Pregnancy duration and ovarian cancer risk: A 50-year nationwide cohort study.

A woman's reproductive history is strongly associated with her risk of ovarian cancer. However, it is unclear how pregnancies of different duration impact a woman's ovarian cancer risk, and therefore, what part of a pregnancy explains the protective effect. Using a cohort of all Danish women followed from 1968 to 2018, with prospectively registered information on reproductive history (eg, gestational duration of pregnancies, tubal ligation and resection and hormonal pharmaceutical use), we investigated the effect of pregnancy duration on ovarian cancer risk. We adjusted for potential confounders, such as age at pregnancy and time since pregnancy, using log-linear Poisson regression to isolate the effect of pregnancy duration on ovarian cancer risk. Among 2.5 million Danish women with 4.4 million pregnancies, a pregnancy was associated with a reduction of ovarian cancer risk of 21% (95% CI, 14%-28%), 26% (95% CI, 21%-31%), 12% (95% CI, 7%-17%) and 3% (95% CI, -5% to 11%) compared to one less, for the first, second, third and fourth pregnancy, respectively (P < .001 for heterogeneity), with similar effects of induced abortions, spontaneous abortions and childbirths. Sensitivity analysis of age at pregnancy, time since pregnancy and other potential confounders did not change these findings. The reduced ovarian cancer risk associated with pregnancy is primarily driven by the first three pregnancies, with similar effects of induced abortion, spontaneous abortions and childbirth, suggesting that mainly exposure to early pregnancy factors, and not pregnancy duration, protect against ovarian cancer.

Vasectomy and Prostate Cancer Risk: A 38-Year Nationwide Cohort Study.

BACKGROUND: A man's risk of prostate cancer has been linked to his prior reproductive history, with low sperm quality, low ejaculation frequency, and a low number of offspring being associated with increased prostate cancer risk. It is, however, highly controversial whether vasectomy, a common sterilization procedure for men, influences prostate cancer risk. METHODS: We established a cohort of all Danish men (born between 1937 and 1996) and linked information on vasectomy, doctor visits, socioeconomic factors, and cancer from nationwide registries using unique personal identification numbers. Incidence risk ratios for prostate cancer by time since vasectomy and age at vasectomy during the follow-up were estimated using log-linear Poisson regression. RESULTS: Overall, 26 238 cases of prostate cancer occurred among 2 150 162 Danish men during 53.4 million person-years of follow-up. Overall, vasectomized men had an increased risk of prostate cancer compared with nonvasectomized men (relative risk = 1.15, 95% confidence interval = 1.10 to 1.20). The increased risk of prostate cancer following vasectomy persisted for at least 30 years after the procedure and was observed regardless of age at vasectomy and cancer stage at diagnosis. Adjustment for the number of visits to the doctor and socioeconomic factors did not explain the association. CONCLUSIONS: Vasectomy is associated with a statistically significantly increased long-term risk of prostate cancer. The absolute increased risk following vasectomy is nevertheless small, but our finding supports a relationship between reproductive factors and prostate cancer risk.

Pregnancy duration and endometrial cancer risk: nationwide cohort study.

OBJECTIVE: To explore the association between pregnancy duration and risk of endometrial cancer. DESIGN: Nationwide register based cohort study. SETTING: Denmark. PARTICIPANTS: All Danish women born from 1935 to 2002. MAIN OUTCOME MEASURES: Relative risk (incidence rate ratio) of endometrial cancer by pregnancy number, type, and duration, estimated using log-linear Poisson regression. RESULTS: Among 2 311 332 Danish women with 3 947 650 pregnancies, 6743 women developed endometrial cancer during 57 347 622 person years of follow-up. After adjustment for age, period, and socioeconomic factors, a first pregnancy was associated with a noticeably reduced risk of endometrial cancer, whether it ended in induced abortion (adjusted relative risk 0.53 (95% confidence interval 0.45 to 0.64) or childbirth (0.66, 0.61 to 0.72). Each subsequent pregnancy was associated with an additional reduction in risk, whether it ended in induced abortion (0.81, 0.77 to 0.86) or childbirth (0.86, 0.84 to 0.89). Duration of pregnancy, age at pregnancy, spontaneous abortions, obesity, maternal birth cohort, fecundity, and socioeconomic factors did not modify the results. CONCLUSIONS: The risk of endometrial cancer is reduced regardless of whether a pregnancy ends shortly after conception or at 40 weeks of gestation. This reduction in risk could be explained by a biological process occurring within the first weeks of pregnancy, as pregnancies ending in induced abortions were associated with similar reductions in risk as pregnancies ending in childbirth.

Pregnancy duration and breast cancer risk.

Full-term pregnancies reduce a woman's long-term breast cancer risk, while abortions have been shown to have no effect. The precise minimal duration of pregnancy necessary to lower a woman's breast cancer risk is, however, unknown. Here we provide evidence which point to the protective effect of pregnancy on breast cancer risk arising precisely at the 34th pregnancy week. Using a cohort of 2.3 million Danish women, we found the reduction in breast cancer risk was not observed for pregnancies lasting 33 weeks or less, but restricted to those pregnancies lasting 34 weeks or longer. We further found that parity, socioeconomic status, and vital status of the child at birth did not explain the association, and also replicated our finding in data from 1.6 million women in Norway. We suggest that a distinct biological effect introduced around week 34 of pregnancy holds the key to understand pregnancy-associated breast cancer protection.

Unplanned readmission and outpatient examination 90-days after acute appendectomy in adults.

BACKGROUND: The aim of this study was to determine the frequency and indications for unplanned readmission and outpatient examination after acute appendectomy. METHODS: Adults who underwent acute appendectomy from 2008-2013 were included in the study and events occurring within 90-days from discharge recorded. RESULTS: A total of 710 patients underwent surgery. The appendix was removed in 622 patients and post-discharge contact occurred in 99 (15.9%): readmission in 60 (9.6%), outpatient examination in 39 (6.3%). The main reasons for post-discharge contact were infection (n = 25; intraabdominal, n = 16; superficial) and abdominal pain of uncertain cause (n = 25). Use of prophylactic antibiotics was associated with lower rates of contact, 8.5% versus 20.9% (p = 0.006), respectively. Removal of non-inflamed appendix was borderline associated with higher rates of contact, 21.7% versus 8.0% (if left in-situ; p = 0.058), respectively. CONCLUSIONS: A substantial number of patients underwent readmission or outpatient examination within 90-days after appendectomy in the current study. The procedure is common and attempts to prevent readmissions are important. Correct use of antibiotics and not removing a non-inflamed appendix may be key points.

A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations.

Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes.

DNA sequence profiles of the colorectal cancer critical gene set KRAS-BRAF-PIK3CA-PTEN-TP53 related to age at disease onset.

The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients.