Search

Background: In 2016, the WHO introduced an updated classification for testicular tumors. The application of this updated classification to cancer registry data requires some recoding of tumors. Objectives: The aim of this study was to provide up‐to‐date population‐based incidence estimates of subtypes of testicular germ cell tumors (TGCT) according to the updated classification. Material and methods: We reviewed 2251 pathology reports (42.9%) out of 5252 testicular tumors at the cancer registry of North Rhine‐Westphalia for the years 2008–2013. We used population counts to estimate age‐standardized incidence rates per million person‐years (EUROSTAT revised European Standard Population). Results: The application of the updated WHO classification resulted in a recoding of 8.9% of all testicular tumors. While the recodings have no influence on the incidence of seminomatous and non‐seminomatous TGCTs that include mixed TGCTs, they influence the incidence of individual histological types of seminomatous and non‐seminomatous TGCTs. Among the 4935 testicular germ cell tumors (TGCT), 23.7% were mixed TGCTs. Overall, 46.9% of all mixed TGCTs included seminoma and age‐standardized incidence rates were highest for the combination seminoma plus embryonal carcinoma (5.9 per million person‐years) and embryonal carcinoma plus teratoma (4.9 per million person‐years). The median age at diagnosis was higher for mixed TGCTs including seminoma (31 years) than those that did not include seminoma (28 years). Discussion and conclusions: Population‐based incidence time trends for seminomatous and non‐seminomatous TGCTs that include mixed TGCTs are not distorted by the introduction of the WHO update. Trend distortions can only be expected if time trends of individual histological subtypes of the seminomatous and non‐seminomatous TGCTs are examined. [ABSTRACT FROM AUTHOR]

Summary: Preliminary evidence suggests that sex steroid hormones, such as danazol (a synthetic sex steroid hormone), may be involved in enhancing telomerase activity. Elucidating underlying mechanisms of telomerase activity may further therapeutic options for individuals with telomeropathies and potentially avert certain age‐related conditions. Therefore, we conducted a cross‐sectional study to investigate the relationship between circulating sex steroid hormones and SHBG with leukocyte telomere length among 499 males in NHANES (1999–2002 surveys). Sample‐weighted linear regression analyses were conducted to assess age‐adjusted and multivariable‐adjusted estimates of associations. Estimates were rescaled to represent telomere length change in base pairs per half the value of the interquartile range of the independent variable. Estradiol and free estradiol were significantly inversely associated with leukocyte telomere length (βcontinuous per §IQR = −61, p = 0.04; free estradiol βcontinuous per §IQR = −67, p = 0.03). Testosterone, free testosterone, androstanediol glucuronide, and SHBG were not associated with leukocyte telomere length. The inverse association seen in this study indicates that a danazol‐induced hypoestrogenic state could partly underlie the previously observed association between danazol therapy and increased leukocyte telomere length. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Marijuana has been reported to have several effects on the male reproductive system. Marijuana has previously been linked to reduced adult testosterone, however, a study in Denmark reported increased testosterone concentrations among marijuana users. This study was performed to estimate the effect of marijuana use on testosterone in U.S. males. Data on serum testosterone, marijuana use, and covariates for 1577 men from the 2011-2012 U.S. National Health and Nutrition Examination Survey ( NHANES) were analyzed. Information on marijuana use was collected by a self-administered computer-assisted questionnaire. Serum testosterone was determined using isotope dilution liquid chromatography tandem mass spectrometry. The effects of marijuana use on serum testosterone concentrations were examined by frequency, duration, and recency of use. Adjusted means and 95% confidence intervals ( CI) of serum testosterone across levels of marijuana use were estimated using multiple linear regression weighted by the survey weights. The majority (66.2%) of the weighted study population reported ever using marijuana with 26.6% reporting current marijuana use. There was no difference in serum testosterone between ever users (adjusted mean = 3.69 ng/mL, 95% CI: 3.46, 3.93) and never users (adjusted mean = 3.70 ng/mL, 95% CI: 3.45, 3.98) upon multivariable analysis. However, serum testosterone was inversely associated with time since last regular use of marijuana ( p-value for trend = 0.02). When restricted to men aged 18-29 years, this relationship strengthened ( p-value for trend <0.01), and serum testosterone was also inversely associated with time since last use ( p-value for trend <0.01), indicating that recency of use, and not duration or frequency, had the strongest relationship with testosterone levels. Serum testosterone concentrations were higher in men with more recent marijuana use. Studies are needed to determine the extent to which circulating testosterone concentrations mediate the relationship of marijuana use with male reproductive outcomes. [ABSTRACT FROM AUTHOR]

