Cancer Risk Research Articles

Taxane/anthracycline combinations reduced incidence of breast cancer recurrence in young women across molecular subtypes: a real-world evidence of Taiwan from 2011 to 2019.

Adolescent and young adult (AYA) patients with breast cancer generally have poor prognoses and a higher risk of secondary cancers compared to those at the same cancer stage. Notably, AYA patients in Asia exhibit a higher incidence rate of breast cancer, with Luminal A as the predominant molecular subtype, which contrasts with the trends observed in Western countries. This study aims to compare the efficacy of Taxane/Anthracycline combination-based regimens (TACB) versus Anthracycline-based regimens (AB) in AYA patients with stage I-II breast cancer, focusing on different molecular subtypes. This study utilized data from the Taiwan National Health Insurance Research Database (NHIRD) and the Taiwan Cancer Registry (TCR) from 2011 to 2019. The study cohort included patients aged 15 to 39years who were diagnosed with stage I-II breast cancer and received either TACB or AB regimens. Propensity score matching and Cox proportional hazards regression models were used to calculate the hazard ratios (HR) for recurrence. The results showed that TACB regimens significantly reduced the risk of recurrence compared to AB regimens across all patients (aHR 0.73, 95% CI 0.55-0.97). Specifically, for low/middle-recurrence risk groups, the aHR was 0.68 (95% CI 0.49-0.96), and for high-recurrence risk groups, it was 0.43 (95% CI 0.21-0.87). The analysis further indicated no significant differences in recurrence risk between AYA and non-AYA patients using TACB regimens. The TACB regimens showed a more favorable prognosis than AB regimens across all molecular subtypes. Furthermore, TACB regimens not only outperformed AB treatments but also closed the gap in prognostic outcomes between AYA and non-AYA patients. We believe the findings of this study are highly reliable and can provide valuable guidance for physicians in choosing the most appropriate treatment strategies for AYA patients with stage I-II breast cancer.

Calcium Channel Blocker Versus Renin-Angiotensin System Inhibitor in Risk of Kidney Cancer Among Patients With Hypertension: A Propensity Score-Matched Cohort Study.

Use of antihypertensive medications could be associated with an increased risk of kidney cancer. Despite their various mechanisms of action, whether this association differs between different classes of medications remains unclear. The objective of this study is to compare the risk of kidney cancer between first-line treatment options of antihypertensive medications in a hypertensive population. In this retrospective cohort study, we used the MarketScan Databases (2007-2021). We included individuals older than 30 years of age with a diagnosis of hypertension who received first-line medications for hypertension, which included three classes: angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and dihydropyridine calcium channel blockers (dCCB). We applied a propensity score matching method and created three separate cohorts: (1) ARB versus ACEI, (2) dCCB versus ACEI, and (3) dCCB versus ACEI. For non-dCCB, we repeated the analyses. The primary outcome was kidney cancer incidence. To assess kidney cancer risk, we applied multivariable conditional Cox proportional hazards models. In the first cohort, ARB use was associated with an increased risk of kidney cancer compared to ACEI use (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.02-1.18). In the second cohort, dCCB use was associated with an increased risk of kidney cancer compared to ACEI use (HR 1.29, 95% CI 1.18-1.40). In the third cohort, dCCB use was associated with a higher risk of kidney cancer compared to ARB use (HR 1.17, 95% CI 1.08-1.28). Null association was shown when comparing non-dCCB with ACEI or ARB use. Use of dCCB showed a higher risk of kidney cancer compared to ACEI or ARB use in patients with hypertension.

Human Health Risks Assessment of Toxic Metals via Water, Food, and Soil: A Case Study of Northern Areas (Ghizer and Gilgit) of Pakistan

Health concerns have arisen worldwide as a result of contaminated food and water. This study was aimed to determine the levels of selected heavy metals i.e. cadmium (Cd), chromium (Cr), copper (Cu) manganese (Mn), and nickel (Ni) in various sources such as drinking water, vegetables, and soil in districts Ghizer and Gilgit, Pakistan. Human health risks were assessed using deterministic indices, a probabilistic approach, and multivariate analysis. The determinations were carried out by spectrophotometrically (AAS-700, Perkin Elmer, USA) following the standard procedures for heavy metal levels. The mean concentration was recorded as Cd 0.036 mg/L, Cr 0.076 mg/L, and Ni 0.394 mg/L, respectively. It revealed an exceeded level for Cd (0.03 mg/L) and Cr (0.07 mg/L) against the safe limits in drinking water of Gilgit and Ghizer. The highest hazard quotient (HQ) was recorded as Cd 3000, Cr 3863.33, Cu 21.7, Mn 45.71, and Ni 22.35 for children regarding the consumption of vegetables from district Ghizer. Whereas higher HQ values were recorded for adults regarding consumption of vegetables from district Gilgit. A hazard index (HI) indicates significant non-carcinogenic health risks (HI > 1) in Ghizer and Gilgit drinking water and vegetables. Gilgit soil HI values exceeded more than one due to dermal contact, while HI > 1 due to oral and dermal exposure in Ghizer. Furthermore, drinking water samples and vegetables from both districts showed cancer risk (CR) > 1× 10-4. The cumulative lifetime cancer risk (CR) was observed as 88.61 and 65.61 for adults whereas 2. 98 and 0.38 for children pertaining to vegetable consumption from Ghizer and Gilgit. It was found that the lifetime cancer risk (LCR) for Ghizer was higher than that for Gilgit, based on soil dermal and oral contact. Monte Carlo Simulation revealed adverse health risks in children as compared to adults. As a result of exposure to toxic metals, drinking water and vegetable consumption have higher cancer-causing risks. Therefore, we recommend that both districts implement strict monitoring regulations for drinking water and vegetables.

Association between cholelithiasis, cholecystectomy, and risk of breast and gynecological cancers: Evidence from meta-analysis and Mendelian randomization study.

Observational studies have shown that cholelithiasis and cholecystectomy are associated with the risk of breast cancer (BC) and gynecological cancers, but whether these relationships are causal has not been established and remains controversial. Our study began with a meta-analysis that synthesized data from prior observational studies to examine the association between cholelithiasis, cholecystectomy, and the risk of BC and gynecological cancers. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing genetic variant data to investigate the potential causal relationship between cholelithiasis, cholecystectomy, and the aforementioned cancers. The results of the meta-analysis demonstrated a significant association between cholecystectomy and the risk of BC (risk ratio [RR]=1.04, 95% confidence interval [CI]: 1.01-1.06, p=0.002) and endometrial cancer (EC) (RR=1.26, 95% CI: 1.02-1.56, p=0.031). Conversely, no significant association was observed between cholelithiasis and the risk of BC, EC, and ovarian cancer. The MR analysis revealed no discernible causal connection between cholelithiasis and overall BC (p=0.053), as well as BC subtypes (including estrogen receptor-positive/negative). Similarly, there was no causal effect of cholecystectomy on BC risk (p=0.399) and its subtypes. Furthermore, no causal associations were identified between cholelithiasis, cholecystectomy, and the risk of gynecological cancers (ovarian, endometrial, and cervical cancer [CC]) (all p>0.05). This study does not support a causal link between cholelithiasis and cholecystectomy and an increased risk of female cancers such as breast, endometrial, ovarian, and CC.

Exploring causal correlations between inflammatory cytokines and colorectal cancer: A 2-sample Mendelian randomization study.

Colorectal cancer (CRC) is a significant global public health concern. Several observational studies have examined the association between inflammatory cytokines and the risk of colorectal cancer, but the findings have been inconsistent. In this study, we employed a 2-sample Mendelian randomization (MR) analysis, primarily using the inverse variance weighted approach, to investigate the causal relationship between inflammatory cytokines and CRC. The forward MR analysis revealed a positive association between higher levels of interleukin (IL)-16 (OR: 1.37, P = .002), vascular endothelial growth factor (OR: 1.44, P = .001), and MIG (OR: 1.23, P = .040) with an increased risk of rectal cancer. Conversely, higher levels of macrophage colony-stimulating factor (OR: 0.80, P = .010) may potentially decrease the risk of colon cancer. In the reverse MR analysis, it was found that rectal cancer is linked to higher levels of IL-1b (OR: 0.93, P = .022), IL-1ra (OR: 0.90, P = .001), IL-5 (OR: 0.93, P = .022), IL-9 (OR: 0.93, P = .017), and TNF-a (OR: 0.91, P = .003). Additionally, colon cancer is associated with elevated levels of FGF-Basic (OR: 1.10, P = .028). Consistent results were also found in MR-Egger, weighted median, and weighted mode analysis. Our study presents novel evidence supporting the causal relationship between inflammatory cytokines and CRC.

