Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor-positive/progesterone receptor-negative breast cancer.

Over the last few decades, improved and more individualized treatment has contributed to the increased survival rate of patients with breast cancer. However, certain patients may receive excessive treatment resulting in undesired side effects. In a previous study, it was demonstrated that systemically untreated patients with estrogen receptor (ER)-positive/progesterone receptor (PR)-negative tumors with high Ras-related protein Rab-6C (RAB6C) expression levels (RAB6C+) had prolonged distant recurrence-free survival compared with that of patients exhibiting low RAB6C (RAB6C-)-expressing tumors. The aim of the present study was to investigate whether RAB6C predicts the effectiveness of tamoxifen treatment. The present study used a dataset comprising 486 female patients with ER+ tumors from a randomized study conducted by the Stockholm Breast Cancer Study Group between November 1976 and August 1990. The patients were considered as low-risk if their tumor size was ≤30 mm and their lymph node status was negative. Patients were followed up until distant recurrence, mortality or when 25 years after randomization was achieved, whichever occurred first. For patients with ER+/PR-/RAB6C+ tumors, prolonged distant recurrence-free survival could not be observed if the patients were treated with tamoxifen [hazard ratio (HR), 1.82; 95% confidence interval (CI), 0.69-4.79; P=0.23], whereas patients with ER+/PR-/RAB6C- tumors had 75% reduced distant recurrence risk (HR, 0.25; 95% CI, 0.09-0.70; P=0.008). In the ER+/PR+ subgroup, patients with RAB6C- and RAB6C+ tumors benefited from tamoxifen treatment, though it was most evident in the RAB6C+ group (HR, 0.27; 95% CI, 0.13-0.58; P=0.001). The results of the present study indicated that, for patients with ER+/PR- tumors, those with low RAB6C expression benefited from tamoxifen treatment, whereas no benefit was observed in patients with high RAB6C levels.

RAB6C is an independent prognostic factor of estrogen receptor-positive/progesterone receptor-negative breast cancer.

The majority of breast cancer tumors are estrogen receptor-positive (ER+) and can be treated with endocrine therapy. However, certain patients may exhibit a good prognosis without systemic treatment. The aim of the present study was to identify novel prognostic factors for patients with ER+ breast cancer tumors using gene copy data, and to investigate if these factors have prognostic value in subgroups categorized by progesterone receptor status (PR). Public data, including the whole genome gene copy data of 199 systemically untreated patients with ER+ tumors, were utilized in the present study. To assess prognostic value, patients were divided into two groups using the median gene copy number as a cut-off for the SNPs that were the most variable. One SNP was identified, which indicated that the Ras-related protein Rab-6C (RAB6C) gene may exhibit prognostic significance. Therefore, RAB6C protein expression was subsequently investigated in a second independent cohort, consisting of 469 systematically untreated patients (of which 310 were ER+) who received long term follow-up. In the public data set, a distant recurrence risk reduction of 55% was determined for copy numbers above the median value of RAB6C compared with numbers below [multivariable adjusted hazard ratio (HR), 0.45; 95% CI 0.28-0.72; P=0.001)]. It was also more pronounced in the ER+/PR- subgroup (HR, 0.15; 95% CI, 0.05-0.46; P=0.001). In the second cohort, patients of the ER+/PR- subgroup who exhibited high RAB6C expression had a reduced distant recurrence risk (HR, 0.17; 95% CI, 0.05-0.60; P=0.006). However, this was not identified among ER+/PR+ tumors (HR, 1.31; 95% CI, 0.69-2.48; P=0.41). The results of the present study indicated that RAB6C serves as an independent prognostic factor of distant recurrence risk in systemically untreated patients with an ER+/PR- tumor.

Long-term effects on the incidence of second primary cancers in a randomized trial of two and five years of adjuvant tamoxifen.

BACKGROUND: Tamoxifen is a well established treatment for breast cancer, but its long-term effects on the incidence of secondary cancers are not fully evaluated. MATERIAL AND METHODS: We have studied 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after two years of tamoxifen, and who were randomized to receive totally two or five years of therapy. RESULTS: Compared to patients randomized to two years of tamoxifen the incidence of contralateral breast cancer [hazard ratio (HR) 0.73; 95% CI 0.56-0.96] and of lung cancer (HR 0.45; 95% CI 0.27-0.77), especially squamous cell and small cell lung cancer, were reduced in the five-year group, and similar results were seen when restricting the analysis to the 10-year period after treatment stopped. An increased incidence of endometrial cancer was observed in the five-year group, but the excess risk decreased over time. CONCLUSION: Further studies of the effects of tamoxifen on the risk of different histological types of lung cancer are needed.

Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden.

Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61-3.50. Stage III-IV vs I: OR = 2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; p < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95% CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis.

Intergenerational Cohort Study of Preterm and Small-for-Gestational-Age Birth in Twins and Singletons.

To date, several studies have investigated the intergenerational effect of preterm and small-for-gestational-age (SGA) births. However, most studies excluded both twin mothers and twin offspring from the analyses. Thus, the objective of this study was to investigate the intergenerational effect of preterm birth and SGA births among twins and singletons. A prospective population-based register study of mother-firstborn offspring pairs recorded in the Swedish Medical Birth Register was performed. The study included 4,073 twins and 264,794 singletons born from 1973-1983 and their firstborns born from 1986-2009. Preterm birth was defined as birth at <37 weeks of gestation, and SGA as birth weight <2 standard deviations of the Swedish standard. Logistic regressions were performed to estimate the intergenerational effect of each birth characteristic. Adjustments were made for maternal grandmothers' and mothers' socio-demographic factors, in addition to maternal birth characteristics. Among mothers born as singletons, being born preterm was associated with an increased risk of delivering a preterm child (adjusted odds ratio (OR) 1.39, 95% Confidence Interval (CI) = 1.29-1.50), while being born SGA increased the likelihood of having an SGA child (adjusted OR 3.04, 95% CI = 2.80-3.30) as well as a preterm child (adjusted OR 1.30, 95% CI = 1.20-1.40). In twin mothers, the corresponding ORs tended to be lower, and the only statistically significant association was between an SGA mother and an SGA child (adjusted OR 2.15, 95% CI = 1.40-3.31). A statistically significant interaction between twinning and mother's size for gestational age was identified in a multivariate linear regression analysis, indicating that singleton mothers born SGA were associated with a lower birth weight compared with mothers not born SGA. Preterm birth and SGA appear to be transferred from one generation to the next, although not always reaching statistical significance. These effects seem to be less evident in mothers born as twins compared with those born as singletons.

Experience of a serious life event increases the risk for childhood type 1 diabetes: the ABIS population-based prospective cohort study.

AIMS/HYPOTHESIS: The aim of this study was to prospectively investigate whether psychological stress during childhood may be a risk factor for manifest type 1 diabetes. METHODS: The All Babies In Southeast Sweden (ABIS) study invited all families with babies born between 1 October 1997 and 30 September 1999 in southeast Sweden to participate. Our study subsample includes 10,495 participants in at least one of the data collections at 2-3, 5-6, 8 and 10-13 years of age not yet diagnosed with type 1 diabetes at inclusion; 58 children were subsequently diagnosed. Age at diagnosis was obtained from the national register SweDiabKids in 2012. Family psychological stress was measured via questionnaires given to the parents assessing serious life events, parenting stress, parental worries and the parent's social support. RESULTS: Childhood experience of a serious life event was associated with a higher risk of future diagnosis of type 1 diabetes (HR 3.0 [95% CI 1.6, 5.6], p = 0.001) after adjusting for heredity of type 1 diabetes and age at entry into the study. The result was still valid when controlling for heredity of type 2 diabetes, size for gestational age, the parents' education level and whether the mother worked at least 50% of full time before the child's birth (HR 2.8 [95% CI 1.5, 5.4], p = 0.002), and also when childhood BMI was added to the model (HR 5.0 [95% CI 2.3, 10.7], p < 0.001). CONCLUSIONS/INTERPRETATION: This first prospective study concluded that experience of a serious life event in childhood may be a risk factor for manifest type 1 diabetes.

Co-morbidities increase the risk of disability pension among MS patients: a population-based nationwide cohort study.

BACKGROUND: Multiple sclerosis (MS) is a chronic and often disabling disease. In 2005, 62% of the MS patients in Sweden aged 16-65 years were on disability pension. The objective of this study is to investigate whether the presence of common co-morbidities increase MS patients' risk for disability pension. METHODS: This population-based cohort study included 4 519 MS patients and 4 972 174 non-MS patients who in 2005 were aged 17-64 years, lived in Sweden, and were not on disability pension. Patients with MS were identified in the nationwide in- and outpatient registers, while four different registers were used to construct three sets of measures of musculoskeletal, mental, and cardiovascular disorders. Time-dependent proportional hazard models with a five-year follow up were performed, adjusting for socio-demographic factors. RESULTS: All studied disorders were elevated among MS patients, regardless of type of measure used. MS patients with mental disorders had a higher risk for disability pension than MS patients with no such co-morbidities. Moreover, mental disorders had a synergistic influence on MS patients' risk for disability pension. These findings were also confirmed when conducting sensitivity analyses. Musculoskeletal disorders appeared to increase MS patients' risk for disability pension. The results with regard to musculoskeletal disorders' synergistic influence on disability pension were however inconclusive. Cardiovascular co-morbidity had no significant influence on MS-patients' risk for disability pension. CONCLUSIONS: Co-morbidities, especially mental disorders, significantly contribute to MS patients' risk of disability pension, a finding of relevance for MS management and treatment.

Later stage at diagnosis and worse survival in cutaneous malignant melanoma among men living alone: a nationwide population-based study from Sweden.

PURPOSE: To investigate the association between cohabitation status, clinical stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma (CMM). METHODS: This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based registers followed up through 2012. RESULTS: After adjustment for age at diagnosis, level of education, living area, period of diagnosis, and tumor site, the odds ratios (ORs) of higher stage at diagnosis were significantly increased among men living alone versus men living with a partner (stage II v stage I: OR, 1.42; 95% CI, 1.29 to 1.57; stage III or IV v stage I: OR, 1.43; 95% CI, 1.14 to 1.79). The OR for stage II versus stage I disease was also increased among women living alone (OR, 1.15; 95% CI, 1.04 to 1.28). After adjustments for the factors listed earlier, the CMM-specific survival was significantly decreased among men living alone (hazard ratio [HR] for death, 1.48; 95% CI, 1.33 to 1.65; P < .001). After additional adjustments for all potential and established prognostic factors, CMM-specific survival among men living alone versus men living with a partner remained significantly decreased (HR, 1.31; 95% CI, 1.18 to 1.46; P < .001), suggesting a residual adverse effect on survival not accounted for by these parameters. CONCLUSION: In all age groups among men, living alone is significantly associated with reduced CMM-specific survival, partially attributed to a more advanced stage at diagnosis. This emphasizes the need for improved prevention and early detection strategies for this group.

Change in paternal grandmothers' early food supply influenced cardiovascular mortality of the female grandchildren.

