Association of Lung Cancer Risk With the Presence of Both Lung Nodules and Emphysema in a Lung Cancer Screening Trial.

Background: The coexistence of emphysema and lung nodules could interact with each other and then lead to potential higher lung cancer risk. The study aimed to explore the association between emphysema combined with lung nodules and lung cancer risk. Methods: A total of 21,949 participants from the National Lung Screening Trial (NLST) who underwent low-dose computed tomography (LDCT) examination were included. Participants were categorized into four groups (NENN group (non-emphysema and non-nodules), E group (emphysema without nodules), N group (nodules without emphysema), and E + N group (nodules with emphysema)) according to whether there were lung nodules and emphysema. Multivariable Cox regression and stratified analyses were performed to estimate the association between the four groups and lung cancer risk. Results: Among the 21,949 participants, there were 9,040 (41.2%), 5,819 (26.5%), 4,737 (21.6%), and 2,353 (10.7%) participants in the NENN group, E group, N group, and E + N group. The risk of lung cancer incidence increased in turn in NENN group, E group, N group and E + N group. Compared with NENN group, the age-adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of lung cancer incidence were 2.07 (1.69 - 2.54) for E group, 4.13 (3.47 - 5.05) for N group, and 6.26 (5.14 - 7.62) for E + N group. The association was robust to adjustment for potential confounders (1.83 (1.47 - 2.27) for E group, 3.97 (3.24 - 4.86) for N group, and 5.23 (4.28 - 6.48) for E + N group). Comparable results as the lung cancer incidence were observed for lung cancer mortality, whether in age-adjusted model (E group: 1.85 (1.39 - 2.46), N group: 2.49 (1.89 - 3.29), E + N group: 4.27 (3.21 - 5.68)) or fully adjusted model (E group: 1.56 (1.15 - 2.11), N group: 2.43 (1.81 - 3.26), E + N group: 3.39 (2.50 - 4.61)). However, the trend of all-cause mortality risk among the four groups was somewhat different from that of lung cancer risk, whether in age-adjusted model (1.37 (1.21 - 1.54) for E group, 1.06 (0.92 - 1.21) for N group, and 1.75 (1.51 - 2.02) for E + N group) or fully adjusted model (1.26 (1.10 - 1.44) for E group, 1.09 (0.94 - 1.27) for N group, and 1.52 (1.30 - 1.79) for E + N group). Conclusion: Based on a large-scale lung cancer screening trial in the United States, this study demonstrated that either emphysema or lung nodules can increase lung cancer risk, and lung nodules combined with emphysema can further increase the lung cancer risk and all-cause mortality. The significance of these findings for lung cancer screening should be evaluated.

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis.

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials.

Background: Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE. Methods: Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/). Results: A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%). Conclusions: Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

A new risk stratification strategy for fatty liver disease by incorporating MAFLD and fibrosis score in a large US population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed definition of fatty liver disease (FLD) independent of excessive alcohol consumption (EAC) and hepatitis viral infection. Evidence on the mortality risk in different types of FLD [nonalcoholic FLD (NAFLD), alcoholic FLD (AFLD), and MAFLD] is sparse, hindering the identification of high-risk populations for preferential clinical surveillance. METHODS: A total of 11,000 participants in the Third National Health and Nutrition Examination Survey were enrolled. Participants were categorized into three groups [FLD( - ), MAFLD( - ), and MAFLD( +)] according to FLD and MAFLD criteria, and further categorized into six groups by EAC. Multivariate Cox proportional hazard model was used to estimate the risk of all-cause, cardiovascular-related, and cancer-related mortality. RESULTS: During a median follow-up of 23.2 years, a total of 3240 deaths were identified. Compared with FLD( - )/EAC( - ) participants, MAFLD( +) individuals had higher all-cause mortality risk [hazard ratio (HR) = 1.28, 95% confidence interval (CI) = 1.18-1.39] regardless of EAC status [MAFLD( +)/NAFLD: HR = 1.22, 95%CI = 1.11-1.34; MAFLD( +)/AFLD: HR = 1.83, 95%CI = 1.46-2.28], while not for MAFLD( - ) individuals. Furthermore, diabetes-driven-MAFLD had higher mortality risk (HR = 2.00, 95%CI = 1.77-2.27) followed by metabolic dysregulation-driven-MAFLD (HR = 1.30, 95%CI = 1.06-1.60) and overweight/obesity-driven-MAFLD (HR = 1.11, 95%CI = 1.00-1.22). Additionally, MAFLD( - ) participants with elevated fibrosis score were also associated with statistically significantly higher mortality risk (HR = 3.23, 95%CI = 1.63-6.40). CONCLUSIONS: Utilizing a representative sample of the US population, we proved the validity of MAFLD subtype and fibrosis score, rather than the traditional definition (NAFLD and AFLD), in the risk stratification of FLD patients. These findings may be applied to guide the determination of surveillance options for FLD patients.