Internationally, ovarian cancer is the 7th leading cancer diagnosis and 8th leading cause of cancer mortality among women. Ovarian cancer incidence varies by region, particularly when comparing high vs. low-income countries. Temporal changes in reproductive factors coupled with shifts in diagnostic criteria may have influenced incidence trends of ovarian cancer and relative rates by histologic subtype. Accordingly, we evaluated trends in ovarian cancer incidence overall (1973-1977 to 2003-2007) and by histologic subtype (1988-1992 to 2003-2007) using volumes IV-IX of the Cancer Incidence in Five Continents database (CI5plus) and CI5X (volume X) database. Annual percent changes were calculated for ovarian cancer incidence trends, and rates of histologic subtypes for individual countries were compared to overall international incidence. Ovarian cancer incidence rates were stable across regions, although there were notable increases in Eastern/Southern Europe (e.g., Poland: Annual Percent Change (APC) 1.6%, p = 0.02) and Asia (e.g., Japan: APC 1.7%, p = 0.01) and decreases in Northern Europe (e.g., Denmark: APC −0.7%, p = 0.01) and North America (e.g., US Whites: APC −0.9%, p < 0.01). Relative proportions of histologic subtypes were similar across countries, except for Asian nations, where clear cell and endometrioid carcinomas comprised a higher proportion of the rate and serous carcinomas comprised a lower proportion of the rate than the worldwide distribution. Geographic variation in temporal trends of ovarian cancer incidence and differences in the distribution of histologic subtype may be partially explained by reproductive and genetic factors. Thus, histology-specific ovarian cancer should continue to be monitored to further understand the etiology of this neoplasm. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association of body size-captured via whole-body dual-energy X-ray absorptiometry (DXA) and physical measurement-with serum sex steroid hormones and sex hormone binding globulin (SHBG), we utilized cross-sectional data and serum samples from the National Health and Nutrition Examination Survey (NHANES; 1999-2004).Methods: Testosterone, androstanediol glucuronide (3-alpha-diol-G), estradiol, and SHBG were measured via immunoassay in serum samples from a total of 898 adult men (ages 20-90) participating in the morning examination. As part of the NHANES data collection, DXA scans and measurements of weight, height, and waist circumference were performed by trained staff. Linear regression was used to estimate associations between body size and hormone levels adjusted for potential confounders and NHANES sampling procedures.Results: Total bone area (cm(2)) was inversely associated with total testosterone (ng/mL) [beta = -0.12; p value < 0.01], while bone mineral density (g/cm(2)) was inversely associated with SHBG (nmol/L) [beta = -17.16; p value = 0.01]. Increased percent body fat was associated with lower concentrations of total testosterone [beta = -0.16; p value < 0.01] and SHBG [beta = -1.11; p value < 0.01] and higher concentrations of free estradiol (fg/mL) [beta = 12.52; p value < 0.01].Conclusions: Clinical measures of body fat (measured via DXA scan) and anthropometric measures of body fat (BMI and waist circumference) provided similar inferences regarding the association between increased body fat and hormone levels in men. Increased body fat was associated with lower circulating levels of testosterone (total and free) and SHBG and higher circulating levels of free estradiol in men, while decreased bone mineral density was associated with higher circulating levels of SHBG. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation has been proposed as a risk factor for ovarian cancer. Some data suggest that anti-inflammatory medications may be protective against ovarian cancer; however, results have been inconsistent.Methods: We evaluated the risk of epithelial ovarian cancer with regular use of NSAIDs prospectively in the NIH-AARP Diet and Health Study, using Cox proportional hazard models. We also examined the risk of common subtypes of epithelial ovarian cancer (serous, mucinous, endometrioid, clear cell, and other epithelial) with regular use of NSAIDs. In addition, we performed meta-analyses summarizing the risk of ovarian cancer with "regular use" of NSAIDs in previously published studies.Results: We did not observe a significant association between regular use of NSAIDs with ovarian cancer risk in the AARP cohort (aspirin: RR 1.06, 95 % CI 0.87-1.29; non-aspirin NSAIDs: RR 0.93, 95 % CI 0.74-1.15); however, summary estimates from prospective cohort studies demonstrated that use of non-aspirin NSAIDs may reduce the risk of ovarian cancer (RR 0.88, 95 % CI 0.77-1.01). Although not significant, we found that mucinous tumors were inversely associated with non-aspirin NSAID use (RR 0.69, 95 % CI 0.23-2.10) in the AARP cohort, which was supported by the meta-analysis (RR 0.69, CI 0.50-0.94.)Conclusion: Although results from the NIH-AARP cohort study were not statistically significant, our meta-analysis suggests that non-aspirin NSAIDs may be protective against ovarian cancer. Additional analyses, focusing on dose, duration, and frequency of NSAID use and accounting for ovarian cancer heterogeneity are necessary to further elucidate the association between NSAID use and ovarian cancer risk. [ABSTRACT FROM AUTHOR]

Background:Women using unopposed estrogens during menopause are at increased risk of ovarian cancer. It is uncertain whether oestrogen plus progestin therapy exerts similar effects.Methods:We evaluated menopausal hormone use and incident ovarian cancer (n=426) in 92 601 post-menopausal women enrolled in the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study. Participants were administered questionnaires in 1996-1997 and followed through 2006. Hazard rate ratios (RR) and 95% confidence intervals (CIs) were estimated using Cox regression.Results:Increased risks were associated with long duration (10+ years) use of unopposed oestrogen (RR 2.15, 95% CI: 1.30-3.57 among women with a hysterectomy) and oestrogen plus progestin (RR 1.68, 95% CI: 1.13-2.49 among women with intact uteri) therapy. Similar risks were associated with progestins that were used sequentially (<15 days progestin per month) (RR 1.60, 95% CI: 1.10-2.33) or continuously (>25 days progestin per month) (RR 1.43, 95% CI: 1.032-2.01; P-value for heterogeneity=0.63).Conclusion:Our findings suggest that long duration use of both unopposed estrogens and oestrogen plus progestins are associated with increased risks of ovarian cancer, and that risk associated with oestrogen plus progestin use does not vary by regimen (sequential or continuous). [ABSTRACT FROM AUTHOR]

Background:Similarities between the age-specific incidence pattern of testicular germ cell tumours (TGCTs) and the age-specific incidence pattern of cancers of viral origin prompted us to evaluate the relationship between common infections occurring during childhood or young adult life and TGCT using existing data from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study.Methods:TGCT cases diagnosed between 2002 and 2005 (n=767) were matched on age, race and serum draw date to at least one control (n=929).Results:None of the infections evaluated were associated with TGCT risk. Further, a meta-analysis of mumps and mumps orchitis or orchitis infection did not support an association with TGCT (mumps pooled odds ratio (OR): 1.03, 95% confidence interval (CI): 0.89-1.20; mumps orchitis or orchitis pooled OR: 1.80, 95% CI: 0.74-4.42).Conclusion:Based on our evaluation of childhood and early life infections and meta-analyses of mumps and mumps orchitis and/or orchitis, TGCT does not appear to be associated with common childhood infections. [ABSTRACT FROM AUTHOR]

PURPOSE: This study sought to describe the physical activity-endometrial cancer association and potential mediation of this relationship by obesity in midlife. METHODS: Participants were 67,705 women (aged 50-71 years) enrolled in the NIH-AARP cohort who reported their historical leisure-time physical activity patterns starting at age 15-18 years. We identified five long-term physical activity patterns between adolescence and cohort entry (i.e., inactive, maintained-low, maintained-high, increasers, decreasers). We used Cox regression (Hazard ratio - HR [95% CI]) to assess the relationship between these patterns and midlife obesity and endometrial cancer, adjusting for covariates. Mediation analysis was used to decompose the physical activity patterns-endometrial cancer association to estimate the proportion of the physical activity-endometrial cancer association mediated by midlife obesity. RESULTS: During an average 12.3 years of follow-up 1,468 endometrial cancers occurred. Long-term physical activity patterns were inactive, maintained-low, maintained-high, increasers, and decreasers. Compared to long-term inactive women, women who maintained-high or increased activity levels had a 19-26% lower risk for endometrial cancer (maintained-high: HR = 0.81 [0.67, 0.98]; increasers: HR = 0.74 [0.61, 0.91]). They also had a 45-77% lower risk for obesity in midlife (e.g., maintained-high, BMI 30-39.9: HR = 0.50 [0.46, 0.55]; maintained-high, BMI 40+: HR = 0.32 [0.26, 0.39]). Obesity was a significant mediator and appeared to account for 55-63% of the physical activity-endometrial cancer associations observed. CONCLUSIONS: Both initiating and maintaining physical activity throughout adulthood can play a role in preventing obesity and in turn, lowering the risk for endometrial cancer. [ABSTRACT FROM AUTHOR]

