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ABSTRACT: Available data correlating symptoms of colon cancer patients with the severity of the disease are very limited. In a population-based setting, we correlated information on symptoms of colon cancer patients with several pathological tumor parameters and survival. Information on all patients diagnosed with colon cancer in Iceland in 1995-2004 for this retrospective, population-based study was obtained from the Icelandic Cancer Registry. Information on symptoms of patients and blood hemoglobin was collected from patients' files. Pathological parameters were obtained from a previously performed standardized tumor review. A total of 768 patients entered this study; the median age was 73 years. Tumors in patients presenting at diagnosis with visible blood in stools were significantly more likely to be of lower grade, having pushing border, conspicuous peritumoral lymphocytic infiltration, and lower frequency of vessel invasion. Patients with abdominal pain and anemia were significantly more likely to have vessel invasion. Logistic regression showed that visible blood in stools was significantly associated with protecting pathological factors (OR range 0.38-0.83, p < 0.05). Tumors in patients presenting with abdominal pain were strongly associated with infiltrative margin and scarce peritumoral lymphocytic infiltration (OR = 1.95; 2.18 respectively, p < 0.05). Changes in bowel habits were strongly associated with vessel invasion (OR = 2.03, p < 0.05). Cox regression showed that blood in stools predicted survival (HR = 0.54). In conclusion, visible blood in stools correlates significantly with all the beneficial pathological parameters analyzed and with better survival of patients. Anemia, general symptoms, changes in bowel habits, acute symptoms, and abdominal pain correlate with more aggressive tumor characteristics and adverse outcome for patients.
Apmis 05/2013; · 1.99 Impact Factor
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ABSTRACT: Colon cancer is the second most common cause of cancer death in Iceland and accounts for 8% of malignancies. We related information on symptoms of colon cancer patients with information on tumor location and pTNM-stage.
The study is retrospective and population-based. Information on all patients diagnosed with colon cancer in Iceland in 1995-2004 was obtained. Information on symptoms of patients and blood hemoglobin was collected from patients' files. The pathological parameters were derived from a previously performed study.
A total of 768 patients (422 males, 346 females) participated in this study. Median age was 73 years. Nearly 60% had anemia at the time of diagnosis, 53% had visible blood in stools, and 65% had changes in bowel habits. Around 84% had visible blood in stools and/or anemia. Of those with right-sided tumors, 75% had anemia and were more likely to be diagnosed incidentally (40%) than those with left-sided tumors (20%). Left-sided tumors were associated with blood in stools (68% compared to 41%, p < 0.05) and changes in bowel habits (74% compared to 57%, p < 0.05). Multivariate analysis indicated that blood in stools was strongly associated with a lower TNM-stage (OR = 0.75, p < 0.05). Anemia was strongly associated with a higher TNM-stage (OR = 1.84, p < 0.05).
Right-sided tumors were associated with anemia and incidental diagnosis; left-sided tumors were associated with visible blood in stools and changes in bowel habits. Visible blood in stools was significantly associated with lower TNM-stage, whereas abdominal pain, general and acute symptoms were associated with higher TNM-stage.
Scandinavian journal of gastroenterology 04/2012; 47(7):795-801. · 2.08 Impact Factor
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ABSTRACT: Routinely used prognostic factors fail to predict clinical outcome in a significant proportion of breast cancer patients, implying that they can not detect some important biological characteristics. Chromosomal changes have been described in breast carcinomas for many years but their significance is not clear. We compared chromosomal changes with clinico-pathological characteristics and clinical outcome in 203 breast cancer patients with a follow-up of 9-18 years. Combining data from classical cytogenetics and flow cytometry revealed chromosomal abnormalities in 142 cases (70%). Of these, 51 (35.9%) contained two or more cytogenetically abnormal clones. Polyclonality was significantly associated with poor breast-cancer-specific survival (P = 0.03) within 5 years, independent of tumor size, lymph node metastases, and hormone receptors. Specific changes were similar to those previously described, but a new finding was a significant association between del 3p12p21 and poor survival. Polyclonality was significantly associated with TP53-mutations but not with a germline BRCA2 mutation. Less than one third of the polyclonal samples were identified by flow cytometry alone. Cytogenetic changes were detected in 17 out of 114 samples from non-tumorous tissue (15%), two of them identical with a clone in the corresponding tumor. Several samples contained clearly unrelated clones within the tumor and outside, implying either multifocal origin or early divergence. In conclusion, the common deletion on Chromosome 3p12p21 was associated with poor clinical outcome. Chromosomal polyclonality is common in breast carcinomas and predicts poor survival. Polyclonality was poorly detected by one-sample flow cytometry. Multiple sampling might improve the detection rate.
