Adaptations of membrane trafficking in cancer and tumorigenesis.

Membrane trafficking, a fundamental cellular process encompassing the transport of molecules to specific organelles, endocytosis at the plasma membrane and protein secretion, is crucial for cellular homeostasis and signalling. Cancer cells adapt membrane trafficking to enhance their survival and metabolism, and understanding these adaptations is vital for improving patient responses to therapy and identifying therapeutic targets. In this Review, we provide a concise overview of major membrane trafficking pathways and detail adaptations in these pathways, including COPII-dependent endoplasmic reticulum (ER)-to-Golgi vesicle trafficking, COPI-dependent retrograde Golgi-to-ER trafficking and endocytosis, that have been found in cancer. We explore how these adaptations confer growth advantages or resistance to cell death and conclude by discussing the potential for utilising this knowledge in developing new treatment strategies and overcoming drug resistance for cancer patients.

Publisher Correction: Somatic APP gene recombination in Alzheimer's disease and normal neurons.

In this Article, the top label in Fig. 5d should read 'DISH 3/16' instead of 'DISH 3/17'. This error has been corrected online.

Mitochondrial DNA D-Loop Polymorphisms among the Galla Goats Reveals Multiple Maternal Origins with Implication on the Functional Diversity of the HSP70 Gene.

Despite much attention given to the history of goat evolution in Kenya, information on the origin, demographic history, dispersal route, and genetic diversity of Galla goats remains unclear. Here, we examined the genetic background, diversity, demographic history, and population genetic variation of Galla goats using mtDNA D-loop and HSP70 single-nucleotide polymorphism markers. The results revealed 90 segregating sites and 68 haplotypes in a 600-bp mtDNA D-loop sequence. The overall mean mitochondrial haplotype diversity was 0.993. The haplotype diversities ranged between 0.8939 ± 0.0777 and 1.0000 ± 0.0221 in all populations supporting high genetic diversity. Mitochondrial phylogenetic analysis revealed three Galla goat haplogroups (A, G, and D), supporting multiple maternal ancestries, of which haplogroup A was the most predominant. Analysis of molecular variance (AMOVA) showed considerable variation within populations at 94.39%, evidence of high genetic diversity. Bimodal mismatch distribution patterns were observed while most populations recorded negative results for Tajima and Fu's Fs neutrality tests supporting population expansion. Genetic variation among populations was also confirmed using HSP70 gene fragment sequences, where six polymorphic sites which defined 21 haplotypes were discovered. Analysis of molecular variance revealed a significant FST index value of 0.134 and a high FIS index value of 0.746, an indication of inbreeding. This information will pave the way for conservation strategies and informed breeding to improve Galla or other goat breeds for climate-smart agriculture.

Somatic APP gene recombination in Alzheimer's disease and normal neurons.

The diversity and complexity of the human brain are widely assumed to be encoded within a constant genome. Somatic gene recombination, which changes germline DNA sequences to increase molecular diversity, could theoretically alter this code but has not been documented in the brain, to our knowledge. Here we describe recombination of the Alzheimer's disease-related gene APP, which encodes amyloid precursor protein, in human neurons, occurring mosaically as thousands of variant 'genomic cDNAs' (gencDNAs). gencDNAs lacked introns and ranged from full-length cDNA copies of expressed, brain-specific RNA splice variants to myriad smaller forms that contained intra-exonic junctions, insertions, deletions, and/or single nucleotide variations. DNA in situ hybridization identified gencDNAs within single neurons that were distinct from wild-type loci and absent from non-neuronal cells. Mechanistic studies supported neuronal 'retro-insertion' of RNA to produce gencDNAs; this process involved transcription, DNA breaks, reverse transcriptase activity, and age. Neurons from individuals with sporadic Alzheimer's disease showed increased gencDNA diversity, including eleven mutations known to be associated with familial Alzheimer's disease that were absent from healthy neurons. Neuronal gene recombination may allow 'recording' of neural activity for selective 'playback' of preferred gene variants whose expression bypasses splicing; this has implications for cellular diversity, learning and memory, plasticity, and diseases of the human brain.

The role of CaMKK2 in Golgi-associated vesicle trafficking.

