Unraveling the complexities of early-onset colorectal cancer: a perspective on dietary and microbial influences.

While advances in screening have resulted in declining rates of colorectal cancer (CRC) among adults ≥50 years of age since the mid-2000s, the incidence of early-onset CRC (EOCRC) has steadily increased over the last decade. This increase is not fully accounted for by hereditary factors, and the hypothesis that a sedentary lifestyle and obesity are the primary culprits is not fully supported by recent reports indicating that many affected individuals lead active lifestyles, maintain normal weight, and are otherwise healthy. Attention has shifted toward dietary patterns, notably the consumption of processed and ultra-processed foods found in Western diets, which are suspected of disrupting the gut microbiome balance that potentially leads to EOCRC. The impact of antibiotic use on the gut microbiome is also posited as a contributing factor, given its rising prevalence in medical and agricultural practices. We propose that a paradigm shift is necessary for EOCRC research, moving beyond metabolic factors to a broader exploration of dietary and microbial influences. Future research must prioritize understanding the relationship between dietary habits, particularly processed food intake, antibiotic exposure, and gut microbiome dynamics, to unravel the complex etiology of EOCRC. This will be crucial in developing comprehensive preventive strategies to address the increasing incidence of this malignancy in younger populations.

Does Community Affluence Improve Survival of Colorectal Cancer?

Introduction: Colorectal cancer is the second most common cause of cancer-related death in the U.S. Lower SES and lack of health insurance coverage are 2 known risk factors for lower colorectal cancer survival. The primary objective of this research is to evaluate the survival rates of patients diagnosed with colorectal cancer who reside in an affluent suburb and to examine factors that may impact mortality. Methods: Information was collected from the Stony Brook Cancer Center registry for all cases of colorectal cancer diagnosed between 2010 and 2020. The Distressed Community Index, a proxy for SES based on geographic location and data obtained from the U.S. Census, was paired with patient ZIP codes to evaluate the impact of prosperity on survival. Chi-square tests, Kaplan-Meier survival curves, and hazard ratios are presented. Results: Among 946 patients with colorectal cancer, more than half resided in a prosperous (Distressed Community Index ≤ 20) ZIP code. Age and sex were similar between Distressed Community Index groups; however, a significant association was found between Black race and Distressed Community Index score >20 (p<0.01). Patients who were married were more likely to live in a prosperous ZIP code (p<0.01), whereas those with Medicaid health insurance were more likely to reside in a nonprosperous community (p<0.01). More than 75% of cases were diagnosed at Stage 2 or higher, and survival rates at 1 year and 5 years were 84.6% and 59.2%, respectively. Stage at diagnosis and overall survival were not associated with Distressed Community Index status. Older age (≥70 years) (hazard ratio=2.43, 95% CI=1.18, 5.01) and late stage at diagnosis (hazard ratio= 12.24, 95% CI=6.86, 21.81) were found to be associated with increased mortality at 5 years. Conclusions: In this relatively affluent study population from a tertiary care facility registry, improved survival rates among patients with colorectal cancer were not observed compared with national averages. Advanced stage of diagnosis and older age increased mortality in persons with colorectal cancer. Because early detection remains one of the most important tools for improving survival outcomes, efforts to increase screening education and reduce barriers as well as address challenges with screening adherence would likely benefit the population at risk, irrespective of community prosperity.

A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US.

