L-MYC gene polymorphism and risk of thyroid cancer

L-myc gene polymorphism is a representative genetic trait responsible for an individual’s susceptibility to several cancers. However, there have been no reports concerning the association between thyroid cancer and L-myc gene polymorphism. Aim: To analyze the distribution of L-myc gene polymorphism in Turkish patients with thyroid disorders and thyroid cancers. Methods: We used a molecular genotyping method, polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). We studied 138 patients of whom 47 had multinodular goiter, 13 had follicular cancer and 69 had papillar cancer, in comparison with control group of 109 healthy individuals. Results: No significant difference in the distribution of genotypes was observed between thyroid patients and controls. Carrying SS or LS genotype revealed a 1.96-fold (95% CI 0.573–6.706) risk for the occurrence of follicular cancer when compared with controls, and 3.11-fold (95% CI 0.952–10.216), when compared with multinodular goiter patients (p = 0.04). Conclusion: We suggest that L-myc genotype profiling together with other susceptibility factors, may be useful in the screening for thyroid nodular malignancy.Для ряда опухолей человека показана корреляция между риском развития опухоли и определенным вариантом гена L-MYC. Данные о наличии такой связи при раке щитовидной железы к настоящему времени отсутствуют. Цель: проанализировать распределение полиморфных типов гена L-MYC в популяции больных с доброкачественными и злокачественными поражениями щитовидной железы, включая рак щитовидной железы, в Турции. Методы: для анализа полиморфизма гена L-MYC использован метод молекулярного генотипирования, в частности, метод определения полиморфизма длины рестрикционных фрагментов, основанный на полимеразной цепной реакции (PCR-RFLP). Определение проводили в лейкоцитах 138 больных, в том числе 48 больных с узловым зобом, 13 больных фолликулярным раком щитовидной железы и 69 больных папиллярным раком. Контрольную группу составляли 109 здоровых лиц. Результаты: статистически достоверных различий в распределении исследуемых генотипов у больных с патологией щитовидной железы и здоровых лиц не выявили. Показано, что относительный риск фолликулярного рака щитовидной железы у больных-носителей генотипа SS или LS составляет 1,96 по сравнению со здоровыми лицами (при 95% доверительном интервале от 0,573 до 6,706) и 3,11 по сравнению с больными с узловым зобом (при 95% доверительном интервале от 0,952 до 10,216) (р = 0,04). Выводы: по нашему предположению, определение профиля полиморфизма гена L-MYC с учетом других факторов, определяющих предрасположенность к развитию опухолей, может быть полезным при скрининге озлокачествления узелковых образований щитовидной железы

Regulation of CLU gene expression by oncogenes and epigenetic factors implications for tumorigenesis

In no other field has the function of clusterin (CLU) been more controversial than in cancer genetics. After more than 20 years of research, there is still uncertainty with regard to the role of CLU in human cancers. Some investigators believe CLU to be an oncogene, others-an inhibitor of tumorigenesis. However, owing to the recent efforts of several laboratories, the role of CLU in important cellular processes like proliferation, apoptosis, differentiation, and transformation is beginning to emerge. The "enigmatic" CLU is becoming less so. In this chapter, we will review the work of research teams interested in understanding how CLU is regulated by oncogenic signaling. We will discuss how and under what circumstances oncogenes and epigenetic factors modify CLU expression, with important consequences for mammalian tumorigenesis

Genetic Associations in the Vitamin D Receptor and Colorectal Cancer in African Americans and Caucasians

Low vitamin D levels are associated with an increased incidence of colorectal cancer (CRC) and higher mortality from the disease. In the US, African Americans (AAs) have the highest CRC incidence and mortality and the lowest levels of vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been previously associated with CRC, but few studies have included AAs. We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for association adjusting for West African ancestry, age, gender, and multiple testing. Untyped markers were imputed using MACH1.0. We analyzed associations by gender and anatomic location in the whole study group as well as by vitamin D intake in the North Carolina AA group. In the joint analysis, none of the SNPs tested was significantly associated with CRC. For four previously tested restriction fragment length polymorphisms, only one (referred to as ApaI), tagged by the SNP rs79628898, had a nominally significant p-value in AAs; none of these polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs, for whom we had vitamin D intake data, we found a significant association between an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene-environment interaction in AAs. In summary, using a systematic tagSNP approach, we have not found evidence for significant associations between VDR and CRC in AAs or Caucasians