Cancer In Caucasian Population Research Articles

Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients.

Simple SummaryMelanoma has become the most rapidly increasing cancer in Caucasian populations, causing 90% of skin cancer mortality. FDG-PET/CT has been recommended by the European 2019 guidelines for melanoma for staging and treatment response assessment in advanced melanoma highlighting the need for new outcome predictive biomarkers. In the context of melanoma, the evidence on the predictive value of semiquantitative parameters derived from FDG-PET/CT is still very limited. We here provide evidence, in a large cohort of metastatic melanoma patients, that FDG-PET/CT can be used to predict the early response to immune checkpoint inhibition. On a patient-basis, total tumor volume and semiquantitative parameters, such as total metabolic tumor volume MTV and total lesion glycolysis TLG of all metastases three months after treatment start are promising predictive biomarkers for the outcome in metastatic melanoma patients. Also, early complete response on a metastasis- and patient-level seems to be predictive for lasting complete response.We aimed to investigate, whether 18F-2-fluoro-2-desoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) scans performed at baseline (time point 0; TP 0) and three months after initiation of immunotherapy (time point 1; TP 1) can be used on a metastasis- and patient-level to predict the response to immune-checkpoint inhibition using FDG-PET/CT six months after treatment start (time point 2; TP 2) in metastatic melanoma patients. This single-center retrospective study considered metastatic melanoma patients treated with immune checkpoint inhibition from TP 0 to TP 2. An analysis on a metastasis- and patient-level was carried out. Tumor volume, standardized uptake values SUV (mean, maximum, and peak), metabolic tumor volume MTV and total lesion glycolysis TLG of each included metastasis were recorded at each time point, respectively TP 0, TP 1 and TP 2. Total tumor volume, total metabolic tumor volume and total lesion glycolysis per patient were also calculated at TP 0, TP 1 and TP 2. Treatment response was assessed at metastasis- and patient-level based on FDG-PET/CT scans at TP 2. 612 melanoma metastases in 111 patients were included. The analysis on a metastasis-level showed that metastatic SUVpeak at TP 1 and volume variation between TP 0 and TP 1 were the strongest negative predictive biomarkers for response. However, at TP 0, metastatic SUVmean and SUVpeak indicated a low negative prediction power, whereas initial metastatic volume was not a predictive biomarker. Also, melanoma metastases located in bone structures had a negative influence on the outcome at TP 2, particularly in women. The analysis on a patient-level showed, that total tumor volume, total metastatic tumor volume and total lesion glycolysis of all metastases three months after treatment initiation were strong negative predictive biomarkers for response to immunotherapy six months after initiation. Age and female sex were also found to be negative predictive biomarkers with lower predictive power. Interestingly, total tumor volume at TP 0 and number of metastases at TP 0 as well as the occurrence of early immune-related adverse events between TP 0 and TP 2 did not have any predictive value for early treatment response. FDG-PET/CT performed for treatment response assessment three months after initiation of immune checkpoint inhibition in metastatic melanoma patients can also be used to predict early response to treatment. On a metastasis-level SUV peak and volume variation of metastases are strong outcome predictive biomarkers. On a patient-level total tumor volume and semiquantitative parameters such as total metabolic tumor volume MTV and total lesion glycolysis TLG of all metastases are promising outcome predictive biomarkers. Also, early complete response on a metastasis- and patient-level seems to be predictive for lasting complete response.

Cytoplasmic Increase in Hsp70 Protein: A Potential New Biomarker of Early Infiltration of Cutaneous Squamous Cell Carcinoma Arising from Actinic Keratosis.

Background: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non-melanoma skin cancer and is the second leading cause of death by skin cancer in Caucasian populations. However, at present it is difficult to predict patients with poor SCC prognosis. Objective: To identify proteins with expression levels that could predict SCC infiltration in SCC arising from actinic keratosis (SCC-AK). Methods: A total of 20 biopsies from 20 different patients were studied; 10 were SCC-AK samples and 10 were taken from normal skin. Early infiltrated SCC-AK samples were selected based on histological examination, and to determine the expression of proteins, fresh skin samples were processed by two-dimensional electrophoresis. Results: The expression levels of three proteins, namely alpha hemoglobin and heat shock proteins 27 and 70 (Hsp27 and Hsp70, respectively) were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immunohistological examination suggested that increased expression of Hsp70 proteins seemed to mainly occur in the cytoplasm of keratinocytes. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western blot experiments. Conclusion: Cytoplasmic expression of Hsp70 could be a potential biomarker of early infiltration of SCC arising from AK.

The impact of propranolol on apoptosis in cutaneous squamous cell carcinomas.

Cutaneous squamous cell carcinoma (cSCC) is a common cancer in Caucasian populations. Treatments registered for high-risk cSCC are still undetermined. Experimental data have demonstrated possibly useful effects of a combined application of beta‑blockers in cancer therapy. The goal of this study was to examine the efficacy of propranolol in the treatment of cSCC and its impact on apoptosis. Thus, we aimed to investigate the apoptotic pathway protein levels and activity in beta‑blocker‑treated cSCC cells. The study was performed on human cSCC cancer cell line culture. One of the cSCC cell lines was treated with propranolol, whereas no treatment was given to the other group. Then, the levels of apoptotic pathway proteins were determined by ELISA test in both groups. The propranolol treatment group exhibited a remarkable difference as compared with the other group. It was found that propranolol treatment enhanced the activity of caspase-3 while the expression of bax, wee1, gadd153, grp78 and AIF decreased bcl-2 which is antiapoptotic protein in cSCC cell lines. Our results suggest that propranolol treatment has anti-cancer properties with an effect on various apoptotic pathways in cSCC. These data are important because propronalol may be involved in future cSCC treatment (Tab. 1, Fig. 3, Ref. 22).

Relationship between Aurora-A V57I Polymorphism and the Risk of Cancer: A Meta-Analysis and Trial Sequential Analysis.

Background: It is still conflicting for the correlation between cancer susceptibility and Aurora-A V57I (rs1047972) gene variant from the published researches. This meta-analysis was performed to access the correlation between cancer susceptibility and Aurora-A rs1047972 gene polymorphism by using meta-analysis methods.Methods: Eligible studies published before Nov 1, 2019 were systematically searched in PMC, PubMed, EMBASE, Web of Science, Cochrane Library Database, China National Knowledge Infrastructure, Wanfang databases, in order to collect qualified case-control or cohort studies. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to evaluate the correlation between Aurora-A rs1047972 gene polymorphism and cancer risk. Sensitivity analysis was used to examine the stability of the results; Egger's test and Begg's funnel chart were used to assess possible publication bias. Trial sequential analysis (TSA) was used to access whether the sample size of our meta-analysis was sufficient.Results: The sample set extracted from 24 case-control studies involving 35,926 subjects (14,639 cases and 21,287 controls) for the association of Aurora-A rs1047972 gene polymorphism with cancer susceptibility. In our meta-analysis, Aurora-A rs1047972 polymorphism was associated with an increased risk of cancer susceptibility in overall populations (GA+GG vs. AA: P=0.039, OR=1.106; 95% CI 1.005-1.218; AA vs. GG: P=0.003, OR= 0.814; 95% CI, 0.710-0.934), and the GA/GG variant might be a risk factor for cancer susceptibility. In the stratified analysis by ethnicity, we found a significant association between Aurora-A rs1047972 variant and the susceptibility of the cancer in Caucasian population. In a subgroup analysis by cancer type, we observed a significantly increased susceptibility of lung cancer. In addition, an increased risk was found between Aurora-A rs1047972 polymorphism and cancer susceptibility in MALDI-TOF group and among population-based study (PB) patients. Our results were in a sufficiently large number of participants according to TSA and did not require more studies to confirm such association.Conclusion: Our meta-analysis revealed that the susceptibility of cancer was associated with Aurora-A rs1047972 polymorphism, especially in Caucasians. And the GA/GG variant might be a risk factor for cancer susceptibility.

Vitamin D receptor rs2228570 polymorphism and susceptibility to ovarian cancer: An updated meta-analysis.

