The role of pregnancy, perinatal factors and hormones in maternal cancer risk: a review of the evidence.

An understanding of the origin of cancer is critical for cancer prevention and treatment. Complex biological mechanisms promote carcinogenesis, and there is increasing evidence that pregnancy-related exposures influence foetal growth cell division and organ functioning and may have a long-lasting impact on health and disease susceptibility in the mothers and offspring. Nulliparity is an established risk factor for breast, ovarian, endometrial and possibly pancreatic cancer, whilst the risk of kidney cancer is elevated in parous compared with nulliparous women. For breast, endometrial and ovarian cancer, each pregnancy provides an additional risk reduction. The associations of parity with thyroid and colorectal cancers are uncertain. The timing of reproductive events is also recognized to be important. Older age at first birth is associated with an increased risk of breast cancer, and older age at last birth is associated with a reduced risk of endometrial cancer. The risks of breast and endometrial cancers increase with younger age at menarche and older age at menopause. The mechanisms, and hormone profiles, that underlie alterations in maternal cancer risk are not fully understood and may differ by malignancy. Linking health registries and pooling of data in the Nordic countries have provided opportunities to conduct epidemiologic research of pregnancy exposures and subsequent cancer. We review the maternal risk of several malignancies, including those with a well-known hormonal aetiology and those with less established relationships. The tendency for women to have fewer pregnancies and at later ages, together with the age-dependent increase in the incidence of most malignancies, is expected to affect the incidence of pregnancy-associated cancer.

Mendelian randomisation analysis provides no evidence for a relationship between adult height and testicular cancer risk.

Observational studies have suggested anthropometric traits, particularly increased height are associated with an elevated risk of testicular cancer (testicular germ cell tumour). However, there is an inconsistency between study findings, suggesting the possibility of the influence of confounding factors. To examine the association between anthropometric traits and testicular germ cell tumour using an unbiased approach, we performed a Mendelian randomisation study. We used genotype data from genome wide association studies of testicular germ cell tumour totalling 5518 cases and 19,055 controls. Externally weighted polygenic risk scores were created and used to evaluate associations with testicular germ cell tumour risk per one standard deviation (s.d) increase in genetically-defined adult height, adult BMI, adult waist hip ratio adjusted for BMI (WHRadjBMI), adult hip circumference adjusted for BMI (HIPadjBMI), adult waist circumference adjusted for BMI (WCadjBMI), birth weight (BW) and childhood obesity. Mendelian randomisation analysis did not demonstrate an association between any anthropometric trait and testicular germ cell tumour risk. In particular, despite good power, there was no global evidence for association between height and testicular germ cell tumour. However, three SNPs for adult height individually showed association with testicular germ cell tumour (rs4624820: OR = 1.47, 95% CI: 1.41-1.55, p = 2.7 × 10-57 ; rs12228415: OR = 1.17, 95% CI: 1.11-1.22, p = 3.1 × 10-10 ; rs7568069: OR = 1.13, 95% CI: 1.07-1.18, p = 1.1 × 10-6 ). This Mendelian randomisation analysis, based on the largest testicular germ cell tumour genome wide association dataset to date, does not support a causal etiological association between anthropometric traits and testicular germ cell tumour aetiology. Our findings are more compatible with confounding by shared environmental factors, possibly related to prenatal growth with exposure to these risk factors occurring in utero.

Hyperemesis gravidarum and long-term mortality: a population-based cohort study.

