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BACKGROUND: Aggressive malignancies, such as pancreatic cancer, are increasingly impacting young, female populations. Our investigation centered on whether the observed trends in cancer incidence were unique to pancreatic cancer or indicative of a broader trend across various cancer types. To delve deeper into this phenomenon, we analyzed cancer incidence trends across different age and sex groups. Furthermore, we explored differences in cancer incidence within specific young subgroups aged 18 to 26 and 27 to 34, to better understand the emerging incidence trend among young individuals. METHODS: This study collected cancer incidence data from one of the Surveillance, Epidemiology, and End Results cancer registry databases (SEER22), with 10,183,928 total cases from 2000 to 2020. Data were analyzed through Joinpoint trend analysis approach to evaluate sex- and age-specific trends in cancer incidence. Exposure rates were reported as Average Annual Percentage Changes (AAPCs). RESULTS: The analysis revealed significant age and sex-specific disparities, particularly among individuals aged 18-26 and 27-34. Pancreatic cancer incidence rates increased more in females aged 18-26 (AAPC, 9.37% [95% CI, 7.36-11.41%]; p < .0001) than in males (4.43% [95% CI, 2.36-6.53%]; p < .0001). Notably, among gender, age, and other malignancies, young females had the highest AAPCs for pancreatic cancer. Additionally, the incidence of gastric cancer, myeloma, and colorectal malignancies also showed higher AAPCs in young females compared to males. CONCLUSIONS: Recognizing emerging risk populations for highly lethal malignancies is crucial for early detection and effective disease management.

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BACKGROUND: Anal cancer is increasing globally, with a high number of new cases occurring in highly developed countries, including the U.S. The incidence of anal cancer is higher among people living with HIV (PLHIV), and the U.S. South continues to see higher HIV incidence rates and lagging HPV vaccination rates. We aimed to identify factors associated with early onset anal cancer in Alabama which may help explain cancer disparities in the South. METHODS: Using a cross-sectional study design, we examined demographic, clinical, and social characteristics among anal cancer patients stratified by diagnosis age (<50 and ≥50 years) in the Alabama cancer registry between 2012 and 2018. We used Wilcoxon rank sums and Pearson chi-square tests to assess associations between age at diagnosis, demographic (i.e., sex, race, marital status), clinical (i.e., BMI, HIV infection, site, stage, and histological type), and social (i.e. social vulnerability) characteristics, and multivariable logistic regression to estimate the odds of early onset cancer. RESULTS: Among 519 patients with anal cancer in Alabama, 92 (17.7 %) were diagnosed at <50 years. The majority of patients were female (66.5 %) and White (83.4 %). Male sex, Black race, and HIV infection were associated with younger age at diagnosis. Black patients had a 4-fold increased odds of early onset anal cancer compared to White patients (AOR=4.39, CI=1.54-12.49). Black patients disproportionately lived in areas with higher social vulnerability. About 42 % of patients in areas with the highest social vulnerability were diagnosed with stage 3 or 4 cancer. About 8 % of cases were among people aged 35-44 years, which is close to double the proportion of anal cancer cases in this age group in the U.S. (4.7 %). CONCLUSIONS: Patients who are Black, male, and PLHIV may be at higher risk of early onset anal cancer compared to other populations in the South.

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BACKGROUND AND OBJECTIVE: Early-onset pancreatic cancer (EOPC) is associated with poor prognosis and high disease burden. Metabolic risk factors such as diabetes and obesity are considered risk factors of EOPC. Recently, there has been an increasing number of EOPCs worldwide. However, the analysis of EOPC, including its metabolic risk factors, in the Middle East and North Africa (MENA) region has not been fully addressed. METHODS: Data from the Global Burden of Disease Study between 2000 and 2019 was used to analyze the prevalence, incidence, deaths and disability-adjusted life years (DALYs) associated with EOPC and its metabolic risk factors. The analysis further categorized the data based on countries, income status and sex and examined the annual percentage change (APC). RESULTS: Approximately 2800 cases, 2400 deaths and 114,000 DALYs were attributable to EOPC in the MENA region. The incidence (APC + 3.42%), death (APC + 0.73%) and DALYs (APC + 3.23%) rates of EOPC increased. In addition, the death and DALY rates of EOPC attributable to obesity and diabetes increased. High and upper-middle-income countries exhibited a higher burden of EOPC than lower-income countries. CONCLUSION: Over the past two decades, the burden of EOPC and its associated metabolic risk factors has increased. There is an urgent need for region-wide policy development, including screening methods and risk factor reduction, to mitigate the high and rising burden of EOPC in the MENA region.

