Risk Of Early Onset Research Articles

Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries

BackgroundFamily history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control.MethodsIn a cross-sectional analysis of the prospective Joint Asia Diabetes Evaluation Register including patients from 427 clinics in 11 Asian countries/regions in 2007–2021, we defined positive FamH as affected parents/siblings and self-management as (1) healthy lifestyles (balanced diet, non-use of alcohol and tobacco, regular physical activity) and (2) regular self-monitoring of blood glucose (SMBG).ResultsAmong 86,931 patients with type 2 diabetes (mean±SD age: 56.6±11.6 years; age at diagnosis of diabetes: 49.8±10.5 years), the prevalence of FamH ranged from 39.1% to 85.3% in different areas with FamH affecting mother being most common (32.5%). The FamH group (n=51,705; 59.5%) was diagnosed 4.6 years earlier than the non-FamH group [mean (95% CI): 47.9 (47.8–48.0) vs. 52.5 (52.4–52.6), logrank p<0.001]. In the FamH group, patients with both parents affected had the earliest age at diagnosis [44.6 (44.5–44.8)], followed by affected single parent [47.7 (47.6–47.8)] and affected siblings only [51.5 (51.3–51.7), logrank p<0.001]. The FamH plus ≥2 healthy lifestyle group had similar age at diagnosis [48.2 (48.1–48.3)] as the non-FamH plus <2 healthy lifestyle group [50.1 (49.8–50.5)]. The FamH group with affected parents had higher odds of hyperglycemia, hypertension, and dyslipidemia than the FamH group with affected siblings, with the lowest odds in the non-FamH group. Self-management (healthy lifestyles plus SMBG) was associated with higher odds of attaining HbA1c<7%, blood pressure<130/80mmHg, and LDL-C<2.6 mmol/L especially in the FamH group (FamH×self-management, pinteraction=0.050–0.001).ConclusionsIn Asia, FamH was common and associated with young age of diagnosis which might be delayed by healthy lifestyle while self management was associated with better control of cardiometabolic risk factors especially in those with FamH.

Clinical Relevance of Sinus Rhythm Mapping to Quantify Electropathology Related to Atrial Fibrillation.

Progression of AF is accompanied by structural and electrical remodelling, resulting in complex electrical conduction disorders. This is defined as electropathology and it increases with the progression of AF. The severity of electropathology, thus, defines the stage of AF and is a major determinant of effectiveness of AF therapy. As specific features of AF-related electropathology are still unknown, it is essential to first quantify the electrophysiological properties of atrial tissue and then to examine the inter- and intra-individual variation during normal sinus rhythm. Comparison of these parameters between patients with and without a history of AF unravels quantified electrophysiological features that are specific to AF patients. This can help to identify patients at risk for early onset or progression of AF. This review summarises current knowledge on quantified features of atrial electrophysiological properties during sinus rhythm and discusses its relevance in identifying AF-related electropathology.

Association of early-onset breast cancer with body mass index, menarche, and menopause in Taiwan