OBJECTIVE: To investigate whether exposure to hyperemesis gravidarum (HG) is associated with increased maternal long-term mortality. DESIGN: Population-based cohort study. SETTING: Medical Birth Registry of Norway (1967-2002) linked to the Cause of Death Registry. POPULATION: Women in Norway with singleton births in the period 1967-2002, with and without HG. Women were followed until 2009 or death. METHODS: Cox proportional hazard regression model was applied to estimate hazard ratios (HRs) with 95% confidence interval (CI). MAIN OUTCOME MEASURES: The primary outcome was all-cause mortality during follow up. Secondary outcomes were cause-specific mortality (cardiovascular mortality, deaths due to cancer, external causes or mental and behavioural disorders). RESULTS: Of 999 161 women with singleton births, 13 397 (1.3%) experienced HG. During a median follow up of 26 years (25 902 036 person-years), 43 470 women died (4.4%). Women exposed to HG had a lower risk of long-term all-cause mortality compared with women without HG (crude HR 0.82; 95% CI 0.75-0.90). When adjusting for confounders, this reduction was no longer significant (adjusted HR 0.92; 95% CI 0.84-1.01). Women exposed to HG had a similar risk of cardiovascular death as women not exposed (adjusted HR 1.04; 95% CI 0.83-1.29), but a lower long-term risk of death from cancer (adjusted HR 0.86; 95% CI 0.75-0.98). CONCLUSION: In this large population-based cohort study, HG was not associated with an increased risk of long-term all-cause mortality. Women exposed to HG had no increase in mortality due to cardiovascular disease, but had a reduced risk of death from cancer. TWEETABLE ABSTRACT: Population-based cohort study: Hyperemesis was not associated with an increased risk of long-term mortality.

Profiling of the small RNA populations in human testicular germ cell tumors shows global loss of piRNAs.

BACKGROUND: Small non-coding RNAs play essential roles in gene regulation, however, the interplay between RNA groups, their expression levels and deregulations in tumorigenesis requires additional exploration. In particular, a comprehensive analysis of microRNA (miRNA), PIWI-interacting RNAs (piRNAs), and tRNA-derived small RNAs in human testis and testicular germ cell tumor (TGCT) is lacking. RESULTS: We performed small RNA sequencing on 22 human TGCT samples from 5 histological subtypes, 3 carcinoma in situ, and 12 normal testis samples. miRNA was the most common group among the sequences 18-24 nt in length and showed histology-specific expression. In normal samples, most sequences 25-31 nucleotides in length displayed piRNA characteristics, whereas a large proportion of the sequences 32-36 nt length was derived from tRNAs. Expression analyses of the piRNA population demonstrated global loss in all TGCT subtypes compared to normal testis. In addition, three 5' small tRNA fragments and 23 miRNAs showed significant (p < 10(-6)) differential expression in cancer vs normal samples. CONCLUSIONS: We have documented significant changes in the small RNA populations in normal adult testicular tissue and TGCT samples. Although components of the same pathways might be involved in miRNA, piRNA and tRNA-derived small RNA biogenesis, our results showed that the response to the carcinogenic process differs between these pathways, suggesting independent regulation of their biogenesis. Overall, the small RNA deregulation in TGCT provides new insight into the small RNA interplay.

Tumour gastrin expression and serum gastrin concentrations in dogs with gastric carcinoma are poor diagnostic indicators.

Hypergastrinaemia is observed commonly in human patients with gastric carcinoma and is associated with atrophic gastritis and Helicobacter pylori infection, both of which predispose to development of gastric tumours. Increased expression of gastrin is also described as a prognostic indicator for gastric carcinoma in man. Gastric carcinoma is rare in dogs and generally carries a grave prognosis. In this study, the expression of gastrin was investigated immunohistochemically in gastric biopsy samples from 64 dogs with gastric carcinoma. Serum gastrin concentrations were measured in 15 of these dogs and compared with those of seven healthy control dogs. Tumour tissue expressed gastrin in 8% (5/64) of the dogs with gastric carcinoma. There was no significant difference in serum gastrin concentrations between dogs with gastric carcinoma and healthy controls (P = 0.08). Expression of gastrin in gastric carcinomas is less common in dogs than in man and may therefore not be relied on as a prognostic marker in this species. Serum gastrin concentration alone is also not a useful biomarker for gastric carcinoma in dogs.

Perinatal characteristics and breast cancer risk in daughters: a Scandinavian population-based study.