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BACKGROUND AND AIM: In recent years, there has been a growing incidence of gastrointestinal cancer in young individuals. Despite its significant morbidity and mortality, research on upper gastrointestinal (UGI) cancer in young populations has been relatively limited. Therefore, studies on the epidemiological changes of this cancer are needed. METHODS: Using data from the Global Burden of Disease Study 2019, we examined the incidence, death, and disability-adjusted life years (DALYs) from UGI cancers in the young, namely, early-onset esophageal cancer (EOEC) and early-onset gastric cancer (EOGC). These results were stratified by sex, geographical region, country, and sociodemographic index. RESULTS: There was a total of 185 140 cases, 120 289 deaths, and 5.70 million DALYs attributable to early-onset UGI cancers globally. From 2010 to 2019, the global incidence, death, and DALYs rates of early-onset UGI cancers decreased. In contrast, the incidence rates increased in both EOEC (+1.15%) and EOGC (+0.21%) in the Eastern Mediterranean region. CONCLUSIONS: Over the past decade, the burden of UGI cancer in the young has decreased. However, it has increased in the Eastern Mediterranean region. Further research to elucidate the attributable risk factors in this population is warranted.

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Cancer metastasis is the primary cause of cancer deaths. Metastasis involves the spread of cancer cells from the primary tumors to other body parts, commonly through lymphatic and vascular pathways. Key aspects include the high mutation rate and the capability of metastatic cells to form invasive tumors even without a large initial tumor mass. Particular emphasis is given to early metastasis, occurring in initial cancer stages and often leading to misdiagnosis, which adversely affects survival and prognosis. The present review highlighted the need for improved understanding and detection methods for early metastasis, which has not been effectively identified clinically. The present review demonstrated the clinicopathological and molecular characteristics of early­onset metastatic types of cancer, noting factors such as age, race, tumor size and location as well as the histological and pathological grade as significant predictors. In conclusion, the present review underscored the importance of early detection and management of metastatic types of cancer and called for improved predictive models, including advanced techniques such as nomograms and machine learning, so as to enhance patient outcomes, acknowledging the challenges and limitations of the current research as well as the necessity for further studies.

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Backgrounds/objectives: The escalating incidence of early-onset gastrointestinal cancers is becoming a primary global health concern. Biliary tract cancer (BTC) has been relatively understudied in this regard. We conducted an epidemiological study regarding the burden of this condition. Methods: We utilized data from the Global Burden of Disease Study 2019 to investigate the temporal trends in early-onset BTC (EOBTC), encompassing the estimation of frequencies and age-standardized rates (ASRs) of EOBTC incidence, mortality, and disability-adjusted life-years (DALYs), from 2010 to 2019. Results: EOBTC constituted nearly 7%of all BTC cases worldwide. The incidence rates of EOBTC decreased significantly in most regions, except in the Eastern Mediterranean (annual percentage change +1.04 %), where the incidence is rising. Stratified by the sociodemographic index (SDI), countries with low middle SDI (annual percentage change +0.5 %) show increasing incidence of EOBTC. The ASR of death and DALYs decreased in most regions. The ASR of EOBTC-related death and disability attributable to high body mass index increased in most regions, with the highest increase in Southeast Asia and low, middle SDI strata. Conclusions: There was a reduction in the burden of EOBTC globally, except for Eastern Mediterranean countries and low-middle SDI countries.

