Shaukat Khanum Memorial Cancer Hospital & Research Centre

Genetic anticipation refers to the earlier onset of breast cancer (BC) in successive generations, is underreported in Asian populations. This study investigates the phenomenon in Pakistani familial BC patients.

The study analyzed 171 mother-daughter BC pairs, including BRCA1 (n = 52), BRCA2 (n = 11) pathogenic variant (PV) carriers, and non-carriers (n = 108). Additionally, 741 first-degree female relatives of the mothers and daughters, affected (n = 96) or unaffected (n = 645) with BC, were included. Ages at BC diagnosis in mother-daughter pairs were compared using a paired t-test, while differences in BC occurrence between daughters' and mothers' generations were assessed using odds ratios (ORs).

Daughters were diagnosed with BC significantly earlier than their mothers, with intergenerational age differences of 14.3 years in BRCA1 (33.7 vs. 48.0; P < 0.0001), 11.5 years in BRCA2 (37.4 vs. 48.9; P < 0.0001) PV carriers, and 12.6 years in non-carriers (41.3 vs. 53.9; P < 0.0001). This difference was independent of birth cohort effects and ascertainment bias. While BC incidence was 20 % higher in the mothers' generation compared to the daughters' generation (42.7 % vs. 38.3 %; OR 1.20, 95 % CI 0.94 - 1.53; P = 0.135), the difference was not statistically significant. Survival durations between generations were also comparable (4.49 years vs. 3.94 years; P = 0.465).

This first study on anticipation effect in Pakistani familial BC patients demonstrates significantly earlier BC onset in daughters than in mothers, irrespective of BRCA1/2 PV carrier status. These findings highlight the need to refine BC screening guidelines for high-risk Pakistani populations.

Mycotic aneurysm is defined as the dilatation of the vessel wall. It is a rare entity especially the mycotic pseudoaneurysm of iliac artery due to the underlying infection of the artery wall. Due to the nonspecific signs and symptoms there is often a delayed diagnosis that can lead to high morbidity and mortality. We present a case of a 4 year old patient with B-cell lymphoblastic lymphoma who developed a mycotic aneurysm of the right internal iliac artery while undergoing chemotherapy. The patient underwent the radiological imaging CT scan and MRI for nonspecific symptoms of fever, abdominal pain and lymphadenopathy and aneurysm was found on the scans. Patient health deteriorated fast and he died of cardiopulmonary complications before receiving any surgical or endovascular therapy. This case is unique in its kind as the fast and progressive nature can prove fatal. Therefore, the role of radiological imaging is crucial in making an early diagnosis that can improve the already poor prognosis of this clinical situation.

This study aims to identify miRNA-mediated regulation of the cell cycle in oral tongue cancer.

Comprehensive computational analysis was performed on the GEO dataset "GSE168227". DIANA Tool-mir path v.3, STRING, Cytoscape 3.6.0, Enrichr, and TargetScan Human 7.2 were utilized to identify and analyze miRNAs and their targets in oral tongue cancer. The identified miRNA and its target genes were further analyzed in oral tongue cancer patients using qPCR and immunohistochemistry (IHC).

Computational analysis revealed miR-17 as a differentially expressed miRNA in oral tongue cancer. Database analysis indicated potential binding sites of miR-17 for CDKN1A and CCND1 mRNA at 3'-UTR. In oral tongue cancer samples, miR-17, CDKN1A, and CCND1expression were upregulated compared to controls. IHC demonstrated overexpression of p21 and Cyclin D1 across various tumor grades, with predominant cytoplasmic expression of p21 observed in oral tongue cancer samples.

The findings suggest that miR-17 may regulate the G1-S transition of the cell cycle in oral tongue cancer. Further validation and functional studies are warranted to confirm their role as biomarkers.