 0.00-0.23). Analyses of the composite outcomes indicated overestimation of the effect of high-grade TBI due to selection bias. Scrutiny showed strong residual confounding between HSCT indication and high-grade TBI within AL-patients. The HSCT effect on MetS reflected HSCT effects on high-density-lipoprotein (HDL) and triglycerides. Compared to AL treated with high-grade TBI, nonmalignant diagnoses treated with no/low-grade TBI had higher HDL (+40%, 95% CI: +21% to +62%) and lower triglyceride (-59%, 95% CI: -71% to -42%). CONCLUSION: The TBI effect on MetS may be overestimated in follow-up studies due to selection bias and confounding. The TBI effect was confined to the potentially modifiable MetS criteria  HDL and triglyceride.

Pre- and post-diagnostic intake of whole grain and dairy products and breast cancer prognosis: the Danish Diet, Cancer and Health cohort.

PURPOSE: Fiber rich foods and dairy products have been suggested to be associated with breast cancer prognosis, though existing research is limited and either report on pre- or post-diagnostic dietary intake in relation to breast cancer prognosis. We investigated the associations between intake of whole grain (WG) and dairy products assessed both pre- and post-diagnostically in relation to breast cancer prognosis. METHODS: A total of 1965 women from the Diet, Cancer and Health cohort who were diagnosed with breast cancer between baseline (1993-1997) and December 2013 were included and followed for a median of 7 years after diagnosis. During follow-up, 309 women experienced breast cancer recurrence and 460 women died, of whom 301 died from breast cancer. Dietary assessment by food frequency questionnaires was obtained up to three times, pre- and post-diagnostic, over a period of 18 years. Cox proportional hazard models were used to estimate hazard ratios. RESULTS: No associations were observed between pre- or post-diagnostic intake of total WG or total dairy products and breast cancer prognosis. A high pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality (HR 0.76, 95% CI 0.59-0.99), whereas high post-diagnostic intake of rye bread was associated with higher breast cancer-specific mortality (HR 1.29, 95% CI 1.02-1.63). A generally high intake of cheese was associated with a higher recurrence rate. CONCLUSION: Pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality, and post-diagnostic intake of rye bread was associated with higher breast cancer specific mortality.

Leisure time physical activity and mortality.

BACKGROUND: Some studies indicate that a large part of the beneficial effect of physical activity on mortality is confined to a threshold effect of participation. METHODS: Self-reported physical activity was investigated in relation to all-cause mortality in the Danish Diet, Cancer and Health cohort, including 29,129 women and 26,576 men aged 50-64 years at baseline 1993-1997. Using Cox proportional hazards models we investigated the associations between mortality rate and leisure time physical activity by exploring 1) participation (yes/no) in each type of activity; 2) a simple dose-response relationship with hours spent on each activity, supplemented with indicators of participation in each activity; and 3) inflexion or nonmonotonic dose-response relationships using linear splines. RESULTS: A total of 2696 women and 4044 men died through March 2010. We found lower mortality with participation in sports (for women, mortality rate ratio = 0.75, 95% confidence interval = 0.69-0.81; for men, 0.78, 0.73-0.84), cycling (for women, 0.77, 0.71-0.84; for men, 0.90, 0.84-0.96), or gardening (for women, 0.84, 0.78-0.91; for men, 0.73, 0.68-0.79) and in men participating in do-it-yourself activity (0.77, 0.71-0.84). A weak adverse dose response was seen for walking and gardening, but the association was small (1-2% increase in mortality per additional hour). We found no signs of inflexion or nonmonotonic effects of additional hours spent on each activity. CONCLUSION: Mortality was lower with participation in specific leisure time physical activities, but not with more time spent on those activities. This could suggest that avoiding a sedative lifestyle is more important than a high volume of activity. Nonparticipation in these types of physical activity may be considered as risk factors.

Social relations and smoking abstinence among ever-smokers: a report from two large population-based Danish cohort studies.

AIMS: Relational strain may be a risk factor for relapse after smoking cessation whereas social support may be protective. This study aimed to assess which aspects of social relations were associated with smoking abstinence among ever-smokers. METHODS: This cross-sectional questionnaire study included data from two large Danish cohorts: One including younger women (n=10,107) and one including older men (n=21,091) and women (n=23,800). Structural and functional relations with different counterparts were measured. RESULTS: Contact with and support from close counterparts tended to be associated with an increased probability of being smoking abstinent, and contact with or support from more distant counterparts tended to be associated with a decreased probability of being smoking abstinent. Although not completely consistent across all three samples, more frequently meeting too many demands from the partner or other relatives seemed to be associated with a decreased probability of abstinence. The patterns for strain measured as worries or conflicts were less clear. CONCLUSIONS: Smoking abstinence was associated with structural and functional measures of social relations and depended on the closeness of the persons constituting the relations. Further knowledge about these associations could lead to a potential in involving social relations in smoking cessation programmes.

Physical activities at work and risk of musculoskeletal pain and its consequences: protocol for a study with objective field measures among blue-collar workers.

BACKGROUND: Among blue-collar workers, high physical work demands are generally considered to be the main cause of musculoskeletal pain and work disability. However, current available research on this topic has been criticised for using self-reported data, cross-sectional design, insufficient adjustment for potential confounders, and inadequate follow-up on the recurrent and fluctuating pattern of musculoskeletal pain. Recent technological advances have provided possibilities for objective diurnal field measurements of physical activities and frequent follow-up on musculoskeletal pain.The main aim of this paper is to describe the background, design, methods, limitations and perspectives of the Danish Physical Activity cohort with Objective measurements (DPhacto) investigating the association between objectively measured physical activities capturing work and leisure time and frequent measurements of musculoskeletal pain among blue-collar workers. METHODS/DESIGN: Approximately 2000 blue-collar workers are invited for the study and asked to respond to a baseline questionnaire, participate in physical tests (i.e. muscle strength, aerobic fitness, back muscle endurance and flexibility), to wear accelerometers and a heart rate monitor for four consecutive days, and finally respond to monthly text messages regarding musculoskeletal pain and quarterly questionnaires regarding the consequences of musculoskeletal pain on work activities, social activities and work ability for a one-year follow-up period. DISCUSSION: This study will provide novel information on the association between physical activities at work and musculoskeletal pain. The study will provide valid and precise documentation about the relation between physical work activities and musculoskeletal pain and its consequences among blue-collar workers.

Protocol for a prospective, longitudinal study of cognitive impairment in young patients with cancer: a multidisciplinary neuroscience approach (MyBrain).

INTRODUCTION: The aim of this research is to investigate young cancer patients' cognitive functioning and the underlying neurobiological mechanisms when cognitive functions are impaired. The MyBrain protocol is a multidisciplinary study that investigates cancer-related cognitive impairment in children, adolescents and young adults, combining neuropsychology, cognitive neuroscience and cellular neuroscience. The study is exploratory with a wide focus on trajectories of cognitive functions from diagnosis to the end of treatment and into survivorship. METHODS AND ANALYSIS: Prospective longitudinal study including patients diagnosed with non-brain cancers at age 7-29 years. Each patient is paired with a control matched on age and social circle. PRIMARY OBJECTIVE: Evaluation of neurocognitive function over time. SECONDARY OBJECTIVES: Evaluation of self-perceived quality of life and fatigue, P300 in an electroencephalography (EEG) oddball paradigm, power spectrum in resting state EEG, serum and cerebrospinal fluid levels of biomarkers of neuronal damage, neuroplasticity, proinflammatory and anti-inflammatory markers and their association with cognitive function. ETHICS AND DISSEMINATION: The study is approved by the Regional Ethics Committee for the Capital Region of Denmark (no. H-21028495), and the Danish Data Protection Agency (no. P-2021-473). Results are expected to guide future interventions to prevent brain damage and support patients with cognitive difficulties. TRIAL REGISTRATION NUMBER: The article is registered at clinicaltrials.gov NCT05840575 (https://clinicaltrials.gov/ct2/show/NCT05840575).

Physician-defined severe toxicities occurring during and after cancer treatment: Modified consensus definitions and clinical applicability in the evaluation of cancer treatment.

Overall survival after cancer is increasing for the majority of cancer types, but survivors can be burdened lifelong by treatment-related severe toxicities. Integration of long-term toxicities in treatment evaluation is not least important for children and young adults with cancers with high survival probability. We present modified consensus definitions of 21 previously published physician-defined Severe Toxicities (STs), each reflecting the most serious long-term treatment-related toxicities and representing an unacceptable price for cure. Applying the Severe Toxicity (ST) concept to real-world data required careful adjustments of the original consensus definitions, translating them into standardized endpoints for evaluating treatment-related outcomes to ensure that (1) the STs can be classified uniformly and prospectively across different cohorts, and (2) the ST definitions allow for valid statistical analyses. The current paper presents the resulting modified consensus definitions of the 21 STs proposed to be included in outcome reporting of cancer treatment.

Postoperative speech impairment and surgical approach to posterior fossa tumours in children: a prospective European multicentre cohort study.

BACKGROUND: Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors. METHODS: In this observational prospective multicentre cohort study, we included children (aged <18 years) undergoing primary surgery for a posterior fossa tumour at 26 centres in nine European countries. Within 72 h of surgery, the operating neurosurgeon reported details on the tumour location, surgical approach used, duration of surgery, use of traction, and other predetermined factors, using a standardised surgical report form. At 2 weeks, 2 months, and 1 year after surgery, a follow-up questionnaire was filled out by a paediatrician or neurosurgeon, including neurological examination and assessment of speech. Speech was classified as mutism, reduced speech, or habitual speech. POSI was defined as either mutism or severely reduced speech. Ordinal logistic regression was used to analyse the risk of POSI. FINDINGS: Between Aug 11, 2014, and Aug 24, 2020, we recruited 500 children. 426 (85%) patients underwent primary tumour surgery and had data available for further analysis. 192 (45%) patients were female, 234 (55%) patients were male, 81 (19%) patients were aged 0-2 years, 129 (30%) were aged 3-6 years, and 216 (51%) were aged 7-17 years. 0f 376 with known postoperative speech status, 112 (30%) developed POSI, 53 (14%) developed mutism (median 1 day [IQR 0-2]; range 0-10 days), and 59 (16%) developed reduced speech after surgery (0 days [0-1]; 0-4 days). Mutually adjusted analyses indicated that the independent risk factors for development of POSI were younger age (linear spline, p=0·0087), tumour location (four levels, p=0·0010), and tumour histology (five levels, p=0·0030); surgical approach (six levels) was not a significant risk factor (p=0·091). Tumour location outside the fourth ventricle and brainstem had a lower risk of POSI (with fourth ventricle as reference, odds ratio (OR) for cerebellar vermis 0·34 [95% CI 0·14-0·77] and OR for cerebellar hemispheres 0·23 [0·07-0·70]). Compared with pilocytic or pilomyxoid astrocytoma, a higher risk of POSI was seen for medulloblastoma (OR 2·85 [1·47-5·60]) and atypical teratoid rhabdoid tumour (10·30 [2·10-54·45]). We did not find an increased risk of POSI for transvermian surgical approach compared with telovelar (0·89 [0·46-1·73]). Probability of speech improvement from mutism reached 50% around 16 days after mutism onset. INTERPRETATION: Our data suggest that a midline tumour location, younger age, and high-grade tumour histology all increase the risk of speech impairment after posterior fossa tumour surgery. We found no evidence to recommend a preference for telovelar over transvermian surgical approach in the management of posterior fossa tumours in children in relation to the risk of developing POSI. FUNDING: The Danish Childhood Cancer Foundation, the Swedish Childhood Cancer Foundation, the UK Brain Tumour Charity, the Danish Cancer Society, Det Kgl Kjøbenhavnske Skydeselskab og Danske Broderskab, the Danish Capitol Regions Research Fund, Dagmar Marshall Foundation, Rigshospitalet's Research Fund, and Brainstrust.

Plasma enterolactone and risk of colon and rectal cancer in a case-cohort study of Danish men and women.

This case-cohort study examined the association between plasma enterolactone concentration and incidence of colon and rectal cancer in the Diet, Cancer and Health cohort, which enrolled 57,053 participants aged 50-64. Information about diet and lifestyle was obtained by questionnaire, and data on prescriptions of antibiotics were obtained from the Danish Prescription Registry. Cases diagnosed during 5.9 years of follow-up and a randomly selected sample of the cohort had a plasma sample analyzed for enterolactone by time-resolved fluoro-immuno assay. Associations were analyzed by Cox proportional hazards model. A total of 244 colon cancer cases, 137 rectal cancer cases, and 370 sub-cohort members were included in the statistical analyses. For each doubling in enterolactone concentration, we found lower risk of colon cancer among women [IRR (95% CI) = 0.76 (0.60-0.96)] and a tendency toward lower risk of rectal cancer [IRR (95% CI) = 0.83 (0.60-1.14)]. Among men, a doubling in enterolactone tended to be associated with higher risk of colon cancer [IRR (95% CI) = 1.09 (0.89-1.34)] and was associated with statistically significantly higher risk of rectal cancer [IRR (95% CI) = 1.74 (1.25-2.44)]. Exclusion of antibiotics users strengthened the results slightly. In conclusion, with higher enterolactone levels, we found lower risk of colon cancer among women and higher risk of rectal cancer among men.

Job type and other socio-demographic factors associated with participation in a national, cross-sectional study of Danish employees.

OBJECTIVES: Participation in population-based surveys and epidemiological studies has been declining over the years in many countries. The aim of this study was to examine the association between job type and participation in the work environment and health in Denmark survey with/without taking into account other socio-demographic factors. DESIGN: Cross-sectional survey using questionnaire data on working environment and registry data on job type, industry and socio-economic variables. SETTING: The work environment and health study. PARTICIPANTS: A total of 50 806 employees (15 767 in a stratified workplace sample; 35 039 in a random sample) working at least 35 hours/month and earning at least 3000 Danish Krones. OUTCOME MEASURES: The outcome was participation (yes/no) and logistic regression was used to estimate the OR for participation with 95% CI. RESULTS: In the random sample, women were more likely to participate than men, and married/non-married couples were more likely to participate than persons living alone or more families living together. Participation increased with higher age, higher annual personal income, higher education and Danish origin, and there were marked differences in participation between job types and geographical regions. For armed forces, craft and related trade workers, and skilled agricultural, forestry and fishery workers, the association between job type and participation was strongly attenuated after adjustment for sex and age. Additional adjustment for annual income, education, cohabitation, country of origin and geographical region generally attenuated the association between job type and participation. Similar results were found in the stratified workplace sample. CONCLUSION: In this population of Danish employees, participation varied across types of jobs. Some but not all the variation between job types was explained by other socio-demographic factors. Future studies using questionnaires may consider targeting efforts to (sub-)populations, defined by job type and other factors, where response probability is particularly important.

Does marital status and altered contact with the social network predict colorectal cancer survival?

