The COVID‐19 pandemic has resulted in inequities unique to the Latino population in the United States, and these inequities are driving poor health outcomes, including poor cancer outcomes, and ...unnecessary loss of life in this vulnerable population.
Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, ...we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2 , BRCA1 , or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.
Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC ...risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10−10 and rs6687758, OR = 1.09, P = 2.27 × 10−9), 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10−8), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10−10 and rs7136702, OR = 1.06, P = 4.02 × 10−8) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10−10). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Many individuals with multiple or large colorectal adenomas or early-onset colorectal cancer (CRC) have no detectable germline mutations in the known cancer predisposition genes. Using whole-genome ...sequencing, supplemented by linkage and association analysis, we identified specific heterozygous POLE or POLD1 germline variants in several multiple-adenoma and/or CRC cases but in no controls. The variants associated with susceptibility, POLE p.Leu424Val and POLD1 p.Ser478Asn, have high penetrance, and POLD1 mutation was also associated with endometrial cancer predisposition. The mutations map to equivalent sites in the proofreading (exonuclease) domain of DNA polymerases ɛ and δ and are predicted to cause a defect in the correction of mispaired bases inserted during DNA replication. In agreement with this prediction, the tumors from mutation carriers were microsatellite stable but tended to acquire base substitution mutations, as confirmed by yeast functional assays. Further analysis of published data showed that the recently described group of hypermutant, microsatellite-stable CRCs is likely to be caused by somatic POLE mutations affecting the exonuclease domain.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Gastric cancer is an important cause of death among racial/ethnic minorities in the U.S. The objective of this study was to investigate racial disparities in survival among gastric cancer ...patients within demographic and disease subgroups.
Methods
Patients diagnosed with invasive epithelial gastric cancer between 2006 and 2015 were identified from the California Cancer Registry. Cox proportional hazards regression was used to identify factors associated with survival among non-Hispanic whites (NHWs,
n
= 7,475), non-Hispanic blacks (NHBs, n = 1,246), Hispanics (
n
= 6,274), and Asians/Pacific Islanders (APIs,
n
= 4,204). Survival was compared across race/ethnicity within subgroups of demographic and disease factors. Five-year relative survival was also calculated within subgroups.
Results
There were notable differences in patient characteristics by race/ethnicity, but predictors of survival were similar for each group. Overall, APIs (HR = 0.83, 95% CI: 0.79, 0.88,
p
< 0.0001) and Hispanics (HR = 0.94, 95% CI: 0.90, 0.99,
p
= 0.0104) had better survival than NHWs, but NHBs and NHWs did not have different prognosis (HR = 1.06, 95% CI: 0.98, 1.15,
p
= 0.2237). The survival advantage of APIs persisted in nearly every demographic and disease subgroup, but Hispanics and NHBs had similar survival as NHWs in most groups. Race was not a significant predictor of survival among those with public or no insurance and patients with cardia tumors.
Conclusions
There are some differences in survival by race/ethnicity, but race/ethnicity alone cannot explain disparate outcomes in gastric cancer. Future studies, particularly ones that investigate the role of population-specific etiological factors and molecular tumor profiles, are needed to further understand factors associated with survival.
Several single-nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) susceptibility. Most CRCs arise from adenomas, and SNPs therefore might affect predisposition to CRC ...by increasing adenoma risk. We found that 8 of 18 known CRC-associated SNPs (rs10936599, rs6983267, rs10795668, rs3802842, rs4444235, rs1957636, rs4939827, and rs961253) were over-represented in CRC-free patients with adenomas, compared with controls. Ten other CRC-associated SNPs (rs6691170, rs6687758, rs16892766, rs7136702, rs11169552, rs4779584, rs9929218, rs10411210, rs4813802, and rs4925386) were not associated significantly with adenoma risk. Genetic susceptibility to CRC in the general population is likely to be mediated in part by predisposition to adenomas.
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