Background: Non-Small Cell Lung Cancer (NSCLC), the leading cause of cancer-related death in the United States, is the most diagnosed form of lung cancer. While lung cancer incidence has steadily declined over the last decade, disparities in incidence and mortality rates persist among African American (AA), Caucasian American (CA), and Hispanic American (HA) populations. Researchers continue to explore how genetic ancestry may influence differential outcomes in lung cancer risk and development. The purpose of this evaluation is to highlight experimental research that investigates the differential impact of genetic mutations and ancestry on NSCLC incidence. Methods: This systematic review was conducted using PubMed and Google Scholar search engines. The following key search terms were used to select articles published between 2011 and 2022: "African/European/Latin American Ancestry NSCLC"; "Racial Disparities NSCLC"; "Genetic Mutations NSCLC"; "NSCLC Biomarkers"; "African Americans/Hispanic Americans/Caucasian Americans NSCLC incidence." Systematic reviews, meta-analyses, and studies outside of the US were excluded. A total of 195 articles were initially identified and after excluding 156 which did not meet eligibility criteria, 38 were included in this investigation. Results: Studies included in this analysis focused on racial/ethnic disparities in the following common genetic mutations observed in NSCLC: KRAS, EGFR, TP53, PIK3CA, ALK Translocations, ROS-1 Rearrangements, STK11, MET, and BRAF. Results across studies varied with respect to absolute differential expression. No significant differences in frequencies of specific genetic mutational profiles were noted between racial/ethnic groups. However, for HAs, lower mutational frequencies in KRAS and STK11 genes were observed. In genetic ancestry level analyses, multiple studies suggest that African ancestry is associated with a higher frequency of EGFR mutations. Conversely, Latin ancestry is associated with TP53 mutations. At the genomic level, several novel predisposing variants associated with African ancestry and increased risk of NSCLC were discovered. Family history among all racial/ethnic groups was also considered a risk factor for NSCLC. Conclusion: Results from racially and ethnically diverse studies can elucidate driving factors that may increase susceptibility and subsequent lung cancer risk across different racial/ethnic groups. Identification of biomarkers that can be used as diagnostic, prognostic, and therapeutic tools may help improve lung cancer survival among high-risk populations.

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.

BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility. OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry. DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. RESULTS AND LIMITATIONS: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4). CONCLUSIONS: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. PATIENT SUMMARY: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.

Morphologic Severity of Atypia Is Predictive of Lung Cancer Diagnosis.

In cytologic analysis of lung nodules, specimens classified as atypia cannot be definitively diagnosed as benign or malignant. Atypia patients are typically subject to additional procedures to obtain repeat samples, thus delaying diagnosis. We evaluate morphologic categories predictive of lung cancer in atypia patients. This retrospective study stratified patients evaluated for primary lung nodules based on cytologic diagnoses. Atypia patients were further stratified based on the most severe verbiage used to describe the atypical cytology. Logistic regressions and receiver operator characteristic curves were performed. Of 129 patients with cytologic atypia, 62.8% later had cytologically or histologically confirmed lung cancer and 37.2% had benign respiratory processes. Atypia severity significantly predicted final diagnosis even while controlling for pack years and modified Herder score (p = 0.012). Pack years, atypia severity, and modified Herder score predicted final diagnosis independently and while adjusting for covariates (all p < 0.001). This model generated a significantly improved area under the curve compared to pack years, atypia severity, and modified Herder score (all p < 0.001) alone. Patients with severe atypia may benefit from repeat sampling for cytologic confirmation within one month due to high likelihood of malignancy, while those with milder atypia may be followed clinically.

Racial Disparities in Prostate Cancer Stage at Diagnosis Persist Despite Community Affluence.

Purpose: The aims of this investigation were to evaluate racial disparities in prostate cancer among men living in a relatively affluent community with access to high quality healthcare. Patients and Methods: This retrospective study included 1363 cases with prostate cancer entered into the Stony Brook Cancer Center registry between 2010 and 2020. Demographic and other factors, including the Distressed Community Index (DCI) which provides an indicator of socioeconomic status by zip code, were analyzed as predictors of later stage disease using logistic regression. Results: Approximately 60% of cases resided in a "prosperous" zip code (DCI<20) with median (range) DCI of 16.3 (1.1, 61.8). Black men were diagnosed with later stage disease at a higher rate (p=0.03) and were more likely to be diagnosed at a younger age (p<0.01) compared to White men. However, the distribution of cancer stage stratified by DCI and race did not differ among groups. Black men were 3 times more likely to have Medicaid and a history of diabetes, as well as 33% more likely to have hypertension than White men. Black race (OR=2.08, (1.26, 3.42)), older age (OR=2.56 (1.67, 3.90)) and current smoking (OR=1.61 (1.07, 2.42)) were significant contributors of later stage cancer. Conclusion: Black men residing in a relatively affluent suburb were diagnosed at younger ages, later stages, and were more likely to have additional comorbidities compared to White men. This study highlights the complexity of the environmental, societal, and biological contributors to racial disparities that warrants further investigation into the underlying causes for the excess burden on Black men.

Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach.