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BACKGROUND: The incidence of early-onset obesity-related cancers (diagnosed < 50 years) is increasing in the U.S. We examined the reported historical body mass index (BMI) of adults with early and later-onset cancers to explore relation to obesity. METHODS: We queried the 1999-2018 NHANES database for adults diagnosed with obesity-related cancers (colorectal, non-colorectal gastrointestinal, uterine, breast). We classified early and late-onset cancer based on a diagnosis age of < 50 and ≥ 50 years, respectively. Propensity-weighted analysis was used to compare prior historical BMIs between the matched groups. RESULTS: After weighing, we included 2,966,528 patients with obesity-related cancers, 846,211 (28%) of which were < 50 years. In the matched analysis, 69.1% of early-onset CRC cases were diagnosed as obese (BMI ≥ 30 kg/m2) before cancer diagnosis, compared to 47.2% of late-onset cases (p < 0.03). Similarly, a higher percentage of adults with other early-onset gastrointestinal cancers had prior obesity as compared to the late-onset cohort (70.3% vs. 40.5%, p = 0.0002). BMI showed a trend toward higher values at ages 20-24 for early-onset CRC and 30-34 for other gastrointestinal cancers. In contrast, later-onset CRC and other gastrointestinal cancers exhibited higher BMI values at later ages (30-34 and 35-39, respectively). Early-onset uterine cancer was linked to a higher BMI compared to later-onset cancer (34.0 vs. 31.1 kg/m2, p < 0.0001), with a trend towards a higher BMI before 19 years old. CONCLUSIONS: Our nationally representative data reveal that higher and earlier body fatness in adulthood associates with early-onset gastrointestinal and uterine cancers. These findings underscore the importance of intensifying efforts to combat early-life obesity.

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In recent years, the incidence of cancers is continuously increasing in young adults. Early-onset cancer (EOC) is usually defined as patients with cancers under the age of 50, and may represent a unique subgroup due to its special disease features. Overall, EOCs often initiate at a young age, present as a better physical performance but high degree of malignancy. EOCs also share common epidemiological and hereditary risk factors. In this review, we discuss several representative EOCs which were well studied previously. By revealing their clinical and molecular similarities and differences, we consider the group of EOCs as a unique subtype compared to ordinary cancers. In consideration of EOC as a rising threat to human health, more researches on molecular mechanisms, and large-scale, prospective clinical trials should be carried out to further translate into improved outcomes.

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Advanced colorectal cancer, while uncommon, can occur in a young patient. We present a rare case of advanced transverse colon cancer in a young patient with vague symptoms and unique comorbid conditions, while reviewing the literature on colorectal cancer and its association with autoimmune conditions. With a recent increase in the incidence of colon cancer in young patients, further research is needed as to whether colorectal cancer screening is warranted in younger cohorts outside of current recommendations and guidelines. Investigations are needed into the factors that may explain this and the public health interventions that can be employed to improve colon cancer prevention. The objective of this report is to highlight the importance of recognizing alarming symptoms and raise awareness of the increasing incidence of early-onset colon cancer in young patients.

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BACKGROUND: Most lung cancer risk prediction models were developed in European and North-American cohorts of smokers aged ≥ 55 years, while less is known about risk profiles in Asia, especially for never smokers or individuals aged < 50 years. Hence, we aimed to develop and validate a lung cancer risk estimate tool for ever and never smokers across a wide age range. METHODS: Based on the China Kadoorie Biobank cohort, we first systematically selected the predictors and explored the nonlinear association of predictors with lung cancer risk using restricted cubic splines. Then, we separately developed risk prediction models to construct a lung cancer risk score (LCRS) in 159,715 ever smokers and 336,526 never smokers. The LCRS was further validated in an independent cohort over a median follow-up of 13.6 years, consisting of 14,153 never smokers and 5,890 ever smokers. RESULTS: A total of 13 and 9 routinely available predictors were identified for ever and never smokers, respectively. Of these predictors, cigarettes per day and quit years showed nonlinear associations with lung cancer risk (Pnon-linear < 0.001). The curve of lung cancer incidence increased rapidly above 20 cigarettes per day and then was relatively flat until approximately 30 cigarettes per day. We also observed that lung cancer risk declined sharply within the first 5 years of quitting, and then continued to decrease but at a slower rate in the subsequent years. The 6-year area under the receiver operating curve for the ever and never smokers' models were respectively 0.778 and 0.733 in the derivation cohort, and 0.774 and 0.759 in the validation cohort. In the validation cohort, the 10-year cumulative incidence of lung cancer was 0.39% and 2.57% for ever smokers with low (< 166.2) and intermediate-high LCRS (≥ 166.2), respectively. Never smokers with a high LCRS (≥ 21.2) had a higher 10-year cumulative incidence rate than those with a low LCRS (< 21.2; 1.05% vs. 0.22%). An online risk evaluation tool (LCKEY; http://ccra.njmu.edu.cn/lckey/web) was developed to facilitate the use of LCRS. CONCLUSIONS: The LCRS can be an effective risk assessment tool designed for ever and never smokers aged 30 to 80 years.

