Prevalence of PALB2 Germline Mutations in Early-onset and Familial Breast/Ovarian Cancer Patients from Pakistan / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan. MATERIALS AND METHODS: PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations. RESULTS: A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127, 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5' untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (≤ 30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated. CONCLUSION: Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.

Bioethics: awareness, attitudes and opinions among University students and Faculty/researchers

To assess awareness, attitudes and opinions regarding bioethical issues among graduate students and faculty/researchers of universities in Lahore, Pakistan. A questionnaire consisting of 20 questions was designed and sent to 700 students and faculty members/researchers of 14 academic departments/research institutions of seven universities in Lahore, Pakistan. Data were analyzed with descriptive statistics using SPSS 16.0. We obtained responses from 87% [614/700] participants. The sample populations appeared receptive to latest developments in science and technology; and were optimistic that such developments will have positive effect on their lives. On average almost 90% of the respondents were familiar with the term "bioethics"; 75.4% of the respondents desired that bioethics should be taught regularly in the classes. However, students of two important disciplines of knowledge i.e law and Islamic studies had awareness levels of only 43% and '0'% respectively regarding the term bioethics. A vast majority of the respondents were not satisfied with the state laws, policies, rules, regulations and institutions concerned with bioethical issues. The survey indicated that cloning [27.2%], abortion [24.6%] and organ donation [13.2%] are regarded as the most important bioethical issues, probably for specific reasons of the glamour attached to the technology, moral connotations and the hype created by media respectively. Educated youth in general have positive attitude towards S and T and its effect on their lives. Awareness level among students and faculty of life sciences is very high; however it is dismally low among students of Law and Islamic studies. The results of this survey does not necessarily mirror the awareness level, attitudes and opinions in the society at large since literacy level among the masses is low [57%] and prevalence of higher levels of education is even lower