Background/Objectives: Perinatal exposure to malnutrition has been hypothesised to influence the development of young-onset cancer (≤50 years of age). This study aimed to determine if perinatal malnutrition in individuals exposed to the Great Famine of China increased their risk of developing young-onset cancer compared to other individuals born prior to the famine. Subjects/Methods: This cross-sectional study involved 7272 participants from the China Health and Nutrition Survey who were classified into four groups based on birth year: participants born between 1953 and 1955 (before the famine) were designated as the pre-famine group (unexposed); the remainder formed perinatal exposure groups comprised of those exposed during the famine (1959-1961), those exposed in the early post-famine period (1962-1964), and those exposed in the late post-famine period (1965-1967). Multivariable adjusted log-binomial regression models were used to calculate the RR and 95% CI of young-onset cancer (including genitourinary cancer) across four groups. Results: Perinatal exposure to early post-famine (RR 2.08; 95%CI 1.04, 4.34; p = 0.043) and the female sex (RR 15.6, 95%CI 4.54, 60.3; p < 0.001) were noted to have a significantly increased risk of young-onset cancer. In addition, the early (RR 13.8; 95%CI 2.68, 253; p = 0.012) and late post-famine (RR 12.3; 95%CI 2.16, 231; p = 0.020) cohorts demonstrated a significantly increased risk of young-onset genitourinary cancer. The latter was accompanied by an increased risk of hypertension (RR 3.30; 95%CI 1.28, 7.87; p = 0.009). Conclusions: Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. These findings highlight the potential long-term impact of perinatal malnutrition on young-onset carcinogenesis.

Reports of a rise in childhood cancer incidence in Australia and globally prompted the investigation of cancer incidence and survival in South Australia (SA) and the Northern Territory (NT) over a 28-year period, with emphasis on Indigenous peoples.

This cross-sectional analysis of two prospective longitudinal databases, the SA and NT Cancer Registries (1990-2017), included all reported cases of childhood cancers. Poisson regression provided estimates of incidence rate ratios and survival was modelled using Cox proportional hazard models for children aged <5 and ≥5 years.

A total of 895 patients across SA (N = 753) and the NT (N = 142) were ascertained. Overall and in the NT, childhood cancer incidence was higher in males compared with females (IRR 1.19 [1.04-1.35] and 1.43 [1.02-2.01], respectively). Lymphocytic leukemia was the most reported cancer type across all locations. With reference to the 1990-1999 era (181.67/100,000), cancer incidence remained unchanged across subsequent eras in the combined cohort (SA and NT) (2000-2009: 190.55/100,000; 1.06 [0.91-1.25]; 2010-2017: 210.00/100,000; 1.15 [0.98-1.35]); similar outcomes were reflected in SA and NT cohorts. Cancer incidence amongst non-Indigenous children significantly decreased from the 1990-1999 era (278.32/100,000) to the 2000-2009 era (162.92/100,000; 0.58 [0.35-0.97]). Amongst 39 Indigenous children in the NT, incidence rates remained unchanged across eras (p > 0.05). With reference to the 1990-1999 era, overall survival improved in subsequent eras in SA (2000-2009: HR 0.53 [0.38-0.73]; 2010-2017: 0.44 [0.28-0.68]); however, remained unchanged in the NT (2000-2009: 0.78 [0.40-1.51]; 2010-2017: 0.50 [0.24-1.05]). In the NT, overall survival of Indigenous patients was significantly lower compared with the non-Indigenous cohort (3.42 [1.92-6.10]). While the survival of Indigenous children with cancer significantly improved in the last two eras (p < 0.05), compared to the 1990-1999 era, no change was noted amongst non-Indigenous children in the NT (p > 0.05).

The incidence of childhood cancers has remained unchanged over 28-years in SA and the NT. Encouragingly, improved survival rates over time were observed in SA and amongst Indigenous children of the NT. Nevertheless, survival rates in Indigenous children remain lower than non-Indigenous children.

To investigate worldwide incidence, deaths, disability-adjusted life years (DALYs) and risk factors for young-onset pancreatic cancer (YOPC) using the Global Burden of Disease Study 2019-20 data.

We queried the Global Health Data Exchange tool for "pancreatic cancer" and "incidence", "deaths" as the "measure", and "DALYs" as the "cause" for the age group of 15-49 years to determine global, regional, and national trends in the incidence, deaths, and DALYs of YOPC. Sociodemographic index (SDI) was used to evaluate the associations between socioeconomic development and YOPC. Risk factors including smoking, tobacco use, hi2gh body mass index (BMI), and high fasting plasma glucose (FPG) were evaluated, and their attributable burden was estimated.