BACKGROUND: This study investigated whether large fluctuations in food availability during grandparents' early development influenced grandchildren's cardiovascular mortality. We reported earlier that changes in availability of food - from good to poor or from poor to good - during intrauterine development was followed by a double risk of sudden death as an adult, and that mortality rate can be associated with ancestors' childhood availability of food. We have now studied transgenerational responses (TGR) to sharp differences of harvest between two consecutive years' for ancestors of 317 people in Överkalix, Sweden. RESULTS: The confidence intervals were very wide but we found a striking TGR. There was no response in cardiovascular mortality in the grandchild from sharp changes of early exposure, experienced by three of the four grandparents (maternal grandparents and paternal grandfathers). If, however, the paternal grandmother up to puberty lived through a sharp change in food supply from one year to next, her sons' daughters had an excess risk for cardiovascular mortality (HR 2.69, 95% confidence interval 1.05-6.92). Selection or learning and imitation are unlikely explanations. X-linked epigenetic inheritance via spermatozoa seemed to be plausible, with the transmission, limited to being through the father, possibly explained by the sex differences in meiosis. CONCLUSION: The shock of change in food availability seems to give specific transgenerational responses.

Hospitalization in adolescence and young adulthood among twins and singletons: a Swedish cohort study of subjects born between 1973 and 1983.

Children born with non-optimal birth characteristics - that is, are small for gestational age and/or preterm - have an increased risk for several long-term effects such as neurological sequelae and chronic disease. The purpose of this study was to examine whether twins exhibited a different outcome, compared with singletons, in terms of hospitalization during adolescence and early adulthood, and to what extent differences remain when considering the divergence in birth characteristics between singletons and twins. Persons born between 1973 and 1983 in Sweden and surviving until age 13 were included and followed until the end of 2006. Data on birth characteristics, parental socio-demographic factors, and hospitalizations were collected from national registers. Adjusting for parental socio-demographic factors, twins had a higher risk of being hospitalized than singletons (odds ratio, OR = 1.17, 95% confidence interval, CI = 1.10-1.25) and more often due to 'Congenital anomalies' (OR = 1.18, 95% CI = 1.06-1.28), 'Infections' (OR = 1.14; 95% CI = 1.08-1.20), 'External causes of illness' (OR = 1.10, 95% CI = 1.06-1.15), and 'Diseases of the nervous system' (OR = 1.18, 95% CI = 1.10-1.26). Stratifying for birth characteristics, this difference diminishes, and for some diagnoses non-optimal twins seem to do slightly better than non-optimal singletons. Thus, twins with non-optimal birth characteristics had a lower risk of hospitalization than non-optimal singletons on, for example, 'Congenital anomalies' and 'Diseases of the nervous system' (OR = 0.86, 95% CI = 0.77-0.96; OR = 0.88, 95% CI = 0.81-0.97, respectively) and Total (any) hospitalization (OR = 0.87, 95% CI = 0.83-0.92). Among those with optimal birth characteristics, twins had an increased hospitalization due to 'External causes of illness' (OR = 1.07, 95% CI = 1.02-1.13) compared with optimal singletons. Twins have higher hospitalization rates than singletons. In stratifying for birth characteristics, this difference diminishes, and for some diagnoses, non-optimal twins seem to do less poorly than non-optimal singletons.

Family psychological stress early in life and development of type 1 diabetes: the ABIS prospective study.

AIMS: This study investigated whether psychological stress in the family during the child's first year of life are associated with the risk of childhood type 1 diabetes (T1D). According to the beta-cell stress hypothesis all factors that increase the need for, or the resistance to, insulin may be regarded as risk factors for T1D. METHODS: Among 8921 children from the general population with questionnaire data from one parent at child's birth and at 1 year of age, 42 cases of T1D were identified up to 11-13 years of age. Additionally 15 cases with multiple diabetes-related autoantibodies were detected in a sub-sample of 2649 children. RESULTS: Cox regression analyses showed no significant associations between serious life events (hazard ratio 0.7 for yes vs. no [95% CI 0.2-1.9], p=0.47), parenting stress (0.9 per scale score [0.5-1.7], p=0.79), or parental dissatisfaction (0.6 per scale score [0.3-1.2], p=0.13) during the first year of life and later diagnosis of T1D, after controlling for socioeconomic, demographic, and diabetes-related factors. Inclusion of children with multiple autoantibodies did not alter the results. CONCLUSIONS: No association between psychological stress early in life and development of T1D could be confirmed.