BackgroundThe trend of women suffering from early-onset breast cancer is increasing in Taiwan. The association of early-onset breast cancer with body mass index (BMI), menarche, and menopausal status has focused interest on the field of cancer epidemiology; however, few studies have explored the interaction of these factors on early-onset risk. This study aimed to estimate the interaction effects of BMI, menarche, and menopausal status on 40-year-old early-onset breast cancer.MethodsBreast cancer patients were recruited from Kaohsiung Medical University Chung-Ho Memorial Hospital from 2013 to 2020. Multivariable logistic regression was used to estimate odds ratios (ORs) for early-onset breast cancer risk associated with menarcheal age stratified by sociodemographic factors and for the interaction between BMI and menopausal status on early-onset risk.ResultsA total of 775 participants were divided into 131 early-onset cases (≤ 40 years) and 644 late-onset cases (> 40 years). Compared to the age of 13 years at menarche, the age ≤ 11 years was significantly positively associated (OR: 2.62, 95% CI: 1.38–4.97) and ≥ 16 years was negatively associated (OR: 0.13, 95% CI: 0.03–0.53) with 40-year-old early-onset breast cancer respectively. In an adjusted model, the status of BMI < 24 and premenopause had 1.76- and 4.59-fold risk of early-onset breast cancer respectively. Especially in BMI < 24 status, premenopause also had a 6.47-fold early-onset risk and the early-onset risk increased by a significant amount per one year younger at menarche (aOR: 1.26, 95% CI: 1.03–1.55). There was also a positive interaction effect on an additive scale between BMI and menopausal status on early-onset breast cancer (RERIOR = 4.62, Pinteraction = 0.057). Compared to both BMI ≥ 24 and peri-/postmenopausal status, both the status of BMI < 24 and premenopause were associated with early-onset breast cancer (aOR: 7.16, 95% CI: 3.87–13.25).ConclusionsThis study suggests that the status of BMI < 24 and premenopause were associated with an increased risk of early-onset breast cancer and there was a positive interaction on an additive scale. Understanding how obesity and menopausal status affect early-onset breast cancer is important for drafting preventive measures for early-onset breast cancer in Taiwan.

Evaluating longitudinal toxicity of cetuximab in patients with metastatic colorectal cancer (mCRC): A pooled analysis from 1,302 patients in the ARCAD database.

3610 Background: Chronic lower grade adverse events (AE) can negatively affect a patient’s quality of life but it is difficult to capture using a traditional toxicity reporting approach. A novel AE reporting method was recently developed to describe, summarize, and present longitudinal AE profiles(Lopes et al, 2021). We leveraged this method to describe and compare the AE profiles of doublet chemotherapy (DC) + Cetuximab and DC alone in mCRC patients. Methods: This AE reporting method utilizes two additional AE metrics to complement the maximum (max) toxicity grade usually reported in clinical trials. Onset time indicates the time period in which max grade for an AE occurred for the first time, defined here as “early” (i.e. within first 42 days) and “late” (i.e. after the 42nd day). AE Load (AEL) indicates the overall severity of an AE in the entire treatment. AEL varies from 0 to 1. Higher AEL indicates a worse overall severity of that AE over time. AEL is the key metric for describing chronic AE. We included patients receiving DC + cetuximab (n = 738) and DC alone (n = 564 [ref group]) from two randomized first-line trials in the ARCAD database. Diarrhea, rash, hand-foot syndrome (HFS), fatigue, anorexia, and mucositis were examined and adjusted for backbone (FOLFOX vs. FOLFIRI), ECOG PS, sex, site location, dose reduction, and treatment length. Results: For rash, DC + cetuximab had a higher risk of G3+ (21% vs. 0.5%; odds ratio {OR} [95% confidence interval {CI}] = 50 [16,157], p &lt; 0.001), increased overall severity over the entire treatment (AEL = 0.257 vs. 0.069; Adjusted difference in means–Mdiff [95% CI] = 0.22 [0.21,0.23], p &lt; 0.001), and increased risk of early onset (67% vs. 33%; OR [95% CI] = 4.3 [2.7,6.7], p &lt; 0.001). DC + cetuximab also had higher AEL for rash across max grades (p &lt; 0.001 within G1, G2, and G3+). For HFS, DC + cetuximab had a higher risk of G3+ (OR [95% CI] = 6.0 [2.5,14], p &lt; 0.001), increased overall severity (AEL = 0.139 vs. 0.087; Mdiff [95% CI] = 0.03 [0.03,0.04], p &lt; 0.001), and slightly earlier onset (12.4 vs. 13.9 weeks; Mdiff, weeks [95% CI] = -4.9 [-0.80,-9.0], p = 0.021). Within each max grade, DC + cetuximab did not have higher AEL of HFS. No associations were found for diarrhea, fatigue, anorexia, or mucositis. Conclusions: The addition of cetuximab is associated with higher grade, more persistent, and more immediate rash. The higher severity in HFS with the addition of cetuximab appears to be related to higher grade but not chronic HFS. This method may be useful to describe different strategies, e.g. intermittent cetuximab. It provided a comprehensive view of acute and chronic toxicity profiles supporting its potential interest as new metrics in clinical trials. Lopes GS, Tournigand C, Olswold CL, et al. Adverse event load, onset, and maximum grade: A novel method of reporting adverse events in cancer clinical trials. Clinical Trials. 2021;18(1):51-60

