Anu Tiwari

Role of GSTM3 Polymorphism in the Risk of Developing Esophageal Cancer

GSTM3 is involved in detoxification of carcinogens and may be important in modulating cancer susceptibility. GSTM3 genotype frequencies were determined in peripheral blood DNA of 149 esophageal cancer patients and 200 nonmalignant controls using the PCR followed by PAGE. Patients who were heterozygous carriers of GSTM3 AB genotype had an enhanced risk for developing esophageal cancer [odds ratio (OR), 2.1; 95% confidence interval (95% CI), 1.1-3.7; P = 0.01]. In males, the risk due to GSTM3 AB genotype increased further (OR, 3.4; 95% CI, 1.7-6.8; P = 0.000). Interaction of GSTM3 AB + BB and GSTM1 null genotypes marginally modulated risk (OR, 2.3; 95% CI, 1.1-3.7; P = 0.01). Association with histology (adenocarcinoma: OR, 3.4; 95% CI, 1.1-10.9; P = 0.03) and tumor site (middle third location: OR, 2.2; 95% CI, 1.1-4.4; P = 0.01; lower third location: OR, 2.6; 95% CI, 1.2-5.6; P = 0.01) was also documented. Our results suggest that GSTM3 polymorphism may influence esophageal cancer susceptibility, in particular modulating the risk for adenocarcinoma histology and tumors of the mid and lower third region. (Cancer Epidemiol Biomarkers Prev 2007;16(1):178–81)

Carcinoma of uterine cervix with isolated metastasis to fibula and its unusual behavior: Report of a case and review of literature

Bone metastasis from carcinoma cervix is uncommon, especially in the distal appendicular skeleton. A 36 year old lady presented with carcinoma of uterine cervix, FIGO, stage IIb. She was treated with radical radiotherapy. Nine months later, she developed an isolated lytic lesion in right fibula, which turned out to be a metastatic lesion. The patient is doing well, 3 years after the surgical excision of metastasis. This is one of the few documented cases of metastasis to fibula, arising from carcinoma of uterine cervix and probably the first with isolated metastasis of this site. Unlike the dismal outcome commonly seen in patients with bone secondaries, she continues to be disease free and alive at 39 months of follow up, after the development of skeletal metastasis.

Association of genetic polymorphisms of N-acetyltransferase 2 and susceptibility to esophageal cancer in north Indian population.

Esophageal cancer is multifactorial disease involving environmental and genetic risk factors. Tobacco smoke and alcohol are strong environmental risk factors. N-acetyltransferase 2 (NAT2) is known to metabolize heterocyclic amine carcinogens in tobacco smoke. The purpose of this study was to determine whether genetic polymorphism in the NAT2 and their interaction with environmental factors influence the susceptibility for esophageal cancer. For our study, 126 patients and 164 controls were genotyped for NAT2 2 * 5, 2 * 6 and 2 * 7 polymorphisms using PCR-RFLP method. In a case-control study, NAT2 slow acetylator genotype was not significantly associated with risk of esophageal cancer (OR 1.3, 95%CI = 0.78–2.2, P = 0.28). There was significant linkage disequilibrium between 2 * 5–2 * 6 and 2 * 5–2*7 (P < 0.05). Using expectation maximization algorithm, 6 haplotypes were obtained but none of them revealed any significant contribution to disease susceptibility. In case only analysis, the smokers with rapid acetylator were at slightly higher risk of esophageal cancer (OR 1.3, 95%CI = 0.62–3.0, P = 0.43) which was not statistically significant. NAT2 slow or fast genotypes did not affect the risk of esophageal cancer in patients with alcohol consumption or occupational exposure. These results suggest that NAT2 acetylator genotypes did not influence the susceptibility to esophageal cancer. NAT2 polymorphism did not significantly modulate the cancer risk after interaction with environmental factors like tobacco, alcohol or occupational exposure.

Bone metastasis from ovarian cancer

We report a case of epithelial ovarian cancer, which presented with lumbar vertebral metastasis soon after treatment, as a part of distant spread. This patient was then treated by palliative radiotherapy and put on second line chemotherapy i.e, Topotecan. She responded to treatment well.

