Site-specific Cancer Research Articles

Remote Manipulation of TRPV1 Signaling by Near-Infrared Light-Triggered Nitric Oxide Nanogenerators for Specific Cancer Therapy.

Specific activation of transient receptor potential vanilloid member 1 (TRPV1) channels provides a new avenue for cancer treatment by inducing excessive Ca2+ influx. However, controllable manipulation of TRPV1 signaling for clinical application has remained elusive due to the challenge in finding a mild and effective method of exerting external stimulus without adverse side effects in living systems. Herein, a TRPV1-targeting near-infrared (NIR) triggered nitric oxide (NO)-releasing nanoplatform (HCuS@PDA-TRPV1/BNN6) based on polydopamine (PDA) coated hollow copper sulfide nanoparticles (HCuS NPs) is developed for specific cancer therapy. Upon NIR irradiation, the NO donor BNN6 encapsulated in NIR-responsive nanovehicles can locally generate NO to activate TRPV1 channels and induce Ca2+ influx. This NIR controlled mode enables the nanoplatform to exert its therapeutic effects below the apoptotic threshold temperature (43°C), minimizing the photothermal damage to normal tissue. Integrating this special NO-mediated therapy with HCuS NPs mediated chemodynamic therapy, the designed nanoplatform exhibits a boosted anticancer activity with negligible systematic toxicity. Together, this study provides a promising strategy for site-specific cancer therapy by spatiotemporally controlled activation of surface ion channels, thus offering a solution to an unmet clinical need in cancer treatment.

Relationship Between Aspirin Use and Site-Specific Colorectal Cancer Risk Among Individuals With Metabolic Comorbidity.

The relationship between aspirin usage and the risk of colorectal cancer (CRC) among individuals with both hypertension (HTN) and diabetes mellitus (DM) remains unclear. This study aims to explore the impact of aspirin use on the site-specific CRC risk in patients with metabolic comorbidity. A case-control study was conducted among 1,331 CRC patients and 2,771 controls recruited from the Nation Cancer Center in Korea. Multinomial logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between aspirin use, metabolic disease status, and site-specific CRC risk. Among the 4,102 participants, 1,191 individuals had neither HTN nor DM, 2,044 were diagnosed with HTN, 203 with DM, and 664 presented with HTN and DM comorbidity. An increasing number of HTN and DM was associated with an increased risk of overall CRC (HTN or DM: OR, 1.70; 95% CI, 1.39-2.07; HTN and DM: OR, 8.43; 95% CI, 6.37-11.16), while aspirin use was associated with a decreased risk of overall CRC (OR, 0.31; 95% CI, 0.21-0.46). These results remained consistent across anatomical sites. Among individuals with HTN and DM comorbidity, aspirin use notably associated with lower risk of overall CRC (OR, 0.39; 95% CI, 0.21-0.72), proximal colon (OR, 0.32; 95% CI, 0.13-0.71) and rectal cancer (OR, 0.27; 95% CI, 0.08-0.97), but not distal colon cancer (OR, 0.58; 95% CI, 0.27-1.24). This study showed that aspirin use is negatively associated with overall and site-specific CRC, even among individuals with HTN and DM comorbidity.

Spectrum of hepatitis B and hepatitis C-related cancers in India.

