Effect of GSTP1 and ABCC4 gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-5-fluorouracil-based chemotherapy in Bangladeshi breast cancer patients.

The most important cytotoxic drug namely, cyclophosphamide used in breast cancer along with epirubicin and 5-fluorouracil, is transported by ABCC transporters and detoxified by glutathione S-transferases (GSTs). The activities of these enzymes and transporters may vary in different population due to the presence of genetic polymorphisms. This study was aimed to evaluate the effects of GSTP1rs1695 and ABCC4rs9561778 polymorphisms on the response and toxicities produced by chemotherapy used in the treatment of Bangladeshi breast cancer patients. A total of 200 and 56 patients with invasive breast cancers were recruited from different public and private hospitals of Bangladesh of which 117 patients received neoadjuvant chemotherapy to examine the response as well as the toxicity, and another 139 patients received adjuvant chemotherapy to evaluate only the toxicity. Genetic polymorphisms of the mentioned genes were detected by using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR RFLP). Patients carrying AG and AG plus GG genotype of GSTP1rs1695 were more likely to have a good response, whereas no association of ABCC4rs9561778 was found with the chemotherapy response. Patients carrying GT and GT plus TT genotypes of ABCC4rs9561778 were found to be associated with anemia, neutropenia, leukopenia, and gastrointestinal toxicities when compared with GG genotype whereas no association was found with thrombocytopenia. GSTP1rs1695 was not associated with any type of toxicities investigated. Our result indicates that GSTP1rs1695 polymorphism was strongly associated with the response of chemotherapy, whereas ABCC4rs9561778 polymorphism was significantly related with chemotherapy-induced toxicities.

South Asian Declaration-Consensus Guidelines for COVID-19 Vaccination in Cancer Patients.

We provide the South Asian Declaration, containing the consensus guidelines for coronavirus disease 2019 (COVID-19) vaccination in cancer patients.

Comprehensive update on cancer scenario of Bangladesh.

Bangladesh, at 142 million people, is the ninth most populous country in the world. There are 13 to 15 lakh cancer patients in Bangladesh, with about two lakh patients newly diagnosed with cancer each year. As an overview, lung cancer and mouth-oropharynx cancer rank as the top two prevalent cancers in males. Other types of cancers are esophagus cancer and stomach cancer. In women, cancer cervix uteri and breast cancer are most prevalent. Other cancer types, which affect women, are mouth and oropharynx cancer, lung cancer, and esophagus cancer. There are around 150 qualified clinical oncologists and 16 pediatric oncologists working in the different parts of the country. Regular cancer treatment is available in 19 hospitals and 465 hospital beds are attached as indoor or day care facilities for chemotherapy in the oncology/radiotherapy departments. There are about 15 linear accelerators, 12 Co-60 teletherapy and 12 brachytherapy units currently available. Approximately, 56 cancer chemotherapeutic agents are obtainable in Bangladesh. Research facilities are available at tertiary care centers and a few multi country collaborative research activities are ongoing. Bangladesh has a unique National Cancer Control Strategy and Plan of Action 2009-2015 formulated with the assistance of WHO with an objective to develop and implement continuum of cancer care through a comprehensive cancer control programe. Preventive measures taken to reduce the incidence of cancer include reduced tobacco smoking, change of dietary habit and reduced food adulteration, ensuring reproductive hygiene, increased physical activity, and reduced occupational hazard. Awareness buildup and media campaign are going on by organizing the general people, opinion leaders of the society, and boy and girl scout. Training of general physicians on cancer warning signs and setup of early cancer detection centers at each medical college and district levels are ongoing. Beside these, some other major cancer programs have taken place for early detection of breast, cervical and oral cancer by Bangladesh Government and NGOs such as ICDDR'B, BRAC, Ahsania Mission Cancer Hospital, BSMMU, Bangladesh Cancer Society, Ashic Foundation, Amader Gram, AK Khan Healthcare Trust, CANSUP, Oncology club etc. Piloting of cervical cancer vaccination has recently been completed. Improving the cancer scenario overnight is not an easy task but policy makers may become interested and push this agenda forward, if the huge health impact and economic loss caused by cancer become evident to them. Besides, Bangladesh has accepted reduction of cancer morbidity and mortality targets set by United Nations and World Health Organization as a part of global non-communicable disease prevention agreement.

Lung cancer risk in relation to nicotinic acetylcholine receptor, CYP2A6 and CYP1A1 genotypes in the Bangladeshi population.

BACKGROUND: CYP1A1, CYP2A6 and CHRNA5 are biologically plausible genes as risk factors for lung cancer but no studies have been reported in the Bangladeshi population. METHODS: We conducted this study to determine the prevalence and role of CYP1A1, CYP2A6 and CHRNA5 polymorphisms together with tobacco smoking in the development of lung cancer in Bangladesh. A case-control study was carried out on 106 lung cancer patients and 116 controls to investigate three allelic variants of the CYP1A1 gene-rs4646903, rs1048943 and rs1799814; 2 variants of CYP2A6 (CYP2A6*1B1, CYP2A6*4) and 1 variant of CHRNA5 (rs16969968) using Polymerase Chain Reaction Restriction Fragment Length Polymorphism. RESULTS: Lung cancer risk was estimated as odds ratio (OR) and 95% confidence interval (CI) using unconditional logistic regression models adjusting for age, sex and smoking. A significantly elevated lung cancer risk was associated with heterozygous, mutant and combined heterozygous plus mutant variants of CYP1A1 rs4646903. A significant association was also found for heterozygous and heterozygous plus mutant variants of rs1048943 which was in linkage disequilibrium with rs4646903. The risk of lung cancer was decreased significantly in individuals carrying at least one CYP2A6 deletion (CYP2A6*4) allele. No association with lung cancer risk was found for CHRNA5 rs16969968. When stratified by smoking, the effects of CYP1A1 and CYP2A6 polymorphisms on lung cancer susceptibility were found to be significant only in heavy smokers who had smoked 40 pack years or more (54% of all cases) but no associations were seen for lighter smokers. No association was also found with any polymorphism in the non-smokers in this study. CONCLUSIONS: Our results indicate that the CYP1A1*2B allele (rs4646903 and rs1048943) is associated with an increased lung cancer risk and CYP2A6*4 is associated with a decreased lung cancer risk in the study population.