The FokI polymorphism (C>T, rs2228570) of the vitamin D receptor gene is a coding nonsynonymous single nucleotide polymorphism in the translational initiation codon reported to have functional significance. Although the role of rs2228570 in the risk of ovarian cancer has been widely researched, the association is still unclear. We performed an updated meta-analysis to clarify this issue. Eligible studies were retrieved from electronic databases for the period 2007-2016. The association was measured by unadjusted odds ratio combined with 95% confidence intervals (CIs). Random-effect or fixed-effect models were used according to the heterogeneity of the studies. We further appreciated the strength of evidence according to Venice guidance. Fourteen studies (4448 cases and 7242 controls) were included in the meta-analysis. Studies were predominantly conducted in Caucasian populations (4152 cases and 6693 controls). A dominant genetic model was determined to be the most appropriate genetic model. Overall meta-analysis showed a fixed-effect odds ratio of 1.14 (95% CI 1.05-1.23) under a dominant model. The fixed-effect odds ratios were 1.12 (95% CI 1.03-1.21) and 1.49 (95% CI 1.06-2.09) in Caucasian and Asian populations, respectively. The strength of the evidence was moderate. The rs2228570 polymorphism increased the risk of ovarian cancer in Caucasian populations in a dominant genetic model. The role of this polymorphism in the risk of ovarian cancer in Asian populations should be further studied.

Association between polymorphisms of thymidylate synthase gene 5'- and 3'-UTR and gastric cancer risk: meta-analysis.

Gastric cancer is the most common cancer and the most frequent cause of cancer death worldwide. Several studies have identified the role of thymidylate synthase (TS) 5′- and 3′-UTR and gastric cancer susceptibility; however, the results still remain inconclusive. The purpose of this meta-analysis was to reinvestigate this correlation. In the present study, online databases were searched to retrieve relevant articles published between January 2000 and 2016. The odds ratio (OR) and 95% confidence interval (CI) were employed to calculate the strength of association. Overall, a total of 13 articles were screened out, including 2382 gastric cancer patients and 3171 healthy controls. We found that polymorphisms of TS 5′-UTR 2R (double repeats)/3R (triple repeats) of a 28-bp sequence (11 articles) and 3′-UTR del6/ins6 (seven articles) were not significantly associated with increased risk of gastric cancer. Subgroup analysis by ethnicity showed that 2R allele and 2R/2R genotype in TS 5′-UTR were associated with gastric cancer susceptibility in Caucasian and African populations; del6 allele, del6/del6 and del6/ins6 genotypes were correlated with gastric cancer in Caucasian population. In conclusion, our result suggested that TS polymorphisms might be the risk factors for gastric cancer risk in Caucasian population, although this association needs further study, and future large-scale researches are still required.

Cutaneous squamous cell carcinoma

Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6mm but there is currently no evidence concerning prognostic and therapeutic effects. Radiotherapy can be discussed as an alternative to surgery for inoperable tumors or as adjuvant therapy for a high risk of recurrence. In SCC with distant metastases various chemotherapeutic agents are used; however, there is no standard regimen. The epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint blockers can be discussed as treatment options, preferentially in clinical trials. There is no standard follow-up schedule for patients with SCC. Arisk-adapted follow-up is recommended based on the risk of metastatic spread or development of new lesions primarily by dermatological control and supplemented by ultrasound investigations in high risk patients.

Rs61764370 polymorphism of Kras and risk of cancer in Caucasian population: A meta-analysis.

Kras is an important oncogene that plays a pivotal role in carcinogenesis. Rs61764370 polymorphism in Kras 3'-untranslated region is a candidate factor for contributing susceptibility to cancer. However, the results of emerging studies concerning association between rs61764370 and cancer risk remain elusive. The association between rs61764370 and risk of cancer was evaluated in 30 studies including 14936. cases and 15168 controls. Meta-analysis result showed that genotype. GT/GG of rs61764370 was not associated with cancer in Caucasian population. After stratifying the overall population into cancer type subgroups, no significant association was observed between genotype. GT/GG and ovarian, breast, colorectal, non.-small cell lung cancer or head-neck carcinoma in Caucasian population, respectively. These results indicated that genotype. GT/GG of rs61764370 was not a genetic susceptible risk factor for cancer, and rs61764370 could not be used as a biomarker for estimating cancer risk in Caucasian population.

