Maternal autoimmune disease is not associated with cancer in the offspring

Aim Autoimmune disease and its medication are associated with increased cancer risk in adults, but it is unknown whether maternal autoimmune disease and/or medication use in pregnancy are associated with increased cancer risk in offspring. Methods In this case-control study, we identified all patients under 20 years of age with their first cancer diagnosis in 1996-2014 from the Finnish Cancer Registry (n = 2029) and 1:5 population-based controls (n = 10,103) from the Medical Birth Register. We obtained information on maternal autoimmune disease and its medication from the relevant Finnish registries and used conditional logistic regression to analyse the risk of offspring cancer after maternal autoimmune disease exposure. Results The odds ratio (OR) for cancer in offspring following maternal autoimmune exposure was 0.76 (95% confidence interval [CI] 0.47-1.23). Individual ORs for inflammatory bowel and connective tissue diseases were 1.08 (95% CI 0.56-2.01) and 0.50 (95% CI 0.23-1.08), respectively. The OR for maternal autoimmune medication was 0.95 (95% CI 0.80-1.14) overall and similar by drug subtype. There was an increased risk with medication in late pregnancy but the ORs were unstable owing to small numbers. Conclusion Our study does not support an increased cancer risk among offspring of women with autoimmune disease or its medication during pregnancy.Peer reviewe

Pubertal timing and breast density in young women: a prospective cohort study.

BACKGROUND:Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS:From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS:The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS:Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk

Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero

BACKGROUND. Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS. Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS. The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at ≥ 13 weeks to ≥ 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS. Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.National Cancer Institute (N01-CP-21168, N01-CP-51017, N01-CP-01289

Gender Identity and Sexual Orientation Identity in Women and Men Prenatally Exposed to Diethylstilbestrol

We assessed the associations of prenatal diethylstilbestrol (DES) exposure, a potent estrogen, with sexual orientation and gender identity in 3306 women and 1848 men who participated in a study of prenatal DES exposure. Odds ratios (OR) and 95% confidence intervals (CI) were derived from logistic regression models adjusted for birth year, study cohort, and education. Among women, the OR for DES in relation to reporting sexual orientation identity as nonheterosexual was 0.61 (95% CI 0.40-0.92) primarily due to a strong inverse association with a lesbian identity (OR 0.44, 95% CI 0.25-0.76). Among men, the OR for DES in relation to reporting a nonheterosexual sexual orientation identity was 1.4 (95% CI 0.82-2.4), and ORs were similar for having a gay identity (1.4, 95% CI 0.72-2.85) and bisexual identity (1.4, 95% CI 0.57-3.5). Only five individuals reported a gender identity not conforming to that assigned at birth, preventing meaningful analysis. Women who were prenatally exposed to DES were less likely to have a lesbian or bisexual orientation, while DES-exposed men were somewhat more likely to report being gay or bisexual, but estimates were imprecise

Sex differences in childhood cancer risk among children with major birth defects: a Nordic population-based nested case-control study

Background Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. Methods We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0–19 years) and 218 980 matched population controls, born 1967–2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects. Results Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6–12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8–2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6–3.1) than males (OR = 2.1, 95% CI = 1.9–2.2, Pinteraction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, PNIE <0.001), although more at younger ages (10% below years and 28% below 1 year). Conclusions The birth defect–cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.publishedVersio

Pregnancy-related risk factors for sex cord-stromal tumours and germ cell tumours in parous women : a registry-based study

Background Non-epithelial ovarian cancers are divided into sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Whereas parity and other pregnancy-related factors are protective for epithelial ovarian cancer, their associations with SCSTs and GCTs remains unclear. Methods Using data from the medical birth registries from Denmark, Finland, Norway and Sweden, we compared all parous women with a diagnosis of SCSTs (n = 420) or GCTs (n = 345) 1970-2013 with up to 10 parous controls (SCSTs n = 4041; GCTs n = 2942) matched on the cases' birth year and country. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of associations between pregnancy-related factors and SCSTs and GCTs. Results The risk of SCSTs, but not GCTs, decreased with higher age at last birth [>= 40 versusPeer reviewe

Urogenital Abnormalities in Men Exposed to Diethylstilbestrol in Utero: A Cohort Study

Background: Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters. Studies of prenatally-exposed males have yielded conflicting results. Methods: In data from a collaborative follow-up of three U.S. cohorts of DES-exposed sons, we examined the relation of prenatal DES exposure to occurrence of male urogenital abnormalities. Exposure status was determined through review of prenatal records. Mailed questionnaires (1994, 1997, 2001) asked about specified abnormalities of the urogenital tract. Risk ratios (RR) were estimated by Cox regression with constant time at risk and control for year of birth. Results: Prenatal DES exposure was not associated with varicocele, structural abnormalities of the penis, urethral stenosis, benign prostatic hypertrophy, or inflammation/infection of the prostate, urethra, or epididymus. However, RRs were 1.9 (95% confidence interval 1.13.4) for cryptorchidism, 2.5 (1.54.3) for epididymal cyst, and 2.4 (1.54.4) for testicular inflammation/ infection. Stronger associations were observed for DES exposure that began before the 11th week of pregnancy: RRs were 2.9 (1.65.2) for cryptorchidism, 3.5 (2.06.0) for epididymal cyst, and 3.0 (1.75.4) for inflammation/infection of testes. Conclusion: These results indicate that prenatal exposure to DES increases risk of male urogenital abnormalities and that the association is strongest for exposure that occurs early in gestation. The findings support the hypothesis that endocrine disrupting chemicals may be a cause of the increased prevalence of cryptorchidism that has been seen in recent years

Art in HCI: A View from the UAL Creative Computing Institute

We are staff from the Creative Computing Institute (CCI) at University of the Arts London. In this pictorial submission, we outline key questions of interest at the intersection of art and HCI, and we illustrate how some of the staff and students at CCI are bringing together ideas and practices at this intersection. This pictorial shares some of our perspectives on opportunities and challenges in this space

Cervical Screening and General Physical Examination Behaviors of Women Exposed In Utero to Diethylstilbestrol

Objective. To estimate whether women exposed in utero to diethylstilbestrol (DES) report receiving more cervical and general physical examinations compared to unexposed women. Materials and Methods. 1994 Diethylstilbestrol Adenosis cohort data are used to assess the degree of recommended compliance of cervical screenings found in 3,140 DES-exposed and 826 unexposed women. Participants were enrolled at 4 sites: Houston, Boston, Rochester, and Los Angeles. Logistic regression modeling was used to analyze mailed questionnaire data, which included reported frequency over the preceding 5 years (1990-1994) of Papanicolaou smears and general physical examinations. Results. Diethylstilbestrol-exposed women exceeded the recommended frequency of Papanicolaou smear screenings [adjusted odds ratio (aOR) = 2.15, 95% CI (confidence interval) = 1.60-2.88] compared to the unexposed. This association held among those without a history of cervical intraepithelial neoplasia (aOR = 1.88, 95% CI = 1.35-2.62). Diethylstilbestrol-exposed women exceeded annual recommendations for physical examinations (aOR = 2.27, 95% CI = 1.16-4.43) among women without a history of chronic disease when compared to unexposed women. Conclusions. Most DES-exposed women are receiving cervical cancer screening at least at recommended intervals, but one third of the women are not receiving annual Papanicolaou smear examinations

Pubertal timing and breast density in young women: a prospective cohort study

Background Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. Methods From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006–2008, 182 participants then aged 25–29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. Results The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2–86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2–26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9–17.5%)). Conclusions Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk