No abstract

The vitamin B group, including riboflavin, plays paramount roles in one-carbon metabolism (OCM), and disorders related to this pathway have been linked to cancer development. The variants of genes encoding OCM enzymes and the insufficiency of B vitamins could contribute to carcinogenesis. Very few observational studies have revealed a relationship between riboflavin and gastric cancer (GC), especially under conditions of modified genetic factors. We carried out a study examining the association of riboflavin intake and its interaction with MTRR (rs1532268) genetic variants with GC risk among 756 controls and 377 cases. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated using unconditional logistic regression models. We observed protective effects of riboflavin intake against GC, particularly in the female subgroup (OR=0.52, 95% CI 0.28-0.97, p-trend=0.031). In the MTRR (rs1532268) genotypes analysis, the dominant model showed that the effects of riboflavin differed between the CC and CT+TT genotypes. Compared with CC carriers, low riboflavin intake in T+ carriers was significantly associated with a 93% higher GC risk (OR=1.93, 95% CI 1.09-3.42, p-interaction=0.037). In general, higher riboflavin intake might help reduce the risk of GC in both CC and TC+TT carriers, particularly the T+ carriers, with marginal significance (OR=0.54, 95% CI 0.28-1.02, p-interaction=0.037). Our study indicates a protective effect of riboflavin intake against GC. Those who carry at least one minor allele and have low riboflavin intake could modify this association to increase GC risk in the Korean population.

Breast cancer is the leading cause of cancer death in Vietnamese women, but its mutational landscape and actionable alterations for targeted therapies remain unknown. After treatment, a sensitive biomarker to complement conventional imaging to monitor patients is also lacking. In this prospective multi‐center study, 134 early‐stage breast cancer patients eligible for curative‐intent surgery were recruited. Genomic DNA from tumor tissues and paired white blood cells were sequenced to profile all tumor‐derived mutations in 95 cancer‐associated genes. Our bioinformatic algorithm was then utilized to identify top mutations for individual patients. Serial plasma samples were collected before surgery and at scheduled visits after surgery. Personalized assay tracking the selected mutations were performed to detect circulating tumor DNA (ctDNA) in the plasma. We found that the mutational landscape of the Vietnamese was largely similar to other Asian cohorts, showing higher TP53 mutation frequency than in Caucasians. Alterations in PIK3CA and PI3K signaling were dominant, particularly in our triple‐negative subgroup. Using top‐ranked mutations, we detected ctDNA in pre‐operative plasma in 24.6–43.5% of the hormone‐receptor‐positive groups and 76.9–80.8% of the hormone‐receptor‐negative groups. The detection rate was associated with breast cancer subtypes and clinicopathological features that increased the risk of relapse. Interim analysis after a 15‐month follow‐up revealed post‐operative detection of ctDNA in all three patients that had recurrence, with a lead time of 7–13 months ahead of clinical diagnosis. Our personalized assay is streamlined and affordable with promising clinical utility in residual cancer surveillance. We also generated the first somatic variant dataset for Vietnamese breast cancer women that could lay the foundation for precision cancer medicine in Vietnam.

BackgroundColorectal cancer (CRC) is the fifth most common cancer with rising prevalence in Vietnam. However, there is no data about the mutational landscape and actionable alterations in the Vietnamese patients. During post-operative surveillance, clinical tools are limited to stratify risk of recurrence and detect residual disease.MethodIn this prospective multi-center study, 103 CRC patients eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissue and paired white blood cells were sequenced to profile all tumor-derived somatic mutations in 95 cancer-associated genes. Our bioinformatic algorithm identified top mutations unique for individual patient, which were then used to monitor the presence of circulating tumor DNA (ctDNA) in serial plasma samples.ResultsThe top mutated genes in our cohort were APC, TP53 and KRAS. 41.7% of the patients harbored KRAS and NRAS mutations predictive of resistance to Cetuximab and Panitumumab respectively; 41.7% had mutations targeted by either approved or experimental drugs. Using a personalized subset of top ranked mutations, we detected ctDNA in 90.5% of the pre-operative plasma samples, whereas carcinoembryonic antigen (CEA) was elevated in only 41.3% of them. Interim analysis after 16-month follow-up revealed post-operative detection of ctDNA in two patients that had recurrence, with the lead time of 4-10.5 months ahead of clinical diagnosis. CEA failed to predict recurrence in both cases.ConclusionOur assay showed promising dual clinical utilities in residual cancer surveillance and actionable mutation profiling for targeted therapies in CRC patients. This could lay foundation to empower precision cancer medicine in Vietnam and other developing countries.

The bioactive compounds in coffee have several antioxidant properties that may beneficially impact colorectal cancer development (CRC). The aryl-hydrocarbon receptor (AhR) is an important transcription factor that regulates an enzyme related to the caffeine metabolism pathway. We investigated the modification effect on coffee of AhR gene polymorphism in the risk of CRC. A case-control study was conducted with 699 cases and 1393 controls to investigate the interaction between coffee intake and the AhR rs2066853 variant in CRC risk. The odds ratios [ORs] and 95% confidence intervals [CIs] were assessed using multiple logistic regression analyses. We observed a significant protective effect of coffee against CRC in the overall and male populations. Consuming ≥3cups of coffee per day may significantly lower CRC risk in all subjects by 77% and in men by 83% (OR=0.23, 95%CI 0.14-0.39 and OR=0.17, 95%CI 0.09-0.34, respectively, p-trends<0.001). No association between AhR rs2066853 and CRC risk was found. In the dominant model, the G/G genotype had a strongest synergistic effect with coffee on protection against CRC (OR=0.12, 95%CI 0.06-0.26, p-interaction=0.014). The interaction remained significant in men and the distal colon cancer subgroup. In the additive model, the interaction was clearly shown strongest in G/G carriers (OR=0.12, 95%CI 0.06-0.27, p-interactions=0.039), followed by A/A and G/A carriers. The interaction remained significant in men and the rectal cancer subgroup. In conclusion, the protective effect of coffee on CRC risk might interact with the genetic variant AhR rs2066853, and this joint effect was determined by sex and site-specific cancer.