DHCR7 rs12785878 T&gt;C Polymorphism Is Associated With an Increased Risk of Early Onset of Alzheimer's Disease in Chinese Population

Background: Vitamin D insufficiency has been considered a risk factor for Alzheimer's disease (AD) in several studies. Recently, four single-nucleotide polymorphisms (SNPs) to be genome-wide significant for 25-hydroxyvitamin D [25(OH)D] were identified to have an association with the risk of AD. These include GC rs2282679 A>C, CYP2R1 rs10741657 T>C, DHCR7 rs12785878 T>C, and CYP24A1 rs6013897 T>A. However, the association between these polymorphisms and AD susceptibility in the Chinese population remains unclear.Methods: A case-control cohort study was conducted in 676 AD patients (mean age at onset was 69.52 ± 10.90 years, male: 39.2%) and 551 healthy controls (mean age was 67.73 ± 6.02 years, male: 44.8%). Genotyping was determined by PCR and SNaPshot sequencing. To determine whether the four SNPs account for risks in AD in Chinese population, multivariate logistic regression models were performed. Stratified analysis was performed based on gender and age of onset of AD, separately. Statistical significance was set at 0.0125 (0.05/4) based on Bonferroni correction.Findings: DHCR7 rs12785878 T>C was found to be significantly associated with an increased risk of early-onset Alzheimer's disease (EOAD) (n = 300, risk allele C, adjusted OR = 1.542, adjusted 95% CI = 1.176–2.023, p = 0.002). There was no statistical significance of the other three SNPs between the two groups.Interpretation: Our results suggested that DHCR7 rs12785878 T>C might be associated with an increased risk of EOAD in the Chinese population, while other polymorphisms related to vitamin D insufficiency might not be. However, due to the limited data in this study, replication studies in a larger sample are required.

Abstract 2300: Deleterious germline mutations in the BRCA1 gene are associated with increased risk for cancers of the female reproductive system other than breast and ovarian as well as other cancers

Abstract Introduction: Mutations within the BRCA1 gene have been linked to up to an 80% lifetime risk of breast cancer as well as increased risk for ovarian, pancreatic and melanoma cancers. In this study we examined families with known germline mutations in BRCA1 after long-term follow-up to determine whether carriers experience higher rates of other cancers that have not yet been associated with germline mutations in the BRCA1 gene. Methods: We studied 127 Hereditary Breast and Ovarian Cancer (HBOC) syndrome families (N = 23,078 individuals who have been followed at Creighton University) in which a causal mutation in the BRCA1 gene was identified. We performed survival analysis and a mixed effects cox regression with age at follow-up or cancer event as our time variable and presence or absence of BRCA1-related or other cancers (separate analyses) as our indicator variable. Results: The survival curves showed a significant age effect with carriers having a younger age at cancer onset for BRCA1-related (as expected) as well as other cancers than that of non-carriers. The cox regression models were also highly significant (P = 1.77E-37 and P = 1.04E-07 for the BRCA1-related and other cancers, respectively). Of the cancers with enough samples to do stratified analyses, uterine, skin, lymphoma and colon cancers occurred at higher rates and at earlier ages in mutation carriers. Conclusions: These analyses support the hypothesis that the BRCA1 mutations carriers of HBOC syndrome have increased risk for early onset of several additional cancer types, especially cancers that arise in estrogen-influenced tissues. Citation Format: Candace Middlebrooks, Kenzhane Pantin, Mark Stacey, Carrie Snyder, Murray J. Casey, Trudy Shaw, Joan E. Bailey-Wilson, Henry T. Lynch. Deleterious germline mutations in the BRCA1 gene are associated with increased risk for cancers of the female reproductive system other than breast and ovarian as well as other cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2300.

