Contribution of germline PALB2 variants to an unselected and prospectively registered pancreatic cancer patient cohort in Pakistan.

BACKGROUND: Partner and localizer of BRCA2 (PALB2) is a pancreatic cancer (PC) susceptibility gene reported in Caucasians. However, limited data are available among Asians. We investigated the contribution of PALB2 germline variants to Pakistani PC patients. METHODS: 150 unselected and prospectively enrolled PC patients were comprehensively screened for PALB2 variants, using denaturing high-performance liquid chromatography and DNA sequencing. Novel variants were investigated for their pathogenic effect using in-silico tools. Potentially functional variants were screened in 200 controls. RESULTS: Twenty-two different PALB2 variants were identified. A missense variant (p.Arg37His) was identified in a 48-years-old male patient with a family history of breast cancer. Another missense variant (p.Trp898Arg) was identified in a 48-years-old male patient with a family history of esophageal cancer. A novel 3' downstream variant (c.∗480A>G) was detected in a 34-years-old female patient with family history of lung cancer. Another novel 3' downstream variant (c.∗417A>C) was identified in a 41-years-old male patient. All these variants were absent in 200 controls. p.Arg37His and p.Trp898Arg were predicted as likely pathogenic. c.∗417A>C and c.∗480A>G were classified as variants of uncertain significance. CONCLUSION: This is the first study that suggests a minimal contribution of PALB2 variants to PC risk in Pakistani population.

Rectal Carcinoma: Demographics and Clinicopathological Features from Pakistani Population Perspective.

BACKGROUND: Colorectal carcinoma is ranked as the second most common cancer diagnosis in females and third in males. It is the third leading cause of cancer-related deaths worldwide. Disease burden has been attributed to a myriad of factors comprising genetic, environmental, and dietary factors. Rectal cancer has been shown to demonstrate variance according to the geographical location. METHODS: A retrospective review of 477 rectal cancer patients treated at Shaukat Khanum Memorial Cancer Hospital & Research Centre from 2006 to 2014 was performed. Demographic and clinicopathological features were compared between the two age groups (≤40 or >40 years). These included sex, ethnicity, family history of cancer, the location of tumor, clinical staging, histopathological type, and response to chemoradiation. Chi-square was used to compare the frequencies between the two age groups. p-value < 0.05 was taken as significant. RESULTS: Mean age of the study group was 44.62 ± 16.11 years. 43.8% were ≤40 years of age, and 70.2% were male. 50.3% patients belong to Punjab province, 287 (60.2%) had lower rectal cancer, family history of cancer was present in 82 (17.2%) patients. 432 (90.5%) patients had T1/T2 disease and 296 (62.1%) had N2 disease. Metastatic disease at presentation was observed in 37 (7.8%). Progressive disease was found in 90 (18%) patients. CONCLUSION: High frequency of young onset rectal cancers and the lack of family history emphasize the need of indigenous strategies and national awareness of this disease for an early identification of these patients.

A deleterious BRCA1 mutation in a young Pakistani woman with metaplastic breast carcinoma.

Metaplastic breast carcinoma (MBC) is a relatively rare subtype of breast cancer that encompasses a pathologically heterogeneous group of tumors. Pathogenic germ line mutations in the major breast cancer susceptibility genes BRCA1 and BRCA2 genes have been rarely found or described in MBC. We report the identification of the BRCA1 185delAG mutation in a 22-year-old Pakistani woman with triple-negative MBC that showed biphasic morphological features, including sarcomatous and malignant epithelial components. A comprehensive description of the clinical, histopathological, morphological, and immunohistochemical features of the tumor and the patient's treatment course is presented.