Hepatitis-B virus infection contributes to 40%-50% of the Hepato-cellular carcinomas (HCC) in India, while hepatitis-C virus infection accounts for 12%-32% of cases. This study aimed at determining the patterns of cancers among patients with hepatitis B and C. This was a retrospective study of cancer patients with histologically proven diagnoses of cancer registered at Tata Memorial Hospital in Mumbai between 2017 and 2018. The proportional incidence ratio (PIR) was computed by dividing the observed number of site-specific cancer cases by the expected number. The study participants' mean (SD) age was 48.69 (±16.91) years with a male-to-female ratio of 1.36. The prevalence of hepatitis B and C was 1.93% and 1.17%, respectively. Liver cancer showed the highest occurrence rate with notably increased PIR among individuals positive for hepatitis B (males: 14.41, females: 10.89) and hepatitis C (males: 7.15, females: 10.42). Furthermore, hepatitis B-positive patients showed elevated PIR for haemato-lymphoid malignancies such as multiple myeloma and non-Hodgkin's lymphoma. The correlation between HBsAg and specific cancer types (PIRs) is limited by small case numbers, requiring careful interpretation of these findings. The PIR for liver cancer was heightened in both hepatitis B and C patients. Strengthened surveillance, including pre-screening for hepatitis B and C positive infection among cancer patients, as well as screening for HCCs among hepatitis seropositive individuals, is crucial to mitigate the incidence of HCC.

Causal relationship between genetically predicted uterine leiomyoma and cancer risk: a two-sample Mendelian randomization.

Studies have demonstrated that hormonal imbalance, such as elevated level of estrogen or reduced level of progesterone, was the main inducing factor of uterine leiomyoma (UL) development and some cancers. UL has been reported to be associated with several cancers in observational studies. However, the causal associations between UL and cancers remain unclear. A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal associations between UL and 16 site-specific cancers using the public databases. Four methods, namely, the inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode, were applied in our MR analysis. Sensitivity tests were also performed to evaluate the robustness of these causal associations. The IVW analysis indicated that genetically predicted UL increased the risk of low malignant potential ovarian cancer [odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.06-1.40, p = 0.004], serous ovarian cancer (OR = 1.29, 95% CI: 1.10-1.52, p = 0.002), invasive mucinous ovarian cancer (OR = 1.24, 95% CI: 1.08-1.44, p = 0.003), clear cell ovarian cancer (OR = 1.25, 95% CI: 1.03-1.51, p = 0.023), breast cancer (OR = 1.07, 95% CI: 1.02-1.11, p = 0.002), and brain tumor (OR = 1.23, 95% CI: 1.06-1.42, p = 0.007). Conversely, genetically predicted UL reduced the risk of gastric cancer (OR = 0.91, 95% CI: 0.85-0.98, p = 0.008). The causal effects were consistent in the sensitivity analysis. Our results demonstrated that UL exhibits a causal relationship with high risk of several cancers. We suggest reinforcing the cancer screening in UL patients to enable the early detection of cancers.

Risk of Breast Cancer After Diabetes in Pregnancy: A Population-based Cohort Study

ObjectivesDiabetes is associated with an increased risk of several cancers, including postmenopausal breast cancer. The evidence for higher breast cancer risk after diabetes in pregnancy is conflicting. We compared the incidence of breast and other cancers between pregnant women with and without diabetes. MethodsThis work was a propensity-matched, retrospective cohort study using population-based health-care databases from Ontario, Canada. Those deliveries with gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (pregestational DM) were identified and matched to deliveries without diabetes mellitus (non-DM). Deliveries from each diabetes cohort were matched 1:2 on age, parity, year of delivery, and propensity score to non-DM deliveries. Matched subjects were followed from delivery for incidence of breast cancer as a primary outcome, and other site-specific cancers as secondary outcomes. We performed Cox proportional hazards regression to compare rates of breast cancer between matched groups. ResultsOver a median of 8 (interquartile range 4 to 13) years of follow-up, compared with non-DM deliveries, the incidence of breast cancer was significantly lower for GDM but similar for pregestational DM deliveries (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.82 to 0.98; and HR 0.92, 95% CI 0.80 to 1.07, respectively). GDM was associated with a significantly higher incidence of pancreatic and hepatocellular cancer, and pregestational DM was associated with a higher incidence of thyroid, hepatocellular, and endometrial cancers. ConclusionsDiabetes in pregnancy does not have a higher short-term risk of subsequent breast cancer, but there may be a higher incidence of other cancers.