Genes Chromosomes and Cancer 11/2011; 50(11):930-9. · 3.31 Impact Factor
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Patrick Sulem,
Daniel F Gudbjartsson,
Thorunn Rafnar,
Hilma Holm, Elinborg J Olafsdottir,
Gudridur H Olafsdottir,
Thorvaldur Jonsson,
Peter Alexandersen,
Bjarke Feenstra,
Heather A Boyd, [......],
Gudmar Thorleifsson,
Gudmundur Hardarson,
Jeffrey Gulcher,
Augustine Kong,
Lambertus A Kiemeney,
Mads Melbye,
Claus Christiansen,
Laufey Tryggvadottir,
Unnur Thorsteinsdottir,
Kari Stefansson
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ABSTRACT: Earlier menarche correlates with shorter adult height and higher childhood body fat. We conducted a genome-wide association study of age at menarche (AAM) on 15,297 Icelandic women. Combined analysis with replication sets from Iceland, Denmark and the Netherlands (N = 10,040) yielded a significant association between rs314280[T] on 6q21, near the LIN28B gene, and AAM (effect = 1.2 months later per allele; P = 1.8 × 10(-14)). A second SNP within the same linkage disequilibrium (LD) block, rs314277, splits rs314280[T] into two haplotypes with different effects (0.9 months and 1.9 months per allele). These variants have been associated with greater adult height. The association with adult height did not account for the association with AAM or vice versa. Other variants, previously associated with height, did not associate significantly with AAM. Given the link between body fat and AAM, we also assessed 11 variants recently associated with higher body mass index (BMI) and 5 of those associated with earlier AAM.
Nature Genetics 06/2009; 41(6):734-8. · 35.53 Impact Factor
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Daniel F Gudbjartsson,
G Bragi Walters,
Gudmar Thorleifsson,
Hreinn Stefansson,
Bjarni V Halldorsson,
Pasha Zusmanovich,
Patrick Sulem,
Steinunn Thorlacius,
Arnaldur Gylfason,
Stacy Steinberg, [......],
Diane M Becker,
Lisa R Yanek,
Lewis C Becker,
Laufey Tryggvadottir,
Thorunn Rafnar,
Jeffrey Gulcher,
Lambertus A Kiemeney,
Augustine Kong,
Unnur Thorsteinsdottir,
Kari Stefansson
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ABSTRACT: Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.
Nature Genetics 06/2008; 40(5):609-15. · 35.53 Impact Factor
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ABSTRACT: Earlier studies have shown that cancer risk is related to educational level in many countries. The relationship between education and cancer risk has not been studied in the small, but ethnically homogenous, Icelandic population postulated to be outstanding as regards social equity.
We conducted a follow-up study of a cohort of 60,194 males and 58,505 females aged 20-64 at census 1981 in Iceland. Information on education from the census was classified into three educational groups and linked with the population-based Icelandic Cancer Registry. Standardized incidence ratios (SIRs) were calculated for the period 1982 to 2004.
We found a significant association between educational level and cancer risk. Among males with academic education, the SIR was elevated for prostate cancer (SIR=1.17, 95% CI 1.05-1.30) and melanoma (SIR=1.41, 95% CI 1.00-1.93) and lowered for cancers of the lung (SIR=0.72, 95% CI 0.59-0.87) and stomach (SIR=0.67, 95% CI 0.48-0.90). Women with academic education had an increased risk of breast cancer (SIR=1.19, 95% CI 1.07-1.33) and a decreased risk of lung cancer (SIR=0.49, 95% CI 0.36-0.65). Increasing educational level was associated with a lowered risk of cervical cancer (p trend=0.017).
The association between education and cancer incidence seen in this study resembles observations from other countries and probably reflects concordance between social status and certain risk factors for cancer. Our study confirms health-related socioeconomic differences in Iceland and must be taken into account when programmes for health promotion are planned.
Acta oncologica (Stockholm, Sweden) 02/2008; 47(3):385-90. · 2.27 Impact Factor
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ABSTRACT: Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear.
In a case-control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis.
An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years.
The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast.
Breast cancer research: BCR 02/2003; 5(5):R121-8. · 5.24 Impact Factor
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Gudmar Thorleifsson,
G Bragi Walters,
Daniel F Gudbjartsson,
Valgerdur Steinthorsdottir,
Patrick Sulem,
Anna Helgadottir,
Unnur Styrkarsdottir,
Solveig Gretarsdottir,
Steinunn Thorlacius,
Ingileif Jonsdottir, [......],
Lewis C Becker,
Laufey Tryggvadottir,
Thorunn Rafnar,
Diane M Becker,
Jeffrey Gulcher,
Lambertus A Kiemeney,
Oluf Pedersen,
Augustine Kong,
Unnur Thorsteinsdottir,
Kari Stefansson
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ABSTRACT: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.