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We aim to report about the clinico-pathological characteristics of early-age gastric cancer in North-East India. It is a retrospective and observational study conducted in a tertiary care cancer centre in North-East India. We reviewed physical case records and the hospital electronic medical record system. The study population included all patients of age 40 years or less, with a confirmed diagnosis of gastric adenocarcinoma, who received treatment in the institute. The duration of the study was from 2016 to 2020. Data was collected using a pre-designed proforma, and the results were presented as percentages, ratios, median values and range. A total of 79 patients with early-age gastric cancer were found during the study period. There was female preponderance (45:34). Out of the total, 43% presented in stage IV. Most of them had good performance status (87.3% had ECOG 0-2), and none of them had documented co-morbid illness. Poorly differentiated adenocarcinoma and signet ring cell carcinoma were seen in 36.7% and 25.3% patients, respectively. Only 25 patients (31.6%) underwent definitive surgery, and they had a high nodal burden with a median metastatic lymph nodal ratio of 0.35 (range 0 to 0.91). Out of them, 40% developed systemic recurrence within a short span of time (median time to recurrence being 9.5 months). Peritoneal recurrence was the most common site of failure (80%). Early-age gastric cancer has been associated with aggressive pathological features and poor clinical outcomes in North-East India.

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In modern society, there is a growing population affected by circadian clock disruption through night shift work, artificial light-at-night exposure, and erratic eating patterns. Concurrently, the rate of cancer incidence in individuals under the age of 50 is increasing at an alarming rate, and though the precise risk factors remain undefined, the potential links between circadian clock deregulation and young-onset cancers is compelling. To explore the complex biological functions of the clock, this review will first provide a framework for the mammalian circadian clock in regulating critical cellular processes including cell cycle control, DNA damage response, DNA repair, and immunity under conditions of physiological homeostasis. Additionally, this review will deconvolute the role of the circadian clock in cancer, citing divergent evidence suggesting tissue-specific roles of the biological pacemaker in cancer types such as breast, lung, colorectal, and hepatocellular carcinoma. Recent evidence has emerged regarding the role of the clock in the intestinal epithelium, as well as new insights into how genetic and environmental disruption of the clock is linked with colorectal cancer, and the molecular underpinnings of these findings will be discussed. To place these findings within a context and framework that can be applied towards human health, a focus on how the circadian clock can be leveraged for cancer prevention and chronomedicine-based therapies will be outlined.

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Rising incidence of specific types of early-age onset cancers in adults aged 18-49 years has been reported in high-income countries. In this review, we summarise the epidemiology of early-onset cancers using exemplar data from a high-income UK region, discuss supportive care needs for young patients and outline future research directions. The incidence rate of early-onset cancers increased by 20.5% from 1993 to 2019 in Northern Ireland. Differences in types of cancer were observed between sexes and across age groups of 18-29, 30-39 and 40-49 years. One and five-year net survival was mostly better in 18-29-year-olds for all cancers combined compared to older age groups for both sexes, but there were variations in specific cancer types. Poorer survival was observed for patients with brain/central nervous system, connective and soft tissue or lung cancers. Patients with early-onset cancers face unique supportive care needs and require holistic care. The impact of cancer treatment on fertility and fertility preservation treatments is an important consideration. Social media can be used for patient support, information, fundraising, advocacy work and recruitment to research studies. We also outline suggested future research priorities for early-onset cancers, spanning prevention, diagnosis, treatment and supportive care needs.