Association of angiotensin ІІ type 1 receptor (A1166C) polymorphism with breast cancer risk: An update meta-analysis.

Previous studies on the relationship between angiotensin ІІ type 1 receptor (AT1R) gene (A1166C) polymorphism and breast cancer did not reach the same conclusion. In the present study, we aimed to further evaluate the relationship between the AT1R gene A1166C polymorphism and breast cancer risk. We selected five case-control studies related to AT1R gene A1166C polymorphism and breast cancer by searching PubMed, EMBase, Chinese Biomedical Literature Database, Chinese CNKI, Web of Science, and the Wanfang database. We utilized Q-test and I(2) test to detect the heterogeneity between each study. A random-effects model (I(2) > 50%; p < 0.10) or a fixed-effects model (I(2) < 50%; p > 0.10) was utilized to merge the odds ratio (OR) and 95% confidence interval (CI) during the meta- analyses. The present study included 972 patients with breast cancer and 1336 cancer-free control subjects. By meta-analysis, we found A1166C polymorphism was associated with decreased risk for breast cancer in Caucasian population in an additive model (C vs. T: OR = 0.77, 95% CI: 0.62-0.96, p = 0.02). However, we did not find associations in other genetic models (AC+CC vs. AA: OR = 0.78, 95% CI: 0.50-1.22, p = 0.28; CC vs. AA+AC: OR = 1.64, 95% CI: 0.94-2.85, p = 0.08). We concluded that AT1R gene A1166C polymorphism was associated with reduced risk for breast cancer.

Associations between ghrelin and ghrelin receptor polymorphisms and cancer in Caucasian populations: a meta-analysis.

BackgroundThere is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its receptor, the growth hormone secretagogue receptor (GHSR), play a role in cancer progression. Ghrelin gene and ghrelin receptor gene polymorphisms have been reported to have a range of effects in cancer, from increased risk, to protection from cancer, or having no association. In this study we aimed to clarify the role of ghrelin and ghrelin receptor polymorphisms in cancer by performing a meta-analysis of published case–control studies.We conducted searches of the literature published up to January 2013 in MEDLINE using the PubMed search engine. Individual data on 8,430 cases and 14,008 controls from six case–control studies of an all Caucasian population were evaluated for three ghrelin gene (GHRL; rs696217, rs4684677, rs2075356) and one ghrelin receptor (GHSR; rs572169) polymorphism in breast cancer, esophageal cancer, colorectal cancer and non-Hodgkins lymphoma.ResultsIn the overall analysis, homozygous and recessive associations indicated that the minor alleles of rs696217 and rs2075356 GHRL polymorphisms conferred reduced cancer risk (odds ratio [OR] 0.61-0.78). The risk was unchanged for breast cancer patients when analysed separately (OR 0.73-0.83). In contrast, the rs4684677 GHRL and the rs572169 GHSR polymorphisms conferred increased breast cancer risk (OR 1.97-1.98, p = 0.08 and OR 1.42-1.43, p = 0.08, respectively). All dominant and co-dominant effects showed null effects (OR 0.96-1.05), except for the rs572169 co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05).ConclusionsThis study suggests that the rs696217 and rs2075356 ghrelin gene (GHRL) polymorphisms may protect carriers against breast cancer, and the rs4684677 GHRL and rs572169 GHSR polymorphisms may increase the risk among carriers. In addition, larger studies are required to confirm these findings.

Genetic association of BSF2 polymorphism and susceptibility to lung cancer.

BSF2 polymorphism is believed to affect the transcriptional capability of the gene. Studies of lung cancer have associated BSF2 polymorphism with risk of lung cancer, only failing to identify whether this polymorphism predisposes an individual variation in the susceptibility to the malignant cancer. The primary aim of this study was to determine the association. An exhaustive literature search was conducted in the Medline and CNKI databases. Based on the data extracted from each of the included studies, we estimated the risk of lung cancer ascribed to BSF2 polymorphism by calculating ORs and its 95 % CIs. When pooling all eligible studies into the meta-analysis, we did not see any evidence suggesting there was a significant association between BSF2 polymorphism and risk of lung cancer. For the studies of Caucasian sample, the effects were exactly the same as those observed in the overall comparison. Our results suggest that BSF2 polymorphism may not predispose genetic susceptibility toward lung cancer in Caucasian populations, which nevertheless requires additional investigation.

