Localized prostate cancer in Norway, the United States, and Spain: between-country differences of variables before treatment among patients eligible for curative treatment

Between-country differences in medical and sociodemographic variables, and patient-related outcomes (PROs) before treatment might explain published variations of side effects after radical prostatecomy (RP) or radiotherapy (RAD) for prostate cancer (PCa). This hypothesis was tested among 1908 patients from the United States, Spain, and Norway. Significant between-country differences were observed for most factors investigated before treatment. The observations should be considered in comparison of the frequency and severity of internationally published studies. Background: In men with PCa, large variations of PROs after RP or high-dose RAD might be related to betweencountry differences of medical and sociodemographic variables, and differences in PROs before treatment in the sexual and urinary domains. Patients and Methods: In 1908 patients with localized PCa from Norway, the United States, or Spain, the relation between medical (prostate-specific antigen, Gleason score, cT-category) and sociodemographic variables (age, education, marital status) before treatment was investigated. Using the Expanded Prostate Cancer Index Composite questionnaire, PROs before treatment within the sexual and urinary domains were also considered. Results: Compared with the European patients, American patients were younger, fewer had comorbid conditions, and more had a high education level. Fifty-three percent of the US men eligible for RP had low-risk tumors compared with 42% and 31% among the Norwegian and the Spanish patients, respectively. Among the Spanish RAD patients, 54% had had low-risk tumors compared with 34% of the American and 21% of the Norwegian men planned for RAD, respectively. Compared with the European patients, significantly fewer US patients reported moderate or severe sexual dysfunction and related problems. In most subgroups, the number of patients with sexual or urinary dysfunction exceeded that of patients with bother related to the reported dysfunction. Conclusion: Statistically significant between-country differences were observed in medical and sociodemographic variables, and in PROs before treatment within the sexual and urinary domains. Large differences between reported dysfunction and related problems within the sexual and urinary domains indicate that dysfunction and bother should be reported separately in addition to calculation of summary scores. The documented differences, not at least regarding PROs, might in part explain the large variation of side effects after treatment evident in the medical literatur

NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations

<p>Abstract</p> <p>Background</p> <p>A recent genome-wide association study (GWAS) has identified a single nucleotide polymorphism (SNP) rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger in patients with estrogen receptor (ER)⁺versus ER^-cancer.</p> <p>Results</p> <p>We found association between SNP rs11249433 and expression of the <it>NOTCH2 </it>gene located in the 1p11.2 region. Examined in 180 breast tumors, the expression of <it>NOTCH2 </it>was found to be lowest in tumors with <it>TP53 </it>mutations and highest in <it>TP53 </it>wild-type/ER⁺tumors (p = 0.0059). In the latter group, the <it>NOTCH2 </it>expression was particularly increased in carriers of the risk genotypes (AG/GG) of rs11249433 when compared to the non-risk AA genotype (p = 0.0062). Similar association between <it>NOTCH2 </it>expression and rs11249433 was observed in 60 samples of purified monocytes from healthy controls (p = 0.015), but not in total blood samples from 302 breast cancer patients and 76 normal breast tissue samples. We also identified the first possible dominant-negative form of <it>NOTCH2</it>, a truncated version of <it>NOTCH2 </it>consisting of only the extracellular domain.</p> <p>Conclusion</p> <p>This is the first study to show that the expression of <it>NOTCH2 </it>differs in subgroups of breast tumors and by genotypes of the breast cancer-associated SNP rs11249433. The NOTCH pathway has key functions in stem cell differentiation of ER⁺luminal cells in the breast. Therefore, increased expression of <it>NOTCH2 </it>in carriers of rs11249433 may promote development of ER⁺luminal tumors. Further studies are needed to investigate possible mechanisms of regulation of <it>NOTCH2 </it>expression by rs11249433 and the role of <it>NOTCH2 </it>splicing forms in breast cancer development.</p

Morbidity associated with "self-rated health" in epithelial ovarian cancer survivors