Global incidence, death, and DALY rates of YOPC significantly increased from 1990 to 2019 ((0.30 (p = 0.001), 0.25 (p = 0.001), and 11.18 (p = 0.002), respectively). Regions with the highest and lowest incidence, death, and DALY rates of YOPC were Eastern Europe and Central Sub-Saharan Africa, respectively. Incidence, death, and DALY rates increased with increasing age and SDI. Leading risk factors for YOPC in 2019 were smoking and tobacco use. DALYs attributable to smoking and tobacco use decreased from 1990 to 2019, especially in females, while those attributable to high BMI and FPG increased during the same period.

The global incidence, death and DALY rates of YOPC have significantly increased over 3 decades. Certain regions and nations are witnessing a higher increase in this trend. There is an urgent need for global efforts targeting preventable causes of YOPC.

Evidence is lacking on the impact of alcohol consumption on colorectal cancer (CRC) risk (overall and by age at diagnosis) by polygenic risk score (PRS) levels, and it is unclear how the magnitude of CRC risk associated with alcohol consumption compares to the magnitude of genetically determined risk.

Multiple logistic regression was used to assess the association between alcohol consumption and colorectal cancer (CRC) across PRS levels based on 140 CRC-related loci among 5104 CRC cases and 4131 controls from a large population-based case-control study. We compared the effects for alcohol consumption and PRS on CRC risk using the "Genetic Risk Equivalent (GRE)" for effective risk communication. Specific analyses were conducted for early-onset CRC (EOCRC, <55 years) and late-onset CRC (LOCRC, ≥55 years).

High alcohol consumption, and to a lower extent, also alcohol abstinence were associated with increased CRC risk. Compared to low alcohol consumption (0·1-<25 g/d), lifetime average alcohol consumption ≥25 g/d was more strongly associated with EOCRC [odds ratio (OR) 1·8, 95% confidence interval (CI) 1·2-2·8] than with LOCRC risk (OR 1·3, 95% CI 1·1-1·4) (P-value for interaction with age =0·011). Interactions between alcohol consumption and PRS did not reach statistical significance for either EOCRC or LOCRC risk. The estimated impact of high lifetime alcohol consumption on EOCRC was equivalent to the effect of having 47 percentiles higher PRS (GRE 47, 95% CI 12-82), stronger than the impact on LOCRC (GRE 18, 95% CI 8-29).

Excessive alcohol use was strongly associated with EOCRC risk, independent of PRS levels. Abstaining from heavy drinking could reduce risk for CRC, in particular for EOCRC to an extent that would be equivalent to having a much lower genetically determined risk.

The first author (X.C.) was supported by the Guangzhou Elite Project (GEP). The DACHS study was supported by grants from the German Research Council (BR 1704/6-1, BR1704/6-3, BR 1704/6-4, BR 1704/6-6, CH 117/1-1, BR 1704/17-1, HO 5117/2-1) and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01GL1712).

Background and Aims: A concerning rise in incidence of young-onset cancers globally led to the examination of trends in incidence and survival of gastrointestinal (GI) adenocarcinomas in the Northern Territory (NT), Australia, over a 28-year period, with a special emphasis on Indigenous peoples. Methods: This cross-sectional analysis of a prospective longitudinal database, NT Cancer Registry (1990−2017), includes all reported cases of GI (oesophagus, gastric, small intestinal, pancreas, colon, and rectum) adenocarcinomas. Poisson regression was used to estimate incidence ratio ratios, and survival was modelled using Cox proportional hazard models separately for people aged 18−50 years and >50 years. Results: A total of 1608 cases of GI adenocarcinoma were recorded during the time of the study. While the overall incidence in people 18−50 years remained unchanged over this time (p = 0.51), the rate in individuals aged >50 years decreased (IRR = 0.65 (95% CI 0.56−0.75; p < 0.0001)). Incidence rates were significantly less in females >50 years (IRR = 0.67 95% CI 0.59−0.75; p < 0.0001), and their survival was significantly better (HR = 0.84 (95%CI 0.72−0.98; p < 0.03)) compared to males. Overall survival across all GI subsites improved in both age cohorts, especially between 2010 and 2017 (HR = 0.45 (95%CI 0.29−0.72; p < 0.0007) and HR = 0.64 (95%CI 0.52−0.78; p < 0.0001), respectively) compared to 1990−1999, driven by an improvement in survival in colonic adenocarcinoma alone, as the survival remained unchanged in other GI subsites. The incidence was significantly lower in Indigenous patients compared to non-Indigenous patients, in both age cohorts (18−50 years IRR = 0.68 95% CI 0.51−0.91; p < 0.009 and >50 years IRR = 0.48 95% CI 0.40−0.57; p < 0.0001). However, Indigenous patients had worse survival rates (18−50 years HR = 2.06 95% CI 1.36−3.11; p < 0.0007 and >50 years HR = 1.66 95% CI 1.32−2.08; p < 0.0001). Conclusions: There is a trend towards an increased incidence of young-onset GI adenocarcinomas in the NT. Young Indigenous patients have lower incidence but worse survival across all GI subsites, highlighting significant health inequities in life expectancy. Targeted, culturally safe Indigenous community-focussed programs are needed for early detection and patient-centred management of GI adenocarcinomas.