Changes in salivary flow rates in head and neck cancer after chemoradiotherapy

BACKGROUND Changes in salivary flow rate were studied in head and neck (H and N) cancer patients who, after receiving moderately accelerated radiotherapy (RT) and concurrent chemotherapy (CT), were free of disease at 1 year. MATERIALS AND METHODS Between July 2003 and July 2005, saliva estimation was performed for 36 patients of locally advanced (AJCC stages III and IV) squamous cell carcinoma of the H and N. RT, moderately accelerated (70 Gy/35 fx/6 weeks) along with concurrent weekly cisplatin at 35 mg/m 2 (capped at 50 mg) with standard hydration and anti-emetic cover, was planned using conventional planning on telecobalt or 6 MV photons. The saliva flow rate was estimated for 5 min at rest (unstimulated) and after using lemon drops (stimulated) for the next 5 min at baseline (pre-treatment), 3, 6 and 12 months following treatment. RESULTS The median follow-up of this study was 29 months. Compared with baseline, by 3 months, a significant reduction in unstimulated (0.35 ml/min and 0.10 ml/min) and stimulated (0.97 ml/min and 0.28 ml/min) salivary flow rate was observed, respectively. This continued to decrease further till 6 months (0.06 ml/min and 0.17 ml/min) and, by 12 months, a minimal and non-significant recovery was observed in both unstimulated (0.08 ml/min) and stimulated salivary flow rates (0.22 ml/min), respectively. CONCLUSIONS Salivary flow rates fall to a fourth of the baseline value with the above CT + RT protocol, with minimal recovery at 12 months following completion of treatment.

Implications of p53 over-expression in the outcome with radiation in head and neck cancers

BACKGROUND Abnormalities in the p53 tumor suppressor gene and in the expression of its protein are commonly seen in several tumors. The prognostic implication of these p53 abnormalities was studied in 55 patients with advanced head and neck cancers. PURPOSE To identify p53 as a prognostic factor in assessment of response and survival outcome to radiotherapy in head and neck malignancies. MATERIALS AND METHODS This prospective study was carried out from April 1998 to December 1999. Fifty five patients with proven squamous cell carcinoma of the head and neck region were treated by radiotherapy (RT) (n=34) with or without chemotherapy (CT) (n=21). A dose of 70 Gy/35#/7 weeks was given with or without concurrent administration of weekly cisplatin (35 mg/m2). Paraffin sections obtained at the time of diagnosis, were examined immunohistochemically for p53 overexpression with monoclonal antibody DO-7 (DAKO). The scoring of p53 positive cells was carried out by a trained pathologist. Selected areas of p53 positive cells were viewed under high power field for quantitative assessment of the p53 over expression. A minimum of 1000 cells were counted and the labeling index (LI) was calculated in terms of percentage of p53 positive cells over the total number of cells counted. A 10% nuclear reactivity exhibiting chromogen positivity cutoff point was established. OBSERVATIONS The data was analyzed as of January 2006. Median follow-up of all the patients was eight months (1-95 months). The median age of this study group was 58 years and of the 55 patients, 48 were males. Positive expression of p53 gene protein was documented by immunohistochemistry in 24 (44%) patients. Over expression of p53 was not associated with T or N stage, site of disease, radiation response or survival outcomes (P=0.143). Stage was the only independent prognostic variable, both for the response to treatment (radiation) and survival (P=0.01). CONCLUSIONS Over expression of p53 protein, when detected immunohistochemically, does not predict for radiation response in these tumors.

Role of videofluorography in assessing functional abnormalities in patients of head and neck cancer treated with chemoradiotherapy

Aim:  The major toxicity following treatment for head neck cancer is swallowing dysfunction which can be easily assessed by videofluorography (VFG), allowing documentation of the site and extent of abnormality thereby facilitating directed management.

Comparative assessment of late toxicity in patients of carcinoma cervix treated by radiotherapy versus chemo-radiotherapy – Minimum 5 years follow up

BACKGROUND A randomised trial was carried out comparing chemo-radiation (CTRT) vs. radiotherapy (RT) in patients of carcinoma cervix and showed similar rates of pelvic disease control, disease free survival and overall survival. Late toxicity is presented. METHODS Between December 2000 and July 2006, 180 patients of carcinoma cervix were randomly assigned to RT + weekly cisplatin (n = 94) or RT alone (n = 86). Late toxicity was prospectively scored using RTOG criteria in 156 evaluable patients, 79 and 77 respectively and is presented as crude incidence for rectum, bladder, small intestine, vagina, skin and bone and also as actuarial incidence for rectum and bladder. RESULTS The median follow up of surviving patients was 10.4 years (minimum - 6.5 years). Crude incidence, CTRT vs. RT, of late toxicities were: rectal (7.5% vs. 5%, p = 0.22), bladder (15% vs. 10.4%, p = 0.76), small bowel (3% vs. 1.2%, p = 0.51), vagina (25% vs. 35%, p = 0.35) while the actuarial risk of grades 3-5 rectal and bladder toxicities by 5 years were 13% vs. 10% (p = 0.698) and 16% vs. 14.8% (p = 0.783) respectively. Bladder toxicity appeared later then rectal toxicity (median 49.4 vs. 21.4 months). Severe bone toxicity (fractures) were higher in the CTRT arm, 5% vs. 0%, p = 0.018. On multivariate analysis vaginal involvement (p = 0.016) and bulky tumor (p = 0.020) were associated with severe vaginal morbidity while rectal point dose > 80% (p = 0.040) was associated with a higher incidence of rectal toxicity. CONCLUSION Bone toxicity was significantly increased by addition of CT to RT and patients continued to experience toxicity at longer periods of follow up albeit disease free.