Air Quality Near Middle East's Large Dried Lake: Heavy Metal Emissions, Machine learning Analysis, and Health Risks

The present study aimed to measure the concentrations and chemical compositions of suspended particulate matters smaller than 10 μm (PM10) in the ambient air of Bakhtegan Lake and to assess the health risks associated with exposure to metal elements through inhalation. Ambient air samples were collected from a rural area close to the lake. The levels of metal elements bonded to PM10 were measured by the Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The mean ambient PM10 concentration around the studied lake (78.12 μg/m3) was higher than the 24 hours guidelines PM10 standards proposed by World Health Organization (WHO) (50 μg/m3). The highest and lowest concentrations were related to Fe and V, respectively. Lifetime Cancer Risk (LCR) was higher for adults than for children. Additionally, the LCR value was higher for As compared to other metals, indicating that the cancer risk in the adults group was mainly due to As. Besides, health risk assessments indicated that adults suffered from higher cancer risks compared to children, while both adults and children did not suffer from non-carcinogenic risks. Through Principal component analysis (PCA) and random forest (RF) analysis, it was determined that metallic concentrations in the air samples are influenced by both natural and anthropogenic sources, with copper and lead identified as pivotal predictors for nickel levels. Therefore, monitoring and addressing such metal-induced pollution is essential for regional public health.

Impact of Modern Lifestyle on Circadian Health and Its Contribution to Adipogenesis and Cancer Risk.

Recent research underscores a crucial connection between circadian rhythm disruption and cancer promotion, highlighting an urgent need for attention. Explore the molecular mechanisms by which modern lifestyle factors-such as artificial light exposure, shift work, and dietary patterns-affect cortisol/melatonin regulation and cancer risk. Employing a narrative review approach, we synthesized findings from Scopus, Google Scholar, and PubMed to analyze lifestyle impacts on circadian health, focusing on cortisol and melatonin chronobiology as molecular markers. We included studies that documented quantitative changes in these markers due to modern lifestyle habits, excluding those lacking quantitative data or presenting inconclusive results. Subsequent sections focused solely on articles that quantified the effects of circadian disruption on adipogenesis and tumor microenvironment modifications. This review shows how modern habits lead to molecular changes in cortisol and melatonin, creating adipose microenvironments that support cancer development. These disruptions facilitate immune evasion, chemotherapy resistance, and tumor growth, highlighting the critical roles of cortisol dysregulation and melatonin imbalance. Through the presented findings, we establish a causal link between circadian rhythm dysregulation and the promotion of certain cancer types. By elucidating this relationship, the study emphasizes the importance of addressing lifestyle factors that contribute to circadian misalignment, suggesting that targeted interventions could play a crucial role in mitigating cancer risk and improving overall health outcomes.

Interaction of base excision repair gene polymorphism and estrogen-DNA adducts in breast cancer risk among East Asian women.

In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.

Causal effect of breast cancer on endometrial cancer risk: A two-sample Mendelian randomization study

BackgroundObservational studies have indicated a higher incidence of endometrial cancer in individuals with breast cancer. However, to date, there is a dearth of Mendelian randomization studies that explore the causal relationship between breast cancer and the risk of endometrial cancer. Material and methodsWe conducted Mendelian randomization (MR) to investigate the causal relationship between breast cancer and endometrial cancer risk in European populations. ResultsA total of 112 valid instrumental variables were included in the analysis. Our research has revealed a compelling causal association between genetic predisposition for breast cancer and an augmented likelihood of developing endometrial cancer (Inverse variance weighted (IVW) method, odds ratio (OR) = 1.105, 95 % confidence interval (CI): 1.025 to 1.181, p = 0.003; Weighted median method, OR = 1.109, 95 % CI: 1.020 to 1.205, p = 0.015; Weighted mode method: OR = 1.101, 95 % CI: 1.013 to 1.195, p = 0.025). ConclusionTo our knowledge, this study is the first to report a causal association between breast cancer and endometrial cancer risk. Robust results were obtained through rigorous testing for heterogeneity and pleiotropy. Our findings indicate a causal effect of breast cancer on the risk of endometrial cancer.

