OBJECTIVE: Using a nested case-referent design, we evaluated the relationship between plasma levels of the lignan enterolactone and the risk of developing breast cancer. METHODS: 248 cases and 492 referents were selected from three population-based cohorts in northern Sweden. Blood samples were donated at enrollment. All blood samples were stored at -80 degrees C. Cases and referents were matched for age, date of blood sample and sampling centre. Breast cancer cases were identified through the regional and national cancer registries. RESULTS: Plasma enterolactone was lower among smokers in all cohorts and in subjects with BMI 28 in one of the cohorts. Low plasma concentrations of enterolactone, below the 12.5(th) percentile (mean plasma enterolactone 2.9 nmol/l), were associated with an increased risk of breast cancer. Also, high values of plasma enterolactone, above the 87.5(th) percentile (mean plasma enterolactone 58.2 nmol/l) were significantly associated with an increased breast cancer risk among women from two cohorts with only incident cases and a higher number of pre-menopausal women. High plasma enterolactone concentrations among older women from a mammary screening project with mostly prevalent cases were associated with a non-significant slightly reduced breast cancer risk. CONCLUSION: Very low plasma concentrations of enterolactone were associated with an increased breast cancer risk in all three cohorts. In two of the cohorts, with only incident cases, very high plasma concentrations were also associated with an increased breast cancer risk. In the third cohort with mainly screen-detected cases from a mammary screening program, high plasma enterolactone concentrations were associated with a weak decreased breast cancer risk.
BACKGROUND: Indigenous people often have a pattern of mortality that is disadvantageous in comparison with the general population. The knowledge on causes of death among the Sami, the natives of northern Scandinavia, is limited. The aim of the present study was to compare gender and cause specific mortality patterns for reindeer herding Sami, non-herding Sami, and non-Sami between 1961 and 2000. METHODS: A Sami cohort was constructed departing from a group of index-Sami identified as either reindeer herding Sami or Sami eligible to vote for the Sami parliament. Relatives of index-Sami were identified in the National Kinship Register and added to the cohort. The cohort contained a total of 41 721 people (7482 reindeer herding Sami and 34 239 non-herding Sami). A demographically matched non-Sami reference population four times as large, was compiled in the same way. Relative mortality risks were analysed by calculating standardized mortality ratios (SMRs). RESULTS: The differences in overall mortality and life expectancy of the Sami, both reindeer herding and non-herding, compared with the reference population were relatively small. However, Sami men showed significantly lower SMR for cancers but higher for external causes of injury. For Sami women, significantly higher SMR was found for diseases of the circulatory system and diseases of the respiratory system. An increased risk of dying from subarachnoid haemorrhage was observed among both Sami men and women. CONCLUSIONS: The similarities in mortality patterns are probably a result of centuries of close interaction between the Sami and the non-Sami, while the observed differences might be due to lifestyle, psychosocial and/or genetic factors.
Comments to the letters by Per-Henrik Zahl and Jan Maehlen and by Peter C. Gotzsche concerning our article: Increased incidence of invasive breast cancer after the introduction of service screening with mammography in Sweden.
Preoperative irradiation with 5 × 5 Gy in randomized trials reduces local recurrence rate and may improve survival in patients with resectable rectal cancer.
The aim of this study was to determine whether the same favorable effects could be observed in a population-based study.
This study was conducted via a retrospective analysis of prospectively collected data from the Swedish Rectal Cancer Registry.
This study examined population-based data from Sweden.
All newly diagnosed rectal cancers in Sweden are reported to the Swedish Rectal Cancer Registry.
Between 1995 and 2001, 6878 patients (stages I-III) were operated on with an anterior resection, an abdominoperineal resection, or a Hartmann's procedure. Short-course irradiation was given to 41% of patients preoperatively. To reduce bias, patients operated on with a Hartmann procedure or older than 75 years were excluded when 5-year survival was analyzed (n = 3466). Tumors were analyzed according to height (0-5 cm, 6-10 cm, 11-15 cm).