The in utero origins of breast cancer are an increasing focus of research. However, the long time period between exposure and disease diagnosis, and the lack of standardized perinatal data collection makes this research challenging. We assessed perinatal factors, as proxies for in utero exposures, and breast cancer risk using pooled, population-based birth and cancer registry data. Birth registries provided information on perinatal exposures. Cases were females born in Norway, Sweden or Denmark who were subsequently diagnosed with primary, invasive breast cancer (n = 1419). Ten controls for each case were selected from the birth registries matched on country and birth year (n = 14,190). Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using unconditional regression models. Breast cancer risk rose 7% (95% CI 2-13%) with every 500 g (roughly 1 s.d.) increase in birth weight and 7% for every 1 s.d. increase in birth length (95% CI 1-14%). The association with birth length was attenuated after adjustment for birth weight, while the increase in risk with birth weight remained with adjustment for birth length. Ponderal index and small- and large-for-gestational-age status were not better predictors of risk than either weight or length alone. Risk was not associated with maternal education or age, gestational duration, delivery type or birth order, or with several pregnancy complications, including preeclampsia. These data confirm the positive association between birth weight and breast cancer risk. Other pregnancy characteristics, including complications such as preeclampsia, do not appear to be involved in later breast carcinogenesis in young women.

Genetic variation in AKT1, PTEN and the 8q24 locus, and the risk of testicular germ cell tumor.

STUDY QUESTION: Is there an association between testicular germ cell tumor (TGCT) and genetic polymorphisms in AKT1, PTEN and the 8q24 locus? SUMMARY ANSWER: Our findings suggest that genetic variation in PTEN may influence the risk of TGCT. WHAT IS KNOWN ALREADY: There is strong evidence that genetic variation influences the risk of TGCT. The oncogene, AKT1, the tumor suppressor gene, PTEN and the chromosome 8q24 locus play important roles in cancer development in general. STUDY DESIGN, SIZE, DURATION: We have conducted a population-based Norwegian-Swedish case-parent study, based on cases diagnosed in 1990-2008, including 831 triads (TGCT case and both parents), 474 dyads (TGCT case and one parent) and 712 singletons (only the TGCT case). In addition we expanded the study to include 3922 unrelated male controls from the TwinGene project. PARTICIPANTS/MATERIALS, SETTING, METHODS: We genotyped 26 single nucleotide polymorphisms (SNPs) in AKT1, PTEN and the 8q24 locus. First, triads and dyads were included in a likelihood-based association test. To increase the statistical power, case singletons and controls from the TwinGene project were included in a single test for association. We examined if the allelic effect on TGCT risk differed by histological subgroup, country of origin or parent of origin. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated with Bonferroni correction (P bonf) for multiple testing. MAIN RESULTS AND THE ROLE OF CHANCE: In the case-parent analyses, none of the 26 SNPs were significantly associated with TGCT. Of the 23 SNPs investigated in the combined study, one SNP in PTEN (rs11202586) remained associated with TGCT risk after adjusting for multiple testing (OR = 1.16, 95% CI = 1.06-1.28, P bonf = 0.040). We found no difference in risk according to histological subgroup, parent of origin or between countries. LIMITATIONS, REASONS FOR CAUTION: Our study is strengthened by the population-based design and large sample size, which gives high power to detect risk alleles. The reported association was not highly significant, and although it was based on an a priori hypothesis of this tumor suppressor gene being implicated in the etiology of TGCT, replication studies, as well as functional studies of this polymorphism, are warranted. WIDER IMPLICATIONS OF THE FINDINGS: We report, to our knowledge, a novel association between TGCT and a marker in the tumor suppressor gene PTEN. Previous studies have linked PTEN to TGCT etiology, and there is also a link between PTEN and KITLG, which contains TGCT susceptibility loci revealed through recent genome-wide studies.

Effect of ovariohysterectomy at the time of tumor removal in dogs with benign mammary tumors and hyperplastic lesions: a randomized controlled clinical trial.

BACKGROUND: Nonmalignant mammary tumors (NMT) are common in intact female dogs. Little is known about the clinical significance of these tumors, and the effect of ovariohysterectomy (OHE) on their development. HYPOTHESIS: Ovarian hormone ablation through OHE decreases the risk of new tumors and thereby improves long-term prognosis for dogs with NMT. ANIMALS: Eighty-four sexually intact bitches with NMT. METHODS: Dogs were allocated to undergo OHE (n = 42) or not (n = 42) at the time of NMT removal in a randomized clinical trial. Tumor diagnosis was confirmed histologically in all subjects. Information about new tumor development was collected via follow-up phone calls and recheck examinations. Separate survival analyses were performed with the endpoints new tumor development and death. Cause of death was classified as related or unrelated to mammary tumor. In addition to OHE status, the influence of age, body weight, breed, tumor size, tumor number, tumor duration, type of surgery, and tumor histology was investigated. RESULTS: New mammary tumor(s) developed in 27 of 42 (64%) intact dogs and 15 of 42 (36%) ovariohysterectomized dogs (hazard ratio 0.47, P = .022). Nine of the 42 dogs (21%) which developed new tumors were euthanized because of mammary tumor. Survival was not significantly different between the 2 treatment groups. In the intact group, nine dogs subsequently developed ovarian-uterine diseases. CONCLUSION: Ovariohysterectomy performed at the time of mammary tumor excision reduced the risk of new tumors by about 50% among dogs with NMT. Survival was not significantly affected. Adjuvant OHE should be considered in adult dogs with mammary tumors.

Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case-parent triad study in a Norwegian-Swedish population.

BACKGROUND: Testicular germ cell tumour (TGCT) is the most common cancer in young men, and an imbalance between the estrogen and androgen levels in utero is hypothesized to influence TGCT risk. Thus, polymorphisms in genes involved in the action of sex hormones may contribute to variability in an individual's susceptibility to TGCT. METHODS: We conducted a Norwegian-Swedish case-parent study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete triads and 474 dyads. To increase the statistical power, the analysis was expanded to include 712 case singletons and 3922 Swedish controls, thus including triads, dyads and the case-control samples in a single test for association. Analysis for allelic associations was performed with the UNPHASED program, using a likelihood-based association test for nuclear families with missing data, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False discovery rate (FDR) was used to adjust for multiple testing. RESULTS: Five genetic variants across the ESR2 gene [encoding estrogen receptor beta (ERß)] were statistically significantly associated with the risk of TGCT. In the case-parent analysis, the markers rs12434245 and rs10137185 were associated with a reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR = 1.21 and 1.19, respectively; both FDRs <5%). In the combined case-parent/case-control analysis, rs12435857 and rs10146204 were associated with an increased risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In addition, we found that three genetic variants in CYP19A1 (encoding aromatase) were statistically significantly associated with the risk of TGCT in the case-parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21, respectively; all FDRs <5%). We found no statistically significant differences in allelic effect estimates between parental inherited genetic variation in the sex hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity between seminomas and non-seminomas, or between the Norwegian and the Swedish population, in any of the SNPs examined. CONCLUSIONS: Our findings provide support for ERß and aromatase being implicated in the aetiology of TGCT. Exploring the functional role of the TGCT risk-associated SNPs will further elucidate the biological mechanisms involved.

IFPA Meeting 2011 workshop report I: Placenta: Predicting future health; roles of lipids in the growth and development of feto-placental unit; placental nutrient sensing; placental research to solve clinical problems--a translational approach.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, four of which are summarized in this report. These workshops related to both basic science and clinical research into placental growth and nutrient sensing and were divided into 1) placenta: predicting future health; 2) roles of lipids in the growth and development of feto-placental unit; 3) placental nutrient sensing; 4) placental research to solve clinical problems: a translational approach.

Breed differences in the proportional morbidity of testicular tumours and distribution of histopathologic types in a population-based canine cancer registry.