Association of XPC polymorphisms and lung cancer risk: a meta-analysis.

BackgroundXeroderma pigmentosum complementation group C gene (XPC) is a key member of nucleotide excision repair pathway and plays an important role in human DNA repair system. It is reported that several common polymorphisms of XPC are associated with susceptibility to lung cancer. However, the conclusion is still elusive.MethodThis meta-analysis was performed to determine the relationship between XPC polymorphisms (Lys939Gln, Ala499Val, and PAT) and lung cancer risk. Published literatures were identified by searching online databases and reference lists of relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias were detected by Egger’s and Begg’s test.ResultAfter strict screening, we identified 14 eligible studies in this meta-analysis, including 5647 lung cancer cases and 6908 controls. By pooling all eligible studies, we found that the homozygote Gln939Gln genotype was associated with a significantly increased risk of lung cancer in Asian population (GlnGln vs LysLys, OR = 1.229, 95% CI: 1.000–1.510; GlnGln vs LysLys/LysGln, OR = 1.257, 95% CI: 1.038–1.522). As for the PAT polymorphism, in Caucasian population, we found carriers of the −/− genotype were associated significantly reduced risk of lung cancer in homozygote comparison model (−/− vs +/+, OR = 0.735, 95% CI: 0.567–0.952).ConclusionIn this meta-analysis we found that Gln939Gln genotype was associated with significantly increased risk of lung cancer in Asian population; the PAT −/− genotype significantly reduced susceptibility to lung cancer in Caucasian population; while the XPC Ala499Val polymorphism was not associated with lung cancer risk.

Association between CCND1 and XPC polymorphisms and bladder cancer risk: a meta-analysis based on 15 case–control studies

Perturbations in cell cycle and DNA repair genes might affect susceptibility to cancer. The aim of this meta-analysis is to generate large-scale evidence to determine the degree to which common Cyclin D1 (CCND1) G870A (dbSNP: rs603965) and xeroderma pigmentosum group C (XPC) Ala499Val (dbSNP: rs2228000) polymorphisms are associated with susceptibility to bladder cancer. The electronic databases PubMed, Embase, Web of Science, and CNKI were searched for relevant studies (with an upper date limit of July 25, 2013). The principal outcome measure for evaluating the strength of association was crude odds ratios (ORs) along with their corresponding confidence intervals (95%CIs). We found and reviewed nine case-control studies on CCND1 G870A with a total of 6,823 subjects and seven studies on XPC Ala499Val with a total of 7,674 subjects. Our meta-analysis provides evidence that the variant genotype of CCND1 G870A showed a significant association in the occurrence of invasive bladder tumors in former and current smokers. The XPC Ala499Val polymorphism correlated with significant differences between patients and unaffected subjects, but when the groups were stratified by ethnicity, the magnitude of the overall effect was similar only among Caucasian populations. Results from our meta-analysis support the view that the G870A polymorphism may modulate the risk of bladder cancer in conjunction with tobacco smoking and that the Ala499Val polymorphism may contribute to the susceptibility to bladder cancer in Caucasian populations. Our findings, however, warrant larger well-designed studies to investigate the significance of these two polymorphisms as markers of susceptibility to bladder cancer.

Inhibiting cycloxygenase and ornithine decarboxylase by diclofenac and alpha-difluoromethylornithine blocks cutaneous SCCs by targeting Akt-ERK axis.