Improving Antibiotic Stewardship Among Asymptomatic Newborns Born at or Greater than 36 Weeks Using the Neonatal Early Onset Risk Calculator

Background: The potential deleterious effects of antibiotic use in newborns have made antibiotic stewardship for asymptomatic newborns a priority. In January 2016, we instituted a newborn sepsis protocol based largely on the 2012 AAP guidelines. By December 2016, we determined that our antibiotic use had not decreased, and resolved to conduct a PDSA cycle to decrease antibiotic usage. Beginning in June of 2017, we adopted a clinical algorithm which integrated the use of the Neonatal Early Onset Sepsis (EOS) Risk Calculator at birth. We were able to decrease the use …

High fetal hemoglobin\xa0level is associated with increased risk of cerebral vasculopathy in children with sickle cell disease in Mayotte

BackgroundUnderstanding the genetics underlying the heritable subphenotypes of sickle cell anemia, specific to each population, would be prognostically useful and could inform personalized therapeutics.The objective of this study was to describe the genetic modulators of sickle cell disease in a cohort of pediatric patients followed up in Mayotte.MethodsThis retrospective cohort study analyzed clinical and biological data, collected between January1st2007 and December 31st2017, in children younger than 18 years.ResultsWe included 185 children with 72% SS, 16% Sβ0-thalassemia and 12% Sβ + thalassemia. The average age was 9.5 years; 10% of patients were lost to follow up. The Bantu haplotype was associated with an increase in hospitalizations and transfusions. The alpha-thalassemic mutation was associated with a decrease of hemolysis biological parameters (anemia, reticulocytes), and a decrease of cerebral vasculopathy. The Single Nucleotide Polymorphisms BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were associated with the group of children with HbF > 10%. Patients with HbF > 10% presented a significant risk of early onset of cerebral vasculopathy.ConclusionsThe most remarkable result of our study was the association of SNPs with clinically relevant phenotypic groups. BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were correlated with HbF > 10%, a group that has a higher risk of cerebral vasculopathy and should be oriented towards the hemolytic sub-phenotype.

Abstract 622: Reproductive factors and breast cancer risk to women in Ghana, West Africa

Abstract Background: Women of African ancestry have a higher proportion of early onset and estrogen receptor (ER) negative cancers compared to women of European descent. Differences in risk associations by age at onset and ER status for reproductive factors, particularly parity and breastfeeding, have been proposed as possible contributors to this racial disparity. We therefore investigated these relations in the Ghana Breast Health Study. Methods: The study population included 1,126 women diagnosed with invasive breast cancer and 2,106 population controls aged 18-74 years at recruitment (2013-2015) in three hospitals in Accra and Kumasi, Ghana. Factors evaluated included age at menarche, number of livebirths, age at first livebirth, and median months breastfeeding per pregnancy. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models overall and stratified by age. Associations by ER status were estimated using polytomous logistic regression models. Results: We observed associations with parity and extended breastfeeding duration per pregnancy that were modified by age at onset (&amp;lt;50 vs. &amp;gt;50 years, P-het &amp;lt;0.02 and 0.01, respectively). For women &amp;lt;50 years, the OR was 0.70 (95% CI 0.42-1.18) for those with &amp;gt;5 v. 0 livebirths, but there was no association with breastfeeding months per pregnancy (&amp;gt;18 vs &amp;lt;12 months: OR (95%CI) = 1.04 (0.75-1.44). For women &amp;gt;50 years, both higher number of livebirths and longer durations of breastfeeding months per pregnancy were associated with lower breast cancer risk: OR (95%CI) = 0.40 (0.20-0.83) for &amp;gt;5 vs 0 livebirths and 0.71 (0.51-0.98) for &amp;gt;18 vs &amp;lt;12 breastfeeding months per pregnancy. Data were consistent with a higher risk of early onset (&amp;lt;50 years) ER-negative breast cancer for parous compared to nulliparous women (1.63 (0.82-3.25), that was attenuated by extended breastfeeding (0.72 (0.45-1.14) for &amp;gt;18 vs &amp;lt;12 breastfeeding months per pregnancy). Conclusion: In this population of women in West Africa, increased number of live births and breastfeeding months per pregnancy were strong protective factors for later onset breast cancer. Among younger women, these trends were modified by ER status, with opposite associations for parity in ER+ vs. ER- tumors and an inverse association with breastfeeding in the ER- tumors that was not seen in the ER+ tumors. Our data support previous reports in African-American women of differential associations of parity and breastfeeding by ER status and age at onset. Further attention should focus on how reproductive factors contribute to observed racial heterogeneity in breast cancer. Citation Format: Jonine D. Figueroa, Brittny Davis Lynn, Lawrence Edusei, Nicolas Titiloye, Ernest Adjei, Joe Nat Clegg-Lamptey, Beatrice Wiafe-Addai, Baffour Awuah, Montserrat Garcia-Closas, Louise A. Brinton. Reproductive factors and breast cancer risk to women in Ghana, West Africa [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 622.