Pouch size influences clinical outcome of pouch construction after total gastrectomy: a meta-analysis.

AIM: To assess the clinical significance of pouch size in total gastrectomy for gastric malignancies. METHODS: We manually searched the English-language literature in PubMed, Cochrane Library, Web of Science and BIOSIS Previews up to October 31, 2013. Only randomized control trials comparing small pouch with large pouch in gastric reconstruction after total gastrectomy were eligible for inclusion. Two reviewers independently carried out the literature search, study selection, data extraction and quality assessment of included publications. Standard mean difference (SMD) or relative risk (RR) and corresponding 95%CI were calculated as summary measures of effects. RESULTS: Five RCTs published between 1996 and 2011 comparing small pouch formation with large pouch formation after total gastrectomy were included. Eating capacity per meal in patients with a small pouch was significantly higher than that in patients with a large pouch (SMD = 0.85, 95%CI: 0.25-1.44, I(2) = 0, P = 0.792), and the operative time spent in the small pouch group was significantly longer than that in the large pouch group [SMD = -3.87, 95%CI: -7.68-(-0.09), I (2) = 95.6%, P = 0]. There were no significant differences in body weight at 3 mo (SMD = 1.45, 95%CI: -4.24-7.15, I(2) = 97.7%, P = 0) or 12 mo (SMD = -1.34, 95%CI: -3.67-0.99, I(2) = 94.2%, P = 0) after gastrectomy, and no significant improvement of post-gastrectomy symptoms (heartburn, RR = 0.39, 95%CI: 0.12-1.29, I(2) = 0, P = 0.386; dysphagia, RR = 0.86, 95%CI: 0.58-1.27, I(2) = 0, P = 0.435; and vomiting, RR = 0.5, 95%CI: 0.15-1.62, I(2) = 0, P = 0.981) between the two groups. CONCLUSION: Small pouch can significantly improve the eating capacity per meal after surgery, and may improve the post-gastrectomy symptoms, including heartburn, dysphagia and vomiting.

Association between the (GT)n polymorphism of the HO-1 gene promoter region and cancer risk: a meta-analysis.

BACKGROUND: Several studies have previously focused on associations between the (GT)n repeat polymorphism of the heme oxygenase-1 (HO-1) gene promoter region and risk of cancers, but results are complex. We conducted the present meta-analysis to integrate relevant findings and evaluate the association between HO-1 (GT)n repeat polymorphism and cancer susceptibility. MATERIALS AND METHODS: Published literature was retrieved from the PubMed/MEDLINE, EMBASE and ISI Web of Science databases before November 2013. For all alleles and genotypes, odds ratios were pooled to assess the strength of the associations using either fixed-effects or random-effects models according to heterogeneity. Subgroup analysis was conducted according to ethnicity and histopathology. RESULTS: A total of 10 studies involving 2,367 cases and 2,870 controls were identified. The results showed there was no association between HO-1 (GT)n repeat polymorphism and the cancer risk both at the allelic and genotypic level. However, in the stratified analysis, we observed an increased risk of squamous cell carcinoma in persons carrying the LL genotype and the LL+LS genotype as compared with those carrying the SS genotype. When the LS and SS genotypes were combined, the odds ratio for squamous cell carcinoma in LL-genotype carriers, were also significantly increased. No publication bias was observed. CONCLUSIONS: The LL genotype and L-allele carrying genotypes (LL+LS) of HO-1 (GT)n repeat polymorphism are potential genetic factors for developing squamous cell carcinoma. More large and well-designed studies are required for further validations.