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Background: Early maternal cancer and fertility treatment each increase the risk for adverse birth outcomes, but the joint effect of these outcomes has not yet been reported. Thus, the aim was to assess the individual and joint effect of maternal cancer and fertility treatment on the risk for adverse birth outcomes. Methods: This population-based cohort study included 5487 live-born singletons identified in the Danish Medical Birth Register (1994-2016) of mothers with previous cancer (<40 years) recorded in the Danish Cancer Registry (1955-2014). We randomly selected 80,262 live-born singletons of mothers with no cancer <40 years matched to mothers with cancer by birth year and month. We calculated odds ratios (ORs) for preterm birth, low birth weight (LBW) (<2500 g) and small for gestational age (SGA), mean differences in birth weight in grams, and additional cases of preterm birth (gestational age<259 days) per 100,000 person-years. Multiplicative and additive interaction of maternal cancer and fertility treatment was compared with outcomes of children conceived naturally to mothers with no maternal cancer (reference group). Findings: Among 84,332 live-born singletons, increased ORs for preterm birth were observed among children born to mothers with previous cancer (1·48, 95% confidence interval [CI] 1·33-1.65) or after fertility treatment (1·43, 95% 1·28-1-61), with 22 additional cases of preterm birth among both group of children (95% CI 15-29; 95% CI 14-30). In the joint analyses, the OR for SGA for children born after fertility treatment to mothers with previous cancer was similar to that of the reference group (OR 1·02, 95% CI 0·72-1·44, P for interaction=0·52). Children with both exposures had increased ORs for LBW (1·86, 95% CI 1·17-2·96, P for interaction=0·06) and preterm birth (2·31, 955 CI 1·66-3·20, P for interaction = 0·56), with 61 additional cases of preterm birth (95% CI 27-95, P for interaction=0.26) over that of children in the reference group. The mean birth weight was also lower in children born to mothers with both exposures (-140 g, 95% CI -215; -65) (P for interaction=0.06) but decreased to -22 g (95% CI -76; 31) after adjustment for GA. Interpretation: Although we did not find any statistically significant additive interaction between maternal cancer and fertility treatment, children born after fertility treatment of mothers with previous cancer were at increased risk for adverse birth outcomes. Thus, pregnant women with both exposures need close follow-up during pregnancy. Funding: The Danish Cancer Society and the Danish Childhood Cancer Foundation.

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BACKGROUND: Colorectal cancer (CRC) rates are increasing in individuals below the age of 50 and this trend has been projected to continue for the foreseeable future. Health officials are calling for increased awareness of rising rates in affected populations to promote discussion and early detection. METHODS: In May 2018, we surveyed an online purposive sample of adults below the age of 50 (N = 624). We conducted an exploratory analysis examining knowledge of current CRC screening guidelines, knowledge of available CRC screening methods, perceived risk of CRC, and perceived importance of screening for CRC by gender, race, and previous CRC screening activity. RESULTS: The sample was 56% female, averaged 36 years of age, largely identified as Caucasian (84%), married (48%), and well educated (70% with some college or a college degree). 36% correctly identified the current age of recommended CRC screening initiation. Few (8%) correctly identified all CRC screening options presented. Genetics was thought to be the most relevant determinant of CRC. African American or black participants perceived themselves to be at lower risk of CRC, while women rated the importance of screening significantly lower than men. CONCLUSION: We identified a lack of CRC knowledge in individuals below the age of 50. Interventions should correct perceptions of risk of CRC and highlight the importance of screening. Complete knowledge of the range of screening options may reduce barriers to screening while a greater knowledge of modifiable risk factors of CRC can promote healthy behaviors.

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Young adult cancer has increased in incidence worldwide, but its molecular etiologies remain unclear. We systematically characterize genomic profiles of young adult tumors with ages of onset ≤50 years and compare them to later-onset tumors using over 6,000 cases across 14 cancer types. While young adult tumors generally show lower mutation burdens and comparable copy-number variation rates compared to later-onset cases, they are enriched for multiple driver mutations and copy-number alterations in subtype-specific contexts. Characterization of tumor immune microenvironments reveals pan-cancer patterns of elevated TGF-ß response/dendritic cells and lower IFN-γ response/macrophages relative to later-onset tumors, corresponding to age-related responses to immunotherapy in several cancer types. Finally, we identify prevalent clinically actionable events that disproportionally affect young adult or later-onset cases. The resulting catalog of age-related molecular drivers can guide precision diagnostics and treatments for young adult cancer.

