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.

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; pamp;lt;0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-horn patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95 h 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.

Background Clinical stage at diagnosis is a strong prognostic factor for death in cutaneous malignant melanoma (CMM), with worse prognosis at higher stages. However, few studies have investigated how direct healthcare cost per patient varies with clinical stage.

Objective The aim of this study was to determine the stage-specific direct healthcare costs for CMM patients compared to the healthcare costs in the general population in the County of Östergötland, Sweden.

Methods CMM patients in the County of Östergötland diagnosed 2005-2012 were identified from the Swedish cancer registry. Information on clinical stage was collected from the Swedish Melanoma Register (SMR) and cost data from the Cost per Patient database (CPP) for 1 075 CMM patients in Östergötland. CPP contains costs associated with all healthcare contacts per patient including inpatient, outpatient, and primary care. The CMM-related costs were defined as the difference in mean healthcare costs between CMM patients and general population.

Results The first year after CMM diagnosis, the average healthcare costs for CMM patients was 2.8 times higher than in the general population. The healthcare cost ratio varied from 2.0 (stage I) to 10.1 (stage IV) and the CMM-related costs per patient-year varied from €2 670 (stage I) to €29 291 (stage IV). The mean healthcare costs decreased over time but remained significantly higher than in the general population for all clinical stages. During the first year after diagnosis, patients in clinical stage III-IV (7% of CMM patients) accounted for 27% of the total CMM-related healthcare costs.

Conclusions The direct healthcare costs for CMM patients were significantly higher than in the general population independent of clinical stage. CMM patients diagnosed in clinical stage III-IV were associated with particularly high costs and the healthcare system may save resources by finding CMM patients in earlier stages.

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 parents 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 childs 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 less than 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.

To date several studies have investigated the intergenerational effect of preterm and small-for-gestational-age 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 small for gestational age (SGA) among twins and singletons.

A prospective population based register study of mother-first-born offspring pairs recorded in the Swedish Medical Birth Register was performed. The study included 4073 twins and 264,794 singletons born in 1973-1983 and their firstborns born in 1986-2009. Preterm birth was defined as birth <37 weeks of gestation and SGA as < 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 mother’s socio-demographic factors in addition to maternal birth- characteristics.

Among mothers born as singletons, being born preterm was associated with an increased risk for delivering a preterm child (adjusted OR 1.39, 95% CI 1.29-1.50) while being born SGA increased the likelihood of a 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 a SGA mother and a SGA child (adjusted OR 2.15, 95% CI 1.40-3.31). A statistically significant interaction between twinning and mother’s size for gestational was identified in a multivariate linear regression analysis indicating that singleton mothers born SGA were associated with a lower birth weight compared to 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.

Background Twinning has been shown to be associated with a reduced reproductive rate compared to singletons. This can partly be explained by the birth-characteristics pertaining to twinning as many twins are born preterm, with low birth weight or small for gestational age. However, the intergenerational reproductive rate may also be due to familial factors such as number of siblings.

Methods This is a register-based study of all men and women born in Sweden between 1973 and 1993 who were living in Sweden at 13 years of age. Data on the study objects’ own births as well as their offspring, parental socio-demographic factors were collected from Swedish population based registers. Hazard ratios for the likelihood of becoming a parent were estimated using Cox’s proportion hazard models. All models were adjusted for socio-demographic and birth characteristics.

Results Adjusting for number of siblings, socio-demographic factors and birth characteristics, twinning was associated with a decreased likelihood of becoming a first-time parent, compared with singletons both for females (HR (95% CI)=0.90 (0.88-0.93) and males (HR (95% CI)=0.96 (0.93-0.99). Having 3 or more siblings increased the chance of becoming a first-time parent among both male twins (HR (95% CI)=1.17 (1.08-1.27)) and singletons (HR (95% CI)=1.16 (1.15-1.18)) compared to having fewer than 3 siblings. This increased likelihood of becoming a parent was also present among female twins (HR (95% CI)=1.18 (1.10-1.26)) and singletons (HR (95% CI)=1.22 (1.21-1.24)).

Conclusions Twins have a decreased likelihood of becoming a parent compared to singletons even when adjusting for number of siblings.

This study aims to investigate the association between experiences of serious life events assessed by checklists longitudinally across childhood (at age 5-6, age 8, and age 12-14 years) and level of mental health problems in early adolescence (at age 12-14), and the mediating role of family climate factors across childhood. Questionnaire data from the All Babies In Southeast Sweden (ABIS) population based cohort-study were used (n=1132). The association were best modelled with a sequential cumulative approach; that means that the number of time-periods at least one serious life event was experienced were linearly related to the level of mental health problems (SDQ-score) after controlling for age, sex/gender, parental educational level, immigrant status and fuzzy/difficult temperament at age 2-3 (b=0.58 [95% CI 0.28, 0.87], p<0.001). Parenting stress and the parents size and satisfaction of social support were found as moderating factors, where the association between serious life events and mental health problems only were found in the subgroups of families where the parent perceive chronically high levels of parenting stress (high at 3-4 times of 4 possible; n=163, b=1.28 [0.55, 2.01], p=0.001), have a small social network (n=108, p=1.75 [0.86, 2.64], p<0.001), and are dissatisfied with their social support (n=95, p=1.22 [0.36, 2.09], p=0.006). An absence of parenting stress across childhood and adequate social support for the parents are suggested as resilient factors. To avoid negative consequences for child mental health after experiences of stressful life events, parents should get adequate support in child health services.

Background: Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most western countries, though the rate of improvement in survival appears to have declined in Sweden at the end of last millennium.

Objectives: To analyse the most recent trends in the distribution of tumour thickness (T-category) as well as CMM-specific survival in Swedish patients diagnosed 1997-2011.

Methods: This nationwide population-based study included 30 590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM 1997-2011. The patients were followed through 2012 in the national Cause-of-Death Register.

Results: Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site, and health care region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P = 0·0008) and the CMM-specific survival significantly improved in men diagnosed 2007-2011 compared to men diagnosed 1997-2001 (hazard ratio=0·81; 95% CI 0·72-0·91, P = 0·0009) while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared to those diagnosed earlier 1997-2001 and later 2007-2011.

Conclusion: In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men.

BACKGROUND:

Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties.

METHODS:

The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay.

RESULTS:

The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence (P=0.009) and worse disease-free survival (P=0.007). Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines.

CONCLUSIONS:

The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse.

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.