Histologically verified tumours submitted to the Norwegian Canine Cancer Register from 1990 to 1998 were studied (n=14,401). The proportion of testicular tumours (n=345) was 2.4%, and the breakdown of histological tumour diagnoses is presented. The frequency of the most common histopathological types was 33% interstitial (Leydig), 26.4% Sertoli and 33.9% seminomas/germ cell tumours. The average age at diagnosis was 10 years, but was significantly lower for Sertoli cell tumours (8.6 years) than for the other tumour types. Following a histopathological re-evaluation, 22.5% of the original tumor diagnoses were modified. Proportional morbidity ratios were calculated and individuals from the breeds Shetland sheepdog and Collie were five times more likely to have testicular tumours than the overall average for the registry. Breed differences in the distribution of histopathologic types were observed. Shetland sheepdog and Collie were most commonly diagnosed with Sertoli cell tumours, while all tumours from Norwegian elkhound in this material were seminomas.

Risk factors for testicular cancer--differences between pure non-seminoma and mixed seminoma/non-seminoma?

The origin of testicular germ cell cancer (TGCC) is believed to be carcinoma in situ cells developed in utero. Clinically, TGCCs are divided into two major histological groups, seminomas and non-seminomas, where the latter group includes non-seminomatous TGCCs with seminomatous components (mixed S/NS TGCC). Recent studies, however, have suggested that non-seminomas and mixed S/NS TGCCs could have certain differences in aetiology, and in this study the TGCCs were divided into three, rather than the conventional two histological groups. A large case-control study was undertaken on data on all live-born boys registered in the Medical Birth Registry of Norway during the period 1967-1998 (n=961 396). Among these were 1087 TGCC cases registered in the Cancer Registry of Norway until February 2004. We found several risk factors for TGCC, including low parity, low gestational age, epilepsy and retained placenta. Several of the variables studied seemed to be risk factors for specific histological groups, e.g. parity 0 vs. 2 and low gestational age being associated with increased risk of non-seminomas, but not of mixed S/NS TGCC, and low maternal age being associated with increased risk of mixed S/NS TGCC, but not of non-seminomatous TGCC. Therefore, our results might suggest that non-seminomas and mixed S/NS TGCCs have partially different risk factors, whose associations may be obscured by combining these two histological groups. The histological groups were not significantly different, however. Most of our findings on risk factors for TGCC are in agreement with at least some previous studies. An unexplainable exception is low birth weight being associated with reduced risk of TGCC in our study.

Biopsy of colorectal polyps is not adequate for grading of neoplasia.

BACKGROUND AND STUDY AIM: Valid tissue sampling of colorectal adenomas is crucial for their management in terms of treatment and follow-up. The aim of this study was to assess the validity of a cold biopsy sample as representative for the whole polypectomy specimen, with regard to histopathological features. PATIENTS AND METHODS: As part of the Norwegian Colorectal Cancer Prevention trial, 442 participants (60% men) who fulfilled the criterion of colonoscopic recovery of adenoma that had been biopsied at flexible sigmoidoscopy, had their adenomas subsequently removed by polypectomy (snare resection) at colonoscopy. Logistic regression analysis was used to determine which variables contributed to the histopathological discrepancy between cold biopsy and polypectomy specimens. RESULTS: Among the 532 colorectal adenomas biopsied at flexible sigmoidoscopy and removed by colonoscopy, the assessment of intraepithelial neoplasia (dysplasia) status was changed in 51 adenomas (10%), and 38 (7%) of them had been underestimated at biopsy compared with polypectomy. Likewise, the assessment of villousness was changed in 45 adenomas (9%), being upgraded in 26 (6%) at polypectomy compared with biopsy. In a multivariate model, the diameter of neoplasia at polypectomy was positively associated with increased risk of the underestimation of intraepithelial neoplasia and/or villousness influencing a diagnosis of advanced colorectal neoplasia, when cold biopsy and polypectomy specimens were compared ( Ptrend=0.01). Among 56 cases of advanced neoplasia, 35 (63%) showed only low-grade intraepithelial neoplasia on biopsy. CONCLUSIONS: Biopsy-based diagnosis underestimated histopathological diagnosis in about 10% of colorectal adenomas detected by flexible sigmoidoscopy screening, but advanced neoplasia was underestimated in more than 60%. Efforts must be made to obtain polypectomy specimens to secure precise diagnosis.