Association between circadian physical activity patterns and cancer incidence through regulation of inflammation: A UK biobank study

BackgroundPhysical activity (PA) has been linked with cancer incidence. However, the effects and mechanisms underpinning circadian PA trajectories on cancer remain elusive. This study aimed to explore the optimal PA patterns in reducing cancer incidence and the associated potential mediators. MethodsBetween 2006 and 2010, 502,400 participants were recruited from the UK Biobank. Out of these, 102,323 participants wore accelerometers, which allowed for collecting acceleration data continuously over 7 days. After excluding participants with previous cancer history, 96,687 participants were included in K-means cluster analysis to identify PA trajectories. The association between PA and cancer incidence was assessed using Cox regression analysis. Additionally, we investigated the mediating role of inflammation. ResultsA total of 5995 cancer cases were recorded during a median follow-up of 7.1 years. Four distinct PA trajectories (persistent low, single peak, double peak, and vigorous) were identified. The ideal PA patterns reduced the risk of 7 out of 17 site-specific cancers, with the lowest hazard ratios and 95% confidence intervals of cancer for bladder (0.59, 0.40–0.86), breast (0.73, 0.60–0.89), kidney (0.45, 0.26–0.78), lung (0.59, 0.41–0.84), myeloma (0.49, 0.27–0.88), and oral & pharynx (0.51, 0.26–0.98) in the vigorous pattern and for colorectal (0.71, 0.54–0.93) in the double peak pattern. Moreover, the mediating effects of inflammation were significant. ConclusionOptimal PA trajectories reduced cancer incidence, especially in double peak and vigorous patterns. The protective effect was associated with both intensity and circadian rhythm. Crucially, this protection was mediated by inflammation regulation.

Controlling Risk Factors Reduces Cancer Risk in Patients with Atherosclerotic Cardiovascular Disease: A Cohort Study

BackgroundThe association of atherosclerotic cardiovascular disease (ASCVD) with cancer occurrence is not well examined, and the impact of common risk factors on the risk of cancer in ASCVD patients is not known. This study aimed to explore the effect and possible causes of ASCVD on cancer risk through a cohort study. MethodsA total of 14,665 age- and sex-matched pairs of participants were recruited from the Kailuan cohort (ASCVD vs non-ASCVD). A competing risk model was used to calculate the risk of cancer after ASCVD. ResultsA total of 1124 cancers occurred after 5.80 (3.05-9.44) years of follow-up. The ASCVD group had a reduced risk of cancer (hazard ratio 0.74; 95% confidence interval, 0.65-0.85). Also, the risk of cancer in the digestive system, respiratory system, urinary system, and reproductive system was reduced by 17%, 16%, 14%, and 52%, respectively. According to the status of systolic and diastolic blood pressure, fasting blood glucose, high-sensitivity C-reactive protein and body mass index after ASCVD, the risk of overall cancer and digestive system cancer decreased with the increase in the number of ideal indicators (P for trend < .01). With the increase of follow-up time, the risk of cancer and the 5 site-specific cancers gradually decreased. ConclusionsCancer risk can be reduced by controlling for common risk factors after ASCVD event. This risk reduction is site-specific-, time-, and the number of ideal indicator-dependent.

Long-term exposure to ambient fine particulate matter constituents and mortality from total and site-specific gastrointestinal cancer

