Affiliation:
1. FRIGE’s Institute of Human Genetics
2. Gastro1 Hospital
3. Zydus Cancer Hospital
4. Sushrut Hospital
5. Nishtha Surgical Hospital and Research Centre
6. Dwarika Clinic
7. Mission Gastro Hospital
8. Marengo-CIMS Hospital
9. GastroPlus Digestive Disease Centre
10. HOC Vedanta
11. Newcastle University
12. MedGenome Laboratory Pvt. Ltd
13. Strand Life Sciences Pvt. Ltd
Abstract
Abstract
Purpose
Colorectal cancer (CRC) is the fifth most common cancer in India, however, there is a paucity of systematically collected data related to its molecular epidemiology, specifically related to tumour microsatellite instability (MSI) and Lynch syndrome prevalence.
Methods
We prospectively recruited 207 unrelated patients who were diagnosed with CRC from whom primary tumour biopsy along with a matched blood sample was obtained. A sequential genetic testing approach for Lynch syndrome detection in colorectal cancer patients in accordance with the UK’s National Institute of Health and Care Excellence’s guideline (DG27) was utilised. Briefly, DNA from tumour biopsies were tested for MSI status followed BRAF V600E testing in samples which showed MSI-high result. Germline testing for the mismatch repair genes was carried in patients who had MSI-high and BRAF V600E negative tumours. Seventeen patients recanted their consent to participate in the study and therefore, results from 190 out of 207 patients is presented here.
Results
Mean age at cancer diagnosis across the cohort was 52.3 years with male to female ratio of 2:1 and 57.3% of the patients had tumours in the descending colon or rectum. MSI-high status was observed in 79 patients (42.6%) and, was inversely associated with age (OR = 0.95, 95% CI = 0.92–0.97, p = < 0.001) and cancers in distal colon and rectum (OR = 0.42, 95% CI = 0.22–0.81, p = 0.009 for distal colon; OR = 0.13, 95% CI = 0.04–0.40, p < 0.001 for rectum). Of these, 76 patients had BRAF V600E negative mutation status (96%) and of these, 48 were diagnosed with Lynch syndrome (63%; MLH1 = 38, MSH2 = 4, MSH6 = 4, PMS2 = 1, EPCAM = 1). The variants c.154del and c.306G > T in the MLH1 gene were most commonly observed across Lynch syndrome patients in our cohort.
Conclusions
This is the first systematic evaluation of the molecular epidemiology of CRC in India. We observe a high proportion of patients with young onset CRC coupled with high prevalence of MSI-high status and Lynch syndrome. The study provides a unique opportunity to explore development of novel Lynch syndrome detection and cancer prevention pathway in Indian healthcare settings.
Publisher
Research Square Platform LLC
Reference31 articles.
1. Sung H, Ferlay J, Siegel RL et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians 71:209–249, 2021
2. Worldwide variation in lynch syndrome screening: case for universal screening in low colorectal cancer prevalence areas;Das Villgran KJohnG;Fam Cancer,2021
3. WHO Classification of Tumours Editorial Board: Digestive System Tumours [Internet] (ed 5). 2022Available from: https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/Digestive-System-Tumours-2019
4. National Institute of Health and Care Excellence. : Molecular testing strategies for Lynch syndrome in people with colorectal cancer, Diagnostics Guidance [DG27] [Internet], 2017Available from: https://www.nice.org.uk/guidance/dg27
5. Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation;Snowsill T;Health Technol Assess,2017