Effects of adjuvant tamoxifen therapy on cardiac disease: results from a randomized trial with long-term follow-up.

Tamoxifen is associated with a reduced risk of coronary heart disease (CHD). However, there are few reports on long-term effects. Using data from a large Swedish randomized trial of 5 and 2 years of adjuvant tamoxifen in women with early breast cancer, we here present results on morbidity and mortality from cardiac diseases during treatment and long-term after treatment. A total of 4,150 patients were breast cancer recurrence-free after 2 years. Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry were used to define events of disease. Hazard ratios were estimated using Cox regression. Patients assigned to 5 years in comparison with 2 years of postoperative tamoxifen experienced a reduced incidence of CHD [hazard ratio (HR), 0.83; 95 % CI 0.70-1.00], especially apparent during the active treatment period (HR 0.65; 95 % CI 0.43-1.00). The mortality from CHD was significantly reduced (HR 0.72; 95 % CI 0.53-0.97). During the active treatment, the morbidity of other heart diseases was also significantly reduced (HR 0.40; 95 % CI 0.25-0.64) but not after treatment stopped (HR 1.06; 95 % CI 0.87-1.30). Similar results were seen for both heart failure and atrial fibrillation/flutter. As compared to 2 years of therapy, 5 years of postoperative tamoxifen therapy prevents CHD as well as other heart diseases. The risk reduction is most apparent during the active treatment period, and later tends to diminish.

Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer.

INTRODUCTION: Akt is a signalling modulator for many cellular processes, including metabolism, cell proliferation, cell survival and cell growth. Three isoforms of Akt have been identified, but only a few studies have concerned the isoform-specific roles in the prognosis of breast cancer patients. The aim of this study was to investigate the prognostic value of v-akt murine thymoma viral oncogene homologue 1 (Akt1) and v-akt murine thymoma viral oncogene homologue 2 (Akt2) in oestrogen receptor positive (ER+) and oestrogen receptor negative (ER-) breast cancer with long-term follow-up. MATERIAL AND METHODS: The expression of Akt in tumour tissue was analysed with immunohistochemistry in a cohort of 272 postmenopausal patients with stage II breast cancer. The median follow-up time was 19 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox's proportional hazards model. RESULTS: The risk of distant recurrence was reduced for patients with ER+ tumours expressing Akt2 compared to patients with no Akt2 expression (HR=0.49, 95% CI 0.29-0.82, p=0.007). When adjusting for important clinical tumour characteristics and treatment, Akt2 was still an independent prognostic factor (HR=0.38, 95% CI 0.21-0.68, p=0.001) and the association remained long-term. The prognostic value of Akt2 increased with higher oestrogen receptor levels from no effect among patients with ER- tumours to 68% risk reduction for the group with high ER-levels (P for trend=0.042). Akt1 showed no significant prognostic information. CONCLUSION: Our results indicate that Akt2 expression is associated with a lower distant recurrence rate for patients with ER+ tumours and that this association remains long-term. The prognostic value of Akt2 increases with higher oestrogen receptor expression, motivating further mechanistic studies on the role of Akt2 in ER+ breast cancer.

Reproductive patterns among twins--Swedish register study of men and women born 1973-1983.

BACKGROUND: During the last decades there has been a steady increase of twin births. A combination of improved medical treatment of preterm and small-for-gestational age children has contributed to a higher number of surviving twins. Prematurity is known to affect reproduction in a negative way. Few studies have focused on the potential effect twinning may have on future reproduction. Thus, the aim of this study was to investigate the effect of being born a twin compared to being born a singleton have on future reproduction. METHODS: In a national population-based register study, all individuals born between 1973-1983 who were alive and living in Sweden at 13 years of age (n = 1 016 908) constituted the sample. Data on each study subject's own birth as well as the birth of their first offspring, and parental socio-demographic factors were collected from Swedish population based registers. Hazard ratios and corresponding 95% CI was calculated using Cox proportional hazards model. RESULTS: Twins, both men and women, had a reduced likelihood of reproducing compared to singletons (women: HR = 0.89, 95% CI = 0.86-0.93; men: HR = 0.92, 95% CI = 0.87-0.97). This difference in birth rates can only partly be explained by diverging birth characteristics. Amongst men and women born very preterm, twins had an increased likelihood of reproducing compared to singletons (women: HR = 1.25, 95% CI = 1.02-1.62; men: HR = 1.34, 95% CI = 1.01-1.78). CONCLUSIONS: Twins have lower reproduction rates compared to singletons, which only to a certain degree can be explained by diverging birth characteristics.

