High‐frequency p16INK4A promoter methylation is associated with histone methyltransferase SETDB1 expression in sporadic cutaneous melanoma

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16^INK4A promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation‐specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki‐67 index), p16^INK4A and SETDB1 expression were evaluated by immunohistochemistry. High‐frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16^INK4A promoter methylation was higher in vertical growth‐phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16^INK4A methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1–30%) p16^INK4A expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16^INK4A methylation and p16^INK4A expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0–5/mm² vs >5/mm², P = 0.0869), advanced Clark level (III‐V, P = 0.0380), epidermal involvement (P = 0.0331) and the non‐chronic sun exposure‐associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16^INK4A promoter and several prognostic parameters in melanomas.     

Promoting Breast Cancer Screening Among Asian American Women: the Asian Grocery Store-Based Cancer Education Program

Asian American women's historically low breast cancer mortality rate has remained constant as rates decreased for all other races. From 2000 to 2004, a randomized controlled trial explored the Asian grocery store-based breast cancer education program's impact on Chinese, Filipino, Korean, and Vietnamese women (n?=?1,540). Women aged 40 and older and non-adherent for annual screening mammograms were more likely to schedule a mammogram after receiving the breast cancer education program than women randomized to the prostate cancer program (X ²?=?3.85, p?=?0.05). With the right program ingredients, late adopters of breast cancer screening can be prompted to change.     

ORIGINAL ARTICLE: Associations of the growth hormone receptor (GHR) gene polymorphisms with adiposity and IGF‐I activity in adolescents

Objective: To explore the genetic effect of the GH receptor (GHR) on obesity and related metabolic parameters in Hong Kong Chinese adolescents. Context: Obesity is a growing global epidemic. Increasing evidence suggests that the GH‐IGF‐I axis plays an important role in regulating adiposity and insulin sensitivity. Design: We examined the associations of genetic variants of GHR with serum IGF‐I and IGFBP‐3 levels as well as obesity‐related metabolic traits in Hong Kong Chinese adolescents. Patients: Nine hundred and eighty‐one randomly selected Hong Kong Chinese adolescents from 14 schools. Measurements: We genotyped 17 single nucleotide polymorphisms (SNP) at GHR and measured serum IGF‐I and IGFBP‐3 levels as well as obesity‐related metabolic traits including fasting plasma glucose, insulin and lipid levels. Results: There were significant associations between rs4410646 and the body composition (P = 0·0044) and blood pressure factor scores (P = 0·00017). Carriers of the CC genotype had lower body mass index, percentage body fat, waist and hip circumferences than AC and AA genotype carriers (P = 0·00030–0·0094). There was also association between rs7703713 and the IGF‐I activity factor score (P = 0·0033). The GA and AA carriers of rs7703713 had higher serum IGF‐I, higher serum IGFBP‐3 and higher IGF‐I/IGFBP‐3 molar ratio (P = 0·00069–0·025). Haplotype analysis did not increase the significance of associations. Conclusion: Our results support the role of GHR gene polymorphisms in modulating adiposity and IGF‐I activity in adolescents. Examination of interactions of these SNPs with lifestyle, environmental and perinatal factors may provide further insights into their long‐term effects on obesity and metabolic risks.     

Predictors of common bile duct lithiasis in laparoscopic era

AIM:To analyze retrospectively the records of 294 conse-cutive patients operated upon for gallbladder stones, to determine the predictive factors of synchronous common bile duct (CBD) stones and validate prospectively the generated model. METHODS: The prognostic estimation of a biochemical test and ultrasonography alone to differentiate between the absence and presence of choledocholithiasis was assessed using receiver operating characteristics curve analysis. Multivariate analysis was employed using discriminant analysis for establishment of a best model.Prospective validation of the model was made. RESULTS: Discriminant forward stepwise analysis disclosed that high values (≥2×normal) of SGOT,ALP, conjugated bilirubin and CBD diameter on ultrasound ≥10 mm were all prognostic factors of CBD lithiasis in univariate and multivariate analysis, P<0.01. History was not included in the model.Prospective validation of the model was performed by multivariate analysis using Visual General Stepwise Regression. Positive predictive value, when considering all these predictors,was 93.3%,while the negative predictive value was 88.8%.Sensitivity of the model was 96.5% and specificity 80%. CONCLUSION: The above model can be objectively applied to predict the presence of CBD stones.