Background: Lung cancer is one of the most prevalent malignancies in the world and both incidence and mortality rates are continuing to rise in Pakistan. However, epidemiological studies to identify common lung cancer determinants in the Pakistani population have been limited. Materials and Methods: In this retrospective case-control study, 400 cases and 800 controls were enrolled from different hospitals of all provinces of Pakistan. Information about socio-demographic, occupational, lifestyle and dietary variables was extracted by questionnaire from all subjects. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated. and dose-response associations were also assessed for suitable factors.

We identified four missense substitutions in TYR and a single missense substitution in SLC45A2. One missense substitution (p.Arg77Gln) in TYR was found in five different families that originated from the same geographical area and displayed a common haplotype, suggesting a single origin that then spread to different geographical areas of Azad Kashmir, Pakistan.

The TYR gene (MIM #6069333) is located at position 11q14.3 on the human chromosome, and encodes tyrosinase, which is expressed in melanocytes and controls the biosynthesis of melanin. Most TYR mutations eliminate the activity of tyrosinase, preventing melanocytes from producing any melanin throughout life. People with this form of albinism have white hair, light-coloured eyes and very pale skin. Some mutations in TYR reduce but do not completely eliminate tyrosinase activity, and allow some melanin to be produced. We report a Pakistani family with four members affected by oculocutaneous albinism (OCA). Blood samples were collected from all affected individuals, normal siblings and their parents. Genomic DNA was extracted, and sequence analysis of all the coding exons and adjacent intronic sequences of TYR was performed, which identified a novel missense substitution (p.Ile198Thr). Sequencing of TYR in 90 unrelated healthy individuals showed no sequence variant at this location. Our study expands the mutational spectrum of OCA1.

CHEK2 encodes a serine/threonine-protein kinase which plays a critical role in DNA damage signaling pathways. CHEK2 directly phosphorylates and regulates the functions of p53 and BRCA1. Most women with breast and/or ovarian cancer are not carriers of mutant BRCA1 or BRCA2. Multiple studies have shown that a CHEK2*1100delC confers about a two-fold increased risk of breast cancer in unselected females and a tenfold increase in males. Moreover, studies have shown that first-degree relatives of bilateral breast cancer cases who carried the CHEK2*1100delC allele had an eight-fold increased risk of breast cancer. It has been suggested that CHEK2 functions as a low-penetrance susceptibility gene for cancers and multiplies the risks associated with other gene(s) to increase cancer risk. The main goal of this study was to evaluate and to compare the role of truncating mutations, splice junction mutations and rare missense substitutions in breast cancer susceptibility gene CHEK2. Present study was performed on 140 individuals including 70 breast cancer patients both with and without family history and 70 normal individuals. Written consent was obtained and 3 ml intravenous blood was drawn from all the subjects. DNA was extracted from all the samples through inorganic method published already. Primers were synthesized for all the 14 exons of CHEK2 gene. Coding and adjacent intronic sequences of CHEK2 gene were amplified and sequenced. Two genetic variants (p.H371Y, p.D438Y) were found in exon 10 and exon 11 of gene CHEK2 which were not found in any of the 70 control individuals from same geographical area and ethnic group. The genetic variant c.1312G>T (p.D438Y) identified in a patient with a family history of breast cancer. To our knowledge, this is first mutation scanning study of gene CHEK2 from Balochistan population.

<b><i>Introduction:</i></b> In a consanguineous family, seven siblings born in three sibships showed a syndromic disorder characterized by obesity, seizures, and language impairment phenotypes, which appeared at early age or developed during early childhood. <b><i>Methods:</i></b> By whole-exome sequencing and subsequent Sanger sequencing, a novel homozygous missense variant (c.3371 T&#x3e;A [p.Ile1124Asn]) in exon 20 of the <i>CNTNAP2</i> gene was identified. <b><i>Results:</i></b> The pathogenic variant in this family is located within one of the laminin G-like 4 domains of CASPR2 and may cause loss of hydrophobic interactions of CASPR2 with its partner proteins. Single nucleotide and copy number variants in this gene have previously been related to Gilles de la Tourette syndrome, cortical dysplasia-focal epilepsy syndrome, schizophrenia, Pitt-Hopkins syndrome, and autism spectrum, attention deficit hyperactivity, and obsessive compulsive disorders. Yet, few studies described patients with <i>CNTNAP2</i> variants showing diet-induced obesity. <b><i>Conclusion:</i></b> This report expands the phenotypic spectrum of this rare syndrome and provides deeper insights by documenting the clinical features and genetic findings of the patients.