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana. We randomly divided samples into training and validation sets. We built PRSs using individual-level AA data by a forward stepwise logistic regression and then developed joint PRSs that combined (1) the PRSs built in the AA training dataset and (2) a 313-variant PRS previously developed in women of European ancestry. PRSs were evaluated in the AA validation set. For overall breast cancer, the odds ratio per standard deviation of the joint PRS in the validation set was 1.34 [95% confidence interval (CI): 1.27-1.42] with the area under receiver operating characteristic curve (AUC) of 0.581. Compared with women with average risk (40th-60th PRS percentile), women in the top decile of the PRS had a 1.98-fold increased risk (95% CI: 1.63-2.39). For PRSs of ER-positive and ER-negative breast cancer, the AUCs were 0.608 and 0.576, respectively. Compared with existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.

A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10-4), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10-5; stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10-4; metastatic disease: OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT SUMMARY: A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry.

Associations between age of menarche and genetic variation in women of African descent: genome-wide association study and polygenic score analysis.

INTRODUCTION: Many diseases of adulthood are associated with a woman's age at menarche. Genetic variation affects age at menarche, but it remains unclear whether in women of African ancestry the timing of menarche is regulated by genetic variants that were identified in predominantly European and East Asian populations. METHODS: We explored the genetic architecture of age at menarche in 3145 women of African ancestry who live in the USA, Barbados and Nigeria. We undertook a genome-wide association study, and evaluated the performance of previously identified variants. RESULTS: One variant was associated with age at menarche, a deletion at chromosome 2 (chr2:207216165) (p=1.14×10-8). 349 genotyped variants overlapped with these identified in populations of non-African ancestry; these replicated weakly, with 51.9% having concordant directions of effect. However, collectively, a polygenic score constructed of those previous variants was suggestively associated with age at menarche (beta=0.288 years; p=0.041). Further, this association was strong in women enrolled in the USA and Barbados (beta=0.445 years, p=0.008), but not in Nigerian women (beta=0.052 years; p=0.83). DISCUSSION: This study suggests that in women of African ancestry the genetic drivers of age at menarche may differ from those identified in populations of non-African ancestry, and that these differences are more pronounced in women living in Nigeria, although some associated trait loci may be shared across populations. This highlights the need for well-powered ancestry-specific genetic studies to fully characterise the genetic influences of age at menarche.

Short- and long-term survival outcomes among never smokers who developed lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death in the US. While an extensive literature exists detailing lung cancer risk factors and mortality among patients with a history of tobacco use, the data are more limited among individuals who have never smoked. The purpose of this investigation is to compare survival rates between the two groups and evaluate potential risk factors among never smokers. METHODS: This retrospective study included 3380 smokers and 334 never smokers who were diagnosed with lung cancer at Stony Brook University Hospital between 2003 and 2016. 1-, 3-, 5- and 10-year survival outcomes, stratified by smoking status, were compared and Kaplan-Meier curves for overall survival are provided. Cox Proportional Hazard models were used to evaluate factors influencing survival among never smokers. RESULTS: Never smokers with lung cancer were more likely to be female, be diagnosed with adenocarcinoma histology, and had fewer comorbidities than lung cancer patients who smoked. Although 60% of patients were diagnosed at a later stage of disease development, regardless of smoking status, overall short- and long-term survival was significantly higher among never smokers compared to those with a history of tobacco use. In addition to age and stage at diagnosis, a history of diabetes was found to be a significant prognostic factor for decreased survival among never smokers (HR=3.15, 95% CI (1.74, 5.71)). CONCLUSIONS: Data from the present investigation suggest that, regardless of smoking status, approximately three of every five lung cancer patients are diagnosed at a later stage, and that both short- and long-term survival outcomes are significantly better among never smokers compared to those with a history of tobacco use. Additional studies are required to validate these findings and better explain the mechanistic drivers for the improved outcomes among never smokers.

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.

Clinical Implications of "Atypia" on Biopsy: Possible Precursor to Lung Cancer?