BackgroundAmbient fine particulate matter (PM2.5) exposure has been associated with an increased risk of gastrointestinal cancer mortality, but the attributable constituents remain unclear. ObjectivesTo investigate the association of long-term exposure to PM2.5 constituents with total and site-specific gastrointestinal cancer mortality using a difference-in-differences approach in Jiangsu province, China during 2015–2020. MethodsWe split Jiangsu into 53 spatial units and computed their yearly death number of total gastrointestinal, esophagus, stomach, colorectum, liver, and pancreas cancer. Utilizing a high-quality grid dataset on PM2.5 constituents, we estimated 10-year population-weighted exposure to black carbon (BC), organic carbon (OC), sulfate, nitrate, ammonium, and chloride in each spatial unit. The effect of constituents on gastrointestinal cancer mortality was assessed by controlling time trends, spatial differences, gross domestic product (GDP), and seasonal temperatures. ResultsOverall, 524,019 gastrointestinal cancer deaths were ascertained in 84.77 million population. Each interquartile range increment of BC (0.46 μg/m3), OC (4.56 μg/m3), and nitrate (1.41 μg/m3) was significantly associated with a 27%, 26%, and 34% increased risk of total gastrointestinal cancer mortality, respectively, and these associations remained significant in PM2.5-adjusted models and constituent-residual models. We also identified robust associations of BC, OC, and nitrate exposures with site-specific gastrointestinal cancer mortality. The mortality risk generally displayed increased trends across the total exposure range and rose steeper at higher levels. We did not identify robust associations for sulfate, ammonium, or chlorine exposure. Higher mortality risk ascribed to constituent exposures was identified in total gastrointestinal and liver cancer among women, stomach cancer among men, and total gastrointestinal and stomach cancer among low-GDP regions. ConclusionsThis study offers consistent evidence that long-term exposure to PM2.5-bound BC, OC, and nitrate is associated with total and site-specific gastrointestinal cancer mortality, indicating that these constituents need to be controlled to mitigate the adverse effect of PM2.5 on gastrointestinal cancer mortality.

Blood Lipid Metabolic Profiles and Causal Links to Site-Specific Cancer Risks: A Mendelian Randomization Study

Observational and Mendelian randomization (MR) studies have established links between dyslipidemia and select cancer susceptibilities. However, there is a lack of comprehensive exploration of causal relationships spanning diverse cancer types. Here, we conducted a two-sample MR analysis to elucidate the causative connections between 9 blood lipid metabolic profiles (namely, adiponectin, leptin, lipoprotein A, apolipoprotein A1, apolipoprotein B, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and 21 site-specific cancer risks. Our findings reveal genetically predicted adiponectin levels to be associated with a reduced ovarian cancer risk, while genetically determined leptin increases bladder cancer risk but decreases prostate cancer risk. Lipoprotein A elevates risk of prostate cancer while diminishing risk of endometrial cancer, while apolipoprotein A1 heightens risks of breast and cervical cancers. Furthermore, elevated levels of cholesterol are positively correlated with kidney cancer, and triglycerides demonstrate a positive association with non-melanoma skin cancer but a negative association with breast cancer. Protective effects of genetically predicted LDL-cholesterol on endometrial cancer and adverse effects of HDL-cholesterol on breast cancer are also observed. Our study conclusively establishes that blood lipid metabolic profiles exert causal effects on cancer susceptibility, providing more robust evidence for cancer prevention and prompting contemplation regarding the future health of the human populace.

Estimating cancers attributable to physical inactivity in Australia

ObjectivesIt was previously estimated that 1814 (1.6 % of incident cancers) were attributable to physical inactivity in Australia in 2010, when only three sites were considered. We estimated the burden of cancer due to physical inactivity in Australia for 13 sites. DesignThe population attributable fraction estimated site-specific cancer cases attributable to physical inactivity for 13 cancers. The potential impact fraction was used to estimate cancers that could have been prevented in 2015 if Australian adults had increased their physical activity by a modest amount in 2004–05. MethodsWe used 2004–05 national physical activity prevalence data, 2015 national cancer incidence data, and contemporary relative-risk estimates for physical inactivity and cancer. We assumed a 10-year latency period. ResultsAn estimated 6361 of the cancers observed in 2015 were attributable to physical inactivity, representing 4.8 % of all cancers diagnosed. If Australian adults had increased their physical activity by one category in 2004–05, 2564 cases (1.9 % of all cancers) could have been prevented in 2015. ConclusionsMore than three times as many cancers are attributable to physical inactivity than previously reported. Physical activity promotion should be a central component of cancer prevention programmes in Australia.

Exploring the cross-cancer effect of circulating proteins and discovering potential intervention targets for 13 site-specific cancers.

The proteome is an important reservoir of potential therapeutic targets for cancer. This study aimed to examine the causal associations between plasma proteins and cancer risk and to identify proteins with cross-cancer effects. Genetic instruments for 3991 plasma proteins were extracted from a large-scale proteomic study. Summary-level data of 13 site-specific cancers were derived from publicly available datasets. Proteome-wide Mendelian randomization and colocalization analyses were used to investigate the causal effect of circulating proteins on cancers. Protein-protein interactions and druggability assessment were conducted to prioritize potential therapeutic targets. Finally, systematical Mendelian randomization analysis between healthy lifestyle factors and cancer-related proteins was conducted to identify which proteins could act as interventional targets by lifestyle changes. Genetically determined circulating levels of 58 proteins were statistically significantly associated with 7 site-specific cancers. A total of 39 proteins were prioritized by colocalization, of them, 11 proteins (ADPGK, CD86, CLSTN3, CSF2RA, CXCL10, GZMM, IL6R, NCR3, SIGLEC5, SIGLEC14, and TAPBP) were observed to have cross-cancer effects. Notably, 5 of these identified proteins (CD86, CSF2RA, CXCL10, IL6R, and TAPBP) have been targeted for drug development in cancer therapy; 8 proteins (ADPGK, CD86, CXCL10, GZMM, IL6R, SIGLEC5, SIGLEC14, TAPBP) could be modulated by healthy lifestyles. Our study identified 39 circulating protein biomarkers with convincing causal evidence for 7 site-specific cancers, with 11 proteins demonstrating cross-cancer effects, and prioritized the proteins as potential intervention targets by either drugs or lifestyle changes, which provided new insights into the etiology, prevention, and treatment of cancers.

Dose-response analysis of protracted absorbed organ dose and site-specific cancer incidence in Sweden after the Chernobyl nuclear power plant accident.

Adult males in Sweden exhibit an increased risk of cancer associated with an increased absorbed dose to the colon from the Chernobyl accident. A closed cohort, with information on hunter status, included all individuals living in northern Sweden in 1986. Complete annual information on exposure to 137Cs at the dwelling coordinate was available for a total of 2,104,101 individuals. A nested case-control method with four controls matched for year of cancer diagnosis and year of birth, was used. Individual absorbed organ doses were calculated between 1986 and 2020 including external and internal exposure. Hazard ratios (HR) per mGy with 95% confidence intervals (95% CI) were calculated using conditional logistic regression adjusted for rural/nonrural habitat, education level and pre-Chernobyl cancer incidence 1980 to 1985. A total of 161,325 cancer cases in males and 144,439 in females were included. The adjusted HR per mGy for all cancer sites combined was 1.027 (95% CI = 1.022, 1.031) in males and 1.011 (95% CI = 1.006, 1.017) in females. In a post hoc analysis accounting for both remaining confounding from hunter lifestyle and the pre-Chernobyl cancer incidence by county, the adjusted HR per mGy for all cancer sites combined was 1.014 (95% CI = 1.009, 1.019) in males and 1.000 (95% CI = 0.994, 1.006) in females. The post hoc analysis suggested an increased risk of cancer in the colon, pancreas, and stomach, respectively, in males, and lymphoma in females. Increased cancer risk estimates were found for some specific cancer sites but remaining uncontrolled confounding due to hunter lifestyle could not be ruled out.

