The prevalence of primary ovarian insufficiency in Sweden; a national register study.

BACKGROUND: The current estimates of the prevalence of primary ovarian insufficiency (POI) are very variable, but are in most studies believed to be around 1%. It is also very likely tat the prevalence of POI differs between countries and over time. We therefore aimed to assess the prevalence of primary ovarian insufficiency in Sweden. METHODS: All 1,036,918 women born between 1973 and 1993 in Sweden were included. The prevalence of POI was based on data from the Swedish Patient Register through the diagnosis code or through the Prescribed Drug Register. The number of women below 40 years of age diagnosed with the ICD-10 diagnoses E28.3 or E89.4, and women who had been dispensed drugs for treatment of climacteric symptoms were included. RESULTS: Out of the 1,036,918 women, 19,253 (1.9%) had POI. The prevalence of spontaneous POI was 1.7% and the prevalence of iatrogenic POI was 0.2%. Most women (98.8%) with POI were identified from the Prescribed Drug Register; only 4.1% were found in the Patient Register, whereas 2.9% were identified in both registers. CONCLUSIONS: The total prevalence of POI was 1.9%, 95% CI: 1.7-2.1, indicating a higher prevalence than often previously reported.

Haemochromatosis and gastrointestinal cancer.

Iron overload in patients with haemochromatosis is a strong risk factor for liver cancer, but its influence on other gastrointestinal cancer risk is unclear. The aim was to assess the relative risk of luminal gastrointestinal cancer among patients diagnosed with haemochromatosis. This population-based, nationwide Swedish cohort study included patients with haemochromatosis in Sweden in 1965-2013. The incidence of gastrointestinal cancers was assessed through the Swedish Cancer Registry. The measure of relative risk was the standardised incidence ratio (SIR) with 95% confidence interval (CI), that is, the ratio of the observed number of gastrointestinal cancers in the haemochromatosis cohort divided by the expected number of such cancers, calculated from the entire corresponding background population of Sweden. Among 6,849 patients in the haemochromatosis cohort with up to 48 years of follow-up, the SIRs were 3-fold increased for oesophageal squamous cell carcinoma (SIR = 3.2, 95% CI 1.3-6.6; n = 7) and 40% increased for colon adenocarcinoma (SIR = 1.4, 95% CI 1.1-1.9; n = 54). No associations were found between haemochromatosis and the risk of adenocarcinoma of the oesophagus (SIR = 0.5, 95% CI 0.0-2.5; n = 1), stomach (SIR = 0.7, 95% CI 0.3-1.4; n = 8), small bowel (SIR = 1.2, 95% CI 0.0-6.7; n = 1) or rectum (SIR = 1.0, 95% CI 0.6-1.6; n = 21). These findings indicate that haemochromatosis increases the risk of oesophageal squamous cell carcinoma and colon adenocarcinoma, but might not influence the risk of other types of luminal gastrointestinal cancer. These findings should encourage further research examining the role of iron overload in cancer aetiology.

Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p = 0.002) and in males (p = 0.003), but not in females separately (p = 0.3). This association was found in tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C were associated with risk of EAC in females (p = 0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.

Suicide attempt and future risk of cancer: a nationwide cohort study in Sweden.

PURPOSE: Little is known about cancer incidence among patients with a history of suicide attempt. Suicide attempters have lower levels of oxytocin, a hormone related to lactation, stress, social functioning, and well-being, and recent research indicates influence on carcinogenesis. We hypothesized that the low oxytocin levels among suicide attempters results in an increased risk of cancer in general and in organs with oxytocin receptors in particular. METHODS: A nationwide cohort study of patients aged 15 years or older with hospitalization for self-inflicted injury or attempted suicide was identified from the Swedish patient register in 1968-2011. The cancer outcomes were identified from the Swedish cancer register. Cancer risk in suicide attempters was compared with the risk in the background population of the corresponding age, sex, and calendar period by calculating standardized incidence ratios (SIRs) with 95 % confidence intervals (95 % CI). RESULTS: The 186,627 patients (83,637 men and 102,990 women) hospitalized for self-inflicted injury or attempted suicide contributed with 2.6 million person-years at risk. The SIR for all cancer was 1.3 (95 % CI 1.27-1.33) in men and 1.25 (1.22-1.28) in women. For cancers in organs rich in oxytocin receptors (uterus, breast, and brain), the corresponding SIRs were 1.02 (0.87-1.19) and 1.13 (1.09-1.17), respectively. There was a particularly increased risk of cancers related to alcohol and tobacco in both sexes. CONCLUSION: Patients attempting suicide have an increased risk of cancer. However, this increase does not seem to be associated with low oxytocin levels, but rather to exposures like tobacco smoking and alcohol consumption.