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a serine/threonine-protein kinase, that is involved in maintaining various physiological and cellular processes within the cell that regulate energy homeostasis and cell growth. CaMKK2 regulates glucose metabolism by the activation of downstream kinases, AMP-activated protein kinase (AMPK) and other calcium/calmodulin-dependent protein kinases. Consequently, its deregulation has a role in multiple human metabolic diseases including obesity and cancer. Despite the importance of CaMKK2, its signalling pathways and pathological mechanisms are not completely understood. Recent work has been aimed at broadening our understanding of the biological functions of CaMKK2. These studies have uncovered new interaction partners that have led to the description of new functions that include lipogenesis and Golgi vesicle trafficking. Here, we review recent insights into the role of CaMKK2 in membrane trafficking mechanisms and discuss the functional implications in a cellular context and for disease.

Synthesis and analysis of novel catecholic ligands as inhibitors of catechol-O-methyltransferase.

l-DOPA, a dopamine precursor, is commonly used as a treatment for patients with conditions such as Parkinson's disease. This therapeutic l-DOPA, as well as the dopamine derived from l-DOPA, can be deactivated via metabolism by catechol-O-methyltransferase (COMT). Targeted inhibition of COMT prolongs the effectiveness of l-DOPA and dopamine, resulting in a net increase in pharmacological efficiency of the treatment strategy. Following the completion of a previous ab initio computational analysis of 6-substituted dopamine derivatives, several novel catecholic ligands with a previously unexplored neutral tail functionality were synthesized in good yields and their structures were confirmed. The ability of the catecholic nitriles and 6-substituted dopamine analogues to inhibit COMT was tested. The nitrile derivatives inhibited COMT most effectively, in agreement with our previous computational work. pKa values were used to further examine the factors involved with the inhibition and molecular docking studies were performed to support the ab initio and experimental work. The nitrile derivatives with a nitro substituent show the most promise as inhibitors, confirming that both the neutral tail and the electron withdrawing group are essential on this class of inhibitors.

Toward the validation of VR-HMDs for medical education: a systematic literature review.

The latest technological advancements in the domain of virtual reality (VR) have created new opportunities to use VR as a training platform for medical students and practitioners more broadly. Despite the growing interest in the use of VR as a training tool, a commonly identified gap in VR-training for medical education is the confidence in the long-term validity of the applications. A systematic literature review was undertaken to explore the extent of VR (in particular head-mounted displays) applications for medical training with an additional focus on validation measures. The papers included in this review discussed empirical case studies of specific applications; however, these were mostly concerned with human-computer interaction and were polarized between demonstrating that a conceptual technology solution was feasible for simulation or looked at specific areas of VR usability with little discussion on validation measures for long-term training effectiveness and outcomes. The review uncovered a wide range of ad hoc applications and studies in terms of technology vendors, environments, tasks, envisaged users and effectiveness of learning outcomes. This presents decision-making challenges for those seeking to adopt, implement and embed such systems in teaching practice. The authors of this paper then take a wider socio-technical systems perspective to understand how the holistic training system can be engineered and validated effectively as fit for purpose, through distillation of a generic set of requirements from the literature review to aid design specification and implementation, and to drive more informed and traceable validation of these types of systems. In this review, we have identified 92 requirement statements in 11 key areas against which a VR-HMD training system could be validated; these were grouped into design considerations, learning mechanisms and implementation considerations.

Leadership Development Among Junior Surgery Residents: Communication and Perception.