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The genetic predisposition to head and neck carcinomas (HNSCC) and how the known risk factors (papillomavirus infection, alcohol, and tobacco consumption) contribute to the early-onset disease are barely explored. Although HNSCC at early onset is rare, its frequency is increasing in recent years. Germline and somatic variants were assessed to build a comprehensive genetic influence pattern in HNSCC predisposition and patient outcome. Whole-exome sequencing was performed in 45 oral and oropharynx carcinomas paired with normal samples of young adults (≤49 years). We found FANCG, CDKN2A, and TPP germline variants previously associated with HNSCC risk. At least one germline variant in DNA repair pathway genes was detected in 67% of cases. Germline and somatic variants (including copy number variations) in FAT1 gene were identified in 9 patients (20%) and 12 tumors (30%), respectively. Somatic variants were found in HNSCC associated genes, such as TP53, CDKN2A, and PIK3CA. To date, 55 of 521 cases from the large cohort of TCGA presented < 49 years old. A comparison between the somatic alterations of TCGA-HNSCC at early onset and our dataset revealed strong similarities. Protein-protein interaction analysis between somatic and germline altered genes revealed a central role of TP53. Altogether, germline alterations in DNA repair genes potentially contribute to an increased risk of developing HNSCC at early-onset, while FAT1 could impact the prognosis.

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Gastric adenocarcinoma (GC) is a common tumor with high morbidity and mortality. Only 7% of patients with GC are diagnosed before age 50 (early onset gastric cancer (EOGC)), and their characteristics have been poorly described. We aimed to describe clinical, molecular, and genetic characteristics of EOGC. A total of 309 patients with EOGC were retrospectively studied in four Spanish centers. Personal information, family history, and tumor information were registered. Germinal genetic analysis was performed in patients who met current criteria of a hereditary syndrome at the time of diagnosis. The median age at diagnosis was 44 years. The majority (73.3%) of tumors were diffuse, and 78.3% were diagnosed in an advanced stage. Familial aggregation of GC was present in 18/117 (15.4%) cases, and 5/117 (4.3%) met criteria for familial GC. MMR-IHC was performed in 126/309 (40.7%) tumors: 4/126 (3.1%) had loss of expression in MLH1/PMS2, without an associated germline mutation. Sixteen germline genetic analyses were performed, detecting a pathogenic variant in four (25%) cases: one in BRCA2, one in TP53, and two in CDH1. Most EOGC are diffuse and diagnosed in an advanced stage. In these patients, DNA MMR system deficiency is uncommon. Although familial aggregation was observed in only 15% of cases, a germline mutation was found in 25% of patients tested with clinical criteria. This demonstrates that EOGC has a marked genetic heterogeneity, reinforcing the importance of an accurate genetic counseling and enhancing the emerging use of multigene panels.

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Background: The role of race/ethnicity in genetic predisposition of early-onset cancers can be estimated by comparing family-based cancer concordance rates among ethnic groups. Methods: We used linked California health registries to evaluate the relative cancer risks for first-degree relatives of patients diagnosed between ages 0 and 26, and the relative risks of developing distinct second primary malignancies (SPMs). From 1989 to 2015, we identified 29,631 cancer patients and 62,863 healthy family members. We calculated the standardized incident ratios (SIRs) of early-onset primary cancers diagnosed in proband siblings and mothers, as well as SPMs detected among early-onset patients. Analyses were stratified by self-identified race/ethnicity. Results: Given probands with cancer, there were increased relative risks of any cancer for siblings and mothers (SIR = 3.32; 95% confidence interval [CI]: 2.85-3.85) and of SPMs (SIR = 7.27; 95% CI: 6.56-8.03). Given a proband with solid cancer, both Latinos (SIR = 4.98; 95% CI: 3.82-6.39) and non-Latino Blacks (SIR = 7.35; 95% CI: 3.36-13.95) exhibited significantly higher relative risk of any cancer in siblings and mothers when compared to non-Latino White subjects (SIR = 3.02; 95% CI: 2.12-4.16). For hematologic cancers, higher familial risk was evident for Asian/Pacific Islanders (SIR = 7.56; 95% CI: 3.26-14.90) compared to non-Latino whites (SIR = 2.69; 95% CI: 1.62-4.20). Conclusions: The data support a need for increased attention to the genetics of early-onset cancer predisposition and environmental factors in race/ethnic minority families in the United States. Funding: This work was supported by the V Foundation for funding this work (Grant FP067172).

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