Genetic profiles of different ethnicities living in Karachi as regards to tobacco-metabolising enzyme systems and the risk of oral cancer.

OBJECTIVE To detect polymorphisms of CYP1A1, GSTM1 and GSTT1 gene loci among various tobacco-consuming ethnicities in an urban centre, and to relate these with susceptibility to oral cancer. METHODS The cross-sectional, case-control study was conducted at Ziauddin University, Karachi, and the Dow University of Health Sciences, Karachi, from 2011 to 2016, and comprised patients having oral squamous cell carcinoma in group A, with oral precancerous lesions in group B, and tobacco habit-matched controls in group C. Routine histopathology was followed by molecular analysis through polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism techniques. Data was analysed using SPSS 20. RESULTS Of the 358 subjects, 150(42%) were in group A, 100(28%) in group B, and 108(30%) in group C. There were 190(53.1%) Urdu-speaking subjects, 42(11.7%) Memoni-speaking, 37(10.3%) Sindhi-speaking, 34(9.5%) Balochi-speaking, 25(7%) Pashto-speaking, 15(4.2%) Punjabi-speaking, and 15(4.2) of other ethnicities. Among the Urdu-speaking ethnicity, CYP1A1 MspI heterozygous variant was the most prevalent genotype ingroup A 50(66.7%), group B 37(62.7%) and group C 36(64.3%). The homozygous variant was equally distributed in group A 8(13.5%) and group B 10(13.3%), while it remained quite low in group C 4(7.1%). Homozygous genotype was most common in Pashto-speaking subjects in group A 4(57.1%). In Urdu-speaking subjects, GSTM1-null genotype was mostly found in group B 19(32.2%), while GSTT1-null genotype was most common in group A 12(16%). Other than Urdu-speaking, GSTM1-null variant was most frequent in Sindhi-speaking subjects in group B 8(80%). CONCLUSIONS Intra-ethnic distribution of tobacco-metabolising enzyme genes can be considered an important contributor to oral cancer risk in the population of Karachi.

[1]  Nichola Khan.  Sindh in Karachi: A topography of separateness, connectivity, and juxtaposition , 2020, Environment and Planning C: Politics and Space.

[2]  Hassan Mohammad Naif,et al.  Association of Cytochrome CYP1A1 Gene Polymorphisms and Tobacco Smoking With the Risk of Breast Cancer in Women From Iraq , 2018, Front. Public Health.

[3]  Ahmed Rebai,et al.  Polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes, CYP1A1 xenobiotic metabolism gene, and tobacco are associated with bladder cancer susceptibility in Tunisian population , 2017, Environmental Science and Pollution Research.

[4]  Ning Li,et al.  The Association of CYP1A1 Gene With Cervical Cancer and Additional SNP–SNP Interaction in Chinese Women , 2016, Journal of clinical laboratory analysis.

[5]  F. Ahmad,et al.  Detecting Human Papillomavirus 6 & 11 in a Set of Pakistani Population , 2016 .

[6]  S. Kannan,et al.  Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator. , 2007, Carcinogenesis.

[7]  D. Roy,et al.  An Insight Of DNA Repair Gene Polymorphism In Oral Premalignant Disorders Associated With Habitual Risk Factors , 2020 .

[8]  N. Hadi,et al.  ROLE OF CHEWING HABITS AND CIGARETTE SMOKING IN DIFFERENTIATION OF ORAL SQUAMOUS CELL CARCINOMA , 2016 .

[9]  Zakiullah,et al.  Genetic susceptibility to oral cancer due to combined effects of GSTT1, GSTM1 and CYP1A1 gene variants in tobacco addicted patients of Pashtun ethnicity of Khyber Pakhtunkhwa province of Pakistan. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[10]  B. Mittal,et al.  Associations of CYP1A1, GSTM1 and GSTT1 polymorphisms with lung cancer susceptibility in a Northern Indian population. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[11]  T. Mirza,et al.  Clinico-pathological Parameters Of 50 Oral Squamous Cell Carcinoma Cases in Karachi , 2013 .