Five-year cumulative local recurrence and survival rates.
The 5-year cumulative local recurrence rate was 6.3% (95% CI 5.4-7.4) for patients receiving preoperative irradiation and 12.1% (95% CI 10.8-13.5) for patients not receiving preoperative irradiation. Multivariate analyses indicated the risk of local recurrence was 50% lower for patients receiving preoperative irradiation compared with patients not receiving irradiation (hazard ratio = 0.50; 95% CI 0.40-0.62). Among patients younger than 76 years and operated on with an anterior resection or abdominoperineal resection, the 5-year cumulative survival rate was 0.70 (95% CI 0.69-0.72). Disease-free and overall survivals were higher in irradiated patients, and the difference was statistically significant in low tumors.
In this population-based analysis, the favorable effect of preoperative short-course irradiation on local recurrence rates, seen in randomized trials, was confirmed for the entire Swedish population irrespective of tumor height and stage. Data also suggested an effect on 5-year survival, especially in patients with low tumors (0-5 cm).
Germline mutations in tumour suppressor genes cause various cancers. These genes are also somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic breast tumours.
After excluding the well-characterized breast cancer (BC) genes, we screened 15 novel genes consistently classified as BC driver genes in next-generation sequencing approaches for single nucleotide polymorphisms (SNPs). Altogether 40 SNPs located in the core promoter, 5'- and 3'-UTR or which were nonsynonymous SNPs were genotyped in 782 Swedish incident BC cases and 1,559 matched controls. After statistical analyses, further evaluations related to functional prediction and signatures of selection were performed.
TBX3 was associated with BC risk (rs2242442: OR?=?0.76, 95% CI 0.64-0.92, dominant model) and with less aggressive tumour characteristics. An association with BC survival and aggressive tumour characteristics was detected for the genes ATR (rs2227928: HR?=?1.63; 95% CI 1.00-2.64, dominant model), RUNX1 (rs17227210: HR?=?3.50, 95% CI 1.42-8.61, recessive model) and TTN (rs2303838: HR?=?2.36; 95% CI 1.04-5.39; rs2042996: HR?=?2.28; 95% CI 1.19-4.37, recessive model). According to the experimental ENCODE data all these SNPs themselves or SNPs in high linkage disequilibrium with them (r (2)?=?0.80) were located in regulatory regions. RUNX1 and TTN showed also several signatures of positive selection.
The study gave evidence that germline variants in BC driver genes may have impact on BC risk and/or survival. Future studies could discover further germline variants in known or so far unknown driver genes which contribute to cancer development.
Chromosomal instability is a known hallmark of many cancers. DNA polymerases represent a group of enzymes that are involved in the mechanism of chromosomal instability as they have a central function in DNA metabolism. We hypothesized that genetic variation in the polymerase genes may affect gene expression or protein configuration and by that cancer risk and clinical outcome. We selected four genes encoding for the catalytic subunits of the polymerases ß, d, ? and ? (POLB, POLD1, POLQ and REV3L, respectively) and two associated proteins (MAD2L2 and REV1) because of their previously reported association with chromosomal instability and/or tumorigenesis. We selected potentially functional and most informative tagging single nucleotide polymorphisms (SNPs) for genotyping in a population-based series of 783 Swedish breast cancer (BC) cases and 1562 controls. SNPs that showed a significant association in the Swedish population were additionally genotyped in a Polish population consisting of 506 familial/early onset BC cases and 568 controls. SNPs in all three polymerase ? subunit genes associated either with BC risk or prognosis. Two SNPs in REV3L and one SNP in MAD2L2 associated with BC risk: rs462779 (multiplicative model: OR 0.79, 95% CI 0.68-0.92), rs3204953 (dominant model: OR 1.28, 95% CI 1.05-1.56) and rs2233004 (recessive model: OR 0.49, 95% CI 0.28-0.86). Homozygous carriers of the minor allele C of the third SNP in REV3L, rs11153292, had significantly worse survival compared to the TT genotype carriers (HR 2.93, 95% CI 1.34-6.44). Minor allele carriers of two REV1 SNPs (rs6761391 and rs3792142) had significantly more often large tumours and tumours with high histological grade and stage. No association was observed for SNPs in POLB, POLQ and POLD1. Altogether, our data suggest a significant role of genetic variation in the polymerase ? subunit genes regarding the development and progression of BC.
