Cyclin D1 had been associated with different clinical and pathological stages of cervical cancer; however, few studies had focused on its correlation with cervical cancer prognosis. Therefore, this study aimed to assess the expression of cyclin D1a and D1b in normal tissue, cervical cancer and cervical intraepithelial neoplasia and their effect on prognosis.

Expression of cyclin D1a and D1b was detected by immunohistochemical staining in 78 cases of primary cervical cancer, 40 cases of cervical intraepithelial neoplasia, and 40 cases of normal cervical tissue.

No significant difference was observed in the expression of cyclin D1a between normal and cervical cancer tissues (P = 0.201); however, its expression was significantly higher in cervical cancer than in cervical intraepithelial neoplasia tissues (P = 0.000). Expression of cyclin D1b was higher in normal tissues than in cervical cancer tissues (P = 0.000). No significant difference was observed in the expression of cyclin D1a in cervical cancer tissues with respect to age, pathological type, clinical-stage, depth of tumor invasion, or presence of lymph node metastases (P = 0.111,0.119,0.539,0.084,0.539). COX survival analysis showed that lymph node metastasis might be an independent factor affecting postoperative recurrence (hazard risk [HR] = 0.240; 95% confidence interval [CI] = 0.968–30.156; P = 0.034).

Cyclin D1a expression was associated with tumor tissue size and degree of differentiation. The expression of cyclin D1b in cervical cancer was associated with the presence of lymph node metastases. Cyclin D1a and D1b expression in cervical cancer tissue was significantly correlated. Cox survival analysis showed that the presence of lymph node metastases might serve as an independent factor affecting postoperative recurrence. The expression of cyclin D1a and D1b was not associated with cervical cancer prognosis.

Assessment of cyclin D1a and D1b expression in cervical cancer and cervical intraepithelial neoplasia revealed that cyclin D1 could not be used as a reference to assess cervical cancer patient prognosis.

• cervical cancer
• cyclin D1 protein isoforms
• expression
• prognosis

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by heterozygous mutations in the mismatch repair (MMR) genes. Biallelic mutations in these genes lead however, to constitutive mismatch repair deficiency (CMMRD). In this study, we follow the diagnostic journey of a 12-year old patient with CRC, with a clinical phenotype overlapping CMMRD. We perform molecular and functional assays to discard a CMMRD diagnosis then identify by exome sequencing and validation in a cohort of 134 LS patients, a candidate variant in the MLH1 UTR region in homozygosis. We propose that this variant, together with other candidates, could be responsible for age-of-onset modulation. Our data support the idea that low-risk modifier alleles may influence early development of cancer in LS leading to a LS-to-CMMRD phenotypic continuum. Therefore, it is essential that larger efforts are directed to the identification and study of these genetic modifiers, in order to provide optimal cancer prevention strategies to these patients.

• CMMRD
• Lynch syndrome
• genetic modifiers
• phenotypic continuum
• whole-exome sequencing

• Adenocarcinoma/diagnosis
• Adenocarcinoma/metabolism
• Adenocarcinoma/virology
• Adult
• Blotting, Western
• Cervix Uteri/metabolism
• Cervix Uteri/pathology
• Cervix Uteri/virology
• Cyclin D1/biosynthesis
• Female
• Global Health
• Human papillomavirus 16/isolation & purification
• Human papillomavirus 16/physiology
• Humans
• Immunohistochemistry
• Jagged-1 Protein/biosynthesis
• Papillomavirus Infections/diagnosis
• Papillomavirus Infections/metabolism
• Papillomavirus Infections/virology
• Receptor, Notch3/biosynthesis
• Uterine Cervical Neoplasms/diagnosis
• Uterine Cervical Neoplasms/metabolism
• Uterine Cervical Neoplasms/virology

• Indian Council of Medical Research (ICMR)

• Adenoma
• Chromosomal instability
• Colonoscopy
• Colorectal cancer
• CpG island methylation
• LINE-1 hypomethylation
• Lynch syndrome
• Microsatellite instability

Alterations in the CCND1 gene affect the cell cycle and are frequently observed in a variety of cancers. While the most frequent mutations that occur in thyroid tumor tissue have been characterized, the genetic factors that predispose individuals to differentiated thyroid cancer (DTC) remain to be elucidated. The present study examined whether the CCND1 c.723G>A (rs9344; p.Pro241=) and c.669C>T (rs3862792; p.Phe223=) variants have an impact on DTC susceptibility. A cohort consisting of 652 patients diagnosed with DTC were analyzed and comapred with a reference group of 799 subjects from the general population. Pyrosequencing was used as the genotyping technique. In order to determine the statistical significance of differences observed in the genotypic and allelic frequencies between the compared groups, GraphPad Prism 4 was used. At the rs9344 locus in the DTC patients, a higher frequency of allele A [P=0.032; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.014–1.361] and the AA homozygous genotype (P=0.028; OR, 1.41; 95% CI, 1.059–1.989) was observed compared with the control population group. The differences were stronger for papillary carcinomas (OR 1.45; 95% CI, 1.059–1.989), but were not significant in follicular tumors. No statistically significant differences were noted in the frequency of genotypes or alleles at the rs3862792 locus in the examined groups. The present findings indicate that the c.723A variant of the CCDN1 gene may be a susceptibility low penetrance allele in the development of papillary thyroid cancer in the population studied, however it does not impact on multifocality, metastatic ability or age at diagnosis. A cumulative effect of the analyzed CCND1 gene variants was also excluded.

• CCND1 gene
• cancer susceptibility alleles with low penetrance
• differentiated thyroid carcinoma
• papillary thyroid carcinoma

Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a “sporadic” subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the “sporadic” subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this “sporadic” early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.

• Early-onset colorectal cancer
• Epidemiology
• Hereditary syndrome
• Lynch syndrome
• MUTYH-associated polyposis

• Adult
• Age of Onset
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology
• Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
• Female
• Genetic Predisposition to Disease
• Genetic Variation
• Heredity
• Humans
• Male
• Middle Aged
• Neoplastic Syndromes, Hereditary/epidemiology
• Neoplastic Syndromes, Hereditary/genetics
• Neoplastic Syndromes, Hereditary/pathology
• Pedigree
• Peutz-Jeghers Syndrome/epidemiology
• Peutz-Jeghers Syndrome/genetics
• Phenotype
• Prevalence
• Prognosis
• Risk Factors
• Young Adult

• Cyclin D1b
• apoptosis
• cervical cancer
• proliferation

• Animals
• Apoptosis/physiology
• Blotting, Western
• Cell Proliferation/physiology
• Cyclin D1/genetics
• Cyclin D1/metabolism
• Female
• Flow Cytometry
• HeLa Cells
• Heterografts
• Humans
• In Situ Nick-End Labeling
• In Vitro Techniques
• Mice
• Mice, Nude
• Protein Isoforms/genetics
• Protein Isoforms/metabolism
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Uterine Cervical Neoplasms/genetics
• Uterine Cervical Neoplasms/metabolism
• Uterine Cervical Neoplasms/pathology