Feature Paper in Section 'Cancer Epidemiology and Prevention' in 2024

Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next (“third”) generation of offspring. Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI. Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36–1.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37–32.42). Based on mothers’ reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49–1.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70–2.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported. Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed. Full article

Background & Aims: 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. Methods: 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. Results: 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). Conclusions: 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. Full article

Background: Helicobacter pylori (H. Pylori) eradication has been the mainstream for preventing and treating gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Prior data showed disparities in eradication rates of H. Pylori between different populations. This can potentially impact the occurrence of gastric MALT lymphoma. There are limited data on the incidence and mortality rates and trends of gastric MALT lymphoma in the US. Therefore, the aim of the current study was to conduct a time-trend analysis of gastric MALT lymphoma incidence and mortality rates in different populations. Methods: The incidence rates of gastric MALT lymphoma were calculated from the United States Cancer Statistics (USCS) database (which covers nearly 98% of the US population) between 2001–2020 and were age-adjusted to the standard 2000 US population using SEER*Stat software (version 8.4.3, national cancer institute “NCI”). Incidence-based mortality (IBM) rates, also age-adjusted to the standard 2000 US population, were calculated from the Surveillance Epidemiology and End Results (SEER) database. Tumor location was specified using ICD-O-3 codes C 160–C 169 with malignant behavior. Histopathology was specified using the ICD-O-3 code 9699. The rates were categorized by sex, age, race/ethnicity, and tumor stage at diagnosis. Age groups were older adults (aged 55 years or older) and younger adults (aged younger than 55 years). Race/ethnic groups included Non-Hispanic White (White), Non-Hispanic Black (Black), Hispanic, Non-Hispanic Asian/Pacific Islander (API), and Non-Hispanic American Indian/Alaska Native (AI/AN), as reported in the database. Stage at diagnosis included early stage (in situ and localized tumors) and late stage (regional and distant site tumors). Joinpoint Regression Software (version 5.0.2, NCI) using the weighted Bayesian Information Criteria method was used to generate time trends. Trends were reported as annual percentage change (APC) and average APC (AAPC). Parametric estimations were used with a two-sided t-test to evaluate the trends with a p-value cutoff at 0.05. Results: There were 21,625 patients diagnosed with gastric MALT lymphoma in the US between 2001 and 2020. Overall, incidence rates were significantly decreasing over the study period (AAPC = −1.93). This decrease was seen in males (AAPC = −1.67) and in females (AAPC = −1.66) (Figure). When categorized by age groups, older adults also experienced a significant decrease in gastric MALT lymphoma incidence rates (AAPC = −1.66). While this was also seen in younger adults, the rates were decreasing at a slower pace (AAPC = −1.38). When categorizing the trends by race/ethnicity, incidence rates were significantly decreasing in White (AAPC = −2.09), Hispanic (AAPC = −1.61), and API (AAPC = −3.92) populations. However, the rates were stable among Blacks. While early-stage tumors experienced a significant decrease (AAPC = −1.10), the rates were stable for late-stage tumors. When evaluating mortality, there were 11,036 patients whose death was attributed to gastric MALT lymphoma between 2000 and 2020. IBM rates were decreasing in males (AAPC = −1.47), older adults (AAPC = −1.55), Whites (AAPC = −1.23), Hispanics (AAPC = −1.73), APIs (AAPC = −2.30), and early-stage tumors (AAPC = −1.08). On the other hand, IBM rates were stable in females, younger adults, Blacks, and late-stage tumors. Discussion: An extensive nationwide data analysis encompassing nearly 98% of patients diagnosed with gastric MALT lymphoma in the US unveils a declining trend in the incidence of cancer overall over the past two decades. This decline is observed in both sexes and various age groups. When stratifying by race and ethnicity, this incidence has been decreasing in all populations except among Black individuals. While early-stage tumors have also demonstrated a significant decrease in incidence rates, late-stage tumors have shown no parallel decline. Mortality evaluation also revealed an improvement in most of the US population except among females, younger adults, Black individuals, and late-stage tumors. While the cause of our findings is unclear, it could be driven by disproportionate exposure to risk factors, including H. Pylori, and disparities in screening, management, and outcomes. Future studies are warranted to investigate factors contributing to worse outcomes of gastric MALT lymphoma, especially in the Black population. Full article

Purpose: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. Results: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy. Full article