A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P = 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 × 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted., Other Research Unit

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Purpose: Hysterectomy is associated with subsequent changes in circulating hormone levels, but the evidence of an association for tubal ligation is unclear. We evaluated whether circulating concentrations of androgens and estrogens differ by tubal ligation or hysterectomy status in postmenopausal women from the Women's Health Initiative (WHI)-Observational Study (OS)., Methods: Serum androgens and estrogens were measured in 920 postmenopausal women who did not use menopausal hormone therapy at the time of blood draw, of whom 139 self-reported a history of tubal ligation and 102 reported hysterectomy (with intact ovaries). Geometric mean hormone concentrations (GMs) and 95% confidence intervals (CIs) associated with a history of tubal ligation or hysterectomy (ever/never), as well as time since procedures, were estimated using adjusted linear regression with inverse probability of sampling weights to account for selection., Results: Circulating levels of 12 androgen/androgen metabolites and 20 estrogen/estrogen metabolites did not differ by tubal ligation status. Among women reporting prior hysterectomy compared to women without hysterectomy, we observed lower levels of several androgens (e.g., testosterone (nmol/L): GM yes 0.46 [95% CI:0.37-0.57] vs. GM no 0.62 [95% CI:0.53-0.72]) and higher levels of estrogen metabolites, for example, 2-hydroxyestrone-3-methyl ether (GM yes 11.1 [95% CI:8.95-13.9] pmol/L vs. GM no 8.70 [95% CI:7.38-10.3]) and 4-methoxyestrone (GM yes 6.50 [95% CI:5.05-8.37] vs. GM no 4.92 [95% CI:4.00-6.05])., Conclusion: While we did not observe associations between prior tubal ligation and postmenopausal circulating hormone levels, our findings support that prior hysterectomy was associated with lower circulating testosterone levels and higher levels of some estrogen metabolites, which may have implications for future hormone-related disease risks., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Racial and ethnic disparities in gynecologic cancer care have been documented. Treatment at academic facilities is associated with improved survival, yet no study has examined independent associations between race and ethnicity with facility type among gynecologic cancer patients., Materials & Methods: We used the National Cancer Database and identified 484,455 gynecologic cancer (cervix, ovarian, uterine) patients diagnosed between 2004 and 2020. Facility type was dichotomized as academic vs. non-academic, and we used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between race and ethnicity and facility type. Secondarily, we examined joint effects of race and ethnicity and facility type on overall survival using Cox proportional hazards regression., Results: We observed higher odds of treatment at academic (vs. non-academic) facilities among American Indian/Alaska Native (OR = 1.42, 95% CI = 1.28-1.57), Asian (OR = 1.64, 95% CI = 1.59-1.70), Black (OR = 1.69, 95% CI = 1.65-1.72), Hispanic (OR = 1.70, 95% CI = 1.66-1.75), Native Hawaiian/Pacific Islander (OR = 1.74, 95% CI = 1.57-1.93), and other race (OR = 1.29, 95% CI = 1.20-1.40) patients compared with White patients. In the joint effects survival analysis with White, academic facility-treated patients as the reference group, Asian, Hispanic, and other race patients treated at academic or non-academic facilities had improved overall survival. Conversely, Black patients treated at academic facilities [Hazard Ratio (HR) = 1.10, 95% CI = 1.07-1.12] or non-academic facilities (HR = 1.19, 95% CI = 1.16-1.21) had worse survival., Discussion: Minoritized gynecologic cancer patients were more likely than White patients to receive treatment at academic facilities. Importantly, survival outcomes among patients receiving care at academic institutions differed by race, requiring research to investigate intra-facility survival disparities., Competing Interests: Declaration of competing interest Dr. Plascak reports honoraria payments from National Comprehensive Cancer Network and North American Association of Central Cancer Registries. Dr. Backes reports personal fees from Agenus, CEC Oncology, Clovis, Eisai, Merck, AstraZeneca, GSK, ImmunoGen, BioNTech, Daiichi Sankyo, EMD Serono, and Myriad and research funding from Clovis, Eisai, Immunogen, Merck, Beigene, Tempus, and Natera. All other authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality., Methods: Body composition from 500 women in the Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal or low skeletal muscle index (SMI), a proxy for sarcopenia, and high or low adiposity. Four phenotypes were classified as fit (normal SMI and low adiposity; reference; 16.2%), overweight or obese (normal SMI and high adiposity; 51.2%), sarcopenia and overweight or obese (low SMI and high adiposity; 15.6%), and sarcopenia or cachexia (low SMI and low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC)., Results: Overweight or obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC [Hazard Ratio (HR)] = 1.51, 95% CI = 1.05 to 2.19 and HR = 2.04, 95% CI = 1.29 to 3.21). Sarcopenia and overweight or obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI = 1.13 to 2.45 and HR = 1.67, 95% CI = 1.05 to 2.68). Sarcopenia or cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI = 1.14 to 2.63 and HR = 2.09, 95% CI = 1.25 to 3.50)., Conclusions: Overweight or obesity, sarcopenia and overweight or obesity, and sarcopenia or cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background Little is known about current characteristics of individuals with tattoos. We quantified the prevalence of tattooing and associations of demographic, health, and risk-behavior factors with tattooing. Methods We computed adjusted prevalence ratios (PR) of tattooing in a population-based analysis of > 18,000 Utah adults from the 2020-2021 Behavioral Risk Factor Surveillance System survey. Results The prevalence of tattooing was 26% among women and 22% among men, with the highest prevalence among women ages 25-29 (45%). Tattoo prevalence was higher among younger individuals, individuals with a lower education level, and those without religious affiliation. Tattoo prevalence was higher among indviduals with current tobacco (women: PR = 2.89 [95% confidence interval (CI): 2.60, 3.20]; men: 3.39 [2.98, 3.86]), e-cigarette (women: 2.44 [2.21, 2.69]; men: 2.64 [2.37, 2.94]), and heavy alcohol use (women: 2.16 [1.93, 2.43]; men: 1.89 [1.63, 2.19]). Tattoo prevalence was lower among individuals receiving a flu (women: 0.84 [0.76, 0.92]; men: 0.75 [0.67, 0.84]) or COVID-19 vaccine (women: 0.65 [0.54, 0.79]; men: 0.75 [0.61, 0.92]). Conclusions Several risk-taking behaviors were associated with tattooing. Tattoo studios/conventions may present opportunities for partnership with tobacco cessation, alcohol reduction, and vaccination public health initiatives.