INTRODUCTION: Leadership is necessary for effective health care teams, particularly for surgeons. Trainees similarly must acquire foundational leadership skills to maximize effectiveness. However, surgical leadership is rarely formally assessed, particularly for junior trainees. We aimed to establish themes of communication, perception and engagement styles, as well as strengths and weaknesses among junior surgical residents at a single institution. METHODS: The Data Dome Inc. (datadome.com) DISC personality assessment was administered in 2018-2021 to junior residents at an academic general surgery training program at a single institution. Resident demographics were recorded, and themes from deidentified reports were analyzed by year (PGY-1 and PGY-2) using JMP 16 Pro Text Explorer. RESULTS: PGY-1 communication was most frequently described as "accomplished best by well-defined avenues" with "duties and responsibilities of others who will be involved explained" in "friendly terms." PGY-2 communication involved "deal [ing] with people," "strong feelings about a particular problem," and being "good at giving verbal and nonverbal feedback." In ideal environments, PGY-1s self-perceived as "good listener [s]," "good-natured," and "team player [s]." However, under stress, PGY-1s were perceived by others as "poor listener [s]," "self-promoter [s]," "detached," and "insensitive." In ideal environments, PGY-2s were also "good listener [s]," "good-natured," and "team player [s]." However, under stress, PGY-2 external perception was "overly confident," "poor listener [s]," and "self-promoter [s]." CONCLUSIONS: Clear expectations, friendly work environments, and opportunities to succeed are key to effectively train junior surgical residents. In environments where time is often a limited resource, surgical simulation, stress training, and standardized teaching methods from attending surgeons are needed to develop competent trainees.

Evaluating the role of negative affect and negative interpretation biases in emotional eating behavior.

OBJECTIVE: The study of emotional eating, or (over)eating in response to emotions, may inform transdiagnostic interventions for eating pathology. Prior work has focused on the role of negative affect in promoting emotional eating. The present study sought to extend this work through examining the role of cognitive biases. METHOD: Women who self-reported (n = 50) and did not self-report (n = 40) emotional eating completed self-report questionnaires of negative affect and negative interpretation biases, an implicit measure of cognitive bias, and a behavioral assay of emotional eating involving an ad lib test meal following a stress induction task. RESULTS: The emotional eating group endorsed elevated trait negative affect, explicit shame biases, and implicit negative biases compared to controls. In addition, state negative affect increased after the stress induction task, and the emotional eating group endorsed greater state negative affect before and after the task and consumed more food following the stress induction. Only explicit cognitive shame biases demonstrated significant indirect effects in the association between group and food consumption. Specifically, elevated explicit shame biases were positively associated with amount of food consumed for the emotional eating group. DISCUSSION: Future research should examine whether interventions that target cognitive biases related to shame reduce emotional eating. PUBLIC SIGNIFICANCE: Individuals with emotional eating consumed more food than controls following a stress induction. Explicit shame cognitive biases were positively associated with amount of food consumed for the emotional eating group. Shame cogntiive biases may be fruitful targets for reducing emotional eating.

Suicidal ideation, suicide attempts, and suicide death among Veterans and service members: A comprehensive meta-analysis of risk factors.

Suicide is the tenth leading cause of death in America. Particularly at risk, Veterans are 1.5 times more likely to die by suicide than non-Veterans, and the suicide rate among service members has risen over the last decade. In the present study, we (1) assessed risk factors for suicidal ideation, suicide attempts, and suicide death within and between Veterans and service members, (2) identified the most commonly studied and (3) the strongest risk factors for suicide-related outcomes among Veterans and service members, and (4) compared overall and risk factor-specific meta-analytic prediction of suicide-related outcomes in Veterans and service members, as determined in the present meta-analysis, to that of the general population. Authors harvested longitudinal effects predicting suicidal ideation, suicide attempts, or suicide deaths in Veterans or service members until May 1, 2020. Traumatic Brain Injury, substance/alcohol use disorders, prior Self-Injurious Thoughts and Behavior, PTSD, and depressive symptoms were among the most commonly studied risk factors. Anger/aggression was particularly strong risk factors, providing a source for future study and intervention efforts. When combined, risk factors conferred similar risk for suicide attempts and suicide death among Veterans, service members, and the general population. However, when analyzing p-values, factors conferred significantly more risk of suicidal ideation among Veterans and service members as compared to the general population. That is, p-values for risk factors were lower in an absolute sense but not necessarily to a statistically significant degree.

Does Chair of Surgery Gender Influence Divisional or Residency Program Director Gender Diversity?