How does comorbidity influence healthcare costs? A population-based cross-sectional study of depression, back pain and osteoarthritis.

OBJECTIVES: To analyse how comorbidity among patients with back pain, depression and osteoarthritis influences healthcare costs per patient. A special focus was made on the distribution of costs for primary healthcare compared with specialist care, hospital care and drugs. DESIGN: Population-based cross-sectional study. SETTING: The County of Östergötland, Sweden. PATIENTS: Data on diagnoses and healthcare costs for all 266 354 individuals between 20 and 75 years of age, who were residents of the County of Östergötland, Sweden, in the year 2006, were extracted from the local healthcare register and the national register of drug prescriptions. MAIN OUTCOME MEASURES: The effects of comorbidity on healthcare costs were estimated as interactions in regression models that also included age, sex, number of other health conditions and education. RESULTS: The largest diagnosed group was back pain (11 178 patients) followed by depression (7412 patients) and osteoarthritis (5174 patients). The largest comorbidity subgroup was the combination of back pain and depression (772 patients), followed by the combination of back pain and osteoarthritis (527 patients) and the combination of depression and osteoarthritis (206 patients). For patients having both a depression diagnosis and a back pain diagnosis, there was a significant negative interaction effect on total healthcare costs. The average healthcare costs among patients with depression and back pain was SEK 11 806 lower for a patient with both diagnoses. In this comorbidity group, there were tendencies of a positive interaction for general practitioner visits and negative interactions for all other visits and hospital days. Small or no interactions at all were seen between depression diagnoses and osteoarthritis diagnoses. CONCLUSIONS: A small increase in primary healthcare visits in comorbid back pain and depression patients was accompanied with a substantial reduction in total healthcare costs and in hospital costs. Our results can be of value in analysing the cost effects of comorbidity and how the coordination of primary and secondary care may have an impact on healthcare costs.

PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy--a study in a Swedish rectal cancer trial of preoperative radiotherapy.

BACKGROUND: The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients. METHODS: PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by western blot. RESULTS: In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (P = 0.03). No survival relationship in patients with RT was observed (P = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (P = 0.68)/inner tumour area (P = 0.49). In patients with RT, strong PINCH expression was related to a higher grade of LVD (lymphatic vessel density) (P = 0.01) CONCLUSIONS: PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.

NF-κB p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients.

INTRODUCTION: The NF-κB transcription factor protein family has diverse cellular and biological functions, and posttranslational modification is important to regulate these functions. An important site of phosphorylation of NF-κB p65 subunit is at serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization, and protein stability. PATIENTS AND METHODS: In this study, we investigated expression of phospho-Ser536-p65 in colorectal cancers and its relationships with clinicopathological factors. The expression of phospho-Ser536-p65 was examined by immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens, and 18 metastases in the lymph nodes. RESULTS: The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumor (p < 0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumors correlated with worse survival of the patients independently of gender, age, tumor location, stage, and differentiation (p = 0.04; hazard ratio, 1.89; 95% CI 1.03-3.47). CONCLUSION: The NF-κB p65 subunit phosphorylated at serine-536 is an independent prognostic factor in colorectal cancer patients.

Migration and mortality trajectories: a study of individuals born in the rural community of Överkalix, Sweden.

