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Ferroptosis, a form of regulated cell death, is characterized by iron‐dependent lipid peroxidation. It is recognized increasingly for its pivotal role in both cancer development and the response to cancer treatments. We assessed associations between 370,027 single‐nucleotide polymorphisms (SNPs) within 467 ferroptosis‐related genes and survival of non‐small cell lung cancer (NSCLC) patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial served as our discovery dataset, while the Harvard Lung Cancer Susceptibility Study used as our validation dataset. For SNPs that remained statistically significantly associated with overall survival (OS) in both datasets, we employed a multivariable stepwise Cox proportional hazards regression model with the PLCO dataset. Ultimately, two independent SNPs, PARK7 rs225120 C>T and DDR2 rs881127 T>C, were identified with adjusted hazard ratios of 1.32 (95% confidence interval = 1.15–1.52, p =.0001) and 1.34 (95% confidence interval = 1.09–1.64, p =.006) for OS, respectively. We aggregated these two SNPs into a genetic score reflecting the number of unfavorable genotypes (NUG) in further multivariable analysis, revealing a noteworthy association between increased NUG and diminished OS (ptrend =.001). Additionally, an expression quantitative trait loci analysis indicated that PARK7 rs225120T genotypes were significantly associated with higher PARK7 mRNA expression levels in both whole blood and normal lung tissue. Conversely, DDR2 rs881127C genotypes were significantly associated with lower DDR2 mRNA expression levels in normal lung tissue. Our findings suggest that genetic variants in the ferroptosis‐related genes PARK7 and DDR2 are associated with NSCLC survival, potentially through their influence on gene expression levels. [ABSTRACT FROM AUTHOR]

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

The mitotic phase is a vital step in cell division and may be involved in cancer progression, but it remains unclear whether genetic variants in mitotic phase‐related pathways genes impact the survival of these patients. Here, we investigated associations between 31 032 single nucleotide polymorphisms (SNPs) in 368 mitotic phase‐related pathway genes and overall survival (OS) of patients with nonsmall cell lung cancer (NSCLC). We assessed the associations in a discovery data set of 1185 NSCLC patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the findings in another data set of 984 patients from the Harvard Lung Cancer Susceptibility Study. As a result, we identified three independent SNPs (ie, CHEK1 rs76744140 T>C, PRIM2 rs6939623 G>T and CDK6 rs113181986 G>C) to be significantly associated with NSCLC OS with an adjusted hazard ratio of 1.29 (95% confidence interval = 1.11‐1.49, P = 8.26 × 10−4), 1.26 (1.12‐1.42, 1.10 × 10−4) and 0.73 (0.63‐0.86, 1.63 × 10−4), respectively. Moreover, the number of combined unfavorable genotypes of these three SNPs was significantly associated with NSCLC OS and disease‐specific survival in the PLCO data set (Ptrend <.0001 and.0003, respectively). Further expression quantitative trait loci analysis showed that the rs76744140C allele predicted CHEK1 mRNA expression levels in normal lung tissues and that rs113181986C allele predicted CDK6 mRNA expression levels in whole blood tissues. Additional analyses indicated CHEK1, PRIM2 and CDK6 may impact NSCLC survival. Taken together, these findings suggested that these genetic variants may be prognostic biomarkers of patients with NSCLC. [ABSTRACT FROM AUTHOR]

The endosome is a membrane‐bound organ inside most eukaryotic cells, playing an important role in adaptive immunity by delivering endocytosed antigens to both MHC class I and II pathways. Here, by analyzing genotyping data from two published genome‐wide association studies (GWASs), we evaluated associations between genetic variants in the endosome‐related gene‐set and survival of patients with nonsmall cell lung cancer (NSCLC). The discovery included 44,112 (3,478 genotyped and 40,634 imputed) single‐nucleotide polymorphisms (SNPs) in 220 genes in a singlelocus analysis for their associations with survival of 1,185 NSCLC patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. After validation of the 821 survival‐associated significant SNPs in additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study, 14 SNPs remained significant. The final multivariate stepwise Cox proportional hazards regression modeling of the PLCO dataset identified three potentially functional and independent SNPs (i.e., KIF16B rs1555195 C>T, NEDD4L rs11660748 A>G and rs73440898 A>G) with an adjusted hazards ratio (HR) of 0.86 (95% confidence interval [CI] = 0.79–0.94, p = 0.0007), 1.31 (1.16–1.47, p = 6.0 × 10−5) and 1.27 (1.12–1.44, p = 0.0001) for overall survival (OS), respectively. Combined analysis of the adverse genotypes of these three SNPs revealed a trend in the genotype‐survival association (ptrend < 0.0001 for OS and ptrend < 0.0001 for disease‐specific survival). Furthermore, the survival‐associated KIF16B rs1555195T allele was significantly associated with decreased mRNA expression levels of KIF16B in both lung tissues and blood cells. Therefore, genetic variants of the endosome‐related genes may be biomarker for NSCLC survival, possibly through modulating the expression of corresponding genes. What's new? Immunotherapy has become a key component of non‐small cell lung cancer (NSCLC) treatment. However, not all patients benefit from immunotherapy, and there is increasing need to predict immunotherapy response in order to improve treatment efficacy and patient outcomes. In the present investigation of genes involved in endosome‐related pathways, which are suspected of serving important immune‐guided anti‐tumor functions, three variants, located in the genes KIF16B and NEDD4L, were associated with NSCLC survival. The survival‐associated variant in KIF16B was specifically associated with reduced KIF16B mRNA expression levels in lung tissue and blood cells, identifying it as a potentially useful biomarker for NSCLC survival. [ABSTRACT FROM AUTHOR]