BACKGROUND: Workplace diversity is beneficial and results in new ideas and improved performance. Within surgery leadership, the gender gap is improving, but still present. Given the increasing number of women surgery department chairs, we aimed to examine the association of surgery chair gender with division and residency program director gender. We hypothesized that surgery departments with female leadership would have an increase in gender diversity compared to departments led by male chairs. MATERIALS AND METHODS: A list of all surgery departments were compiled from the Society of Surgical Chairs website. Gender of department chair, division director and residency program director were examined and compared. Chair position term length was determined based on online public announcements, publicly available curriculum vitae, and institutional profile biographies. RESULTS: Of 178 department chairs included, 10.7% were female, and 89.3% were male. There was no difference in female residency program director leadership between female versus male led programs (42.1 versus 26.1%, P= 0.147). Of the programs with female department chairs, only 29.4% had any female division directors compared to 54.6% led by male chairs (P= 0.055). When examining departments with ≥5 division directors, there was no difference in the average number of female division directors within departments led by female versus male chairs. There was a significant difference in length of surgery chairship, with female chairs holding the position for fewer years than male chairs (median time 5.3 (IQR = 3.4-5.8) versus 7.0 (IQR=4.3-12.3) years, P= 0.032). CONCLUSIONS: Female department chair leadership was not associated with increased diversity in divisional leadership compared to departments of surgery led by males.

Gaining "The Quarantine 15:" Perceived versus observed weight changes in college students in the wake of COVID-19.

OBJECTIVE: Amidst restrictions to reduce the spread of COVID-19, jokes have surfaced regarding weight gain during the pandemic. The current study documents perceived changes since COVID-19 and compares these to observed longitudinal changes in reported weight, BMI, and how college students described their weight from January to April 2020. METHOD: Undergraduates (N = 90; 88% female) completed on-line assessments before and after students were required to leave campus due to COVID-19. Time 1 and Time 2 surveys collected demographic information, height, weight, and a Likert-scale rating to describe perceived weight, ranging from 1 = very underweight to 5 = very overweight (weight description). Time 2 surveys added questions for perceived changes since COVID-19 in body weight, eating, physical activity, various forms of screen time, and concerns about weight, shape, and eating. RESULTS: Time 2 surveys indicated perceived increases in body weight, eating, and screen time, and decreases in physical activity along with increased concerns about weight, shape and eating since COVID-19. Longitudinal data indicated no significant change in weight, body mass index (BMI), or BMI category, but how participants described their weight changed significantly from January to April 2020. Compared to longitudinal changes in BMI category, students' weight description was significantly more likely to fall into a higher category from Time 1 to Time 2. DISCUSSION: Shifts in how body weight is experienced in the wake of COVID-19 that do not align with observed changes in reported weight may reflect cognitive distortions that could increase risk for disordered eating in some individuals.

Examining the association between body trust and body mass index with quantile regression.

PURPOSE: Schachter's externality theory posits a connection between the inability to eat according to internal cues and higher body mass index (BMI); however, related work has not investigated associations between body trust and the wide range of BMIs found in general samples. This study examined the association between body trust and BMI across levels of BMI to determine whether this relationship differed as a function of BMI level. METHODS: Participants were 534 adults (55.4% female), mean age 36 years, BMIs 15.13-67.90 (M = 27.89, SD = 7.25), recruited via MTurk. They completed self-report assessments of body trust, height, and weight. Quantile regression was utilized to estimate effects of body trust on BMI at five equidistant quantiles of BMI. RESULTS: Overall linear regression analyses indicated that body trust was significantly negatively associated with BMI. Quantile regression revealed a significant negative relationship at each quantile of BMI, and Wald tests indicated the association was significantly stronger at the 0.7 and 0.9 quantiles than at the 0.1, 0.3, and 0.5 quantiles, which did not differ. CONCLUSIONS: Quantile regression identified a stronger relationship between body trust and BMI at 0.7 and 0.9 quantiles than at 0.1, 0.3, and 0.5 quantiles of BMI. Results align with the externality hypothesis, which suggests those at higher weights experience difficulty using internal cues to guide eating. A weaker-than-expected association between body trust and low BMI may be due to restricted range (few low-BMI participants). Replication in eating disorder samples is merited. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Reducing anticipated non-suicidal self-injury by improving body esteem in individuals with weight suppression: A proof of concept study.