ABO blood groups and risk of cancer: a systematic review and meta-analysis.

BACKGROUND: For decades, studies have been performed to evaluate the association between ABO blood groups and risk of cancer. However, whether ABO blood groups are associated with overall cancer risk remains unclear. We therefore conducted a meta-analysis of observational studies to assess this association. MATERIALS AND METHODS: A search of Pubmed, Embase, ScienceDirect, Wiley, and Web of Knowledge databases (to May 2013) was supplemented by manual searches of bibliographies of key retrieved articles and relevant reviews. We included case-control studies and cohort studies with more than 100 cancer cases. RESULTS: The search yielded 89 eligible studies that reported 100,554 cases at 30 cancer sites. For overall cancer risk, the pooled OR was 1.12 (95%CI: 1.09-1.16) for A vs. non- A groups, and 0.84 (95%CI: 0.80-0.88) for O vs. non-O groups. For individual cancer sites, blood group A was found to confer increased risk of gastric cancer (OR=1.18; 95%CI: 1.13-1.24), pancreatic cancer (OR=1.23; 95%CI: 1.15-1.32), breast cancer (OR=1.12; 95%CI: 1.01-1.24), ovarian cancer (OR=1.16; 95%CI: 1.04-1.27), and nasopharyngeal cancer (OR=1.17; 95%CI: 1.00-1.33). Blood group O was found to be linked to decreased risk of gastric cancer (OR=0.84; 95%CI: 0.80-0.88), pancreatic cancer (OR=0.75; 95%CI: 0.70-0.80), breast cancer (OR=0.90; 95%CI: 0.85-0.95), colorectal cancer (OR=0.89; 95%CI: 0.81-0.96), ovarian cancer (OR=0.76; 95%CI: 0.53-1.00), esophagus cancer (OR=0.94; 95%CI: 0.89-1.00), and nasopharyngeal cancer (OR=0.81; 95%CI: 0.70-0.91). CONCLUSIONS: Blood group A is associated with increased risk of cancer, and blood group O is associated with decreased risk of cancer.

Active and passive smoking with breast cancer risk for Chinese females: a systematic review and meta-analysis.

Previous studies suggested that smoking and passive smoking could increase the risk of breast cancer, but the results were inconsistent, especially for Chinese females. Thus, we systematically searched cohort and case-control studies investigating the associations of active and passive smoking with breast cancer risk among Chinese females in four English databases (PubMed, Embase, ScienceDirect, and Wiley) and three Chinese databases (CNKI, WanFang, and VIP). Fifty-one articles (3 cohort studies and 48 case-control studies) covering 17 provinces of China were finally included in this systematic review. Among Chinese females, there was significant association between passive smoking and this risk of breast cancer [odds ratio (OR): 1.62; 95% confidence interval (CI): 1.39-1.85; I2 = 75.8%, P < 0.001; n = 26] but no significant association between active smoking and the risk of breast cancer (OR: 1.04; 95% CI: 0.89-1.20; I2 = 13.9%, P = 0.248; n = 31). The OR of exposure to husband's smoking and to smoke in the workplace was 1.27 (95% CI: 1.07-1.50) and 1.66 (95% CI: 1.07-2.59), respectively. The OR of light and heavy passive smoking was 1.11 and 1.41, respectively, for women exposed to their husband's smoke (< 20 and ≥ 20 cigarettes per day), and 1.07 and 1.87, respectively, for those exposed to smoke in the workplace (< 300 and ≥ 300 min of exposure per day). These results imply that passive smoking is associated with an increased risk of breast cancer, and the risk seems to increase as the level of passive exposure to smoke increases among Chinese females. Women with passive exposure to smoke in the workplace have a higher risk of breast cancer than those exposed to their husband's smoking.