Importance: Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described., Objective: To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype., Design, Setting, and Participants: Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis., Exposures: Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other., Main Outcomes and Measures: Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations., Results: In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85])., Conclusions and Relevance: Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

Background: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain., Methods: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI)., Results: Compared with women who did not drink any green tea, consumption of one or more cups/day was associated with better overall survival (aHR = 0.84, 95% CI 0.71-1.00, p-trend = 0.04). A similar association was seen for ovarian cancer-specific survival in five studies with this information (aHR = 0.81, 0.66-0.99, p-trend = 0.045). There was no consistent variation between subgroups defined by clinical or lifestyle characteristics and adjustment for other aspects of lifestyle did not appreciably alter the estimates. We found no evidence of an association between coffee, black or herbal tea, or caffeine intake and survival., Conclusion: The observed association with green tea consumption before diagnosis raises the possibility that consumption after diagnosis might improve patient outcomes., (© 2024. The Author(s).)

Background: Risk factors have limited ability to predict individuals at high risk of developing ovarian cancer among average risk women, highlighting the need for discovery of novel biomarkers. In the UK Biobank, we investigated serum biomarkers commonly measured in clinical laboratory tests and ovarian cancer risk., Methods: We conducted a prospective analysis of 20 serum biomarkers and ovarian cancer risk in 232,037 female UK Biobank participants (including 1,122 incident ovarian cancer cases diagnosed from 2006-2020). Multivariable adjusted Cox proportional hazards models were used to examine associations between biomarkers and ovarian cancer risk overall and by histotype. False discovery rate was used to account for multiple testing., Results: Overall, higher levels of IGF-1 (RRquartile 4 vs. 1=0.73, 95%CI=0.60-0.87; p-trend=0.002/FDR=0.04), HbA1c (RRquartile 4 vs. 1=0.74, 95%CI=0.62-0.89; p-trend=0.002/FDR=0.04), and alanine aminotransferase (RRquartile 4 vs. 1=0.76, 95%CI=0.63-0.91; p-trend=0.002/FDR=0.04) were significantly associated with lower ovarian cancer risk. When stratified by histotype, higher IGF-1 levels were associated with lower risk of serous (RRquartile 4 vs. 1=0.73, 95%CI=0.58-0.91; p-trend=0.01/FDR=0.20) and clear cell tumors (RRquartile 4 vs. 1=0.18, 95%CI=0.07-0.49; p-trend=0.001/FDR=0.02) and higher HbA1c levels were associated with lower risk of serous tumors (RRquartile 4 vs. 1=0.73, 95%CI=0.59-0.90; p-trend=0.004/FDR=0.08)., Conclusion: We observed that higher levels of circulating IGF-1, HbA1c, and alanine aminotransferase were associated with lower ovarian cancer risk., Impact: These results suggest metabolism of glucose/amino acid and insulin/IGF-1 signaling pathway may be contributing to ovarian carcinogenesis. Further research is needed to replicate our findings and elucidate how systemic changes in metabolism impact ovarian carcinogenesis.

