A cohort study on the association of MDM2 SNP309 with lung cancer risk in Bangladeshi population.

BACKGROUND/AIMS: Bangladesh is a densely populated country with an increased incidence of lung cancer, mostly due to smoking. Therefore, elucidating the association of mouse double minute 2 homolog (MDM2) single nucleotide polymorphism (SNP) 309 (rs2279744) with lung cancer risk from smoking in Bangladeshi population has become necessary. METHODS: DNA was extracted from blood samples of 126 lung cancer patient and 133 healthy controls. The MDM2 SNP309 was genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), using the restriction enzymes MspA1I. Logistic regression was then carried out to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of lung cancer. A meta-analysis of SNP309 was also carried out on 12,758 control subjects and 11,638 patient subjects. RESULTS: In multivariate logistic regression, significantly increased risk of lung cancer was observed for MDM2 SNP309 in the dominant model (TG + GG vs. TT: OR, 2.13; 95% CI, 1.29 to 3.53). Stratification analysis revealed that age, sex, obesity, and smoking also increases the risk of lung cancer when carrying the MDM2 SNP309. Our meta-analysis revealed that MDM2 SNP309 was considerably associated with lung cancer in Asian populations (TG + GG vs. TT: OR, 1.32; 95% CI , 1.12 to 1.56; p = 0.019 for heterogeneity). CONCLUSION: The MDM2 SNP309 was associated with high risk of lung cancer in Bangladeshi and Asian population, particularly with increased age, smoking, and body mass index.

Histopathology of Cervical Cancer and Arsenic Concentration in Well Water: An Ecological Analysis.

Arsenic in drinking water is causally linked with cancer of the skin, lung, and urinary bladder, but there is very little data on a possible role for arsenic in the etiology of cervical cancer, a disease in which human papilloma virus is held to be a necessary but not sufficient cause. All histopathology results from cervical specimens from the National Institute of Cancer Research and Hospital (NICRH), Dhaka (1997-2015), and the Anowara Medical Services (2003-2015), both serving the whole of Bangladesh, were classified by cell type. Arsenic concentrations in well water in the thana of residence were estimated from systematic sampling carried out by the British Geological Survey. In a case-referent analysis arsenic estimates for cases of cervical cancer were compared with those found to have benign lesions. In this study, 3464 NICRH (CH) cervical specimens and 30,050 community medical service (CMS) specimens were available: 3329 (CH) and 899 (CMS) were recorded as malignant. Most were squamous cell carcinoma, of which 4.9% were poorly differentiated. Overall, there was no increase in cervical cancer with increasing arsenic concentration. Among those with squamous cell histology, a strong dose response was seen for poorly differentiated cancer with increasing arsenic exposure. The odds ratio increased monotonically, compared with exposure <10 µg/L, from 1.58 at 10 < 50 µg/L to 8.11 at >200 µg/L (p < 0.001). Given the high proportion of Bangladeshis using drinking water containing >50 µg/L of arsenic, the evidence that arsenic is implicated in cancer grade suggests a need for further investigation and the introduction of cervical screening in high arsenic areas.

Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor-positive breast cancer.

PURPOSE: In premenopausal women with metastatic hormone receptor-positive breast cancer, hormonal therapy is the first-line therapy. Gonadotropin-releasing hormone analogue + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favourably influenced long-term outcomes. METHODS: Two hundred forty-nine premenopausal women with incurable or metastatic hormone receptor-positive breast cancer entered a trial in which they were randomised to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression-free survival (PFS) in the two randomised groups and by hormone-confirmed menstrual cycle phase. RESULTS: Overall survival (OS) and PFS were not demonstrated to be different in the two randomised groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels <2 ng/ml (anovulatory patients; adjusted hazard ratio 1.46, 95% confidence interval [CI]: 0.89-2.41, p = 0.14) compared with those in luteal phase with progesterone level of 2 ng/ml or higher. Median OS was 2 years (95% CI: 1.7-2.3) and OS at 4 years was 26%. CONCLUSIONS: The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT00293540.

Arsenic in Drinking Water, Transition Cell Cancer and Chronic Cystitis in Rural Bangladesh.

In earlier analyses, we demonstrated dose-response relationships between renal and lung cancer and local arsenic concentrations in wells used by Bangladeshi villagers. We used the same case-referent approach to examine the relation of arsenic to biopsy confirmed transition cell cancer (TCC) of the ureter, bladder or urethra in these villagers. As the International Agency for Research on Cancer (IARC) has conclude that arsenic in drinking water causes bladder cancer, we expected to find higher risk with increasing arsenic concentration. We used histology/cytology results from biopsies carried out at a single clinic in Dhaka, Bangladesh from January 2008 to October 2011. We classified these into four groups, TCC (n = 1466), other malignancies (n = 145), chronic cystitis (CC) (n = 844) and other benign (n = 194). Arsenic concentration was estimated from British Geological Survey reports. Odds ratios were calculated by multilevel logistic regression adjusted for confounding and allowing for geographic clustering. We found no consistent trend for TCC with increasing arsenic concentration but the likelihood of a patient with benign disease having CC was significantly increased at arsenic concentrations >100 µg/L. We conclude that the expected relationship of TCC to arsenic was masked by over-matching that resulted from the previously unreported relationship between arsenic and CC. We hypothesize that CC may be a precursor of TCC in high arsenic areas.