Association between dietary factors and breast cancer risk among Chinese females: systematic review and meta-analysis.

BACKGROUND: Evidence for associations between dietary factors and breast cancer risk is inconclusive among Chinese females. To evaluate this question, we conducted a systematic review of relevant case-control and cohort studies. METHODS: Studies were systematically searched among 5 English databases (PudMed, ScienceDirect, Wiley, Clinicaltrials.gov, and Cochrane) and 3 Chinese databases (CNKI, WanFang, and VIP) until November 2012. Random effects models were used to estimate summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). RESULTS: Thirty one case-control studies and two cohort studies involving 9,299 cases and 11,413 controls were included. Consumption of both soy and fruit was significantly associated with decreased risk of breast cancer, with summary ORs of 0.65 (95% CIs: 0.43-0.99; I2=88.9%, P<0.001; N=13) and 0.66 (95% CIs: 0.47-0.91; I2=76.7%, P<0.001; N=7), respectively. Consumption of fat was significantly associated with increased risk of breast cancer (OR=1.36; 95% CIs: 1.13-1.63; I2=47.9%, P=0.088; N=6). There was non- significant association between consumption of vegetables and breast cancer risk (OR=0.72; 95% CIs: 0.51-1.02; I2= 74.4%, P<0.001; N=9). However, sensitivity analysis based on adjusted ORs showed decreased risk of breast cancer was also associated with consumption of vegetables (OR=0.49; 95% CIs: 0.30-0.67). CONCLUSION: Both soy food and fruit are significantly associated with decreased risk of breast cancer among Chinese females, and vegetables also seems to be protective while dietary fatexerts a promoting influence.

A bird's eye view of the air pollution-cancer link in China.

Air pollution in China comes from multiple sources, including coal consumption, construction and industrial dust, and vehicle exhaust. Coal consumption in particular directly determines the emissions of three major air pollutants: dust, sulfur dioxide (SO(2)), and nitrogen oxide (NOx). The rapidly increasing number of civilian vehicles is expected to bring NOx emission to a very high level. Contrary to expectations, however, existing data show that the concentrations of major pollutants [particulate matter-10 (PM10), SO(2), and nitrogen dioxide (NO(2))] in several large Chinese cities have declined during the past decades, though they still exceed the national standards of ambient air quality. Archived data from China does not fully support that the concentrations of pollutants directly depend on local emissions, but this is likely due to inaccurate measurement of pollutants. Analyses on the cancer registry data show that cancer burden related to air pollution is on the rise in China and will likely increase further, but there is a lack of data to accurately predict the cancer burden. Past experience from other countries has sounded alarm of the link between air pollution and cancer. The quantitative association requires dedicated research as well as establishment of needed monitoring infrastructures and cancer registries. The air pollution-cancer link is a serious public health issue that needs urgent investigation.

[Influence on cell proliferation by small interfering RNA of Cyclin Y expression in laryngeal cancer cells].

OBJECTIVE: The effects of lentivirus-mediated suppression of Cyclin Y (CCNY) expression on the proliferation of laryngeal cancer cells were investigated in vitro. METHODS: The lentivirus vectors containing a small hairpin RNA (shRNA) to target CCNY were constructed.Hep-2 cells were divided into the following two experimental groups:the negative control group (control lentivirus infected cells) and CCNY knockdown group (CCNY shRNA-expressing lentivirus infected cells). After Hep-2 cells were infected, Real-time PCR was used to measure CCNY expression. The influence of CCNY on the proliferation of laryngeal cancer cells were assessed using MTT and colony formation experiments.Each experiment was performed in triplicate and repeated three times. RESULTS: Lentiviruses expressing shRNA against CCNY were constructed and Hep-2 cells were infected with above mentioned lentivirus at MOI (Multiplicity of infection) of 120.Real-time PCR analysis showed that the mRNA expression of CCNY in Hep-2 cells in the knockdown group was significantly decreased (P < 0.05); the mRNA level of CCNY was 75.3% lower in the si-CCNY group than in the si-CTRL group. After 5 days of lentiviral infection, the cell viability was significantly lower in cells infected with the CCNY-shRNA lentivirus compared to cells infected with the control lentivirus following a 6-day incubation. The colony number was decreased by 60% in Hep-2 cells infected with the CCNY-shRNA-lentivirus infected cells following a 10-day incubation. CONCLUSIONS: The results suggested that lentivirus-mediated downregulation of CCNY expression decreased the proliferation and growth potency of laryngeal cancer cells.Lentiviruses delivering shRNA against CCNY may be a promising tool for laryngeal cancer therapy.

Tea consumption, alcohol drinking and physical activity associations with breast cancer risk among Chinese females: a systematic review and meta-analysis.

OBJECTIVE: To evaluate associations between tea consumption, alcohol drinking and physical activity and breast cancer risk among Chinese females. METHODS: Three English databases (PubMed, ScienceDirect and Wiley) and three Chinese databases (CNKI, WanFang and VIP) were independently searched by 2 reviewers up to December 2012, complemented by manual searches. The quality of included studies was assessed with the Newcastle-Ottawa Scale items. Random-effects models were used to estimate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Potential publication bias was estimated through Egger's and Begg's tests. Heterogeneity between studies was evaluated with I2 statistics. RESULTS: Thirty-nine studies involving 13,204 breast cancer cases and 87,248 controls were identified. Compared with non-drinkers, regular tea drinkers had decreased risk (OR=0.79, 95%CIs: 0.65-0.95; I2=84.9%; N=16). An inverse association was also found between regular physical activity and breast cancer risk (OR=0.73, 95%CIs: 0.63-0.85; I2=77.3%; N=15). However, there was no significant association between alcohol drinking and breast cancer risk (OR=0.85, 95%CIs: 0.72- 1.02; I2=63.8%; N=26). Most of the results from the subgroup analysis were consistent with the main results. CONCLUSION: Tea consumption and physical activity are significantly associated with a decreased risk of breast cancer in Chinese females. However, alcohol drinking may not be associated with any elevation of risk.

[Relationship of alcohol drinking and tea consumption with the risk of nasopharynx cancer among Chinese population: a meta-analysis].

OBJECTIVE: To evaluate the relationship and strength of association for alcohol drinking and tea consumption with the riskS of nasopharynx cancer among Chinese population so as to provide control rationales for nasopharynx cancer in China. METHODS: A systematic search of 3 Chinese electronic databases (CNKI, VIP, Wanfang) and 3 English databases (Pubmed, ScienceDirect and SpringerLink) up to March 2013 was performed. Two reviewers independently conducted the literature search, examined eligibility and performed data extraction and quality evaluations. Pooled odd ratio (OR) value and 95%CI value were calculated with random-effects model weighted with inverse of variances. RESULTS: A total of 14 studies (including 3 cohort and 11 case-control) involving 6559 cases of nasopharynx cancer and 10 567 controls from 6 provinces were included. The pooled OR between alcohol drinking and risks of nasopharynx cancer was 1.12 (95%CI: 0.98-1.26; I(2) = 44.5%, P = 0.037). Compared with the non-drinkers, the risks of nasopharynx cancer for regular drinkers and occasional drinkers were 1.18 (95%CI: 1.00-1.38; I(2) = 0.0%, P = 0.578) and 0.76 (95%CI: 0.65-0.89; I(2) = 33.4%, P = 0.212). And the association of tea consumption with the risks of nasopharynx cancer was 0.53 (95%CI: 0.43-0.60; I(2) = 17.9%, P = 0.301). CONCLUSIONS: In China, occasional alcohol drinking may decrease the risks of nasopharynx cancer while regular drinking elevates the risks. And there is significantly protective effect for tea consumption on the risks of nasopharynx cancer.

Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis.

Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.