Abstract B126: Disparities in cancer incidence among African American and non-Hispanic White participants in the Agricultural Health Study

Abstract Disparities in the incidence of some cancers (e.g., prostate cancer, multiple myeloma) between African American (AA) and non-Hispanic white (NHW) individuals are well established in the U.S. overall; however, to our knowledge, no previous studies have compared cancer incidence in AA and NHW farming populations. Farmers and their families can face a variety of occupational and environmental exposures that may influence cancer risk, including pesticides, zoonotic diseases, diesel exhaust and air pollution. Given the exposures unique to farming as well as historic discrimination faced by AA farmers, we considered the possibility that racial disparities in cancer incidence might be greater in farmers than in the general population. To explore cancer disparities in farming populations, we conducted an investigation within the Agricultural Health Study (AHS), a prospective cohort of pesticide applicators (mainly malefarmers) and their spouses. Our analyses included 1,505 AA and 27,052 non-Hispanic white (NHW) farmers and spouses from North Carolina who were enrolled in 1993-1997 and followed for cancer incidence through 2014. We examined cancer incidence in AA compared to NHWparticipants, both overall and for specific sites, by estimating hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression models with age as the underlying time metric and adjustment for sex (in analyses of cancer sites that included both sexes) and region (coastal plains, piedmont, and mountains). We identified a total of 4,689 incident cancer cases during follow-up (335 in AA participants and 4,354 in NHW participants). Compared with NHW participants, we observed a higher incidence among AA participants for all cancers (HR = 1.36, 95% CI 1.21 – 1.52) that was apparent among men (n = 272 AA cases; HR 1.45, 95% CI 1.28-1.64) but not among women (n = 63 AA cases; HR 1.12, 95% CI 0.87-1.45). AA participants had a higher incidence of cancers of the prostate (overall: HR 2.01, 95% CI 1.67–2.43; aggressive disease: HR 2.12, 95% CI 1.62–2.79), colon and rectum (HR 1.60, 95% CI 1.15–2.23), larynx (HR 3.52, 95% CI 1.41–8.79), and multiple myeloma (HR = 2.82, 95% CI 1.43 – 5.60). We also observed non-statistically significantly elevated HRs for cancers of the lung, pancreas, kidney, and stomach among AA participants. Findings were similar after excluding participants from the mountain region where few AA participants were enrolled. The observed excesses of cancer incidence overall and for specific cancer sites among AA farmers and spouses compared to their NHW counterparts were generally more apparent than those seen in the overall U.S. population; we plan to further evaluate these disparities through comparisons with statewide cancer incidence rates in North Carolina. Additional efforts are also needed to better understand factors contributing to these disparities, which can inform ways to promote the overall health and well-being of AA farmers and ensure that resources are allocated equitably across all populations. Citation Format: Somayina C. Ezennia, Christine G. Parks, Laura E. Beane-Freeman, Anne Taylor, Gabriella Andreotti, Stella Koutros, Dale P. Sandler, Jonathan N. Hofmann. Disparities in cancer incidence among African American and non-Hispanic White participants in the Agricultural Health Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B126.

Risk of secondary malignancy following radiation therapy for prostate cancer

We investigated whether prostate cancer patients treated with external beam radiation therapy (EBRT) have a higher cumulative incidence of secondary cancer compared with patients treated with radical prostatectomy (RP). We used state-wide linked data from South Australia to follow men with prostate cancer diagnosed from 2002 to 2019. The cumulative incidence of overall and site-specific secondary cancers between 5 and 15 years after treatment was estimated. Fine-Gray competing risk analyses were performed with additional sensitivity analyses to test different scenarios. A total of 7625 patients were included (54% underwent RP and 46% EBRT). Characteristics of the two groups differed significantly, with the EBRT group being older (71 vs. 64 years), having higher comorbidity burden and being more likely to die during follow-up than the RP group. Fifteen-year cumulative incidence for all secondary cancers was 27.4% and 22.3% in EBRT and RP groups, respectively. In the adjusted models, patients in the EBRT group had a significantly higher risk of genitourinary (adjusted subhazard ratio (aSHR), 2.29; 95%CI 1.16–4.51) and lung (aSHR, 1.93; 95%CI 1.05–3.56) cancers compared with patients in the RP group. However, there was no statistically significant difference between the two groups for risk of any secondary cancer, gastro-intestinal, skin or haematologic cancers. No statistically significant differences in overall risk of secondary cancer were observed in any of the sensitivity analyses and patterns for risk at specific cancer sites were relatively consistent across different age restriction and latency/time-lag scenarios. In conclusion, the increased risk of genitourinary and lung cancers among men undergoing EBRT may relate partly to treatment effects and partly to unmeasured residual confounding.

