ABSTRACT
Li Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome due to TP53 gene mutation. There is sparse literature on LFS in the Indian population. We conducted a retrospective study of patients diagnosed with LFS and their family members, registered at our Medical Oncology Department between September 2015 and 2022. 9 LFS families consisted of 29 patients diagnosed currently or historically with malignancies including 9 index cases and 20 first or second-degree relatives. Of these 29 patients, 7 (24.1%) patients developed their first malignancy before the age of 18 years, 15 (51.7%) were diagnosed between 18and and 60 years, and 7 (24.1%) were diagnosed at age more than 60 years. A total of 31 cancers occurred among the families, including 2 index cases who had metachronous malignancies. Each family had a median of three cancers (range 2-5); sarcoma (n = 12, 38.7% of total cancers) and breast cancer (n = 6, 19.3% of total cancers) being the commonest malignancies. Germline TP53 mutations were documented among 11 patients with cancers and 6 asymptomatic carriers. Of these nine mutations, the most common types were missense (n = 6, 66.6%) and nonsense (n = 2, 22.2%), and the commonest aberration was replacement of arginine with histidine (n = 4, 44.4%). Eight (88.8%) families met either classical or Chompret's diagnostic criteria and two (22.2%) satisfied both. Two (22.2%) families fit the diagnostic criteria prior to onset of malignancy in the index cases but were untested till the index cases presented to us. Four mutation carriers from three families are undergoing screening as per the Toronto protocol. No new malignancies have been detected so far during the mean surveillance duration of 14 months. The diagnosis of LFS has socio-economic implications for patients and their families. Delay in genetic testing misses out a crucial window wherein asymptomatic carriers could initiate surveillance in a timely fashion. Greater awareness on LFS and genetic testing in Indian patients is warranted for better management of this hereditary condition.
ABSTRACT
BACKGROUND: Lifestyle-related diseases have assumed significant public health problem across the globe including developing nations. High rate of nonadherence to treatment poses challenges to family physicians in its treatment. OBJECTIVE: To develop a valid and reliable questionnaire for assessment of adherence to lifestyle modification advices. MATERIALS AND METHODS: The questionnaire was developed following a systematic, scientifically accepted methodology which included literature review, focused group discussions, detailed interviews, and expert evaluation. Comprehensibility, replicability, face validity, content validity, patient acceptance, and ease of usage of the questionnaire were analyzed. Five-point Likert scale was employed as response options. Cronbach's alpha was calculated to assess internal consistency of overall questionnaire. A cross-sectional survey was then performed on 100 obese patients with nonalcoholic fatty liver disease to validate the questionnaire. RESULTS: The developed questionnaire consists of 14 questions under two domains, 12 items under diet and 2 items under the physical activity domain. Each of these questions is on a 5-point Likert scale. The tool has shown satisfactory validity. It also has adequate reliability and internal consistency with Cronbach's alpha value of 0.9. CONCLUSION: It is a valid and reliable tool which can be used in clinical practice to assess adherence to lifestyle modification advices by family physicians.