Lifestyle-related risk factors and chemoprevention for colorectal neoplasia: experience from the large-scale NORCCAP screening trial.

The objective of this study was to evaluate the potential beneficial effects of non-steroidal anti-inflammatory drugs (NSAIDs) and/or acetylsalicylic acid (ASA) and hormone replacement therapy (HRT) on colorectal neoplasia, and to compare their effects with those of lifestyle-related risk factors in 12 960 individuals who underwent flexible sigmoidoscopy screening examination. The association between these factors and colonic neoplasia was assessed by logistic regression analysis. NSAIDs and/or ASA intake were associated with decreased risk of distal low grade adenoma (DLGA) (adjusted odds ratio (OR) 0.80, P trend=0.02) in men. The duration of HRT was inversely related to the risk of DLGA (OR 0.89, P trend=0.08). Current smoking increased the risk of DLGA and distal advanced neoplasia (DAN) in both men (OR 2.50, P<0.01) and women (OR 2.30, P<0.01). There was a significant positive trend for increasing risk of DLGA (OR 1.16, P<0.01) and DAN (OR 1.20, P=0.02) with increasing use of alcohol among men, but not among women. Prescription of NSAIDs and/or ASA for chronic conditions may not be expected to have a substantial preventive effect on colorectal neoplasia in comparison with the adverse effect of smoking and alcohol. This may be explained by an increased risk of colorectal neoplasia for patients with conditions for which NSAIDs or ASA are being prescribed.

Early life events and later risk of colorectal cancer: age-period-cohort modelling in the Nordic countries and Estonia.

BACKGROUND: A lowering of colorectal cancer risk for the birth cohorts born around World War II (WWII) has previously been observed in Norway, a country which suffered some 20% caloric restriction during the war. The purpose of the study was to conduct a similar kind of analysis in the other Nordic countries and Estonia, which were also subjected to various degrees of energy restriction during WWII. METHODS: All new cases of colorectal cancer in the Nordic countries and Estonia diagnosed between 40 and 84 years of age and born between 1874 and 1953, were collected from the national cancer registries. The incidence data were fitted to an age-period-cohort model. RESULTS: A transient drop in the estimated colorectal cancer incidence rate was observed for the birth cohorts born around WWII in Estonia, together with a tendency of decreased risk in Sweden and Denmark. CONCLUSION: The previously observed lowering of colorectal cancer risk for persons born during WWII in Norway also prevails in Estonia. Energy restriction is a possible explanation for these findings, since the countries suffered from varying nutritional conditions during the war. Exogenous factors acting during periods early in life may have an impact on later colorectal cancer risk.

Differential distribution of splice variants of estrogen receptor beta in human testicular cells suggests specific functions in spermatogenesis.

A growing number of estrogen receptor beta (ER beta) splice variants are reported. Several of these have been discovered in testis, but with few exceptions little is known about their cellular localization. The aim of this study was to identify and elucidate the mRNA expression pattern of the different ER beta splice variants in human testicular cells. Northern analysis was performed on whole testis and fractions enriched in germ cells from untreated men and from estrogen-treated men undergoing sex change surgery. Probes were constructed in order to systematically screen for and identify various ER beta splice variants. Several ER beta bands were observed in the human testis, in which splice variants constituted the major part of total ER beta transcripts. Interestingly, only two ER beta wild-type transcripts were detected. These seem to be virtually absent from the haploid germ cells and are probably mainly located in somatic cells and/or primary spermatocytes. Several novel ER beta deletion variants were found in high levels in the haploid germ cell fractions and were nearly absent in testicular cells from the estrogen-treated men. The cell-dependent distribution raises the question whether splice variants may have specific functions in spermatogenesis, and whether the differential splicing of ER beta is regulated in a cell-specific manner.