Long-term aspirin use and cancer risk: a 20-year cohort study.

Long-term use of aspirin has been shown to reduce colorectal cancer risk, but the association remains inconclusive for individual noncolorectal cancers. We examined the association between long-term aspirin use and cancer risk in Denmark. Using nationwide registries, we followed individuals aged 40-70 years at baseline (January 1, 1997) for cancer diagnoses through 2018. We assessed low-dose (75-150 mg) aspirin use according to continuity, duration, and cumulative amount. In addition, we explored associations with consistent high-dose (500 mg) aspirin use. Using Cox regression, we estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) with aspirin use for overall and site-specific cancer. Among 1 909 531 individuals, 422 778 were diagnosed with cancer during mean follow-up of 18.2 years. Low-dose aspirin use did not reduce the hazard ratio for cancer overall irrespective of continuity and duration of use (continuous use: HR = 1.04, 95% CI = 1.03 to 1.06). However, long-term (≥5 or ≥10 years) use was associated with at least 10% reductions in hazard ratios for several cancer sites: colon, rectum, esophagus, stomach, liver, pancreas, small intestine, head and neck, brain tumors, meningioma, melanoma, thyroid, non-Hodgkin lymphoma, and leukemia. Substantially elevated hazard ratios were found for lung and bladder cancer. In secondary analyses, consistent high-dose aspirin use was associated with reduced hazard ratios for cancer overall (HR = 0.89, 95% CI = 0.85 to 0.93) and for several cancer sites. Long-term low-dose aspirin use was associated with slight to moderately reduced risks for several cancers but not for cancer overall owing to increased risk for some common cancers. Similar or slightly stronger inverse associations were observed for consistent use of high-dose aspirin.

Adherence to 2018 WCRF/AICR Cancer Prevention Recommendations and Risk of Cancer: The Melbourne Collaborative Cohort Study.

We examined associations between adherence to adaptations of the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and total, exposure-related and site-specific cancer risk. A total of 20,001 participants ages 40 to 69 years at enrollment into the Melbourne Collaborative Cohort Study in 1990 to 1994, who had diet, body size, and lifestyle reassessed in 2003 to 2007 ("baseline"), were followed-up through June 2021. We constructed diet and standardized lifestyle scores based on core WCRF/AICR recommendations on diet, alcohol intake, body size and physical activity, and additional scores incorporating weight change, sedentary behavior, and smoking. Associations with cancer risk were estimated using Cox regression, adjusting for confounders. During follow-up (mean = 16 years), 4,710 incident cancers were diagnosed. For highest quintile ("most adherent") of the standardized lifestyle score, compared with lowest ("least adherent"), a HR of 0.82 [95% confidence interval (CI): 0.74-0.92] was observed for total cancer. This association was stronger with smoking included in the score (HR = 0.74; 95% CI: 0.67-0.81). A higher score was associated with lower breast and prostate cancer risk for the standardized score, and with lung, stomach, rectal, and pancreatic cancer risk when the score included smoking. Our analyses identified alcohol use, waist circumference and smoking as key drivers of associations with total cancer risk. Adherence to WCRF/AICR cancer prevention recommendations is associated with lower cancer risk. With <0.2% of our sample fully adherent to the recommendations, the study emphasizes the vast potential for preventing cancer through modulation of lifestyle habits.