Globally, there has been a concerning rise in the incidence of young-onset cancers. The aim of this study was to provide trends in the incidence and survival of gastrointestinal adenocarcinomas (oesophagus, stomach, pancreas, and colorectal) in South Australia over a 27-year period.

This is a cross-sectional analysis of a prospective longitudinal database including all cases of gastrointestinal adenocarcinomas prospectively reported to the South Australian (State) Cancer Registry from 1990 to 2017.

A total of 28,566 patients diagnosed with oesophageal, stomach, pancreatic, or colorectal adenocarcinoma between 1990 and 2017 were included in the study. While the overall incidence for gastrointestinal adenocarcinomas in individuals >50 years has decreased since 2000 (IRR of 0.97 (95% CI 0.94-1.00; p = 0.06)) compared to 1990-1999, the rate amongst individuals aged 18-50 has significantly increased (IRR 1.41 (95% CI 1.27-1.57; p < 0.001)) during the same reference time period. Although noted in both sexes, the rate of increase in incidence was significantly greater in males (11.5 to 19.7/100,000; p < 0.001). The overall survival from adenocarcinomas across all subsites improved in the >50-year cohort in the last decade (HR 0.89 (95% CI 0.86-0.93; p < 0.001)) compared to 1990-1999. In individuals aged 18-50 years, there has only been a significant improvement in survival for colorectal cancer (HR 0.82 (95% CI 0.68-0.99; p < 0.04)), but not the other subsites. A lower overall survival was noted for males in both age cohorts (18-50 years-HR 1.24 (95% CI 1.09-1.13; p < 0.01) and >50 years-HR 1.13 (95% CI 1.10-1.16; p < 0.001), respectively) compared to females.

This study from South Australia demonstrates a significant increase in young-onset gastrointestinal adenocarcinomas over the last 28 years, with a greater increase in the male sex. The only significant improvement in survival in this cohort has been noted in colorectal cancer patients.

A better understanding of seasonal variations in cancer diagnosis may be the first step toward optimal resource distribution in the National Cancer Screening Program (NCSP). This study aimed to identify seasonal variations in the diagnosis of the top 10 major cancers in Korea.

We conducted a retrospective, observational cohort study in participants aged ≥ 20 years between 2012 and 2016 from the Health Insurance Review and Assessment-National Patient Sample database, previously converted to a common data model. We assessed the overall seasonal variations in the 10 major cancers.

We analyzed the following top 10 cancers: stomach (n = 3435), colorectal (n = 5368), liver (n = 7605), pancreatic (n = 2946), gallbladder (n = 899), lung (n = 1598), prostate (n = 2897), thyroid (n = 1966), breast (n = 1313), and kidney (n = 668) cancers. All cancers showed similar seasonal variations in diagnosis, with a significant winter peak. A winter peak in diagnosis was observed for NCSP-covered cancers, such as stomach, colon, liver, and breast cancers, as well as other cancers not covered by the NCSP. The winter peak for cancer diagnosis was the highest for breast cancer (74.4%) followed by thyroid (51.0%) and stomach cancers, whereas it was the lowest for pancreatic cancer followed by prostate and colorectal cancers.

Significant seasonal variations were found in the diagnosis of the top 10 major cancers, with a winter peak, which may be explained by the participants' behavior pattern with respect to the NCSP. Our findings suggest that trading off of NCSP healthcare resources between winter and other seasons may be beneficial.

The last decade has witnessed a significant rise in cancers in young adults. This spectrum of solid organ cancers occurring in individuals under the age of 40 years (some reports extending the age-group to <50 years) in whom aetiology of cancer cannot be traced back to pre-existing familial cancer syndromes, is referred to as termed young-, or early- onset cancers. The underlying causes for young-onset carcinogenesis have remained speculative. We recently proposed a hypothesis to explain the causation of this entity. We propose that the risk for young-onset cancer begins in the perinatal period as a result of the exposure of the foetus to stressors, including maternal malnutrition, smoking or alcohol, with the consequent epigenomic events triggered to help the foetus cope/adapt. Exposure to the same stressors, early in the life of that individual, facilitates a re-activation of these 'responses designed to be protective' but ultimately resulting in a loss of regulation at a metabolic and/or genetic level culminating in the evolution of the neoplastic process. In this manuscript, we will provide a rationale for this hypothesis and present evidence to further support it by clarifying the pathways involved, including elucidating a role for Acetyl-CoA and its effect on the epigenome. We present strategies and experimental models that can be used to test the hypothesis. We believe that a concerted effort by experts in different, but complementary fields, such as epidemiology, genetics, and epigenetics united towards the common goal of deciphering the underlying cause for young-onset cancers is the urgent need. Such efforts might serve to prove, or disprove, the presented hypothesis. However, the more important aim is to develop strategies to reverse the disturbing trend of the rise in young-onset cancers.