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10 -8 ) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10 -5 ). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Purpose: Uterine sarcomas are a rare group of uterine malignancies. Due to the low incidence and changes in uterine sarcoma classification, risk factors are not well characterized. Our objective was to evaluate risk factors for uterine sarcoma and compare risk factors between uterine sarcoma, malignant mixed Mullerian tumors (MMMTs), and type I endometrial carcinomas., Methods: This nested case-control study utilized linked data from population-based medical birth and cancer registries in Denmark, Finland, Norway, and Sweden. Up to 10 controls were matched on country and birth year for each uterine cancer case. Using multivariable adjusted multinomial logistic regression, estimates of the associations between pregnancy-related factors and risk of uterine sarcoma, MMMTs, and type I endometrial carcinomas were determined., Results: Having a very-low-birth-weight infant (< 1500 vs. 2500-3999 g: OR [95% CI] 2.83 [1.61-4.96]) was associated with an increased risk of uterine sarcoma. Whereas, having a more recent pregnancy was associated with reduced risks of MMMT (< 10 vs. ≥ 30 years: 0.66 [0.20-2.23]) and type 1 endometrial carcinomas (0.35 [0.30-0.41]) but not uterine sarcomas (1.33 [0.90-1.98], p-heterogeneity < 0.01)., Conclusion: Our study provides evidence that risk factors for uterine sarcoma and MMMT, previously grouped with uterine sarcomas, vary substantially. Additionally, MMMT and type I endometrial carcinomas are more similar than uterine sarcoma in that pregnancy complications like gestational hypertension and preeclampsia were associated with reduced risks of both but not uterine sarcoma, suggesting different etiologies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: While previous studies indicate muscle-strengthening exercises may reduce mortality risk, further research is needed to increase certainty of the evidence. We investigated overall and dose-response associations between weight training and the risks of all-cause, cardiovascular disease (CVD) and cancer mortality in a large cohort of older adults with long follow-up time and a large number of deaths. We also investigated the joint associations of weight training and aerobic exercise with mortality risk., Methods: Weight training was assessed via self-report in 2004-05 in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study (USA; n = 216 339), with follow-up to 2019. Cox regression estimated the hazard ratios (HR) and 95% confidence intervals (CI) for the associations between weight training and mortality, after adjusting for confounders including aerobic exercise., Results: Around 25% of participants [mean age = 69.9 years (standard deviation = 5.4), 58% men] reported engaging in weight training over the past year, and there were 79 107 (37%) deaths. Engaging in any weight training (vs none) was associated with lower risks of all-cause (HR = 0.94; 95% CI = 0.93-0.96), CVD (HR = 0.92; 95% CI = 0.90-0.95) and cancer mortality (HR = 0.95; 95% CI = 0.92-0.98). More time spent in weight training was associated with only marginally greater risk reductions. Larger risk reductions were observed among women than men. Performing both aerobic exercise and weight training conferred the greatest mortality risk reduction; weight training was not associated with mortality risk among participants who did no aerobic exercise., Conclusion: Performing any amount of weight training lowered mortality risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Data on the role of circadian related factors in the etiology of endometrial cancer are scarce. We collected individual data on night shift work or daily sleep duration from 7,207 cases and 22,027 controls participating in 11 studies from the Epidemiology of Endometrial Cancer Consortium (E2C2). Main analyses were performed among postmenopausal women: 6,335 endometrial cancer cases and 18,453 controls. Using individual data, study-specific odd ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated with logistic regression and pooled analyses were conducted using random-effects meta-analyses. A non-significant inverse association was observed between endometrial cancer and night shift work (OR=0.89, 95%CI=0.72-1.09; I 2 =0.0%, P heterogeneity= 0.676). Associations did not vary by shift type (permanent or rotating), or duration of night work. Categorizations of short (<7h) or long (≥9h) sleep duration were not associated with endometrial cancer risk (OR short =1.02, 95%CI=0.95-1.10; I 2 =55.3%, P heterogeneity =0.022; OR long =0.93, 95%CI=0.81-1.06; I 2 =11.5%, P heterogeneity =0.339). No associations were observed per 1-h increment of sleep (OR=0.98, 95%CI=0.95-1.01; I 2 =46.1%, P heterogeneity =0.063), but an inverse association was identified among obese women (OR=0.93, 95%CI=0.89-0.98 per 1-h increment; I 2 =12.7%, P heterogeneity =0.329). Overall, these pooled analyses provide evidence that night shift work and sleep duration are not strong risk factors for endometrial cancer in postmenopausal women., Competing Interests: Declaration of competing interest The authors of this paper have no conflicts of interest to disclose relevant to the present work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: It has been hypothesized that poorly functioning Leydig and/or Sertoli cells of the testes, indicated by higher levels of serum gonadotropins and lower levels of androgens, are related to the development of testicular germ cell tumors (TGCT). To investigate this hypothesis, we conducted a nested case-control study within the Janus Serum Bank cohort., Methods: Men who developed TGCT (n = 182) were matched to men who did not (n = 364). Sex steroid hormones were measured using LC/MS. Sex hormone binding globulin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were quantified by direct immunoassay. Multivariable logistic regression was used to calculate ORs and 95% confidence intervals (CI) for associations between hormone levels and TGCT risk., Results: Higher FSH levels [tertile (T) 3 vs. T2: OR = 2.89, 95% CI = 1.83-4.57] were associated with TGCT risk, but higher LH levels were not (OR = 1.26, 95% CI = 0.81-1.96). The only sex steroid hormone associated with risk was androstane-3α, 17β-diol-3G (3α-diol-3G; OR = 2.37, 95% CI = 1.46-3.83). Analysis by histology found that increased FSH levels were related to seminoma (OR = 3.55, 95% CI = 2.12-5.95) but not nonseminoma (OR = 1.19, 95% CI = 0.38-3.13). Increased levels of 3α-diol-3G were related to seminoma (OR = 2.29, 95% CI = 1.35-3.89) and nonsignificantly related to nonseminoma (OR = 2.71, 95% CI = 0.82-8.92)., Conclusions: Higher FSH levels are consistent with the hypothesis that poorly functioning Sertoli cells are related to the development of TGCT. In contrast, higher levels of 3α-diol-3G do not support the hypothesis that insufficient androgenicity is related to risk of TGCT., Impact: Clarifying the role of sex hormones in the development of TGCT may stimulate new research hypotheses., (©2023 American Association for Cancer Research.)

Background: One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus, we assessed its relationship with ovarian cancer risk., Methods: In prospectively collected samples, we evaluated the association of kidney function markers and C-reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, >3.0 mg/L)., Results: Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006-2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: HR, 1.00; 95% confidence intervals, 0.83-1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33, 0.11-0.98) and clear cell (4.74, 1.39-16.16) tumors. Poor kidney function was associated with a nonsignificant increase in ovarian cancer risk among women with CRP>3.0 mg/L (e.g., uric acid Q4 vs. Q1; 1.23, 0.81-1.86), but not CRP≤3.0 mg/L (0.83, 0.66-1.05). Other associations did not vary across CRP categories., Conclusions: Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions., Impact: This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk., (©2023 American Association for Cancer Research.)