We examined whether changes in the frequency of contact with the social network (partner, children, grandchildren, other relatives, friends and colleagues) in a group of colorectal cancer patients were associated with survival. The study was based on a questionnaire survey from 1991. The study population consisted of 770 Danish colorectal cancer patients diagnosed in the period 1985-1990, and followed up for survival until March 2002. Using Cox regression analysis we found a significantly higher mortality among patients who had lost their partner before the operation compared to patients cohabiting with the same partner as before the operation (rate ratio (RR)=1.4, 95% confidence interval (CI): 1.1-1.8) possibly because of less active cancer treatment. This needs investigation in future studies. Contrary to expectations we also found a significantly higher mortality among patients reporting increased contact with their children compared to patients reporting unchanged contact frequency (RR=1.7, 95% CI: 1.3-2.4). However, a low physical functioning of the cancer patient may have confounded the latter result.

Does objectively measured daily duration of forward bending predict development and aggravation of low-back pain? A prospective study.

OBJECTIVES: The aim of this paper was to investigate if objectively measured daily duration of forward bending of the trunk increases the risk of the development or aggravation of low-back pain (LBP) over one year in a working blue-collar population by examining (i) the incidence rate of LBP among workers reporting no LBP at baseline, and (ii) the aggravation of LBP among workers reporting LBP at baseline. METHODS: Using data from the Danish Physical Activity Cohort with Objective Measurements (DPhacto), the study measured forward bending of the trunk (>60˚) at work (FBW) and during leisure time (FBL), diurnally with accelerometers, and LBP with one-year monthly self-reports among 682 blue-collar workers from 15 workplaces. The development of LBP was investigated with Cox's proportional hazards model (N=200), and the aggravation of LBP was investigated with mixed model for repeated measurements (N=482). RESULTS: Workers with no LBP at baseline had a FBW median of 7.9 minutes/day. Workers with LBP at baseline had a FBW median of 7.3 minutes/day. No significant associations were found between daily duration of forward bending of the trunk and development or aggravation of LBP. Similar results were found in the secondary analyses, in which FBL, different degrees of forward bending (>30˚ and >90˚), and varying follow-up time since measurement were considered. CONCLUSION: Using objective measurements of forward bending and monthly follow-up of LBP over one year, this study did not confirm the hypothesis of a positive association between daily duration of forward bending and LBP.

Protein intake at 9 mo of age is associated with body size but not with body fat in 10-y-old Danish children.

BACKGROUND: During the complementary feeding period, infants shift from a daily protein intake (PI) of approximately 1 g/kg body wt to an intake 3-4 times as high. A high PI probably has both endocrine and physiologic effects and may increase the risk of obesity. OBJECTIVE: We examined the associations between PI in infancy and body size and composition in late childhood. DESIGN: We conducted an observational cohort study of 142 Danish healthy term infants (63 boys) born during 1987-1988. At 9 mo of age, diet, weight, length, skinfold thicknesses, insulin-like growth factor I, and serum urea nitrogen were determined. At 10 y of age, 105 children (51 boys) participated in a follow-up study. Diet, weight, height, skinfold thicknesses, percentage of body fat (dual-energy X-ray absorptiometry), insulin-like growth factor I, and serum urea nitrogen were determined. RESULTS: At 9 mo of age, PI (in g/d and percentage of energy) was strongly correlated with body size (length and weight) but not with measures of adiposity. PI at 9 mo of age was positively associated with height and weight but not with percentage of body fat at 10 y of age. Inclusion of parental body size in the models did not change the associations, but the significant associations were attenuated when body size at 9 mo of age was included. CONCLUSIONS: PI in infancy seems to stimulate early growth. This might explain part of the association between early PI and body size at 10 y of age, but a continuous effect of protein on growth during childhood cannot be excluded. PI in infancy was not associated with any measure of body fat at 10 y of age.

In a randomized controlled trial, missing data led to biased results regarding anxiety.