OBJECTIVE: Research suggests that weight suppression (WS) is linked to non-suicidal self-injury (NSSI) and that drive for thinness and depression may explain this association. We conducted a proof-of-concept study using a randomized control trial design to determine if improving body esteem and reducing depressive symptoms reduced NSSI in individuals with WS. METHOD: Weight suppressed participants (N = 60) who engaged in NSSI were recruited from the community and randomly assigned to an on-line intervention or control condition. The on-line intervention was adapted from a cognitive-dissonance intervention originally designed to reduce thin-ideal internalization in females to an intervention to reduce internalization of unhealthy body ideals in both genders. Participants' weight/shape concerns, depressive symptoms, and NSSI were assessed at pre- and post-intervention, or at baseline and 2-week follow-up for controls. RESULTS: Compared to controls, participants in the treatment condition reported greater decreases in likelihood of future NSSI [Cohen's d (95% CI) = -0.38 (-0.90-0.15)], weight/shape concerns [-1.19 (-1.75 to -0.62)], depressive symptoms [-1.00 (-1.56 to -0.45)], and significant improvements in appearance [1.27 (0.70-1.84)] and weight esteem [1.38 (0.80-1.96)]. DISCUSSION: Future work could test this intervention in a larger trial with an active alternative treatment condition.

Examining associations among sensitivity to punishment and reward, shame, and eating pathology through tests of mediation.

This study investigated associations between sensitivity to punishment and reward, shame, and eating pathology by testing alternative mediation models in which shame mediated associations between temperament and eating pathology or eating pathology mediated associations between temperament and shame. Participants were 96 female undergraduate students who completed questionnaires. Results indicated shame fully mediated the relationship between sensitivity to punishment and eating pathology. Further, eating pathology did not mediate the association between sensitivity to punishment and shame. In contrast, for sensitivity to reward, shame fully mediated the relationship between sensitivity to reward and eating pathology, and eating pathology fully mediated the relationship between sensitivity to reward and shame. If associations are supported by longitudinal research, results suggest that it may be valuable to develop prevention approaches targeting shame to reduce risk for the development of eating pathology for those who are high in sensitivity to punishment. For those higher in sensitivity to reward, interventions targeting shame may reduce risk for eating pathology and those targeting eating pathology may reduce shame.

"Not just right" experiences account for unique variance in eating pathology.

"Not just right" experiences (NJREs) are uncomfortable sensations of incompleteness linked to obsessive-compulsive disorder; however, NJREs may be transdiagnostic and play a role in eating pathology. The current study examined relations between NJREs and eating pathology in undergraduate students. Participants (n = 248) completed self-report and behavioral assessments. Controlling for obsessive-compulsive symptoms, negative affect, and perfectionism, NJRE frequency was associated with greater drive for thinness, body dissatisfaction, and bulimic symptoms. Discomfort in response to a visual in vivo NJRE task was positively associated with drive for thinness and body dissatisfaction. The present study provides initial evidence for NJREs in eating pathology. Theoretical implications are discussed.

Examination of parental dieting and comments as risk factors for increased drive for thinness in men and women at 20-year follow-up.

OBJECTIVE: Popular beliefs suggest that parents influence children's eating disorder risk through modeling pathological behaviors and attitudes, and this history may contribute to disordered eating in adulthood. However, the empirical basis for this popular thinking is limited by a reliance on cross-sectional designs that do not distinguish between maternal and paternal influences and use primarily child and adolescent samples. To address these limitations, the present study examined the impact of maternal and paternal dieting and comments about weight and eating, as reported by late adolescents, on the eating pathology of those late adolescents at 20-year follow-up. METHOD: Data were drawn from a longitudinal epidemiological study of health and eating patterns in a cohort of randomly sampled college students established in 1992 (N = 799; mean age: 19.87 [±1.64] years; 70.8% women) and followed 20 years later in 2012 (N = 539). RESULTS: At baseline, there were no gender differences in reported rates of maternal or paternal dieting. Both men and women reported higher levels of maternal versus paternal dieting. Further, women endorsed higher levels of maternal and paternal comments on their own weight and eating. A multivariable model in women supported that maternal dieting and paternal comments significantly predicted drive for thinness at follow-up. No parental variables predicted drive for thinness in men at follow-up. DISCUSSION: While our study supports parental influence on children's eating attitudes, it suggests a need to consider gender and mode of influence. Prevention efforts focused on challenging cultural standards of appearance may benefit from incorporation of parents. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:490-497).