BACKGROUND: It is common for biopsies of concerning pulmonary nodules to result in cytologic "atypia" on biopsy, which may represent a benign response or a false negative finding. This investigation evaluated time to diagnosis and factors which may predict an ultimate diagnosis of lung cancer in these patients with atypia cytology on lung nodule biopsy. METHODS: This retrospective study included patients of the Stony Brook Lung Cancer Evaluation Center who had a biopsy baseline diagnosis of atypia between 2010 and 2020 and were either diagnosed with cancer or remained disease free by the end of the observation period. Cox Proportional Hazard (CPH) Models were used to assess factor effects on outcomes. RESULTS: Among 106 patients with an initial diagnosis of atypia, 80 (75%) were diagnosed with lung cancer. Of those, over three-quarters were diagnosed within 6 months. The CPH models indicated that PET positivity (SUV ≥ 2.5) (HR = 1.74 (1.03, 2.94)), nodule size > 3.5 cm (HR = 2.83, 95% CI (1.47, 5.45)) and the presence of mixed ground glass opacities (HR = 2.15 (1.05, 4.43)) significantly increased risk of lung cancer. CONCLUSION: Given the high conversion rate to cancer within 6 months, at least tight monitoring, if not repeat biopsy may be warranted during this time period for patients diagnosed with atypia.

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

BACKGROUND: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. METHODS: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. RESULTS: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. CONCLUSION: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.

Diagnosis of Dry Eye Disease Using Principal Component Analysis: A Study in Animal Models of the Disease.

PURPOSE: To evaluate whether principal component analysis (PCA) can assess various diagnostic tests of dry eye disease (DED), providing a simplified, more informative measure of disease status than individual clinical test parameters (ICTP). MATERIALS AND METHODS: ICTP were analyzed using PCA in two groups of normal rabbits (Groups 1 and 2). Group 3, not truly normal, was also assessed. DED was induced in Group 1 by complete dacryoadenectomy; in Groups 2 and 3 by injection of concanavalin A. Tear break up time, tear osmolarity, Schirmer's tear test and rose bengal staining were the ICTP measured in all groups. Statistical analysis including descriptive statistics, t test, correlation coefficients and PCA was done. PCA using ICTP data from Group 1 generated axes; Group 2 and 3 were plotted over these axes. RESULTS: All groups had induction of DED. Correlations for all ICTP were in the correct direction and were strongest for Group 1 and weakest in Group 3. PCA clearly separated DED and normal eyes. Principal component (PC) 1, made up of nearly equal contributions from the four clinical tests, explained 73% of the variation and provided a means to separate normal from DED. PC 1 values under 0.52 can be mathematically defined as DED. Of all pairwise comparisons, PC 1 vs PC 2 and PC 1 vs PC 3 were the most informative providing excellent spatial separation and additional information regarding DED status. CONCLUSIONS: PCA proved useful for evaluating DED providing a simpler, more comprehensive assessment than ICTP. PC 1 is a valuable, clinically relevant, and informative metric for DED status and severity having superior diagnostic value and statistical strength compared to ICTP. Spatial information on biplots of PC 1 vs PC 3 is also informative. PCA, and specifically PC 1, has the potential to serve as a biomarker for DED.

An Assessment of Distress Levels of Patients Undergoing Lung Cancer Treatment and Surveillance During the COVID-19 Pandemic.

The purpose of this quality improvement initiative was to identify anxious/distressed lung cancer patients and address their mental health needs directly related to the COVID-19. A total of 441 patients were screened utilizing a national distress thermometer. 47% were counseled by the NP, 32% sent for referral to the social worker. Patients reported reasons for distress as fear of delaying testing, contracting the virus and changes in their lifestyle. We found that screening all patients during the pandemic, yielded a higher than normal percentage of patients who were in need of some level of mental health services.

A Multidisciplinary Lung Cancer Program: Does It Reduce Delay Between Diagnosis and Treatment?

INTRODUCTION: Lung cancer is the leading cause of cancer death in the USA, claiming more than 140,000 deaths annually. Delays in diagnosis and treatment can lead to missed opportunities for both curative and life prolonging therapies. This study aimed to evaluate duration of time to diagnosis and first treatment, as well as investigate reasons for delays in care. METHODS: This retrospective study included all lung cancer cases diagnosed by Stony Brook's Lung Cancer Evaluation Center (LCEC) between 2013 and 2019. Demographic, radiologic, pathologic and clinical variables were investigated, including cancer staging, histology, and medical and family histories. Evaluations included the determination of median time from initial encounter to diagnosis, median time from diagnosis to start of treatment and an exploration of the factors that influence possible causes for delays in care. RESULTS: The LCEC's comprehensive multidisciplinary lung nodule program yielded a median length of time from CT to PET of 11 days, PET to procedure of 13 days, procedure to treatment consult of 9 days, and from consult to treatment of 9 days. LCEC patients experienced an overall median of 44 days from initial presentation to first treatment compared to the national ideal of 62 days, thereby representing a 29% reduction in time from first CT to onset of treatment. CONCLUSION: Delays in lung cancer diagnosis and treatment can negatively impact patient morbidity and mortality. This study suggests that a coordinated multidisciplinary lung cancer program may reduce delays in care, thereby improving patient outcomes.

Lung cancer recurrence and mortality outcomes over a 10-year period using a multidisciplinary team approach.

BACKGROUND: Longitudinal data are limited regarding the impact of a multidisciplinary team (MDT) approach on patient outcomes among those diagnosed with lung cancer. The purpose of this study is to 1) compare 1- and 3-year recurrence and mortality rates among patients receiving a MDT vs. standard model of care; and 2) assess trends in these proportions over a 10-year period. METHODS: This investigation included 2044 lung cancer cases reported to the Stony Brook Cancer Registry between 2006 and 2015. Patients were stratified into 2 groups, those participating in Stony Brook's Lung Cancer Evaluation Center's (LCEC) MDT Program (n = 1179) and those receiving a standard model of care (n = 865). 1- and 3-year stage-stratified recurrence and mortality rates are reported. Logistic regression analyses are performed and linear by linear associations are used to assess trends over time. RESULTS: A higher proportion of patients in the MDT program (LCEC) remained disease-free at 1-year compared those receiving standard care (80.0 % vs 62.3 %, p < 0.01). There were no significant changes in mortality over the 10-year observation period in either group, however the rates were significantly lower among LCEC vs non-LCEC cases after adjusting for possible confounders (OR = 0.68 (0.51,0.90) at 1-year; OR = 0.50 (0.36, 0.70) at 3-years). Recurrence was also lower at 3-years in the MDT group (OR = 0.51 (0.32, 0.79)). CONCLUSIONS: This study suggests that a comprehensive MDT program for lung cancer yields improved patient outcomes compared to the standard model of care and this approach may help to decrease rates of disease recurrence and mortality.

Risk Stratification of Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with Chemo-Radiotherapy: An Institutional Analysis.

BACKGROUND: The purpose of this study was to determine which factors predicted survival and to derive a risk prediction model for patients with locally advanced non-small cell lung cancer (NSCLC) receiving concurrent chemo-radiotherapy (cCRT). METHODS: This investigation included 149 patients with locally advanced NSCLC who were treated with cCRT at Stony Brook University Hospital between 2007 and 2015. A finite set of demographic, clinical, and treatment variables were evaluated as independent prognostic factors. Kaplan-Meier survival curves were generated, and log rank tests were used to evaluate difference in survival between groups. To derive a risk score for mortality, a machine learning approach was utilized. To maximize statistical power while examining replicability, the sample was split into discovery (n=99) and replication (n=50) subsamples. Elastic-net regression was used to identify a linear prediction model. Youden's index was used to identify appropriate cutoffs. Cox proportional hazards regression was used to examine mortality risk; model concordance and hazards ratios were reported. RESULTS: One-quarter of the patients survived for three years after initiation of cCRT. Prognostic factors for survival in the discovery group included age, sex, smoking status, albumin, histology, largest tumor size, number of nodal stations, stage, induction therapy, and radiation dose. The derived model had good risk predictive accuracy (C=0.70). Median survival time was shorter in the high-risk group (0.93 years) vs the low-risk group (2.40 years). Similar findings were noted in the replication sample with strong model accuracy (C=0.69) and median survival time of 0.93 years and 2.03 years for the high- and low-risk groups, respectively. CONCLUSION: This novel risk prediction model for overall survival in patients with stage III NSCLC highlights the importance of integrating patient, clinical, and treatment variables for accurately predicting outcomes. Clinicians can use this tool to make personalized treatment decisions for patients with locally advanced NSCLC treated with concurrent chemo-radiation.

A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry.

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.

A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry.

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.