Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 µg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85-1.56), and the OR100 µg/day = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

Aspirin but not statins is inversely related to gastric cancer with a duration-risk effect: Results from the Stomach Cancer Pooling Project Consortium.

BACKGROUND: Aspirin and statins have been suggested to have potential chemopreventive effects against gastric cancer (GC), although the results of previous studies have been inconsistent. This study therefore aimed to investigate the association between the use of aspirin and statins and GC. METHODS: A pooled analysis of seven case-control studies within the Stomach Cancer Pooling Project, including 3220 cases and 9752 controls, was conducted. Two-stage modeling analyses were used to estimate the association between aspirin and statin use and GC after adjusting for potential confounders. RESULTS: The pooled odds ratio (OR) of GC for aspirin users versus nonusers was 0.72 (95% confidence interval [CI], 0.54-0.95). The protective effect of aspirin appeared stronger in individuals without a GC family history (OR, 0.60; 95% CI, 0.37-0.95), albeit with borderline heterogeneity between those with and without a family history (p = .064). The OR of GC decreased with increasing duration of aspirin use, with an OR of 0.41 (95% CI, 0.18-0.95) for durations of ≥15 years. An inverse, nonsignificant association with the risk of GC was observed for the use of statins alone (OR, 0.79; 95% CI, 0.52-1.18). CONCLUSIONS: These findings suggest that aspirin use, particularly long-term use, is associated with a reduced risk of GC, whereas a similar association was not observed with statins, possibly because of the low frequency of use.

Reproductive factors, hormonal interventions, and gastric cancer risk in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Gastric cancer incidence is higher in men, and a protective hormone-related effect in women is postulated. We aimed to investigate and quantify the relationship in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 2,084 cases and 7,102 controls from 11 studies in seven countries were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) assessing associations of key reproductive factors and menopausal hormone therapy (MHT) with gastric cancer were estimated by pooling study-specific ORs using random-effects meta-analysis. RESULTS: A duration of fertility of ≥ 40 years (vs. < 20), was associated with a 25% lower risk of gastric cancer (OR = 0.75; 95% CI: 0.58-0.96). Compared with never use, ever, 5-9 years and ≥ 10 years use of MHT in postmenopausal women, showed ORs of 0.73 (95% CI: 0.58-0.92), 0.53 (95% CI: 0.34-0.84) and 0.71 (95% CI: 0.50-1.00), respectively. The associations were generally similar for anatomical and histologic subtypes. CONCLUSION: Our results support the hypothesis that reproductive factors and MHT use may lower the risk of gastric cancer in women, regardless of anatomical or histologic subtypes. Given the variation in hormones over the lifespan, studies should address their effects in premenopausal and postmenopausal women. Furthermore, mechanistic studies may inform potential biological processes.

Data quality in Brazilian population-based cancer registries for gastrointestinal cancers.

BACKGROUND: Population-based cancer registries (PBCRs) are the primary source of information for cancer surveillance and monitoring. Currently, there are 30 active PBCRs in Brazil. The objective of this study was to analyze the data quality of five gastrointestinal cancers (esophagus, stomach, colorectal, liver, and pancreas) according to the criteria of comparability, validity, completeness, and timeliness in Brazilian cancer registries. METHODS: This study included data from Brazilian PBCRs with more than ten years of historical data starting in the year 2000, regardless of the type of defined geographical coverage (state, metropolitan region, or capital), totaling 16 registries. Brazilian PBCRs were evaluated based on four international data quality criteria: comparability, validity (accuracy), completeness, and timeliness. All cancer cases were analyzed, except for nonmelanoma skin cancer cases (C44) and five gastrointestinal tumors (esophageal cancer, stomach cancer, colorectal cancer, liver cancer, and pancreatic cancer) per cancer registry and sex, according to the available period. RESULTS: The 16 Brazilian PBCRs represent 17% of the population (36 million inhabitants in 2021) according to data from 2000 to 2018. There was a variation in the incidence in the historical series ranging from 12 to 19 years. The proportion of morphologically verified (MV%) cases varied from 74.3% (Manaus) to 94.8% (Aracaju), and the proportion of incidentally reported death certificate only (DCO%) cases varied from 3.0% (São Paulo) to 23.9% (Espírito Santo). High-lethality malignant neoplasms, such as liver and pancreas, had DCO percentages greater than 30% in most cancer registries. The sixteen registries have more than a 48-month delay in data release compared to the 2022 calendar year. CONCLUSION: The studied Brazilian cancer registries met international comparability criteria; however, half of the registries showed indices below the expected levels for validity and completeness criteria for high-lethality tumors such as liver and pancreas tumors, in addition to a long delay in data availability and disclosure. Significant efforts are necessary to ensure the operational and stability of the PBCR in Brazil, which continues to be a tool for monitoring cancer incidence and assessing national cancer control policies.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

The association between referral by specialists in oral diagnosis on survival rates of patients with oral cancer: A retrospective cohort study.

BACKGROUND: To assess the influence of diagnosis and referral provided by specialists in oral diagnosis on disease-free survival and overall survival of patients with oral cancer. METHODS: A cohort of 282 patients with oral cancer treated at a regional cancer hospital from 1998 to 2016 was analyzed retrospectively. The referral register of the patients was analyzed and assigned to two groups: (1) those referred by oral diagnosis specialists (n = 129), or (2) those referred by nonspecialized professionals (n = 153). The cancer treatment evolution was assessed from the patients' records, and the outcome was registered concerning cancer recurrence and death. Sociodemographic and clinicopathological variables were explored as predictors of disease-free survival and overall survival. RESULTS: Group 1 exhibited lower T stages and a reduced incidence of regional and distant metastases. Surgery was performed in 75.2% of cases in Group 1, while in Group 2, the rate was 60.8%. Advanced T stages and regional metastases reduced the feasibility of surgery. Higher TNM stages and tumor recurrence were associated with decreased disease-free survival, while surgical intervention was a protective factor. Higher TNM stage had a negative impact on the overall survival. CONCLUSION: Specialized oral diagnosis did not directly impact disease-free survival and overall survival and did not influence the indication of surgery in oral cancer; however, it was associated with the diagnosis of early tumors and better prognosis.

The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean.

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

Changes in Body Mass Index Are Associated with Squamous Cell Carcinomas of Oral Cavity, Oropharynx and Larynx: A Case-Control Study in Brazil.

Head and neck cancer (HNC) significantly impacts nutritional status because the tumor limits swallowing function. In this sense, it is important to monitor the nutritional status throughout the life of any individual. A multicenter case-control study was carried out to analyze the BMI at 30 years of age, two years before diagnosis and at the time of diagnosis of individuals with oral cavity, oropharynx, and larynx cancers. It was observed that a 5% reduction in BMI during the two years before enrollment was associated with an increased risk of the oral cavity (OR = 3.73), oropharyngeal OR = 5.25), and laryngeal (OR = 5.22). Reduced BMI of more than 5% over two years before diagnosis was associated with HNC. Weight loss remained significant at diagnosis, but it is not possible to exclude reverse causality since most cases are at an advanced stage. BMI monitoring of individuals at potential risk for HNC can promote early diagnosis and nutritional interventions for HNC.