BACKGROUND AND OBJECTIVE: Randomization does not protect against bias due to missing observations. In addition, different reasons for missing observations may lead to different invalid results. The purpose of this study was to illustrate how randomized intervention studies can be threatened by bias due to missing observations because of death or nonresponse. METHODS: A randomized clinical trial of the effect of psychosocial intervention on well-being after an operation for colorectal cancer was conducted in Denmark. Patients were interviewed 3, 6, 12, and 24 months after discharge from hospital. RESULTS: We found that the probability of nonresponse decreased with increasing anxiety score in the intervention group, but it increased with increasing anxiety score in the control group. This could lead to severe bias in an analysis of the effect of intervention on anxiety. Low physical functioning and low global health status and quality of life were related to an increased probability of dying before the next follow-up, and this association could explain the associations between anxiety and depression, respectively, and the probability of dying observed in crude analyses. CONCLUSION: Our study emphasizes the importance of performing specific missing data analyses in any study of well-being variables.

Validity of diagnoses of and operations for nonmalignant gynecological conditions in the Danish National Hospital Registry.

The recording of surgical procedures for and diagnoses of nonmalignant gynecological conditions in the Danish National Hospital Registry in 1977-1988 were evaluated by comparison with discharge summaries for a sample of 4,919 women. A serious problem was found in the validity of the diagnoses. Little variation was seen over the period of observation. The coding of operations was considered valid. The results of the study raise concern in view of the widespread use of the registry data in medical research. The authors suggest that data from the registry should be thoroughly evaluated before firm conclusions based on such data are published, and that efforts to improve the validity of the data in the Danish National Hospital Registry are increased.

Influence of lifestyle aspects on the association of body size and shape with all-cause mortality in middle-aged men and women.

OBJECTIVE: Waist circumference, BMI and hip circumference are differentially associated with mortality. We investigated the potential influence of selected lifestyle aspects such as smoking, alcohol intake, sports activity and education. METHOD: The Danish prospective study 'Diet, Cancer and Health' recruited 27,179 men and 29,875 women from 1993 to 1997. Cox regression models were used to estimate mortality rate ratios. RESULTS: Adjustment for smoking habits attenuated the associations between mortality and the three body size measurements in both sexes. Adjustment for sport activity and, to a lesser extent, alcohol intake weakened the associations further for the men, whereas alcohol intake slightly weakened associations for the women. In the fully adjusted models, mortality increased highly significantly with higher waist circumference and lower hip circumference, and decreased highly significantly with higher BMI for BMI below 25 kg/m(2). This pattern was seen for all levels of the selected lifestyle factor. CONCLUSION: A large waist circumference remained a strong risk indicator for mortality, and a large hip circumference appeared to be protective when smoking habits, alcohol intake and sport activity were accounted for. BMI below 25 kg/m(2) remained a risk factor, but not above 25 kg/m(2) once waist circumference was adjusted for.

[The growth pattern of 0- to 1-year-old Danish children screened by public health nurses: the Copenhagen County Child Cohort 2000--secondary publication]. / Vaekstmønsteret hos 0-1-årige børn: Københavns Amts Fødselskohorte 2000--sekundaerpublikation.

Use of invalid growth curves can result in false conclusions about the growth and thriving of children. We describe the current growth pattern of 0- to 1-year-old children in Denmark compared to national and international references. The data consist of weights and lengths of 6,090 children born in the County of Copenhagen in the year 2000. The updated growth curves differ markedly from the growth references and show a changed growth pattern of Danish infants, with a more rapid increase in weight during the first six months of life. The curves represent an updated alternative for monitoring growth in Danish infants.

Physical activity and risk of colon cancer in a cohort of Danish middle-aged men and women.