Hormone replacement therapy and oral contraceptives and risk of oesophageal adenocarcinoma: a systematic review and meta-analysis.

There is an unexplained strong male predominance in the aetiology of oesophageal adenocarcinoma (OAC). The hypothesis that oestrogens are protective, deserves attention. A potential protective influence of exogenous oestrogen exposure, that is, hormone replacement therapy (HRT) and oral contraceptives (OC) has been addressed only in studies of limited statistical power, and the individual studies have not provided conclusive results. We conducted a systematic literature search and meta-analysis on HRT and OC and the risk of OAC. We used the databases PubMed and the Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the Mantel-Haenszel random-effect method. A total of five studies were included. Compared to never users, ever users of HRT had a statistically significantly decreased risk of OAC (pooled OR = 0.75; 95% CI: 0.58-0.98), and ever users of OC had a borderline significantly decreased risk of this cancer (pooled OR = 0.76; 95% CI: 0.57-1.00). In conclusion, HRT and OC use seems to be associated with a decreased risk of OAC. However, further research is warranted.

Validation of oesophageal cancer surgery data in the Swedish Patient Registry.

BACKGROUND: The Swedish Patient Registry provides data about diagnoses and surgical procedures for research purposes. There are, however, almost no validation studies of the data on surgical procedures, and none of oesophageal cancer surgery. MATERIAL AND METHODS: This was a validation study of the accuracy of codes representing oesophageal cancer resection, surgical approach and oesophageal substitute in the Swedish Patient Registry during the period 1987-2005. The registered data were compared with a thorough review of the corresponding operation charts collected from medical records. RESULTS: Among 1358 patients with a code representing oesophageal resection in the Patient Registry, the positive predictive value was 99.6%. The dominant surgical procedures in terms of surgical approach (transthoracic) and type of oesophageal substitute (gastric conduit) had positive predictive values of 99.8% and 99.4%, respectively. The more rare procedures with regards to approach (transhiatal) and substitute (bowel) had lower positive predictive values of 68.8% and 68.5%, respectively. CONCLUSION: The high accuracy of the data regarding oesophageal cancer resection in the Swedish Patient Registry stresses its appropriateness for research purposes.

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

BACKGROUND: The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. METHODS: This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). RESULTS: Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. CONCLUSION: Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

Dietary proportions of carbohydrates, fat, and protein and risk of oesophageal cancer by histological type.

BACKGROUND: Dietary habits influence the risk of cancer of the oesophagus and oesophago-gastric junction, but the role of proportions of the main dietary macronutrients carbohydrates, fats and proteins is uncertain. METHODS: Data was derived from a nationwide Swedish population-based case-control study conducted in 1995-1997, in which case ascertainment was rapid, and all cases were uniformly classified. Information on the subjects' history of dietary intake was collected in personal interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, with adjustment for potentially confounding factors. RESULTS: Included were 189 oesophageal adenocarcinomas, 262 oesophago-gastric adenocarcinomas, 167 oesophageal squamous cell carcinomas, and 820 control subjects. Regarding oesophageal or oesophago-gastric junctional adenocarcinoma, a high dietary proportion of carbohydrates decreased the risk (OR 0.50, CI 0.34-0.73), and a high portion of fat increased the risk (OR 1.96, CI 1.34-2.87), while a high proportion of protein did not influence the risk (OR 1. 08, 95% CI 0.75-1.56). Regarding oesophageal squamous cell carcinoma, the single macronutrients did not influence the risk statistically significantly. CONCLUSIONS: A diet with a low proportion of carbohydrates and a high proportion of fat might increase the risk of oesophageal adenocarcinoma.