Migration may result in exposure to factors that are both beneficial and harmful for good health. How the act of migration is associated with mortality, or whether the socio-economic condition of migrants prior to migration influences their mortality trajectory, is not well understood. In the present study, a cohort of 413 randomly selected individuals born in the rural community of Överkalix, Sweden, between 1890 and 1935 were followed from birth to either death or old age. Around 50% of the study-population moved away from Överkalix at one time or another. To adjust for a potential bias resulting from self-selection among the migrants, the father's occupational status was used together with parents' and grandparents' longevity. Overall, migration could not be shown to predict mortality when the backgrounds of the migrants were taken into account. Nonetheless, socio-economic background conditions appeared to moderate the association, decreasing the mortality rates for migrants with relatively good pre-migratory socio-economic conditions, while increasing it for migrants with poorer pre-migratory conditions. However, further scrutiny revealed that this effect modification mainly affected the female migrants' mortality. In conclusion, the study suggests that there is no general association between migration and mortality, but that migrants with better socio-economic resources are more likely to improve their mortality trajectories than migrants with poorer resources. Better pre-migratory conditions hence appear to be important for avoiding health-adverse circumstances and gaining access to health beneficial living conditions when moving to foreign environments - especially for women.

Co-morbidity and health care utilisation five years prior to diagnosis for depression. A register-based study in a Swedish population.

BACKGROUND: Depressive disorders have been associated with a number of co-morbidities, and we hypothesized that patients with a depression diagnosis would be heavy users of health care services, not only when first evaluated for depression, but also for preceding years. The aim of this study was to investigate whether increased health care utilisation and co-morbidity could be seen during five years prior to an initial diagnosis of depression. METHODS: We used a longitudinal register-based study design. The setting comprised the general population in the county of Östergötland, south-east Sweden. All 2470 patients who were 20 years or older in 2006 and who received a new diagnosis of depression (F32 according to ICD-10) in 2006, were selected and followed back to the year 2001, five years before their depression diagnosis. A control group was randomly selected among those who were aged 20 years or over in 2006 and who had received no depression diagnosis during the period 2001-2006. RESULTS: Predictors of a depression diagnosis were a high number of physician visits, female gender, age below 60, age above 80 and a low socioeconomic status.Patients who received a diagnosis of depression used twice the amount of health care (e.g. physician visits and hospital days) during the five year period prior to diagnosis compared to the control group. A particularly strong increase in health care utilisation was seen the last year before diagnosis. These findings were supported with a high level of co-morbidity as for example musculoskeletal disorders during the whole five-year period for patients with a depression diagnosis. CONCLUSIONS: Predictors of a depression diagnosis were a high number of physician visits, female gender, age below 60, age above 80 and a low socioeconomic status. To find early signs of depression in the clinical setting and to use a preventive strategy to handle these patients is important.

The association of immigrant- and non-immigrant-specific factors with mental ill health among immigrants in Sweden.

BACKGROUND: It has often been shown that immigrants are particularly at risk for mental ill health. The aim of the study was to investigate the association of immigrant- and non-immigrant-specific factors with mental ill health within a diverse immigrant population. METHOD: An extensive questionnaire was sent out to a stratified random sample of three immigrant populations from Finland, Iraq and Iran. The 720 respondents completed a Swedish, Arabic or Farsi (Persian) version of the questionnaire including the WHO (10) Well-Being Index and the HSCL-25. RESULTS: The results indicate that mental ill health among immigrants is independently associated with non-immigrant-specific factors (i.e. high number of types of traumatic episodes, divorced/widowed, poor social network, economic insecurity and being female) and immigrant-specific factors (i.e. low level of sociocultural adaptation). These results were obtained regardless of whether mental ill health was operationalized as low subjective well-being or a high symptom level of anxiety/depression. CONCLUSIONS: These findings support the notion that mental ill health among immigrants is a multi-faceted phenomenon that needs to be tackled within a wide range of sectors - e.g. the healthcare system, the social service sector and, of course, the political arena.