OBJECTIVE: To investigate the effects of occupational activity and leisure time activity on incident colon cancer risk in a Danish middle-aged population. METHODS: In the cohort, Diet, Cancer and Health, which included 28,356 women and 26,122 men aged 50-64 years at baseline, 140 women and 157 men were diagnosed with colon cancer from 1993 to 2003. The associations between occupational and leisure time activity in terms of a MET-score and the single activities, sports, cycling, walking, gardening, housework and do-it-yourself work, and incident colon cancer were investigated. Leisure time activity was investigated in two ways using the Cox proportional hazards model: by comparison of active versus non-active and by investigating a possible dose-response relationship while allowing a separate association for non-active individuals. RESULTS: No associations were found between risk of colon cancer and occupational activity, MET-hours per week of total leisure time activity, residuals from a regression of each activity on the total MET-hours or the time spent on any of the six types of leisure time activities. However, a borderline significant association was found with the number of activities in which the participants were active. For each additional activity IRR = 0.87 (0.76-1.00) for women and IRR = 0.88 (0.78-1.00) for men. CONCLUSION: Our data do not support the evidence of an inverse association between colon cancer risk and occupational activity or leisure time activity, but avoiding a sedentary lifestyle by participating in different activities may reduce colon cancer risk.

Bulky DNA adducts as risk indicator of lung cancer in a Danish case-cohort study.

Little is known of the predictive value of the levels of DNA adducts in terms of cancer risk. We examined the association between bulky DNA adducts and risk of lung cancer in a population-based cohort, comprising of 25,717 men and 27,972 women aged 50-64 years at entry. We included 245 cases (137 men and 108 women) with lung cancer and a comparison group of 255 individuals (137 men and 118 women), matched on sex, age and smoking duration. Bulky adducts in white blood cells collected at enrollment and stored at -150 degrees C were analyzed by (32)P-postlabeling method, using the butanol enrichment procedure. The median level of bulky DNA adducts was 0.196 adduct/10(8) nucleotides (5-95 percentiles: 0.094-0.595) among current smokers who were later diagnosed with lung cancer and 0.163 adduct/10(8) nucleotides (5-95 percentiles: 0.091-0.455) among current smokers in the comparison group. The smoking adjusted incidence rate ratios (IRR) for lung cancer in relation to one log unit (natural logarithm) difference in adduct levels were 1.22 (95% CI 0.85-1.74), 1.33 (95% CI 0.89-1.98) and 0.76 (95% CI 0.39-1.47) among all, current and former smokers, respectively. Current smokers with bulky DNA adduct levels above the median had a significant higher lung cancer rate than those with adduct levels below the median (IRR = 1.61; 95% CI 1.04-2.49). The results are compatible with previous studies, suggesting a slightly higher risk of lung cancer with higher levels of adducts among smokers. Our results indicate that bulky DNA adducts may have a weak association with lung cancer risk.

The role of smoking and alcohol intake in the development of high-grade squamous intraepithelial lesions among high-risk HPV-positive women.

BACKGROUND: Infection with human papillomavirus is considered a necessary factor in developing high-grade squamous intraepithelial lesions of the cervix. However, most human papillomavirus positive women do not develop high-grade squamous intraepithelial lesions and other factors may be important for this transition. The objective of the present study was to examine if smoking and alcohol intake are associated with the risk of developing high-grade squamous intraepithelial lesions in women positive for high-risk human papillomavirus types. METHODS: We used baseline information on exposures on 548 high-risk human papillomavirus positive women with normal cytology, comparing 94 women who developed high-grade squamous intraepithelial lesions with 454 women who remained cytologically normal. Logistic regression was applied for statistical analysis. RESULTS: Compared with never smokers, the odds ratio for high-grade squamous intraepithelial lesions among current smokers was 1.99 (95% CI: 1.21-3.28). Among current smokers, number of cigarettes, years of smoking, and early age at smoking initiation were associated with increased risk. However, when modeled simultaneously, it seemed that smoking duration and age at smoking initiation were more associated with risk of high-grade squamous intraepithelial lesions than amount of smoking. Alcohol intake was not associated with risk of high-grade squamous intraepithelial lesions among these women. CONCLUSION: Smoking is associated with an increased risk of developing high-grade squamous intraepithelial lesions in women who are infected with oncogenic human papillomavirus.