Non-melanoma skin cancer (NMSC) is the most common type of skin cancer in Caucasian populations. Its increasing incidence has been a major public health concern. Elevated expressions of ODC and COX-2 are associated with both murine and human NMSCs. Inhibition of these molecular targets singly employing their respective small molecule inhibitors showed limited success. Here, we show that combined blockade of ODC and COX-2 using their potent inhibitors, DFMO and diclofenac respectively abrogates growth of A431 epidermal xenograft tumors in nu/nu mice by more than 90%. The tumor growth inhibition was associated with a diminution in the proliferation and enhancement in apoptosis. The proliferation markers such as PCNA and cyclin D1 were reduced. TUNEL-positive apoptotic cells and cleaved caspase-3 were increased in the residual tumors. These agents also manifested direct target-unrelated effects. Reduced expression of phosphorylated MAPKAP-2, ERK, and Akt (ser473 & thr308) were noticed. The mechanism by which combined inhibition of ODC/COX attenuated tumor growth and invasion involved reduction in EMT. Akt activation by ODC+COX-2 over-expression was the key player in this regard as Akt inhibition manifested effects similar to those observed by the combined inhibition of ODC+COX-2 whereas forced over-expression of Akt resisted against DFMO+diclofenac treatment. These data suggest that ODC+COX-2 over-expression together leads to pathogenesis of aggressive and invasive cutaneous carcinomas by activating Akt signaling pathway, which through augmenting EMT contributes to tumor invasion.

The effect of oxoguanine glycosylase 1 rs1052133 polymorphism on colorectal cancer risk in Caucasian population

Human oxoguanine glycosylase 1 (OGG1) is an important part of the base excision repair pathway in the DNA repair. Numerous epidemiological studies have evaluated the association between OGG1 rs1052133 polymorphism and the risk of colorectal cancer, but the results of these studies from the Caucasian population were conflicting. To derive a more precise assessment on the association between OGG1 rs1052133 polymorphism and risk of colorectal cancer in Caucasian population, we performed a meta-analysis. The odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of the association. Thirteen case-control studies with a total of 4,103 cases and 5,400 controls were finally included into the meta-analysis. Meta-analysis of all 13 studies showed that OGG1 rs1052133 polymorphism was significantly associated with the risk of colorectal cancer in Caucasian population (Cys versus Ser OR = 1.20, 95% CI = 1.03-1.39, P = 0.02; CysCys versus SerSer OR = 1.44, 95% CI = 1.04-2.00, P = 0.03; CysCys versus SerSer/SerCys OR = 1.39, 95% CI = 1.15-1.67, P = 0.0005). In the sensitivity analysis, omitting each study one at a time had no obvious influence on the pooled OR, which confirmed the stability of meta-analysis. The meta-analysis suggests that OGG1 rs1052133 polymorphism is significantly associated with the risk of colorectal cancer in Caucasian population.

Basal cell carcinoma and anthropometric factors in the U.S. radiologic technologists cohort study.

Basal cell carcinoma (BCC) is the most common cancer in Caucasian populations. Although several risk factors are well-established, including ultraviolet radiation (UVR) sensitivity and exposure, few studies have examined anthropometric measures and BCC. Using Cox proportional hazards regression analysis, we prospectively investigated the relationship between height, weight and body mass index (BMI) and BCC in 58,213 Caucasian participants (11,631 men and 46,582 women) from the United States Radiological Technologists cohort. This analysis was limited to participants who were cancer-free at baseline. The baseline questionnaire provided self-reported anthropometric factors and the subsequent questionnaire collected skin cancer susceptibility factors, lifetime UVR exposure derived from residential and personal UVR exposure (time outdoors) and health outcomes. During 509,465 person-years of follow-up, we identified 2,291 BCC cases (486 men; 1,805 women). BCC risk increased with increasing height, and decreased with increasing weight and BMI in both sexes, even after adjusting for UVR susceptibility factors and exposures. For BMI categories: <25 (reference); 25-<30; 30-<35 and ≥ 35 kg m(-2) , multivariate hazard ratios (HR) in women were: 1.00; 0.74 (95% CI = 0.66-0.83); 0.67 (0.56-0.81) and 0.57 (0.44-0.74), respectively, p-trend ≤ 0.0001. Risks were similar in men. The inverse association between BMI and BCC was unaffected by controlling for sun-related exposures. Nevertheless, it may at least partly reflect residual UVR confounding. Further research with more detailed sun exposure data, including clothing patterns, would help clarify the relationship between BMI and BCC.

Modification of allele-specific polymerase chain reaction for hMYH mutation analysis in Taiwanese patients with colorectal cancer

hMYH, a putative human E. coli MutY homology, can effectively remove adenine opposite to GO or G in duplex oligonucleotides with its glycosylase and AP lyase activities. Its germline mutations have been reported to be associated with colorectal cancer in Caucasian population. Plasmid DNA containing hMYH was employed to optimize the allele-specific polymerase chain reaction analysis conditions. The reliability of analysis was further improved by reducing the template concentration and adjusting annealing temperature. Genomic DNA of Taiwanese patients who had been diagnosed as colorectal cancer by the Taichung Veterans General Hospital were then examined for the mutations of hMYH, including G382D, Y165C and V232F. However, none of patients were detected with those reported mutations in hMYH. The relationship between the reported mutations of hMYH and colorectal cancer in Taiwan population is uncertain. Our results implicate that the frequencies of hMYH mutations may depend on the pathology of colorectal cancer and vary among different ethnic groups.

Association Between NFKB1 -94ins/delATTG Promoter Polymorphism and Cancer Risk: A Meta-Analysis

The aim of our meta-analysis was to assess the association between NFKB1 -94ins/delATTG promoter polymorphism and cancer risk. Eleven studies that included data from 2,743 cases and 2,195 controls were identified. When all groups were pooled, we did not detect the association between NFKB1 -94ins/delATTG promoter polymorphism and cancer risk. In the subgroup analysis, we detected the association of NFKB1 -94ins/delATTG promoter polymorphism with cancer in Caucasian population. The association also was found in Asian population. This meta-analysis demonstrates the association of NFKB1 -94ins/delATTG promoter polymorphism with cancer in Caucasian and Asian populations, and this association is ethno-specific.

GPC5 rs2352028 variant and risk of lung cancer in never smokers

We read with interest the genome-wide association study by Li and colleagues1 in the April, 2010, issue of The Lancet Oncology, which showed an association (OR 1·46, 95% CI 1·26–1·70) between the single nucleotide polymorphism rs2352028 at chromosome 13q31·3 and risk of lung cancer in never smokers. We sought to replicate this finding using data from seven genome-wide association studies of lung cancer in white populations,2–5 with rs2352028 genotype data for 754 never smokers with lung cancer and 10 580 controls.

GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: A comprehensive meta-analysis

Glutathione S-transferases (GSTs) catalyse reactions between glutathione and lipophilic compounds with electrophilic centres, leading to neutralisation of toxic compounds, xenobiotics and products of oxidative stress. Controversy exists about whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, GSTP1 Ile105Val and GSTA1∗A/∗B) represent risk factors for colorectal cancer. This meta-analysis aims to examine the associations between the above-mentioned polymorphisms and colorectal cancer risk. Forty-four studies were eligible for GSTM1 (11,998 colorectal cancer cases, 17,552 controls), 34 studies for GSTT1 (8596 cases, 13,589 controls), 19 studies for GSTP1 (5421 cases, 7671 controls) and four studies for GSTA1 polymorphism (1648 cases, 2039 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Separate analyses were conducted on Caucasian and Chinese populations. Where appropriate, sensitivity analysis concerning the deviation of genotype frequencies in controls from the Hardy–Weinberg equilibrium was performed. GSTM1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR = 1.150, 95% confidence interval (CI): 1.060–1.248, random effects); no significant association was detected for Chinese subjects (pooled OR = 1.025, 95% CI: 0.903–1.163, fixed effects). Similarly, GSTT1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR = 1.312, 95% CI: 1.119–1.538, random effects); the association in Chinese subjects was not significant (pooled OR = 1.068, 95% CI: 0.788–1.449, random effects). Concerning GSTP1 Ile105Val no significant associations were demonstrated in either race. GSTA1∗A/∗B polymorphism was not associated with colorectal cancer risk. GSTM1 and GSTT1 null genotypes confer additional risk for colorectal cancer in Caucasian populations.