Application of electronic laryngoscope combined with narrow band imaging endoscope and its classification in the diagnosis of vocal cord leukoplakia

Objective:To investigate the clinical value of electronic laryngoscope combined with narrow band imaging（NBI） endoscope and its classification in the diagnosis of vocal cord leukoplakia. Methods:A retrospective analysis was performed on 115 cases of patients treated in the Department of Otolaryngology, Head and Neck Surgery, Nanjing Drum Tower Hospital from September 2020 to November 2022. All 115 cases were diagnosed with vocal cord leukogramma using the electronic laryngoscopy and narrow band imaging endoscopy, followed by pathological examination in the outpatient tissue biopsy. The morphological characteristics of vocal cord leukoplakia and the correlation between narrow band imaging classification and pathological results were investigated. Results:Among 115 cases of vocal cord leukoplakia, 46 cases（40.00%） were diagnosed as benign lesions. Low grade intraepithelial neoplasia occurred in 29 cases（25.22%）. High-grade intraepithelial neoplasia（including carcinoma in situ） occurred in 22 cases（19.13%）. Invasive carcinoma（including suspected invasive carcinoma） was found in 18 cases（15.65%）. There were no statistical differences in the unilateral and bilateral distribution of vocal cord leukoplakia and pathological results（P>0.05）, but there were statistical differences in the size, thickness, lesion uniformity, clear boundary, pre-invasion commissure, symmetry,age over 55 years old, morphological classification, NBI classification and pathological results distribution（P<0.05）. The two-by-two comparison among the three groups of morphological classification（flat type, raised type, rough type） showed that P<0.017 was only compared between flat type and rough type, and P>0.017 was compared between the other two groups. The pairwise comparison among the three groups of NBI classification（Ⅲ, Ⅳ, Ⅴ） was statistically significant（P<0.017）. There was a high correlation between NBI classification and pathological diagnosis, and the correlation coefficient was 0.705（P<0.05）. The risk of high intraepithelial neoplasia and cancerization in type Ⅳ was 9.125 times higher than that in type Ⅲ, and the risk of high intraepithelial neoplasia and cancerization in type Ⅴ was 271.078 times higher than that in type Ⅲ. The area under the curve of morphological classification and NBI classification were 0.672 and 0.896, respectively. Conclusion:There is a high match and correlation between NBI classification and pathological diagnosis. Electronic laryngoscope combined with narrow band imaging endoscope has a high diagnostic value for vocal cord leukoplakia, and a strong predictive ability for malignant leukoplakia.

Concordant and discordant breast density patterns by different approaches for assessing breast density and breast cancer risk.

To examine the discrepancy in breast density assessments by radiologists, LIBRA software, and AI algorithm and their association with breast cancer risk. Among 74,610 Korean women aged ≥ 34years, who underwent screening mammography, density estimates obtained from both LIBRA and the AI algorithm were compared to radiologists using BI-RADS density categories (A-D, designating C and D as dense breasts). The breast cancer risks were compared according to concordant or discordant dense breasts identified by radiologists, LIBRA, and AI. Cox-proportional hazards models were used to determine adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)]. During a median follow-up of 9.9years, 479 breast cancer cases developed. Compared to the reference non-dense breast group, the aHRs (95% CIs) for breast cancer were 2.37 (1.68-3.36) for radiologist-classified dense breasts, 1.30 (1.05-1.62) for LIBRA, and 2.55 (1.84-3.56) for AI. For different combinations of breast density assessment, aHRs (95% CI) for breast cancer were 2.40 (1.69-3.41) for radiologist-dense/LIBRA-non-dense, 11.99 (1.64-87.62) for radiologist-non-dense/LIBRA-dense, and 2.99 (1.99-4.50) for both dense breasts, compared to concordant non-dense breasts. Similar trends were observed with radiologists/AI classification: the aHRs (95% CI) were 1.79 (1.02-3.12) for radiologist-dense/AI-non-dense, 2.43 (1.24-4.78) for radiologist-non-dense/AI-dense, and 3.23 (2.15-4.86) for both dense breasts. The risk of breast cancer was highest in concordant dense breasts. Discordant dense breast cases also had a significantly higher risk of breast cancer, especially when identified as dense by either AI or LIBRA, but not radiologists, compared to concordant non-dense breast cases.

The impact of high exposure to perfluoroalkyl substances and risk for hormone receptor-positive breast cancer – A Swedish cohort study

IntroductionPerfluoroalkyl substances (PFAS) are persisting chemicals with endocrine disruptive and carcinogenic properties. Previous studies involving cohorts with high PFAS exposure have not shown an increased risk of breast cancer. Research on PFAS and breast cancer according to hormone receptor status is limited. This study aims to investigate the association between PFAS exposure and hormone receptor-positive breast cancer. Materials and MethodsIn 2013, high levels of PFAS (sum of PFAS > 10,000 ng/L), dominated by perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) were found in the drinking water from one of the two waterworks in Ronneby, Sweden. Breast cancer diagnoses and information of adjuvant endocrine therapy were retrieved from the Swedish Cancer Register and The Prescribed Drug Register 2006–2016 for a cohort of women residing in the municipality between 1985 and 2013 (n = 24,509). Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential addresses. Cox proportional hazards models were used in the analysis. The highest achieved educational level was used as an indicator of socioeconomic position. Sensitivity and subgroup analysis were performed for prepubertal exposure and diagnosis before or after age 50 (assumed menopause). ResultsThere were 313 cases of malignant breast cancer among women ≤ 85 years between 2006 and 2016. Of these, 224 cases (72 %) were considered hormone receptor-positive based on the first prescription of adjuvant endocrine therapy, antiestrogens (40 %) or aromatase inhibitor (60 %). Among women ever living at a residential address with high PFAS exposure, the hazard ratio (HR) for breast cancer classified as hormone receptor-positive was 0.84; 95 % confidence interval (CI) 0.61, 1.14. Findings were similar before and after menopause. ConclusionHigh PFAS exposure from drinking water, dominated by PFOS and PFHxS, was not associated with an elevated risk of hormone receptor-positive breast cancer.

Vulvar lichen sclerosus in girls and adult females: A single-center retrospective study of 744 patients in China.

Vulvar lichen sclerosus (VLS) is a chronic, inflammatory disease which is accompanied by itching and pain, affecting the patient's daily life and sexual activity. However, the disease characteristics of children and adults are not completely the same. Currently, there are few studies in China that compare the characteristics of VLS between girls and adult female patients. The aim of this study was to compare the epidemiology, clinical features, and combined autoimmune diseases of VLS patients between girls and adult females, and to help clinicians better understand VLS in different age groups. We enrolled 744 female patients for analysis, divided by age into a child group (<18 years) and an adult group (≥18 years). Among girl patients, 94.6% had preadolescent onset, while among adult female patients, only 4.6% had preadolescent onset, which was a statistically significant difference. The highest percentage of adult female patients had onset during their child-bearing period (75.4%), while 20% had postmenopausal onset, with a significant difference when the three onset states were compared. White patches were equally common in both girl and adult female patients' external genital area, while mossy lesions and labia minora atrophy were more common in adult female patients. Involvement of the clitoris, labia minora, and vaginal opening area were more common in adult patients. The perianal area was more commonly involved in girl patients. We found eight cases (1.2%) of secondary squamous cell carcinoma in adult female patients. We also found that 13 patients had concurrent lichen sclerosus lesions on the vulva and extragenital region, including two girls and 11 adult females. Extragenital lichen sclerosus (EGLS) occurred mostly in the torso. Clinicians should be aware of these differences so that early diagnosis and treatment of the disease can be achieved, to avoid irreversible anatomical alterations and the risk of cancer.

Pearls for counseling older adults on the indications for stopping colon cancer screening

Colorectal cancer remains a leading cause of mortality, making effective screening procedures like colonoscopy essential in reducing associated risks. The cessation of colorectal cancer screening in older adults presents complex challenges, particularly as guidelines recommend screening initiation at age 45 and emphasize individualized decision-making for older populations. Key considerations include balancing procedural risks, cancer risk, overall health prognosis, and patient preferences. The risks associated with colonoscopy are especially pertinent for older patients with comorbidities, necessitating the use of prognostic tools like ePrognosis and the Charlson Comorbidity Index to inform screening decisions. High-risk individuals may experience increased anxiety about cancer, complicating the decision-making process, as many have historically relied on regular surveillance. Perspectives from both physicians and patients reveal significant uncertainty regarding screening cessation, highlighting the importance of patient involvement in these discussions. Effective communication strategies are crucial, advocating for recommendations that align with patients' broader health goals rather than focusing solely on age-related actuarial data. Ultimately, navigating the intricacies of colorectal cancer screening cessation in older adults requires a patient-centered approach that minimizes risks while respecting individual values and health goals.

Multidimensional structural racism and estimated cancer risk from traffic-related air pollution.

Traffic-related air pollutants have been associated with a variety of adverse human health impacts, including cancers. In the United States, numerous studies have documented racial inequities in neighborhood exposures to traffic-related air pollution. Emerging evidence suggests that structural racism may influence neighborhood exposures to air pollutants. However, existing research has largely focused on residential racial segregation, one indicator of structural racism. This study developed a multidimensional measure of structural racism to examine the relationship between structural racism and estimated cancer risk from air pollutants in Georgia. Carcinogenic air toxics data were obtained from the US Environmental Protection Agency's 2019 Air Toxics Screening Assessment and sociodemographic data from the American Community Survey. Guided by stakeholder input, county-level data on residential segregation, education, employment, incarceration, economic status, political participation, and homeownership were used to create a multidimensional county-level structural racism index. Relative risks (RRs) were estimated for associations between structural racism and elevated (top 10% in Georgia) estimated cancer risk from air toxics. Multilevel analyses revealed a significant association between multidimensional structural racism and exposure to carcinogenic traffic-related air pollutants. Neighborhoods in the highest quartile of structural racism exhibited an elevated cancer risk from traffic-related air pollutants (RR,7.84; 95% CI,5.11-12.05) compared to neighborhoods with lower levels of structural racism. Multidimensional structural racism was associated with estimated cancer risk from traffic-related air pollution in Georgia. Findings can inform future studies and policy interventions that address racial inequalities in exposure to traffic-related air pollution.

Increased Red Cell Superoxide Dismutase Activity Is Associated with Cancer Risk: A Hidaka Cohort Study.

Our study is the first to show that increased R-SOD activity is associated with a significantly higher cancer risk in men but not in women. Antioxidative enzymes such as SOD are essential for maintaining cellular redox balance. Their roles in cancer development and prevention are yet to be fully elucidated.

Menopause age and cancer risk is influenced by rare genetic variants.

Menopause age and cancer risk is influenced by rare genetic variants.

Clustering of TP53 variants into functional classes correlates with cancer risk and identifies different phenotypes of Li-Fraumeni syndrome

Clustering of TP53 variants into functional classes correlates with cancer risk and identifies different phenotypes of Li-Fraumeni syndrome

CPAP recall and cancer risk: should we be concerned?

CPAP recall and cancer risk: should we be concerned?

Investigating the Relationship Between β-Carotene Intake from Diet and Supplements, Smoking, and Lung Cancer Risk

β-carotene is a naturally occurring and safe dietary source of vitamin A that is associated with cancer risk reductions when consumed in typical dietary amounts. However, two clinical trials reported increased incidence of lung cancer and total mortality among heavy smokers taking β-carotene supplements (20 or 30 mg/day). Based on these findings, the Joint FAO/WHO Expert Committee on Food Additives withdrew Acceptable Daily Intake values for β-carotene (0-5 mg/kg bw). We evaluated relevant epidemiological and toxicological literature to assess the biological plausibility of this relationship and identified three mechanisms involving cellular proliferation signaling, a mode of action for cancer promotion. The overall weight of evidence consistently demonstrated typical dietary doses of β-carotene decreased cellular proliferation signaling via these mechanisms, even in the presence of smoke, while co-exposure to smoke and higher, supplemental doses increased cellular proliferation signaling through these same pathways. The production of excessive oxidative β-carotene metabolites via reactions with smoke constituents may be a key event underlying this relationship. Consistent with previous findings, our evaluation indicated consumption of up to 50 mg/day β-carotene does not present safety concerns for the non-smoking general population. Heavy smokers consuming less than 15 mg β-carotene/day are not expected to be at an increased risk of lung cancer.