<p>Abstract</p> <p>Background</p> <p>Epithelial ovarian cancer survivors (EOCSs) frequently report multiple complaints after their treatment. The objective was to study somatic and mental morbidity in EOCSs associated with their Self- Rated Health (SRH) assessed by a single item.</p> <p>Findings were compared to age-matched controls from the general population.</p> <p>Methods</p> <p>In a cross -sectional follow-up design 189/287 (66%) EOCSs treated at The Norwegian Radiumhospital 1979–2003 responded to a mailed questionnaire on demographic data, and somatic and mental morbidity. SRH last week was rated on item #29 of the European Organization and Treatment of Cancer Quality of Life Questionnaire in 84/189 (97%) of responding EOCSs. For comparisons "good" and "poor" SRH groups were defined by the median score on the SRH item.</p> <p>Results</p> <p>EOCSs with "poor SRH" had higher level of somatic symptoms, anxiety, depression and fatigue than those with "good SRH" (p < .001). In multivariate analyses somatic symptoms, age and fatigue, were significantly associated with the SRH score in EOCSs, but not the cancer-related variables (FIGO stage, recurrence in < 6 months or chemotherapy ever). The model explained 70% of the variance in SRH in linear and 77% in logistic regression analyses. The distribution of the SRH scores in EOCSs did not differ significantly from that of normative controls; however a higher proportion of controls recorded a high SRH score.</p> <p>Conclusion</p> <p>SRH is strongly related to common somatic complaints, impairment and fatigue but not to cancer-related variables. A single question concerning SRH last week might be a quick screening method for collecting important information on symptoms in EOCSs, in addition to cancer – related questions.</p

Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

<p>Abstract</p> <p>Background</p> <p>The ATM protein is activated as a result of ionizing radiation, and genetic variants of the <it>ATM </it>gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for <it>ATM </it>mutations have been reported to have an increased risk of malignancy, especially breast cancer.</p> <p>Materials and methods</p> <p>Norwegian breast cancer patients (272) treated with radiation (252 of which were evaluated for radiation-induced adverse side effects), 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR) were screened for sequence variations in all exons of the <it>ATM </it>gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC) followed by sequencing to determine the nature of the variant.</p> <p>Results and Conclusion</p> <p>A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala) substitution in exon 11 (P-value 0.055) between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06). Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe) where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the <it>ATM </it>gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour recurrence and any of the sequence variants found in the American patient material.</p

Morbidity, life style and psychosocial situation in cancer survivors aged 60-69 years: results from The Nord-Trøndelag Health Study (The HUNT-II Study)

<p>Abstract</p> <p>Background</p> <p>Due to considerable health status differences in the elderly population, research limited to narrow age-spans might be an advantage. In this population-based controlled study we compare short-term (<5 years) (STS) and long-term (≥5 years) (LTS) cancer survivors and cancer-free controls aged 60-69 years from two Norwegian health registers; the Health Survey of North-Trøndelag County (HUNT-2 study) and the Cancer Registry of Norway (CRN). We examined possible factors associated with being cancer survivor.</p> <p>Methods</p> <p>Among 9,089 individuals aged 60-69 who participated in HUNT-2, 334 had been diagnosed with invasive primary cancer from 1 month to 42 years before HUNT-2 according to CRN and self-report. An overall random sample of controls without cancer five times larger than the sample of cases (N = 1,670) were drawn from the parent cohort.</p> <p>Results</p> <p>The cancer sample comprised 128 STS and 206 LTS. For most variables no significant differences were observed between LTS and STS. LTS were significantly more women, and cases with gynaecological cancer, with physical impairment and more thyroid diseases compared to STS. When comparing all the survivors with controls, the survivors showed significantly higher rate of pensioning, decreased self-rated health, more physical impairment and thyroid diseases, daily use of medication and psychotropics and higher level of anxiety and Framingham Risk score. Multivariate logistic regression analysis showed that increasing age, being female, physical impairment and thyroid diseases all were significantly associated with being survivor versus controls.</p> <p>Conclusion</p> <p>STS and LTS showed mostly similar situation. Compared to controls, the survivors reported somewhat poorer physical and mental health, but these differences were of doubtful clinical significance.</p