Testing for faecal calprotectin (PhiCal) in the Norwegian Colorectal Cancer Prevention trial on flexible sigmoidoscopy screening: comparison with an immunochemical test for occult blood (FlexSure OBT).

BACKGROUND: Screening for colorectal cancer (CRC) using guaiac based faecal occult blood tests (FOBT) has an estimated programme sensitivity of >60% but <30% for strictly asymptomatic CRC in a single screening round. In search for improved non-invasive tests for screening, we compared a test for faecal calprotectin (PhiCal) with a human haemoglobin immunochemical FOBT (FlexSure OBT). METHODS: In the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, screenees in one screening arm were offered screening with combined flexible sigmoidoscopy (FS) and FlexSure OBT. They were also requested to bring a fresh frozen sample of stool for the PhiCal test which was performed on samples from screenees with CRC (n = 16), high risk adenoma (n = 195), low risk adenoma (n = 592), and no adenoma (n = 1518) (2321 screenees in total). A positive PhiCal test was defined by a calprotectin level > or =50 microg/g. RESULTS: The PhiCal test was positive in 24-27% of screenees whether they had no adenoma, low risk adenoma, or high risk adenoma. Ten (63%) of 16 CRCs gave a positive PhiCal test. The total positivity rate in this population was 25% for the PhiCal test compared with 12% for FlexSure OBT, with a sensitivity for advanced neoplasia of 27% and 35%, respectively. Specificity for "any neoplasia" was 76% for the PhiCal test and 90% for FlexSure OBT. CONCLUSIONS: In colorectal screening, the performance of the PhiCal test on a single spot from one stool sample was poorer than a single screening round with FlexSure OBT and cannot be recommended for population screening purposes. The findings indicate a place for FlexSure OBT in FOBT screening.

The association between nutritional conditions during World War II and childhood anthropometric variables in the Nordic countries.

BACKGROUND: The purpose of the study was to examine the height and weight in Nordic children during the years around World War II (WWII), and compare them with the nutritional situation during the same period. METHODS: Information on food consumption and energy intake were obtained from the literature. Anthropometric data were collected from the Nordic capitals and cover the period from 1930 to 1960 for ages 7-13 years. RESULTS: The greatest energy restriction took place in Norway (20%), followed by Finland (17%), while Sweden and Denmark had a restriction of 4-7% compared to pre-war levels. The most pronounced effect of WWII on height and weight is seen in Norwegian children, while some effect is observed for the youngest children in Finland. Little or no effect is seen in Sweden and Denmark. CONCLUSION: The Nordic children were affected by WWII in terms of a transient reduction in temporal trends in height and weight, and the magnitude of this decrease was associated with the severity of the energy restriction prevailing in the respective country during the war. These findings warrant further studies of the chronic diseases associated with height and weight for cohorts being in their growth periods during WWII.

Colorectal cancer survival trends in Norway 1958-1997.

The purpose of this study was to examine the pattern of survival for colorectal adenocarcinoma (CRC), and to investigate the prognostic factors for the disease. In the analysis, 50993 cases of CRC aged 40-84 years, diagnosed between 1958 and 1997 in Norway, were included. Esteve's relative survival method was used, together with a time trend analysis, conducted by least-squares linear regression. Cox proportional hazards regression analysis was used to examine cause-specific mortality. Five-year relative CRC survival has increased by an estimated 3% per 5-year diagnostic period. In 1958-1962, relative survival was about 40% for both males and females, and increased to 56 and 60%, respectively, in 1993-1997. Rectal cancer had a higher cause-specific mortality (RR 1.26, 95% CI 1.22-1.30) than proximal colon (reference) and distal colon (RR 0.97, 95% CI 0.93-1.00 cancers), while females had a lower cause-specific mortality than males (RR 0.88, 95% CI 0.86-0.90). The increase in the relative survival rate in Norway is probably due to improved treatments and advanced diagnostics. Norway has a higher CRC survival rate than the EUROCARE average.