OBJECTIVE: To investigate the geographical variation in prostate cancer incidence in Sweden, in particular the incidences of screening-detected tumours and curative treatment of prostate cancer. MATERIAL AND METHODS: Data were retrieved from the National Prostate Cancer Register of Sweden for all cases of prostate cancer diagnosed in the year 2000-01. There were a total of 14 376 cases of prostate cancer and the mean total annual age-adjusted incidence was 197/100 000 men. There were 3318 cases in tumour category T1c, i.e. non-palpable tumours diagnosed during work-up for an elevated serum level of prostate-specific antigen, 1006 of which (30%) were asymptomatic and detected at a health check-up. RESULTS: The difference between the counties with the lowest and highest age-adjusted incidences per 100 000 men of total prostate cancer was almost twofold (128 vs 217). The corresponding variation in incidence of category T1c tumours was more than fourfold (13 vs 60); the difference in incidence of T1c tumours detected in asymptomatic men was up to 10-fold (2 vs 20); and there was more than a fourfold variation in incidence of curative treatment between counties (13 vs 67). Measured incidences were mostly highest in urban regions and in counties with university hospitals. CONCLUSION: There are large geographical variations in prostate cancer incidence and in the frequency of curative treatment for prostate cancer in Sweden and there appear to be large geographical variations in the uptake of prostate cancer screening.
Authors' Affiliations: Departments of Obstetrics and Gynecology and Environmental Medicine, NYU Cancer Institute, NYU School of Medicine, New York, New York; Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland; Departments of Medical Biosciences, Clinical Sciences, Radiation Sciences, Public Health and Clinical Medicine, and Clinical Microbiology, University of Umeå, Umeå, Sweden; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; and University of Tampere, Tampere, Finland.
Full-term pregnancies are associated with long-term reductions in maternal risk of breast cancer, but the biological determinants of the protection are unknown. Experimental observations suggest that human chorionic gonadotropin (hCG), a major hormone of pregnancy, could play a role in this association. A case-control study (242 cases and 450 controls) nested within the Northern Sweden Maternity Cohort included women who had donated a blood sample during the first trimester of a first full-term pregnancy. Total hCG was determined on Immulite 2000 analyzer. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. Maternal breast cancer risk decreased with increasing hCG (upper tertile OR, 0.67; CI, 0.46-0.99), especially for pregnancies before age 25 (upper tertile OR, 0.41; CI, 0.21-0.80). The association diverged according to age at diagnosis: risk was reduced after age 40 (upper tertile OR, 0.60; CI, 0.39-0.91) and seemed to increase before age 40 (upper tertile OR, 1.78; CI, 0.72-4.38). Risk was reduced among those diagnosed 10 years or longer after blood draw (upper tertile OR, 0.60; CI, 0.40-0.90), but not so among those diagnosed within 10 years (upper tertile OR, 4.33; CI, 0.86-21.7). These observations suggest that the association between pregnancy hCG and subsequent maternal risk of breast cancer is modified by age at diagnosis. Although the hormone seems to be a determinant of the reduced risk around or after age 50, it might not confer protection against, or it could even increase the risk of, cancers diagnosed in the years immediately following pregnancy. Cancer Res; 70(17); OF1-8. (c)2010 AACR.
The C ? T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk.
We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC.
No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model).
The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.
A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death.
To increase the specificity of screening for lethal PCa at an early stage.
We conducted a case-control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12542 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis.
Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers.
Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (=0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a =1% 15-yr risk of metastasis.
Screening at ages 50-60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making.
For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.