Abstract 2408: Analysis of the CDKN2A gene in FAMMM Syndrome families reveals early age of onset for additional syndromic cancers

Abstract Familial atypical multiple mole melanoma (FAMMM) syndrome is a familial cancer syndrome that results from mutations in several genes including the CDKN2A gene. The syndrome is currently comprised of dysplastic nevi as well as melanoma and pancreatic cancer and is also associated with lung and breast cancer. The aforementioned set of cancers is referred to as “concordant” cancers. As families with known CDKN2A mutations have been studied longitudinally, clinicians observed an abundance of other cancers or “discordant cancers.” However, it was unknown whether these cancers were related to the syndrome. We sought to determine whether these discordant cancers also occur at higher frequencies and at earlier age of onset in carriers than non-carriers. We studied 10 FAMMM syndrome families (N = 1085 individuals) in which a causal mutation in the CDKN2A gene was identified. We performed survival analysis as well as a mixed effects cox regression with age at follow-up or cancer event as our time variable and presence or absence of a concordant or discordant cancer as our censoring variable. The survival curves showed a significant age effect with carriers having a younger age at cancer onset for concordant (as expected) as well as discordant cancers than that of non-carriers. The cox regression models were also highly significant (P = 1.24E-27 and P = 5.00E-13 for the concordant and discordant cancers, respectively). We then performed a sensitivity analysis where we removed non-melanoma skin cancers from the discordant cancer group (coding individuals with these cancers as unaffected with a discordant cancer) to ensure that these cancers were not driving the effect seen. The result was still highly significant. Furthermore, we observed a visible pattern where individuals with multiple primaries presented with melanoma first followed by various combinations of other cancer primaries later on. It is likely that melanoma is the initial cancer to occur in a series of cancer occurrences as the result of a CDKN2A mutation tumor-driving effect paired with almost unavoidable UV light exposure. The additional cancer primaries that occurred in these individuals are likely the result of additional germline or acquired somatic mutations and/or environmental exposures that have latent effects. These analyses support the hypothesis that carriers of mutations in CDKN2A in FAMMM syndrome have increased risk for early onset of several additional cancer types that are not currently screened in these families. This suggests that early screening for these cancers would be beneficial to carriers. The implications from this study could impact clinical guidelines in cancer screening of CDKN2A mutation families as well as policies formulated in regards to insurance coverage. This in turn may reduce the morbidity of these additional cancers (due to earlier investigation and diagnosis and targeting of prevention strategies). Citation Format: Candace D. Middlebrooks. Analysis of the CDKN2A gene in FAMMM Syndrome families reveals early age of onset for additional syndromic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2408.

