G. Steineck

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 × 10−12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 × 10−7).

Dietary acrylamide and cancer of the large bowel, kidney, and bladder: Absence of an association in a population-based study in Sweden

Recently, disturbingly high levels of acrylamide were unexpectedly detected in widely consumed food items, notably French fries, potato crisps, and bread. Much international public concern arose since acrylamide has been classified as a probable carcinogen, although based chiefly on laboratory evidence; informative human data are largely lacking. We reanalysed a population-based Swedish case–control study encompassing cases with cancer of the large bowel (N=591), bladder (N=263) and kidney (N=133), and 538 healthy controls, assessing dietary acrylamide by linking extensive food frequency data with acrylamide levels in certain food items recorded by the Swedish National Food Administration. Unconditional logistic regression was used to estimate odds ratios, adjusting for potential confounders. We found consistently a lack of an excess risk, or any convincing trend, of cancer of the bowel, bladder, or kidney in high consumers of 14 different food items with a high (range 300–1200 μg kg−1) or moderate (range 30–299 μg kg−1) acrylamide content. Likewise, when we analysed quartiles of known dietary acrylamide intake, no association was found with cancer of the bladder or kidney. Unexpectedly, an inverse trend was found for large bowel cancer (P for trend 0.01) with a 40% reduced risk in the highest compared to lowest quartile. We found reassuring evidence that dietary exposure to acrylamide in amounts typically ingested by Swedish adults in certain foods has no measurable impact on risk of three major types of cancer. It should be noted, however, that relation of risk to the acrylamide content of all foods could not be studied.

Waning sexual function - The most important disease-specific distress for patients with prostate cancer

The objective was to investigate how prostate cancer and its treatment affects sexual, urinary and bowel functions and to what extent eventual complications cause distress. A questionnaire was sent to 431 men aged 50-80 years with prostate cancer diagnosed in 1992 in the Stockholm area (Sweden) and 435 randomly selected men with a similar age distribution. Sexual function, as compared with their youth, was diminished in a majority of all men. The prostate cancer patients were, however, more likely to report low frequency and/or intensity in all aspects of sexual function. A majority of the men were distressed by a waning sexual capacity. The proportion of men with prostate cancer who were severely distressed owing to a decline in sexual function was larger than in the reference group. The willingness to trade off an intact sexual function for long-term survival varied considerably among the men in the reference group. Urinary and bowel symptoms were less common than a waning sexual function in both groups, and few appeared to be severely distressed by urinary or bowel symptoms. A decline in sexual functions was the most common cause of disease-specific distress in men with prostate cancer.

Nausea in cancer chemotherapy is inversely related to urinary cortisol excretion

Treatment with corticosteroids can control mild to moderate emesis during chemotherapy (Cassileth et al., 1983) and adds to the antiemetic effect of high-dose metoclopramide in severe emesis (Bruera et al., 1983). Moreover, pregnancy induced nausea is more common among women with low than high cortisol excretion (Jarnfelt-Samsioe et al., 1986). These findings warrant an investigation whether endogenous cortisol secretion is associated with nausea induced by chemotherapy. The aim of the present study was to relate endogenous cortisol secretion to individual differences in chemotherapy induced nausea and vomiting. Urinary cortisol excretion remain stable over time, particularly during resting conditions (Forsman & Lundberg, 1982). Therefore, night time urine was collected to assay cortisol excretion. Self-reports were used to assess nausea and vomiting. Table I summarises the clinical features of the 21 consecutive outpatients and three inpatients receiving chemotherapy at the Karolinska Hospital who participated. None received high emetogenic cytostatics such as, for example, cisplatinum, and 12 subjects received no antiemetic treatment. Patients having received chemotherapy courses within

Factors Associated With Waning Sexual Function Among Elderly Men and Prostate Cancer Patients

PURPOSE We identified factors that affect sexual function in men 50 to 80 years old and, therefore, may confound the comparison among groups of elderly men. In particular, we identified factors that may influence a comparison between prostate cancer patients and the general population, or confound the relationship when comparing subgroups of patients in nonrandomized studies. MATERIALS AND METHODS A questionnaire, including the Radiumhemmet Scale of Sexual Function and modules assessing potential risk factors for waning sexual function, was sent to 431 patients 50 to 80 years old with prostate cancer diagnosed 1.5 to 2 years previously in the Stockholm area (Sweden) and a reference group of 435 age matched randomly selected men. RESULTS Factors associated with physiological impotence included prostate cancer (relative risk 1.9), diabetes mellitus (relative risk 2.3), myocardial infarction (relative risk 1.5), medication with diuretics (relative risk 1.5), hydrogen blockers (relative risk 2.3) and warfarin type anticoagulants (relative risk 1.7). Patients treated for prostate cancer were more likely to be physiologically impotent compared to those with no initial treatment, and this was true for all treatment protocols after adjustment for confounding factors. Men treated with radical prostatectomy were more likely to be physiologically impotent than men treated with external beam radiation therapy (relative risk 1.5). CONCLUSIONS Waning sexual function in the prostate cancer patients was largely due to side effects of the treatment and this could not be explained by confounding factors. In particular, confounding could not explain the greater risk of impotence after radical prostatectomy compared to external beam radiation therapy.

Similarities and differences in assessing nausea on a verbal category scale and a visual analogue scale.

The use of verbal category scales in assessing patient symptoms is evolving, but the extent to which reliability and precision are lost in using them as opposed to a visual analogue scale (VAS) remains uncertain. The present study analyzed the concordance between a four-point verbal category scale and a VAS in assessing nausea intensity in patients undergoing chemotherapy. The analysis of a total of 348 simultaneous ratings by 104 women over four cycles revealed good concordance between the scales. The means of the VAS ratings (range 0-100 mm) corresponding to the four verbal categories divided the scale in four almost equally large parts (no nausea = 0.7, mild = 24.8, moderate = 48.3, severe = 75.1). However, the VAS ranges were wide. On an individual level a one-step change in the verbal category was associated with an average change of 20 mm on the VAS. The choice of scale to use should be based on the need in the particular situation. When measuring intensity of nausea in patients, the VAS is a reasonable choice due to its possibly greater ability to detect changes over time. On the group level, findings on a four-point category scale and a VAS on the average seem similar.

Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study

Background:We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women.Methods:We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records.Results:Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms.Conclusion:Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.

Anxiety is contagious—symptoms of anxiety in the terminally ill child affect long-term psychological well-being in bereaved parents†

We studied the relation between unrelieved symptoms in terminally ill children and the psychological well‐being in the bereaved parents 4–9 years after their loss.

Endogenous cortisol exerts antiemetic effect similar to that of exogenous corticosteroids.

Lower pre-chemotherapy night time cortisol excretion predicted more severe cisplatin induced nausea and vomiting in 42 ovarian cancer patients receiving ondansetron as a single antiemetic agent. Dexamethasone administration added to the antiemetic effect of ondansetron principally in patients who had low excretion of cortisol.

Model selection in Medical Research: A simulation study comparing Bayesian Model Averaging and Stepwise Regression

BackgroundAutomatic variable selection methods are usually discouraged in medical research although we believe they might be valuable for studies where subject matter knowledge is limited. Bayesian model averaging may be useful for model selection but only limited attempts to compare it to stepwise regression have been published. We therefore performed a simulation study to compare stepwise regression with Bayesian model averaging.MethodsWe simulated data corresponding to five different data generating processes and thirty different values of the effect size (the parameter estimate divided by its standard error). Each data generating process contained twenty explanatory variables in total and had between zero and two true predictors. Three data generating processes were built of uncorrelated predictor variables while two had a mixture of correlated and uncorrelated variables. We fitted linear regression models to the simulated data. We used Bayesian model averaging and stepwise regression respectively as model selection procedures and compared the estimated selection probabilities.ResultsThe estimated probability of not selecting a redundant variable was between 0.99 and 1 for Bayesian model averaging while approximately 0.95 for stepwise regression when the redundant variable was not correlated with a true predictor. These probabilities did not depend on the effect size of the true predictor. In the case of correlation between a redundant variable and a true predictor, the probability of not selecting a redundant variable was 0.95 to 1 for Bayesian model averaging while for stepwise regression it was between 0.7 and 0.9, depending on the effect size of the true predictor. The probability of selecting a true predictor increased as the effect size of the true predictor increased and leveled out at between 0.9 and 1 for stepwise regression, while it leveled out at 1 for Bayesian model averaging.ConclusionsOur simulation study showed that under the given conditions, Bayesian model averaging had a higher probability of not selecting a redundant variable than stepwise regression and had a similar probability of selecting a true predictor. Medical researchers building regression models with limited subject matter knowledge could thus benefit from using Bayesian model averaging.