TP53 Codon 72 Polymorphisms and Lung Cancer Risk in the Bangladeshi Population.

OBJECTIVE: To assess associations between codon 72 polymorphisms (Pro or B and Arg or b alleles) of the TP53 gene and lung cancer risk among Bangladeshis. MATERIALS AND METHODS: The distribution of the BB, Bb, and bb genotypes and the frequencies of the B and b alleles were determined by PCR-RFLP method using DNA extracted from leucocytes of 50 confirmed lung cancer patients and 50 age-matched controls and the data were analysed. RESULTS: The ratio of BB, Bb, and bb genotypes were in Hardy-Weinberg equilibrium except for the male patients (χ2=4.6). The B allele is overrepresented among all patients (OR=2.0, p=0.02) and the female patients (OR=4.1, p≤0.01) compared to the controls. The BB/bb ratio was also higher among the patients (OR=3.0, p=0.03). The relative risk of cancer for having BB over bb genotype was 1.8 (p=0.04) but no effect was observed for the Bb genotype. The B allele was overrepresented among patients with adenocarcinomas (OR=2.4, p≤0.01) and squamous cell carcinomas (OR=2.7, p≤0.01) over the controls but the difference was not significant for those with small cell lung carcinomas (OR=1.1, p=0.66). The B allele was overrepresented among patients age 50 or younger (OR=2.7, p≤0.01), but not for older patients (OR=1.7, p=0.07), and among smokers compared to the controls (OR=1.8-10.0, p≤0.01-0.03). However, no correlation between increasing pack-years and lung cancer was observed. CONCLUSIONS: The Pro/Pro (BB) genotype and the B allele are risk factors for lung cancer among Bangladeshis, particularly for people under age 50, women and smokers.

Telecytological diagnosis of space-occupying lesions of the liver.

OBJECTIVE: In this study, the efficiency of telemedical consulting with regard to fine needle aspirates from space-occupying lesions (SOLs) of the liver is investigated for the first time. STUDY DESIGN: The study includes fine needle aspirations from 62 patients, 33 with hepatocellular carcinoma (HCC) and 29 with non-hepatic tumors. Using the Internet-based iPath system, the initial pathologist submitted 1-8 images from smears and cell block sections. One consultant assessed the cytological and another one the histological images. Both made their diagnoses independent of each other. A final diagnosis was made by immunochemistry of cell block sections. The cytological images were analyzed retrospectively for the occurrence of the most typical HCC indicators. The number of these indicators was related to the initial diagnoses of the three pathologists, and possible reasons for diagnostic errors were analyzed based on this analysis. RESULTS: The accuracy of the preliminary telemedical diagnoses regarding HCC was 82.0% for the cytological images and 87.7% for the histological images. Most of the false diagnoses occurred in tumors with unusual cytological and histological patterns. CONCLUSIONS: Telemedical consulting is a valuable tool to obtain a second opinion. However, for improvement of the diagnosis of HCC, supplementary immunochemical tests are necessary.

Frequency of epidermal growth factor receptor mutations in Bangladeshi patients with adenocarcinoma of the lung.

BACKGROUND: Worldwide studies on lung adenocarcinoma have demonstrated a genetic divergence of the epidermal growth factor receptor (EGFR) pathway according to ethnicity, such as higher frequency of activated EGFR mutations among East Asian patients. However, such information is still lacking in some developing countries. METHODS: We investigated the frequency of EGFR mutations among Bangladeshi patients with adenocarcinoma of the lung. Fine-needle aspiration tissue samples were collected from 61 Bangladeshi patients. Polymerase chain reaction-single-strand conformation polymorphism was performed on extracted DNA for mutational analysis of EGFR exons 19 and 21. RESULTS: EGFR mutations were found in 14 of 61 (23.0 %) Bangladeshi patients. There was no significant difference in EGFR mutation rate with regard to patient's age, sex, smoking history, clinical stage of lung cancer, subtypes of adenocarcinoma, and tumor differentiation. CONCLUSION: The present study revealed that the EGFR mutation rate in Bangladeshi patients with adenocarcinoma of the lung was higher than in African-American, Arabian, and white Caucasian patients, and was lower than in East Asia.