Factor modification in the association between high-density lipoprotein cholesterol and liver cancer risk in a nationwide cohort.

BACKGROUND/AIMS: The effect modification by smoking and menopausal status in the association between high-density lipoprotein cholesterol (HDL-C) and liver cancer risk has not been reported. METHODS: This population-based cohort study included 4.486 million cancer-free individuals among those who underwent national cancer screening in 2010 and were followed up until December 2017. We conducted analyses in populations that excluded people with chronic hepatitis B, chronic hepatitis C and liver cirrhosis (Model I) and that included those diseases (Model III). HDL-C level was classified into eight groups at 10-mg/dL intervals. Liver cancer risk by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: During follow-up, 18 795 liver cancers in Model I and 20 610 liver cancers in Model III developed. In Model I, low HDL-C levels (aHR 1.83; 95% CI 1.65-2.04) and extremely high HDL-C levels (aHR 1.24; 95% CI 1.10-1.40) were associated with an increased liver cancer risk compared with a moderate HDL-C level of 50-59mg/dL. This association was similar in both men and women with larger effect size in men (aHR, 1.91; 95% CI, 1.70-2.15). The hazardous association between low HDL-C and liver cancer risk was remarkable in current smokers (aHR, 2.19; 95% CI, 1.84-2.60) and in pre-menopausal women (aHR, 2.91; 95% CI, 1.29-6.58) compared with post-menopausal women (aHR, 1.45; 95% CI, 1.10-1.93). This association was similarly observed in Model III. CONCLUSIONS: Low and extremely high HDL-C levels were associated with an increased liver cancer risk. The unfavourable association between low HDL-C and liver cancer was remarkable in smokers and pre-menopausal women.

High burden of human papillomavirus infection among men in Guangzhou, South China: Implications for HPV vaccination strategies.

The epidemiological and clinical aspects of Human Papillomavirus (HPV) infection in women have been extensively studied. However, there is a lack of information regarding HPV characteristics in males. In this study, we conducted a retrospective and observational study of 3737 consecutive male individuals attending outpatient clinics of Guangdong Women and Children Hospital from 2012 to 2023 in Guangzhou, South China, to determine the age- and genotype-specific prevalence of HPV in men. The results showed the overall prevalence of HPV among men was 42.15% (1575/3737), with variations ranging from 29.55% to 81.31% across distinct diagnostic populations. Low-risk HPV6 (15.47%), HPV11 (8.94%), and high-risk HPV52 (5.51%) were the most common types. The annual HPV prevalence decreased significantly (Z = -3.882, p < .001), ranging from 31.44% to 52.90%. 28.77% (1075/3737) of men manifested infection with a singular HPV type, predominantly identified as a low-risk type. The age-specific distribution of HPV infections revealed distinctive peaks in the < 25 y age group (47.60%, 208/437) and the 40-44 y age group (44.51%, 154/346). Notably, the positive rate of Chlamydia trachomatis was significantly higher among HPV-positive individuals in comparison to HPV-negatives (16.14% vs. 11.25%, p < .05). Our findings reveal a substantial prevalence of HPV infection among outpatient men in Guangzhou, South China. It is recommended to consider the inclusion of HPV vaccination for adolescent males in national immunization schedules, once an adequate supply of vaccines is accessible.

Tumor growth manifested in two-fifths of low-risk papillary thyroid microcarcinoma patients during active surveillance: data from a tertiary center in China.

Purpose: To assess tumor growth using tumor doubling rate (TDR) during active surveillance (AS) in China. Methods: Between January 2016 and June 2020, a total of 219 patients with low-risk papillary thyroid microcarcinoma (PTMC) (aged 23-75 years) were consecutively enrolled in the AS program. Results: Four sections of TDR, >0.5, 0.1~0.5, -0.1~0.1 and <-0.1, corresponded with four categories of tumor volume kinetics: rapid growth, slow growth, stable, and decreased size. We found that 10.5% of PTMCs exhibited rapid growth, 33.33% exhibited slow growth, 26.48% were stable, and 29.68% decreased in size. Tumor growth was associated with two factors: age and volume of PTMC at diagnosis. 85.72% of elderly patients (≥ 61 years old) had tumors that remained stable or even shrank and rapidly growing tumors were not found in them. When the volume was small (≤14.13 mm3), the proportion of rapid growth was high (41.67%), whereas when the volume was large (> 179.5 mm3), the proportion of non-growth was 68.75%. Conclusion: TDR may be a better metric for evaluating tumor growth in observational PTMCs. A certain proportion of PTMCs grow during the period of AS and tumor growth was associated with age and volume of PTMC at initial diagnosis. Therefore, how to block tumor growth during the AS period, especially for young patients and patients with early-stage PTMC (size ≤ 5 mm), will be a new challenge.

ProtecT trial: What's new after 15 years of follow-up: Re: Hamdy FC and colleagues; N Engl J Med. 2023 Apr 27.

Recent results of ProtecT trial published after 15 years of follow-up demonstrate the absence of difference in prostate cancer-specific survival between active monitoring, radiotherapy, or prostatectomy for PSA-detected, localized prostate cancer patients. These results definitively confirm the essential role of active surveillance as the gold standard for men with low-risk and highly selected intermediate-risk prostate cancer. It underlines the importance of shared-decision making process with patients.

Does Pre-Emptive Availability of PREDICT 2.1 Results Change Ordering Practices for Oncotype DX? A Multi-Center Prospective Cohort Study.

For early-stage hormone receptor (HR)-positive and HER2-negative breast cancer, tools to estimate treatment benefit include free and publicly available algorithms (e.g., PREDICT 2.1) and expensive molecular assays (e.g., Oncotype DX). There remains a need to identify patients who de-rive the most benefit from molecular assays and where this test may be of poor value. In this multicenter prospective cohort study, we evaluated whether use of PREDICT 2.1 would impact physician decision making. For the first 6 months of the study, data on physician use of both PREDICT 2.1 and Oncotype DX ordering were collected on all newly diagnosed patients eligible for molecular testing. After 6 months, an educational intervention was undertaken to see if providing physicians with PREDICT 2.1 results affects the frequency of Oncotype DX requests. A total of 602 patients across six cancer centers in Ontario, Canada were recruited between March 2020 and November 2021. Providing PREDICT 2.1 results and an educational intervention did not alter the ordering of an Oncotype DX. For patients with low clinical risk, either by clinico-pathologic features or by PREDICT 2.1, the probability of obtaining a high Oncotype DX recurrence score was substantially lower compared to patients with high-clinical-risk disease. The introduction of an educational intervention had no impact on molecular assay requests. However, routine ordering of molecular assays for patients with low-clinical-risk disease is of poor value.

Congenital Tooth Agenesis and Risk of Early-Onset Cancer.

Importance: There is some evidence that tooth agenesis (congenital absence of 1 or more teeth) is associated with cancer risk, especially carcinomas of the colon and ovaries, but results of previous studies are conflicting, and associations have not yet been evaluated in a population-based setting. Objective: To examine the association between tooth agenesis and specific cancer types before 40 years of age. Design, Setting, and Participants: This population-based cohort study used linking data from nationwide registries in Denmark to assess all Danish live-born singletons born from January 1, 1977, to December 31, 2018, and followed up for up to 40 years. Data were analyzed from January through June 2023. Exposure: Tooth agenesis as documented by the Danish Central Registry of Odontology (Danish municipal pediatric dental care) from January 1, 1988, to December 31, 2018, and from hospital encounters in the Danish National Patient Registry within the entire study period. Main Outcome and Measures: The primary outcome was first cancer diagnosis before 40 years of age obtained from the Danish Cancer Registry. Associations between tooth agenesis and specific cancers were estimated by Cox proportional hazards regression as hazard ratios (HRs) with 95% CIs. Analyses were split into age groups: younger than 1 year, 1 to younger than 3 years, 3 to younger than 10 years, 10 to younger than 20 years, 20 to younger than 30 years, and 30 to younger than 40 years. Associations with nonsyndromic tooth agenesis were evaluated after exclusion of individuals with known syndromes. Results: Among 2 501 715 included individuals (1 284 292 [51.3%] male), 70 288 (2.8%) had a diagnosis of tooth agenesis (mean [SD] age at diagnosis, 13.2 [4.1] years) and 26 308 (1.1%) had a diagnosis of early-onset cancer within the study period; 778 individuals had co-occurrence of tooth agenesis and cancer. Overall, tooth agenesis was positively associated with several cancer types, including neuroblastoma (age 1 to <3 years; HR, 4.20; 95% CI, 2.24-7.88), nephroblastoma (age 1 to <3 years; HR, 4.59; 95% CI, 2.37-8.91), hepatoblastoma (age 1 to <3 years; HR, 7.10; 95% CI, 2.70-18.68), osteosarcoma (age 10 to <20 years; HR, 2.19; 95% CI, 1.11-4.32), colorectal carcinomas (age 30 to <40 years; HR, 2.81; 95% CI, 1.38-5.71), and carcinomas of bladder (age 20 to <30 years; HR, 3.35; 95% CI, 1.35-8.30). Conclusions and Relevance: This cohort study found associations between congenital tooth agenesis and several cancer types, from childhood to early adulthood. Further evaluation of these associations is needed to assess possible clinical implications.

Guidelines to restrict consumption of red meat to under 350 g/wk based on colorectal cancer risk are not consistent with health evidence.

BACKGROUND: The Nordic Nutrition Recommendations of 2023 (NNR2023) incorporate sustainability, health, and nutrition in their food-based dietary guidelines (FBDGs). NNR2023 recommends a consumption of ≤350 g/wk of unprocessed red meat (RM) based on association with colorectal cancer (CRC). This recommendation is lower than other FBDGs such as the World Cancer Research Fund (WCRF) recommendation it is based on (350-500 g/wk). OBJECTIVE: To evaluate the empirical evidence and models cited by the NNR2023 to support the RM guidance. METHODS: We fitted least-assumption (LA) dose-response (DR) models to the studies included in two systematic reviews (SRs) selected by NNR2023 on the RM and CRC association. We compared them against six parametric models reported in the two SRs. We evaluated the statistical significance of modeled relative risks (RR) at different consumption levels. RESULTS: Twenty-one studies (20,604,188 patient-years) were analyzed. We found no significant association (RR = 1.04, 0.99-1.09) between 350g/wk of RM and CRC using the LA models, in agreement with the least restrictive models reported by Lescinsky et al., 2022 (RR = 1.11[0.89-1.38]) and WCRF (RR= 1.01[0.96-1.07]). The association was significant at 350 g/wk only under restricting assumptions such as monotonicity RR=1.3[1.01-1.64], and linearity RR = 1.06 [1.00-1.12]. No significant empirical association is observed under 567 g/wk based on evidence used by NNR2023. CONCLUSIONS: The sources cited by NNR2023 do not support a consumption restriction of ≤350 g/wk of RM due to CRC, and other studies omitted by NNR2023 do not support association between RM and CRC. We show that model assumptions rather than empirical evidence drive this recommendation. Model uncertainty should be explicitly incorporated in FBDGs.

Decision-making for bilateral risk-reducing mastectomy for an increased lifetime breast cancer risk: A qualitative metasynthesis.

OBJECTIVE: Previvor is a term applied to a person with an identified, elevated lifetime cancer risk but without an actual cancer diagnosis. Previvorship entails the selection of risk management strategies. For women with a genetic mutation that increases their predisposition for a breast cancer diagnosis, bilateral risk-reducing mastectomy (BRRM) is the most effective prevention strategy. However, BRRM can change a woman's breast appearance and function. The purpose of this qualitative metasynthesis (QMS) was to better understand the decision-making process for BRRM among previvors. METHODS: A theory-generating QMS approach was used to analyze and synthesize qualitative findings. Research reports were considered for inclusion if: (1) women over 18 years of age possessed a genetic mutation increasing lifetime breast cancer risk or a strong family history of breast cancer; (2) the sample was considering, or had completed, BRRM; (3) the results reported qualitative findings. Exclusion criteria were male gender, personal history of breast cancer, and research reports which did not separate findings based on cancer diagnosis and/or risk-reduction surgery. RESULTS: A theory and corresponding model emerged, comprised of seven themes addressing the decision-making process for or against BRRM. While some factors to decision-making were decisive for surgery, others were more indefinite and contributed to women changing, processing, or suspending their decision-making for a period of time. CONCLUSIONS: Regardless of the decision previvors make about BRRM, physical and psychosocial well-being should be considered and promoted through shared decision-making in the clinical setting.

Relative risks of childhood developmental vulnerabilities in three Australian communities with exposure to per- and polyfluoroalkyl substances: data linkage study.

Background: Aqueous film forming foams (AFFF) containing per- and polyfluoroalkyl substances (PFAS) caused local environmental contamination in three Australian residential areas: Katherine in the Northern Territory (NT), Oakey in Queensland (Qld) and Williamtown in New South Wales (NSW). We examined whether children who lived in these areas had higher risks of developmental vulnerabilities than children who lived in comparison areas without known contamination. Methods: All children identified in the Medicare Enrolment File-a consumer directory for Australia's universal healthcare insurance scheme-who ever lived in exposure areas, and a sample of children who ever lived in selected comparison areas, were linked to the Australian Early Development Census (AEDC). The AEDC data were available from four cycles: 2009, 2012, 2015 and 2018. For each exposure area, we estimated relative risks (RRs) of developmental vulnerability on each of five AEDC domains and a summary measure, adjusting for sociodemographic characteristics and other potential confounders. Findings: We included 2,429 children from the NT, 2,592 from Qld and 510 from NSW. We observed lower risk of developmental vulnerability in the Communication skills and general knowledge domain in Katherine (RR = 0.74, 95% confidence interval (CI) 0.57 to 0.97), and higher risks of developmental vulnerability in the same domain (RR = 1.49, 95% CI 1.18 to 1.87) and in the Physical health and wellbeing domain in Oakey (RR = 1.31, 95% CI 1.06 to 1.61). Risks of developmental vulnerabilities on other domains were not different from those in the relevant comparison areas or were uncertain due to small numbers of events. Conclusion: There was inadequate evidence for increased risks of developmental vulnerabilities in children who ever lived in three PFAS-affected areas in Australia.

Fishing for oil and meat drives irreversible defaunation of deepwater sharks and rays.

The deep ocean is the last natural biodiversity refuge from the reach of human activities. Deepwater sharks and rays are among the most sensitive marine vertebrates to overexploitation. One-third of threatened deepwater sharks are targeted, and half the species targeted for the international liver-oil trade are threatened with extinction. Steep population declines cannot be easily reversed owing to long generation lengths, low recovery potentials, and the near absence of management. Depth and spatial limits to fishing activity could improve conservation when implemented alongside catch regulations, bycatch mitigation, and international trade regulation. Deepwater sharks and rays require immediate trade and fishing regulations to prevent irreversible defaunation and promote recovery of this threatened megafauna group.

Meta-analysis: Risk of pancreatic cancer in patients with inflammatory bowel disease.

BACKGROUND: Studies exploring the association between inflammatory bowel disease (IBD) and pancreatic cancer have reported inconsistent results. AIMS: To provide a comprehensive overview of the risk of pancreatic cancer development in patients with IBD. METHODS: We searched Embase, PubMed, Scopus and ProQuest from inception to 31 October 2023. We included population-based cohort studies examining the risk of incident pancreatic cancer in adult patients with IBD compared to the non-IBD population. We also retrieved Mendelian randomisation (MR) studies investigating the relationship of IBD with pancreatic cancer risk. We conducted random-effects meta-analyses and provided pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We included 13 studies. Among 11 cohort studies, the risk of developing pancreatic cancer increased by 79% in patients with IBD (RR = 1.79 [95% CI: 1.16-2.75]; I2 = 95.7%). Patients either with Crohn's disease (RR = 1.42 [95% CI: 1.24-1.63]) or ulcerative colitis (RR = 1.50 [95% CI: 1.17-1.92]) had increased risk (p for interaction = 0.72). The annual incidence of pancreatic cancer potentially attributable to IBD increased by 55 cases (95% CI: 17-103) per million. Two MR studies demonstrated that genetic liability to IBD was associated with an increased risk of pancreatic cancer. CONCLUSIONS: Our results suggest a moderate increase in the risk of pancreatic cancer in patients with IBD, which may be further heightened by genetic predisposition to IBD. The increased risk of pancreatic cancer is probably similar in Crohn's disease and ulcerative colitis.

A parametric additive hazard model for time-to-event analysis.

BACKGROUND: In recent years, the use of non- and semi-parametric models which estimate hazard ratios for analysing time-to-event outcomes is continuously criticized in terms of interpretation, technical implementation, and flexibility. Hazard ratios in particular are critically discussed for their misleading interpretation as relative risks and their non-collapsibility. Additive hazard models do not have these drawbacks but are rarely used because they assume a non- or semi-parametric additive hazard which renders computation and interpretation complicated. METHODS: As a remedy, we propose a new parametric additive hazard model that allows results to be reported on the original time rather than on the hazard scale. Being an essentially parametric model, survival, hazard and probability density functions are directly available. Parameter estimation is straightforward by maximizing the log-likelihood function. RESULTS: Applying the model to different parametric distributions in a simulation study and in an exemplary application using data from a study investigating medical care to lung cancer patients, we show that the approach works well in practice. CONCLUSIONS: Our proposed parametric additive hazard model can serve as a powerful tool to analyze time-to-event outcomes due to its simple interpretation, flexibility and facilitated parameter estimation.

[Research progress and countermeasures of cancer risk in police officers].

The people's police of public security organs shoulder the important mission of maintaining social security and stability, and ensuring the well-being of people. However, the working environment exposed to a variety of adverse factors has significantly increased the risk of cancer and cancer mortality of public security police, such as bladder cancer, prostate cancer, colon cancer, melanoma cancer, etc. Police related cancer risk research is a noteworthy issue. This article provides a review of existing research on the types and carcinogenic factors of cancer among domestic and foreign police officers, and analyzes various factors that may lead to their cancer based on the actual work situation of Chinese public security police. Corresponding response strategies are proposed to provide a scientific basis for reducing the risk of cancer among public security police.

Benzene Exposure and Lung Cancer Risk: A Systematic Review and Meta-Analysis of Human Studies.

Lung cancer is a leading cause of death with nearly 1.8 million deaths estimated worldwide in 2020. Although benzene is classified as a human carcinogen (Group 1) on the basis of its association with acute myeloid/non-lymphocytic leukaemia, there is still limited evidence that it may influence lung cancer risk. This study examined the potential link between benzene exposure and risk of lung cancer using a systematic review of epidemiological studies and meta-analysis. We searched through PubMed, Web of Science and Scopus databases up to 10 February 2023 to identify all articles on the association between benzene exposure and lung cancer (incidence or prevalence) and/or mortality. We extracted the risk estimates of the highest and the lowest reported categories of benzene exposure and conducted a meta-analysis using a random-effects model. Heterogeneity and publication bias were analysed using an I2 test and funnel plots asymmetry, respectively. Twenty-one studies were included in the final analysis, with a total of 10,750 lung cancer cases and 2899 lung cancer deaths. Overall, risk estimates of lung cancer prevalence and mortality in association with benzene exposure were 1.20 (n = 14; 95% CI 1.05-1.37) and 1.15 (n = 13; 95% CI 1.02-1.30), respectively. In all cases, heterogeneity was quite large, while no significant publication bias was observed. When only studies that adjusted for smoking habit were selected, the risk for lung cancer increased by up to 34% (n = 9; 95% CI 1.10-1.64). Our data, which show a strong association between benzene exposure and lung cancer risk, may have important public health implications. However, further studies are needed to identify the lung cancer risk associated with benzene exposure considering different smoking conditions.