Dramatic improvements in outcome following pancreatoduodenectomy for pancreatic and periampullary cancers.

BACKGROUND: Pancreatoduodenectomy is the only cure for cancers of the pancreas and the periampullary region but has considerable operative complications and uncertain prognosis. Our goal was to analyse temporal improvements and provide contemporary population-based benchmarks for outcomes following pancreatoduodenectomy. METHODS: We empanelled a cohort comprising all patients in Sweden with pancreatic or periampullary cancer treated with pancreatoduodenectomy from 1964 to 2016 and achieved complete follow-up through 2016. We analysed postoperative deaths and disease-specific net survival. RESULTS: We analysed 5923 patients with cancer of the pancreas (3876), duodenum (444), bile duct (504), or duodenal papilla (963) who underwent classic (3332) or modified (1652) Whipple's procedure or total pancreatectomy (803). Postoperative deaths declined from 17.2% in the 1960s to 1.6% in the contemporary time period (2010-2016). For all four cancer types, median, 1-year and 5-year survival improved substantially over time. Among patients operated between 2010 and 2016, 5-year survival was 29.0% (95% confidence interval (CI): 25.5, 33.0) for pancreatic cancer, 71.2% (95% CI: 62.9, 80.5) for duodenal cancer, 30.8% (95% CI: 23.0, 41.3) for bile duct cancer, and 62.7% (95% CI: 55.5, 70.8) for duodenal papilla cancer. CONCLUSION: There is a continuous and substantial improvement in the benefit-harm ratio after pancreatoduodenectomy for cancer.

Occurrence and distribution of Meloidogyne spp. in fields rotated with sweetpotato and host range of a North Carolina population of Meloidogyne enterolobii.

Root-knot nematodes (RKN, Meloidogyne spp.) are some of the most economically important and common plant parasitic nematodes in North Carolina (NC) cropping systems. Soil samples collected from fields planted with crops rotated with sweetpotato [Ipomoea batatas (L.) Lam.] in 39 NC counties in 2015-2018 were processed at the NC Nematode Assay Laboratory. The occurrence of second-stage juvenile (J2) RKN populations was examined based on collection year, month, county, and previous planted crop. The highest number of RKN positive samples originated from Cumberland (53%), Sampson (48%), and Johnston (48%) counties. The highest average RKN population density was detected in Sampson (147 J2/500 cm3 soil) and Nash (135 J2/500 cm3 soil) counties, while Wayne (7 J2/500 cm3 soil) and Greene (11 J2/500 cm3 soil) counties had the lowest average RKN population density. Meloidogyne enterolobii is a new invasive species that is impacting sweetpotato growers of NC. The host status of a NC population of M. enterolobii, the guava-root knot nematode, was determined by examining eggs per gram of fresh root (ER) and the final nematode egg population divided by the initial population egg count (reproductive factor, RF) in greenhouse experiments. This included eighteen vegetable, field, cover crops and weed species. The tomato 'Rutgers' was used as a susceptible control. Cabbage 'Stonehead', pepper 'Red bull', and watermelon 'Charleston gray' and 'Fascination' were hosts and had similar mean ER values to the positive control, ranging from 64 to 18,717. Among field crops, cotton, soybean 'P5018RX', and tobacco were hosts with ER values that ranged from 185 to 706. Members of the Poaceae family such as sweet corn (Zea mays) and sudangrass (Sorghum x drummondii) were non-hosts to M. enterolobii and the mean ER values ranged from 1.85 to 7. The peanut 'Tifguard' and winter wheat (Triticum aestivum) also had lower ER values than the vegetable hosts. Growers should consider planting less susceptible or non-hosts such as peanut, sudangrass, sweet corn, and winter wheat in 2-3 year crop rotations to lower populations of this invasive nematode.

Ideal cardiovascular health and risk of death in a large Swedish cohort.

BACKGROUND: Ideal cardiovascular health (CVH) can be assessed by 7 metrics: smoking, body mass index, physical activity, diet, hypertension, dyslipidemia and diabetes, proposed by the American Heart Association. We examined the association of ideal CVH metrics with risk of all-cause, CVD and non-CVD death in a large cohort. METHODS: A total of 29,557 participants in the Swedish National March Cohort were included in this study. We ascertained 3,799 deaths during a median follow-up of 19 years. Cox regression models were used to estimate hazard ratios with 95% confidence intervals (95% CIs) of the association between CVH metrics with risk of death. Laplace regression was used to estimate 25th, 50th and 75th percentiles of age at death. RESULTS: Compared with those having 6-7 ideal CVH metrics, participants with 0-2 ideal metrics had 107% (95% CI = 46-192%) excess risk of all-cause, 224% (95% CI = 72-509%) excess risk of CVD and 108% (31-231%) excess risk of non-CVD death. The median age at death among those with 6-7 vs. 0-2 ideal metrics was extended by 4.2 years for all-causes, 5.8 years for CVD and 2.9 years for non-CVD, respectively. The observed associations were stronger among females than males. CONCLUSIONS: The strong inverse association between number of ideal CVH metrics and risk of death supports the application of the proposed seven metrics for individual risk assessment and general health promotion.

Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation.

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.

The association of short and long sleep with mortality in men and women.

Both short (< 6 hr) and long (> 8 hr) sleep are associated with increased mortality. We here investigated whether the association between sleep duration and all-cause, cardiovascular disease and cancer mortality differs between men and women. A cohort of 34,311 participants (mean age and standard deviation = 50.5 ± 15.5 years, 65% women), with detailed assessment of sleep at baseline and up to 20.5 years of follow-up (18 years for cause-specific mortality), was analysed using Cox proportional hazards model to estimate HRs with 95% confidence intervals. After adjustment for covariates, all-cause, cardiovascular disease and cancer mortalities were increased for both < 5 hr and ≥ 9 hr sleep durations (with 6 hr as reference). For all-cause mortality, women who slept < 5 hr had a hazard ratio = 1.54 (95% confidence interval = 1.32-1.80), while the corresponding hazard ratio was 1.05 (95% confidence interval = 0.88-1.27) for men, the interaction being significant (p < 0.05). For cardiovascular disease mortality, exclusion of the first 2 years of exposure, as well as competing risk analysis eliminated the originally significant interaction. Cancer mortality did not show any significant interaction. Survival analysis of the difference between the reference duration (6 hr) and the short duration (< 5 hr) during follow-up showed a gradually steeper reduction of survival time for women than for men for all-cause mortality. We also observed that the lowest cancer mortality appeared for the 5-hr sleep duration. In conclusion, the pattern of association between short sleep duration and all-cause mortality differed between women and men, and the difference between men and women increased with follow-up time.

The interaction and mediation effects between the host genetic factors and Epstein-Barr virus VCA-IgA in the risk of nasopharyngeal carcinoma.

Previous studies have demonstrated strong associations between host genetic factors and Epstein-Barr virus (EBV) VCA-IgA with the risk of nasopharyngeal carcinoma (NPC). However, the specific interplay between host genetics and EBV VCA-IgA on NPC risk is not well understood. In this two-stage case-control study (N = 4804), we utilized interaction and mediation analysis to investigate the interplay between host genetics (genome-wide association study-derived polygenic risk score [PRS]) and EBV VCA-IgA antibody level in the NPC risk. We employed a four-way decomposition analysis to assess the extent to which the genetic effect on NPC risk is mediated by or interacts with EBV VCA-IgA. We consistently found a significant interaction between the PRS and EBV VCA-IgA on NPC risk (discovery population: synergy index [SI] = 2.39, 95% confidence interval [CI] = 1.85-3.10; replication population: SI = 3.10, 95% CI = 2.17-4.44; all pinteraction < 0.001). Moreover, the genetic variants included in the PRS demonstrated similar interactions with EBV VCA-IgA antibody. We also observed an obvious dose-response relationship between the PRS and EBV VCA-IgA antibody on NPC risk (all ptrend < 0.001). Furthermore, our decomposition analysis revealed that a substantial proportion (approximately 90%) of the genetic effects on NPC risk could be attributed to host genetic-EBV interaction, while the risk effects mediated by EBV VCA-IgA antibody were weak and statistically insignificant. Our study provides compelling evidence for an interaction between host genetics and EBV VCA-IgA antibody in the development of NPC. These findings emphasize the importance of implementing measures to control EBV infection as a crucial strategy for effectively preventing NPC, particularly in individuals at high genetic risk.

Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions.

Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer (PLGC). Here, a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome, inflammatory proteins and DNA methylation alterations and their roles in PLGC development. The results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor genes. Seven inflammatory biomarkers were identified for antrum and corpus tissues, respectively, amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index (MDI) and methylation status of specific tumour suppressor genes. Notably, mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C-C motif chemokine 20 (CCL20) and tumour necrosis factor receptor superfamily member 9 (TNFRSF9). Overall, these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00118-w.

Apatinib potentiates the therapeutic effect of anti-PD-1 in locally advanced head and neck cancers.

OBJECTIVES: Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. PATIENTS AND METHODS: We investigate the impact of VEGFR2 inhibition on tumor-infiltrating immune cells in vivo and the activity of the combination of apatinib and anti-PD-1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. RESULTS: We found that apatinib increased the infiltration of CD8+ T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+ PD1+ T cells were significantly increased in apatinib-treated tumors. The combined treatment of apatinib and anti-PD-1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. CONCLUSION: Our study demonstrated that apatinib therapy synergized with an anti-PD-1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.

Oral fungal profiling and risk of nasopharyngeal carcinoma: a population-based case-control study.

BACKGROUND: Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC) carcinogenesis has not previously been investigated. METHODS: We characterized the oral salivary fungal mycobiome in 476 untreated incident NPC patients and 537 population-based controls using fungal internal transcribed spacer (ITS)-2 sequencing. The relationship between oral fungal mycobiome and the risk of NPC was assessed through bioinformatic and biostatistical analyses. FINDINGS: We found that lower fungal alpha diversity was associated with an increased odds of NPC [lower vs. higher: observed features (adjusted odds ratio [OR] = 5.81, 95% confidence interval [CI] = 3.60-9.38); Simpson diversity (1.53, 1.03-2.29); Shannon diversity (2.03, 1.35-3.04)]. We also observed a significant difference in global fungal community patterns between cases and controls based on Bray-Curtis dissimilarity (P < 0.001). Carriage of oral fungal species, specifically, Saccharomyces cerevisiae, Candida tropicalis, Lodderomyces elongisporus, Candida albicans, and Fusarium poae, was associated with significantly higher odds of NPC, with ORs ranging from 1.56 to 4.66. Individuals with both low fungal and low bacterial alpha diversity had a profoundly elevated risk of NPC. INTERPRETATION: Our results suggest that dysbiosis in the oral mycobiome, characterized by a loss of fungal community diversity and overgrowth of several fungal organisms, is associated with a substantially increased risk of NPC. FUNDING: This work was funded by the US National Institutes of Health, the Swedish Research Council, the High-level Talents Research Start-up Project of Fujian Medical University, and the China Scholarship Council.

Risk of colorectal adenocarcinoma in men receiving androgen deprivation therapy for prostate cancer; a nationwide cohort study.

PURPOSE: To assess whether androgens play a role in explaining the sex related differences in the incidence of colorectal cancer (CRC). METHODS: A nationwide matched cohort study was conducted employing the Prostate Cancer data Base Sweden (PCBaSe) 4.0 during the study period 2006-2016. Prostate cancer (PC) patients receiving androgen deprivation therapy (ADT) were treated as exposed. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed group. All were followed until a diagnosis of CRC, death, emigration, or end of the study period. The risk of CRC among ADT exposed PC patients compared to unexposed cancer-free men was calculated using a flexible parametric survival model and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: There was an increased risk of CRC among ADT exposed PC patients compared to unexposed cancer-free men (HR 1.27 [95% CI 1.15-1.41]), in particular an increased risk of adenocarcinoma of the colon (HR 1.33 [95% CI 1.17-1.51]) and more specifically an increased risk of adenocarcinoma of the distal colon (HR 1.53 [95% CI 1.26-1.85]). Examination of latency effects yielded significantly decreased HRs over time for CRC (p = 0.049 for trend). CONCLUSIONS: This population-based study found an increased risk of CRC among PC patients exposed to ADT, specifically adenocarcinoma of the distal colon, which indicates an increased association between ADT (PC + ADT) and CRC but not a positive dose-response trend questioning a true causal effect.

High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma.

Large-scale genetic association studies have identified multiple susceptibility loci for nasopharyngeal carcinoma (NPC), but the underlying biological mechanisms remain to be explored. To gain insights into the genetic etiology of NPC, we conducted a follow-up study encompassing 6,907 cases and 10,472 controls and identified two additional NPC susceptibility loci, 9q22.33 (rs1867277; OR = 0.74, 95% CI = 0.68-0.81, p = 3.08 × 10-11) and 17q12 (rs226241; OR = 1.42, 95% CI = 1.26-1.60, p = 1.62 × 10-8). The two additional loci, together with two previously reported genome-wide significant loci, 5p15.33 and 9p21.3, were investigated by high-throughput sequencing for chromatin accessibility, histone modification, and promoter capture Hi-C (PCHi-C) profiling. Using luciferase reporter assays and CRISPR interference (CRISPRi) to validate the functional profiling, we identified PHF2 at locus 9q22.33 as a susceptibility gene. PHF2 encodes a histone demethylase and acts as a tumor suppressor. The risk alleles of the functional SNPs reduced the expression of the target gene PHF2 by inhibiting the enhancer activity of its long-range (4.3 Mb) cis-regulatory element, which promoted proliferation of NPC cells. In addition, we identified CDKN2B-AS1 as a susceptibility gene at locus 9p21.3, and the NPC risk allele of the functional SNP rs2069418 promoted the expression of CDKN2B-AS1 by increasing its enhancer activity. The overexpression of CDKN2B-AS1 facilitated proliferation of NPC cells. In summary, we identified functional SNPs and NPC susceptibility genes, which provides additional explanations for the genetic association signals and helps to uncover the underlying genetic etiology of NPC development.

EBV antibody and gastric cancer risk: a population-based nested case-control study in southern China.

BACKGROUND: We aim to clarify the controversial associations between EBV-related antibodies and gastric cancer risk. METHODS: We analysed the associations between serological Epstein-Barr nuclear antigen 1 immunoglobulin A (EBNA1-IgA) and viral capsid antigen immunoglobulin A (VCA-IgA) by enzyme-linked immunosorbent assay and the risk of gastric cancer in a nested case-control study originated from a population-based nasopharyngeal carcinoma (NPC) screening cohort in Zhongshan, a city of southern China, including 18 gastric cancer cases and 444 controls. Conditional logistic regression was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: All the sera of cases were sampled before diagnosis and the median time interval was 3.04 (range: 0.04, 7.59) years. Both increased relative optical density (rOD) values of EBNA1-IgA and VCA-IgA were associated with higher risks of gastric cancer with age adjusted ORs of 1.99 (95%CI: 1.07, 3.70) and 2.64 (95%CI: 1.33, 5.23), respectively. Each participant was further classified as high or medium/low risk based on a combination of two anti-EBV antibody levels. Participants in the high-risk group had substantially higher odds of developing gastric cancer than that in the medium/low risk group with an age adjusted OR of 6.53 (95%CI: 1.69, 25.26). CONCLUSIONS: Our research reveals positive associations between EBNA1-IgA and VCA-IgA and gastric cancer risk in southern China. We thus postulate that EBNA1-IgA and VCA-IgA might appear to be potential biomarkers for gastric cancer. More research to further validate the results among diverse populations and investigate its underlying biological mechanism is needed.

Cancer risk following surgical removal of tonsils and adenoids - a population-based, sibling-controlled cohort study in Sweden.

BACKGROUND: Removal of tonsils and adenoids is among the most common surgical procedures worldwide. Evidence of increased risk of cancer following such surgery is, however, inconclusive. METHODS: We conducted a population-based, sibling-controlled cohort study of 4,953,583 individuals in Sweden with a follow-up during 1980-2016. History of tonsillectomy, adenotonsillectomy, and adenoidectomy was identified from the Swedish Patient Register whereas incident cases of cancer during follow-up were identified from the Swedish Cancer Register. We used Cox models to calculate hazard ratios (HR) with 95% confidence intervals (CI) of cancer in both a population and a sibling comparison. The sibling comparison was used to assess the potential impact of familial confounding, due to shared genetic or non-genetic factors within a family. RESULTS: We found a modestly increased risk for any cancer following tonsillectomy, adenoidectomy, or adenotonsillectomy in both the population (HR 1.10; 95%CI 1.07-1.12) and sibling (HR 1.15; 95%CI 1.10-1.20) comparisons. The association did not differ greatly by type of surgery, age at surgery, or potential indication for surgery, and persisted more than two decades after surgery. An excess risk was consistently observed for cancer of the breast, prostate, thyroid, and for lymphoma in both population and sibling comparisons. A positive association was observed for pancreatic cancer, kidney cancer, and leukemia in the population comparison whereas a positive association was observed for esophageal cancer in the sibling comparison. CONCLUSIONS: Surgical removal of tonsils and adenoids is associated with a modestly increased risk of cancer during the decades following the surgery. The association is unlikely attributed to confounding due to shared genetic or non-genetic factors with a family.

Behavioral deviations: healthcare-seeking behavior of chronic disease patients with intention to visit primary health care institutions.

BACKGROUND: Although primary health care (PHC) has been proven to be effective in preventing and treating chronic diseases, the visits rate of PHC institutions is still not ideal. Some patients initially express a willingness to visit PHC institutions but end up seeking health services at non-PHC institutions, and the reasons for this behavior remain unclear. Therefore, the objective of this study is to analyze the factors that contribute to behavioral deviations among chronic disease patients who originally intended to visit PHC institutions. METHODS: Data were collected from a cross-sectional survey among chronic disease patients with original intention to visit PHC institutions in Fuqing City, China. The analysis framework was guided by Andersen's behavioral model. Logistic regression models were employed to analyze the factors affecting the behavioral deviations among chronic disease patients with a willingness to visit PHC institutions. RESULTS: A total of 1,048 individuals were finally included and about 40% of the participants with the original willingness to seek care from PHC institutions finally chose non-PHC institutions in their subsequent visits. The results of logistic regression analyses indicated that at the predisposition factor level, older participants (aOR60-69 = 0.602, P < 0.01; aOR70-75 = 0.475, P < 0.01) were less likely to have behavioral deviations. At the enabling factor level, compared to those covered by Urban Employee Basic Medical Insurance (UEBMI) and not reimbursed, those covered by Urban-Rural Resident Basic Medical Insurance (URRBMI) (aOR = 0.297, P < 0.01), and those answering that reimbursement from medical institutions was convenient (aOR = 0.501, P < 0.01) or very convenient (aOR = 0.358, P < 0.001) were less likely to have behavioral deviations. At the need factor level, participants who visited PHC institutions due to illness last year (aOR = 0.348, P < 0.001) and with polypharmacy (aOR = 0.546, P < 0.01) were less likely to have behavioral deviations compared to those without the visit of PHC institutions and not taking polypharmacy, respectively. CONCLUSIONS: The deviations between the original willingness of PHC institution visits and subsequent behavior among chronic disease patients were associated with a number of predisposing, enabling, and need factors. Developing the health insurance system, strengthening the technical capacity of PHC institutions, and steadily developing a new concept of orderly healthcare-seeking behavior among chronic disease patients, will help promote their access to PHC institutions as well as improve the effectiveness of the tiered medical system for chronic disease care.

Risk of malignant lymphomas in patients with inflammatory bowel disease: a population-based cohort study.

OBJECTIVE: To estimate the risk of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) in patients with inflammatory bowel disease (IBD). DESIGN: We undertook a two-country population cohort study with all patients diagnosed with IBD in Norway and Sweden from 1987 and 1993 through 2015 and 2016, respectively, and analysed the risk of NHL and HL. In Sweden, we also analysed prescriptions of thiopurines and anti-tumour necrosis factor (TNF)-α therapy from 2005. We calculated standardised incidence ratios (SIRs) with 95% CIs using the general populations as reference. RESULTS: Among 131 492 patients with IBD with a medium follow-up of 9.6 years, we identified 369 cases of NHL and 44 cases of HL. The SIR of NHL was 1.3 (95% CI 1.1 to 1.5) in ulcerative colitis and 1.4 (95% CI 1.2 to 1.7) in Crohn's disease. We found no compelling heterogeneity in analyses stratified by patient characteristics. We found a similar pattern and magnitude of excess risks for HL. At 10 years, cumulative incidence was 0.26% (95% CI 0.23% to 0.30%) and 0.06% (95% CI 0.04% to 0.08%) for NHL and HL, respectively. Higher excess risks were found among patients with NHL with concomitant primary sclerosing cholangitis (SIR 3.4; 95% CI 2.1 to 5.2) and in those prescribed thiopurines alone (SIR 2.8; 95% CI 1.4 to 5.7) or with anti-TNF-α agents (SIR 5.7; 95% CI 2.7 to 11.9). CONCLUSION: Patients with IBD have a statistically significant increased risk of malignant lymphomas compared with the general population, but the absolute risk remains low.

Prospective study of weight loss and all-cause-, cardiovascular-, and cancer mortality.

Effects of repeated weight changes on mortality are not well established. In this prospective cohort study, we followed 34,346 individuals from 1997 to 2018 for all-cause mortality, and 2016 for cause-specific mortality. At baseline, participants self-reported amount and frequency of prior weight loss. During 20.6 (median) years of follow-up, we identified 5627 deaths; 1783 due to cancer and 1596 due to cardiovascular disease (CVD). We used Cox Proportional Hazards models to estimate multivariable-adjusted Hazard Ratios (HRs) and 95% confidence intervals (CI). Participants with a weight loss > 10 kg had higher rates of all-cause (HR 1.22; 95%CI 1.09-1.36) and CVD mortality (HR 1.27; 95%CI 1.01-1.59) compared to individuals with no weight loss. Men who had lost > 10 kg had higher all-cause (HR 1.55; 95%CI 1.31-1.84) and CVD mortality (HR 1.55; 95%CI 1.11-2.15) compared to men with no weight loss. Participants who had lost ≥ 5 kg three times or more prior to baseline had increased rates of all-cause (HR 1.16; 95%CI 1.03-1.30) and CVD mortality (HR 1.49; 95%CI 1.20-1.85) compared to participants with no weight loss. We found no association between weight loss and cancer mortality. We conclude that previous and repeated weight loss may increase all-cause and CVD mortality, especially in men.

Body mass index and body shape before treatment and nasopharyngeal carcinoma prognosis: A population-based patient cohort study in southern China.

A concern of reverse causation exists about the association between nasopharyngeal carcinoma (NPC) prognosis and body mass index (BMI) at diagnosis, while the prognostic impact of BMI measured years before diagnosis is unknown. Therefore, we investigated associations of prediagnosis and pretreatment BMI and body shape on NPC mortality. From a population-based patient cohort in southern China between 2010 and 2013, we included 2526 incident NPC cases with prospective follow-up through 2018. We assessed the associations of BMI and body shape at age 20 years, 10 years before diagnosis, and at diagnosis with NPC mortality, combining strategies of stratification and statistical adjustment to minimize reverse causation. We observed 25% lower all-cause mortality (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.64-0.89) and 25% lower NPC-specific mortality (HR 0.75, 95% CI: 0.61-0.91) among overweight vs normal-weight NPC cases at diagnosis. Lean body shapes 1 and 2 at diagnosis were associated with 68% and 23% higher all-cause mortality, respectively, compared to normal body shape 3. No effect modification by cancer stage was detected for associations with all-cause or NPC-specific mortality. Associations with BMI and body shape 10 years before diagnosis were similar but attenuated, while body size and shape at age 20 were not associated with mortality. Being overweight at diagnosis decreased mortality, and thinner body shape increased mortality, compared to normal weight/body shape. These associations may be due to poorer nutrition and treatment intolerance, resulting in treatment discontinuation and worse survival outcomes.

Pre-diagnostic anti-EBV antibodies and primary liver cancer risk: a population-based nested case-control study in southern China.

BACKGROUND: We aimed to investigate associations between pre-diagnostic anti-Epstein-Barr virus (EBV) antibodies, including interactions with hepatitis B virus (HBV), and risk of primary liver cancer in southern China. METHODS: In a population-based nested case-control study, we measured pre-diagnostic immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) in 125 primary liver cancer cases and 2077 matched controls. We also explored the interaction between HBV surface antigen (HBsAg) and anti-EBV antibodies. RESULTS: Participants with positive EBNA1-IgA, positive VCA-IgA or single-positive anti-EBV antibodies had two-fold odds of developing liver cancer, compared with seronegative subjects. The odds ratios (ORs) between the relative optical density of EBNA1-IgA and VCA-IgA and primary cancer, controlling for age and HBsAg, were 1.59 (95% confidence interval (CI): 1.17, 2.14) and 1.60 (95% CI: 1.07, 2.41), respectively. Subjects with both HBsAg and anti-EBV antibody seropositivity were at 50-fold increased risk compared with those negative for both biomarkers (OR: 50.67, 95% CI: 18.28, 140.46), yielding a relative excess risk due to interaction of 30.81 (95% CI: 3.42, 114.93). CONCLUSION: Pre-diagnostic seropositivity for EBNA1-IgA and/or VCA-IgA was positively associated with primary liver cancer risk, especially in combination with HBsAg positivity. EBV may interact with HBV in the development of primary liver cancer, and anti-EBV antibodies might be potential biomarkers for primary liver cancer in this high-risk population.

Trace elements in hair or fingernail and gastroesophageal cancers: results from a population-based case-control study.

BACKGROUND: Growing evidence suggests that environmental factors probably play important roles in the development of gastroesophageal cancers (GOC), however, the effects of trace elements on GOC remain unclear. OBJECTIVE: To assess the effect of trace elements on GOC and the effect modification by other factors. METHODS: Hair and fingernail samples were collected from GOC cases and controls in a population-based case-control study in Taixing, China, and were used to detect the concentrations of 12 trace elements using inductively coupled plasma mass spectrometry. Unconditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for concentrations of 12 trace elements in association with GOC after adjusting the other factors. RESULTS: A total of 830 hair samples (581 controls and 249 cases) and 895 fingernail samples (559 controls and 336 cases) were included. Compared to the lowest-tertile concentration, the higher tertiles of Ca, Zn, Fe, Al, Cr, Pb, Se, and V were positively associated with GOC, while the higher tertiles of Mg, Mn, Sr, and As were inversely associated with GOC. Significant interactions between the hair level of Cr and two other risk factors, including smoking (P for interaction = 0.044) and alcohol drinking (P for interaction = 0.028), were observed in association with GOC. SIGNIFICANCE: The current study reveals that these 12 trace elements in hair and fingernails are associated with GOC to varying degrees. Further studies and animal experiments are needed to clarify the associations and explore potential mechanisms. IMPACT STATEMENT: The role of trace elements in the development or inhibition of gastroesophageal cancers (GOC) remains unclear. In this study, we further explored the associations between 12 trace elements and GOC based on a population-based case-control study conducted in Taixing, China. Higher levels of Ca, Zn, Fe, Al, Cr, Pb, Se, and V were positively associated with increased GOC, while inverse associations between higher levels of Mg, Mn, Sr, As, and GOC were observed. Observed associations were consistent in hair and fingernail samples. Moreover, interaction effects between hair level of Cr and smoking or alcohol drinking were identified.