Defining "significant weight loss" in atypical anorexia nervosa.

OBJECTIVE: Atypical anorexia nervosa (AAN) is defined by the symptoms of anorexia nervosa in the presence of "significant weight loss" in individuals who are not underweight. Description of current weight in AAN has been limited, significant weight loss has not been defined, and the distinction between having AAN versus having weight suppression has not been examined. METHOD: Secondary analyses were conducted with data from an epidemiological study of women (n = 1,640) and men (n = 794). Three definitions of significant weight loss (5, 10, and 15%) for AAN were tested in comparisons with controls and a DSM-5 eating disorder group (DSM-5 ED) on measures of eating pathology and clinical significance using ANCOVA and logistic regression, controlling for age and body mass index. Secondary analyses compared AAN to a weight suppressed group (WS-only) and a cognitive concerns group (COG-only). RESULTS: Across weight loss thresholds, ≥25% of adults with AAN were currently overweight/obese. At the 5% and 10% definitions, AAN was associated with elevated eating pathology and distress relative to controls, WS-only, and COG-only in women and men. Women with AAN endorsed less eating pathology and distress than DSM-5 ED at some weight loss definitions, whereas men with AAN did not differ from DSM-5 ED in eating pathology or distress. DISCUSSION: Results support that even a 5% weight loss, combined with cognitive concerns, may produce a group with a clinically significant eating disorder. AAN was observed in both healthy weight and overweight/obese adults, highlighting the importance of screening for restrictive eating disorders at all weights.

Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study.

OBJECTIVE: Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases. DESIGN: A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared between patients with and without a prior BO diagnosis. Overall survival, using Cox models, was compared between patients with and without a prior BO diagnosis. The effect of adjusting the survival differences for histological grade and estimates of lead and length time bias was assessed. RESULTS: There were 716 OAC cases, 52 (7.3%) of whom had a prior BO diagnosis. Patients with a prior BO diagnosis had significantly lower tumour stage (44.2% vs. 11.1% had stage 1 or 2 disease; p<0.001), a higher rate of surgical resection (50.0% vs. 25.5%; p<0.001) and had a higher proportion of low/intermediate grade tumours (46.2% vs. 26.5%; p=0.011). A prior BO diagnosis was associated with significantly better survival (HR for death 0.39; 95% CI 0.27 to 0.58), which was minimally influenced by adjustment for age, sex and tumour grade (adjusted HR 0.44; 95% CI 0.30 to 0.64). Correction for lead time bias attenuated but did not abolish the survival benefit (HR 0.65; 95% CI 0.45 to 0.95) and further adjustment for length time bias had little effect. CONCLUSIONS: The proportion of OAC patients with a prior diagnosis of BO is low; however, prior identification of BO is associated with an improvement in survival in OAC patients.

Application of the Rosner-Wei risk-prediction model to estimate sexual orientation patterns in colon cancer risk in a prospective cohort of US women.

PURPOSE: We examined whether lesbian and bisexual women may be at greater risk of colon cancer (CC) than heterosexual women. METHODS: Working with a large cohort of US women ages 25-64 years, we analyzed 20 years of prospective data to estimate CC incidence, based on known risk factors by applying the Rosner-Wei CC risk-prediction model. Comparing to heterosexual women, we calculated for lesbian and bisexual women the predicted 1-year incidence rate (IR) per 100,000 person-years and estimated incidence rate ratios (IRR) and 95 % confidence intervals (CI), based on each woman's comprehensive risk factor profile. RESULTS: Analyses included 1,373,817 person-years of data from 66,257 women. For each sexual orientation group, mean predicted 1-year CC IR per 100,000 person-years was slightly over 12 cases for each of the sexual orientation groups. After controlling for confounders in fully adjusted models and compared with heterosexuals, no significant differences in IRR were observed for lesbians (IRR 1.01; 95 % CI 0.99, 1.04) or bisexuals (IRR 1.01; 95 % CI 0.98, 1.04). CONCLUSIONS: CC risk is similar across all sexual orientation subgroups, with all groups comparably affected. Health professionals must ensure that prevention, screening, and treatment programs are adequately reaching each of these communities.