The prevalence of ADH1B and OPRM1 alleles predisposing for alcohol consumption are increased in the Hungarian psoriasis population

Alcohol intake affects in great the symptoms and life of psoriasis patients, although the association of SNPs related to increased alcohol consumption with psoriasis has not been elucidated. Therefore, to investigate the association of psoriasis with established alcohol consumption and dependence-related gene variants we conducted a population-based case–control study including 3743 subjects (776 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 23 SNPs at ADH1B, ADH1C, ALDH1A1, ALDH2, SLC6A3, DDC, GABRA2, GABRG1, HTR1B, MAOA, TPH2, CHRM2, GRIN2A, POMC, OPRM1, OPRK1 and BDNF were determined and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Analysis revealed association between C allele of the rs1229984 polymorphism (ADH1B gene) and psoriasis risk (ORadditive = 1.58, 95% CI 1.23–2.03, p < 0.001, ORrecessive = 1.58, 95% CI 1.22–2.04, p = 0.001). Furthermore, the G allele of rs1799971 polymorphism (OPRM1 gene) increased the risk of familial aggregation (ORadditive = 1.99, 95% CI 1.36–2.91, p < 0.001 ORdominant = 2.01, 95% CI 1.35–3.01, p < 0.001). In subgroups of psoriatic patients with history of early onset and familial aggregation effect allele ‘C’ of rs1229984 showed association in the additive and recessive models (ORadditive = 2.41, 95% CI 1.26–4.61, p < 0.01, ORrecessive = 2.42, 95% CI 1.26–4.68, p < 0.01). While effect allele ‘G’ of rs1799971 (OPRM1) also associated with increased risk of early onset and familial aggregation of psoriasis in the additive and dominant models (ORadditive = 1.75, 95% CI 1.27–2.43, p = 0.001, ORdominant = 1.82, 95% CI 1.26–2.63, p = 0.001). Our results suggest that genetically defined high-risk individuals for alcohol consumption are more common in the psoriasis population.

Impact of the use and efficacy of long lasting insecticidal net on malaria infection during the first trimester of pregnancy - a pre-conceptional cohort study in southern Benin

BackgroundMalaria in pregnancy is prevalent in Sub-Saharan Africa. The first trimester of pregnancy is a critical period and the best preventive measure is Long Lasting Insecticidal Nets (LLIN). Unfortunately, few studies have been conducted which focuses on the usage and efficacy of LLIN on malaria prevention during the first trimester.MethodsWe assessed the use and effectiveness of LLIN in early pregnancy in Benin and its impact on malaria infection risk. We followed-up a cohort of 240 pregnant women from pre-conception to the end of the first trimester of pregnancy in Southern Benin. Parasitological, maternal and LLIN data were actively collected before, at the beginning and end of the first trimester of pregnancy. A Cox regression model was used to determine the relationship between the time to onset of the first malaria infection and the use, physical integrity, and bio-efficacy of the LLIN, adjusted for relevant covariables.ResultsThe good use, good physical integrity and biological efficacy of LLIN were associated with a decreased risk of occurrence of the first malaria infection in early pregnancy (HRa = 0.38; (0.18–0.80); p < 0.001; HRa = 0.59; (0.29–1.19); p < 0.07; HRa = 0.97; (0.94–1.00); p < 0.04 respectively), after adjustment for other covariates. Primi/secundigravidity and malaria infection before pregnancy were associated with a risk of earlier onset of malaria infection.ConclusionThe classically used LLIN’s indicators of possession and use may not be sufficient to characterize the true protection of pregnant women in the first trimester of pregnancy. Indicators of physical integrity and bio-efficacy should be integrated with those indicators in evaluation studies.

Alcohol consumption and early-onset risk of colorectal cancer in Japanese patients with Lynch syndrome: a cross-sectional study conducted by the Japanese Society for Cancer of the Colon and Rectum.