Associations between BMIin youth and site-specific cancer in men-A cohort study with register linkage.

This study examined BMI in young men and incident site-specific cancer to estimate population attributable fractions due to BMI based on projected obesity prevalence. A population-based cohort study with measured height and weight at age 18. Cox regression models assessed linear associations for BMI and included age, year, and site of conscription as well as parental level of education as covariates. Primary analyses were performed in 1,489,115 men, of whom 78,217 subsequently developed cancer during a mean follow-up of 31 years. BMI was linearly associated with risk of developing all 18 site-specific cancers assessed (malignant melanoma; leukemia; myeloma; Hodgkin lymphoma; non-Hodgkin lymphoma; and cancer in the lungs, head and neck, central nervous system, thyroid, esophagus, stomach, pancreas, liver and gallbladder, colon, rectum, kidney, and bladder), in some instances evident at BMI levels usually defined as normal (20-25 kg/m2 ). Higher BMI was associated with lower risk of prostate cancer. The highest hazard ratios and population attributable fractions were seen for some gastrointestinal cancers. This study reports linear associations between BMI at age 18 and subsequent site-specific cancers, calling for rapid action to stem the obesity epidemic and to prepare the health care system for steep increases in cancer cases.

Association of low-dose ionising radiation with site-specific solid cancers: Chinese medical X-ray workers cohort study, 1950–1995

BackgroundThe dose–response relationship between cancers and protracted low-dose rate exposure to ionising radiation is still uncertain. This study aims to estimate quantified relationships between low-dose radiation exposures and site-specific solid...

Abbreviated Score to Assess Adherence to the 2018 WCRF/AICR Cancer Prevention Recommendations and Risk of Cancer in the UK Biobank.

The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are lifestyle-based guidelines which aim to reduce cancer risk. This study investigated, in the UK Biobank, associations between an abbreviated score to assess adherence to these Recommendations and the risk of all cancers combined and of 14 cancers for which there is strong evidence for links with diet, adiposity, and physical activity. We used data from 288,802 UK Biobank participants (mean age 56.2 years), cancer-free at baseline. An abbreviated version of the 2018 WCRF/AICR Score was calculated to assess adherence to five Recommendations on (i) body weight, (ii) physical activity, (iii) fruits, vegetables, and dietary fiber, (iv) red and processed meat, and (v) alcohol. Multivariable Cox proportional hazards models were used to analyze associations between the abbreviated score (range, 0-5 points) and cancer incidence, adjusting for confounders. During a median follow-up of 8.2 years (interquartile range, 7.4-8.9), 23,448 participants were diagnosed with cancer. The abbreviated score was inversely associated with risk of cancer overall [HR: 0.93; 95% confidence interval (CI): 0.92-0.95 per 1-point increment], and breast (HR: 0.90; 95% CI: 0.87-0.94), colorectal (HR: 0.86; 95% CI: 0.83-0.90), lung (HR: 0.89; 95% CI: 0.84-0.94), kidney (HR: 0.83; 95% CI: 0.76-0.90), pancreatic (HR: 0.86; 95% CI: 0.79-0.94), uterine (HR: 0.79; 95% CI: 0.73-0.86), esophageal (HR: 0.82; 95% CI: 0.75-0.90), stomach (HR: 0.89; 95% CI: 0.79-0.99), and liver (HR: 0.80; 95% CI: 0.72-0.90) cancers. Greater adherence to the Cancer Prevention Recommendations, assessed using an abbreviated score, was associated with reduced risk of all cancers combined and of nine site-specific cancers. Our findings support compliance to these Recommendations for cancer prevention.

Unveiling the Association between HPV and Pan-Cancers: A Bidirectional Two-Sample Mendelian Randomization Study.

More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships. A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger's intercept P test, MR-PRESSO global test, Cochran's Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment. Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer. An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation.