Search

Eosinophils exhibit anti‐tumor cytotoxic responses in the tumor microenvironment and may contribute to tumor immunosurveillance. To assess the relationship between circulating eosinophils and cancer risk, we analyzed data from 443,542 adults aged 38–73 in the UK Biobank, who were initially cancer‐free, had over a year of follow‐up, and baseline white blood cell count measurements. Using multivariable Cox regression, we estimated hazard ratios (aHR) and 95% confidence intervals (95%CI) for each quartile increase in absolute eosinophil count (AEC) across 58 cancer types, adjusting for relevant confounders. During a median follow‐up of 5.8 years, 22,747 incident cancer cases were diagnosed. We observed an inverse association, which met Bonferroni significance, between AEC and overall cancer risk (aHR, 95%CI 0.97, 0.95–0.98). Notably, 16 cancer types showed borderline associations (p <.05) with AEC, with 12 types displaying an inverse relationship. These included four hematologic cancers (acute and other myeloid leukemia, other lymphocytic leukemia, and chronic lymphocytic leukemia/small lymphocytic lymphoma; aHR range; 0.58–0.87) and eight nonhematologic cancers (melanoma and nose/middle ear, soft tissue/heart, gum/other mouth, tongue, lung, colon, and breast cancers; aHR range: 0.65–0.95). Higher AEC showed a borderline significant association with increased risk for intrahepatic bile duct cancer, Hodgkin lymphoma, diffuse large B‐cell lymphoma, and chronic myeloid leukemia (aHR range: 1.13–1.42). Our study, the largest to date, provides insights into the relationship between blood eosinophils and a comprehensive list of incident cancers. The inverse association between AEC and overall cancer risk suggests a protective role for eosinophils in tumor surveillance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background In the United States, anal squamous cell carcinoma rates have increased rapidly, particularly among women 50 or older than 66 years of age. As immunosuppression is associated with increased risk, autoimmune conditions may be associated with greater risk of anal squamous cell carcinoma. Methods We conducted a population-based, case-control study using Surveillance, Epidemiology, and End Results–Medicare data (2000-2017). Anal squamous cell carcinoma cases (n = 4505) were matched to 200 000 cancer-free controls. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between 47 autoimmune conditions diagnosed before selection, identified using Medicare claims, and anal squamous cell carcinoma. The Bonferroni threshold was used to correct for multiple comparisons. Population attributable fractions were calculated for conditions nominally associated with anal squamous cell carcinoma. Results In total, 18% of anal squamous cell carcinoma cases and 15% of cancer-free controls had a diagnosed autoimmune condition. Any autoimmune condition was associated with an increased risk of anal squamous cell carcinoma (OR = 1.11, 95% CI = 1.02 to 1.21; population attributable fraction = 1.8%). Anal squamous cell carcinoma was associated with systemic lupus erythematosus (OR = 1.79, 95% CI = 1.32 to 2.42; population attributable fraction = 0.4%) and nominally associated (P  < .05) with sarcoidosis (OR = 2.09, 95% CI = 1.30 to 3.37; population-attributable fraction = 0.2%) and psoriasis (OR = 1.28, 95% CI = 1.06 to 1.56; population attributable fraction = 0.5%). Stratified by sex, only women showed statistically significant associations for systemic lupus erythematosus (OR = 1.97, 95% CI = 1.46 to 2.68). Statistically significant interaction was observed by sex for psoriasis (men vs women: OR = 1.68 [95% CI = 1.03 to 4.28] vs OR = 1.12 [95% CI = 0.88 to 1.43]) and polymyalgia rheumatica (OR = 0.33 [95% CI = 0.12 to 0.89] vs OR = 0.99 [95% CI = 0.75 to 1.30]). Conclusion Systemic lupus erythematosus, sarcoidosis, and psoriasis were associated with a moderately increased risk of anal squamous cell carcinoma. Given these conditions' rarity and moderate associations with anal squamous cell carcinoma, autoimmune diseases cannot explain the rising trend in this disease. [ABSTRACT FROM AUTHOR]

Emerging evidence has indicated a possible link between obesity in early life with subsequent cancer risks, but its association with gastric cancer remains unknown. This study aimed to investigate the association of obesity at ages 18–20 and 35 with the later risk of gastric cancer among the Korean population. Included were 122,724 individuals who participated in the large-scale prospective cohort study, the Health Examinees-Gem (HEXA-G) study, during 2004–2017. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for gastric cancer risk associated with body mass index (BMI) at ages 18–20 and 35 years. During a mean follow-up period of 8.6±2.1 years, a total 927 gastric cancer cases (531 men and 396 women) were identified. When compared to normal BMI (18.5–23.0 kg/m2), obesity (BMI ≥30 kg/m2) at age 35 was significantly associated with increased risk of gastric cancer later in life among total participants (HR 1.94, 95% CI 1.26–2.97, p 0.01). When analyzed separately by sex, obesity at 35 years of age was significantly associated with increased risk of gastric cancer among both men (HR 1.79, 95% CI 1.02–3.13, p 0.05) and women (HR 2.35, 95% CI 1.21–4.60, p 0.02). No significant associations were found for obesity at late adolescence in both men and women. Our findings suggest that obesity in early adulthood may be associated with an increased risk of gastric cancer. The results may aid in understanding the etiology of GC in a population with a divergent trend of gastric cancer. [ABSTRACT FROM AUTHOR]

Men develop gastric cancer more frequently than women, yet little is known about the mechanisms underlying this sex difference. Sex steroid hormones may influence gastric cancer risk. We therefore assessed whether major circulating adrenal precursors, androgens and estrogens were associated with gastric cancer in a high-risk Mexican population. Blood samples were collected at time of diagnosis from 50 noncardia gastric cancer patients and 50 histologically confirmed non-atrophic gastritis controls. Serum levels of estradiol, testosterone and dehydroepiandrosterone (DHEA) measured with a validated mass spectrometry method were categorized in tertiles as low (T1), middle (T2), and high (T3). Unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and education. Levels of DHEA were inversely associated with gastric cancer (p -trend per tertile increase: <0.0001), with adjusted ORs (95% CI) of T2 and T3 (vs. T1) of 0.25 (0.09–0.70) and 0.10 (0.03–0.34), respectively. Levels of estradiol and testosterone were not significantly associated with gastric cancer. Our study provides evidence that higher concentration of circulating DHEA may be associated with lower risk of noncardia gastric cancer. Longitudinal studies are needed to evaluate the temporality of this association and investigate mechanisms of disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Although the role of microRNA’s (miRNA’s) biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown. Methods: We used genotype data available from a previously conducted case–control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs) and both disease free survival (DFS) and overall survival (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died. Results: Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4–6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07). Conclusions: Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results. [ABSTRACT FROM AUTHOR]

Gastric cancer is preceded by a chronic inflammatory process. Circulating levels of inflammation-related markers may reveal molecular pathways contributing to cancer development. Our study evaluated risk associations of gastric cancer with a wide range of systemic soluble inflammation and immune-response proteins. We performed a case-cohort analysis within the JPHC Study II, including a subcohort of 410 participants selected randomly within defined age and sex groups, and 414 individuals with incident gastric cancer. Ninety-two biomarkers were measured in baseline plasma using proximity extension assays. Gastric cancer multivariable hazard ratios were calculated for two to four quantiles used as ordinal variables of each biomarker by Cox proportional hazards regression models with age as the time metric. Of 73 evaluable biomarkers, three (CCL11, CCL20 and IL17C) were associated with increased gastric cancer risk and two (CCL23 and MMP1) with reduced cancer risk (P trends < 0.05). However, no association was statistically significant after a false discovery rate correction. This study largely expands the range of inflammation molecules evaluated for gastric cancer risk but failed to identify novel associations with this neoplasia. [ABSTRACT FROM AUTHOR]