We conducted this study to establish whether drinking alcohol alters the risk of early-onset colorectal cancer (CRC) in Japanese patients with Lynch syndrome (LS). The subjects were 66 LS patients with pathogenic mutation of mismatch repair genes (MLH1, MSH2, and MSH6) from the nationwide Japanese retrospective multicenter study. Cox proportional hazards modeling was used to investigate the factors correlating with early-onset CRC diagnosis, using clinical data such as gender, tobacco use, alcohol consumption, body mass index, gene mutation (MLH1, MSH2 vs MSH6), and family cancer history. Alcohol was significantly correlated with an increased risk of early-onset CRC [HR 2.44, 95% CI 1.13-5.16 (p = 0.02)], but tobacco use was not [HR 0.8, 95%CI 0.38-1.62 (p = 0.53)]. These findings suggest that alcohol consumption is correlated with an earlier onset of CRC in Japanese patients with LS.

Young Women's Perceptions Regarding Communication with Healthcare Providers About Breast Cancer, Risk, and Prevention.

Women younger than 45 years old have lower rates of breast cancer, but higher risk of recurrence and mortality after a cancer diagnosis. African American women are at risk for early onset and increased mortality; Ashkenazi Jewish women are at risk for genetic mutations leading to breast and ovarian cancer. Although younger women are encouraged to talk to doctors about their family history, little is known about these discussions. In 2015, 167 women aged 18-44 years participated in 20 focus groups segmented by geographic location, age, race/ethnicity, and family history of breast and ovarian cancer. Transcript data were analyzed using NVivo 10 software. Although the majority of women talked to their doctor about breast and ovarian cancer, these conversations were brief and unsatisfying due to a lack of detail. Topics included family history, breast cancer screening, and breast self-examination. Some women with and without family history reported that healthcare providers offered screening and early detection advice based on their inquiries. However, few women took action or changed lifestyle behaviors with the intent to reduce risk as a result of the conversations. Conversations with young women revealed missed opportunities to: enhance patient-provider communication and increase knowledge about breast cancer screening and surveillance for higher risk patients. Physicians, allied health professionals, and the public health community can better assist women in getting accurate and timely information about breast and ovarian cancer, understanding their family history to determine risk, and increasing healthy behaviors.

The Early Onset Risk Calculator to evaluate early onset sepsis in infants born ?35 weeks’ gestation

The Early Onset Risk Calculator to evaluate early onset sepsis in infants born ?35 weeks’ gestation

The Development of Severe and Chronic Violence Among Youth: The Role of Psychopathic Traits and Reward Processing.

Psychopathic traits are a manifestation of a personality pathology that comprises a core affective-interpersonal dysfunction (callous-unemotional traits) and an impulsive-antisocial behavioral component. Of particular importance, psychopathic traits are associated with the perpetration of some of the most severe acts of violence, and they appear to indicate a subset of youth at risk for earlier onset, greater frequency, and persistence of violent offending. Although these youth represent a minority of the population, they commit a significant proportion of the violence in the general community. In our review, we highlight evidence of a unique neurobiological predisposition that underlies the core affective deficits and describe contemporary accounts for the developmental processes leading to the antisocial behavior associated with psychopathy. Current evidence suggests that, for this subset of youth, the structure and function of neural circuitry supporting emotion processing, reward learning, decision making, and the development of emotion related to empathy may be crucial to understanding why they are at risk for violence. In particular, a reward dominant pattern of neurobehavioral conditioning may explain how these youth progress to some of the most severe and persistent forms of violence. However, this pattern of conditioning may also be essential to the primary prevention of such deleterious behavior. We suspect that effective strategies to prevent such violence may ultimately be informed by understanding these affective and motivational mechanisms.

Three-dimensional Imaging and Computer Navigation in Planning for Hip Preservation Surgery.

Hip preservation surgery is performed to address femoroacetabular impingement, alleviate any associated pain, and reduce the risk of early onset of osteoarthritis. In the last decade, arthroscopy has become more popular in addressing femoroacetabular impingement, due to its minimally invasive approach. However, poor visualization and limited spatial awareness of the joint make arthroscopy of the hip difficult, resulting in a steep learning curve. This paper reviews the utility and benefits of 3-dimensional imaging and computer navigation and what these tools may add to the preoperative planning stages of hip preservation surgery.

A rare case of Turcot syndrome

Turcot’s syndrome is a rare genetic disorder clinically characterised by concomitant occurrence of primary brain tumour and colorectal polyposis. It is commonly seen in association with two other syndromes, namely, hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). It is characterized by an increased risk for early onset of other tumours including of endometrium, stomach, small intestine, hepatobiliary system, kidney, ureter, brain and ovary. We report the rare occurrence of Turcot syndrome in a 13-year-old girl who presented with focal seizure

96-POS

Objectives VEGF is key component in the differentiation, invasion, regulation of vascular remodeling and the survival of cytotrophoblasts. In preeclampsia expression of cytotrophoblasts is disregulated. Evidence supports the hypothesis that VEGF plays an important role in the pathogenesis of preeclampsia. In this study, we aimed to determine whether VEGF genetic polymorphisms are associated with risk of early onset of severe preeclampsia. Methods A cross-sectional study with observational analytic was conducted in 32 pregnant women with early onset severe preeclampsia and 32 normal pregnant women. After peripheral blood was obtained from all women and genomic DNA was isolated, we genotyped +405G>C polymorphisms in the 5′- untranslated region and +936C>T polymorphisms in 3′-untranslated region of the VEGF gene genotype using Allelic Specific Oligonucleotide–Polymerase Chain Reaction (ASO–PCR) methods. Results The distribution of G allele of VEGF +405 more dominant (60.9%) than C allele (39.1%) in early onset severe preeclampsia. Conversely in normal pregnant women, the frequency of C allele of +405 (53.1%) little bit higher than G allele (46.9%). The distribution of the T allele of +936 approximately was the same between early onset severe preeclampsia (35.9%) and normal pregnant women (31.3%). Overall, the genotype and allele frequency distribution of the two polymorphisms (+405 and +936) were not significantly different between women with and without the disease ( p > 0.05). Conclusions There was no evidence of an association between VEGF allele or genotype frequencies and early onset preeclampsia in our study. VEGF gene polymorphisms studied are unlikely to be major predisposing for early onset severe preeclampsia in the Indonesian population. Disclosures M. Susanna: None. E.G. Dachlan: None.

Single nucleotide polymorphisms in the mitochondrial displacement loop and age-at-onset of epithelial ovarian cancer

Objective: The accumulation of the single nucleotide polymorphisms (SNPs) in the mitochondrial displacement loop (D-loop) has been reported in many types of cancers. And the association with the risk and prognosis of cancers also has been described extensively. In the present study, we investigated the association between the age-at onset and SNPs in the D-loop of mitochondria DNA (mtDNA) using a population-based series of primary epithelial ovarian cancer (EOC) patients. Methods: The D-loop region of mtDNA samples from blood were obtained from 89 patients with primary EOC, who underwent surgery. The age-at-onset curves were calculated by Kaplan–Meier method and compared by the log-rank test. Results: The SNP sites of nucleotide 248, 524 and 16,304 alleles were identified for their association with age-at-onset by the log-rank test. The age-at-onset of patients with the minor allele 248 G was lower than that of patients with 248 A. The same was seen for the rare allele 16,304 T genotype when compared with matched allele 16,304 C at the 16,304 site. But the age-at-onset of patients with the minor allele 524 C was higher than that of patients with frequent 524 deletions. Conclusion: Genetic polymorphisms in the D-loop are the predictive markers for age-at-onset in EOC patients. Accordingly, the analysis of genetic polymorphisms may help identify EOC patient subgroups at high risk of early onset.