Cytokine gene variants and treatment outcome of cisplatin-based concomitant chemoradiotherapy in cervical cancer.

Background: Cervical cancer is the second most common cancer among women after breast cancer. Its standard treatment is cisplatin-based concomitant chemoradiotherapy. Chronic inflammation in uterine cervix triggers both pro- and anti-inflammatory pathways. The unpredictability in toxicity and efficacy of treatment is a major challenge. We hypothesized a link between IL-1, IL-6 and TNF gene variants and treatment response.Material & Methods: We genotyped 246 cervical cancer cases and 246 controls by PCR, PCR-RFLP and ARMS-PCR. Treatment and response were evaluated by RECIST criteria. Chemotherapy and radiation doses were same for all patients, whilst 48 were followed-up for 36 months after treatment.Results: SNPs in IL-1RN, IL-1ß, IL-6 and TNFα were linked with cervical cancer. Cases with certain allele combinations in IL-1RN, IL-1ß, IL-6(-597A/G) and TNF-α showed odds ratios (95% CI) of up to 17.54 (2.7-24.08) for the presence of cervical cancer. Variant IL-1ß (-511T/C) was linked to vital status but none were linked to overall survival.Conclusion: Certain cytokine gene variants may help detect susceptibility to cervical cancer and predict response to chemoradiotherapy.

Genotypic analysis of XRCC4 and susceptibility to cervical cancer.

Background: XRCC4 encodes a DNA repair protein which maintains genome stability by repairing double-strand breaks by the error-prone method. Defects in the protein-encoding gene lead to impairment of DNA repair process and accumulation of DNA damage, a hallmark of cancer development. We hypothesised that variants in XRCC4 are linked to cervical cancer.Material and methods: Genotyping of XRCC4 variants viz. intron3 DIP (rs28360071), intron7 DIP (rs28360017), G-1394T(rs6869366) and G-652T (rs2075685) was carried out in 246 women with cervical cancer cases and 246 control women.Results: There were several links to cervical cancer: intron3 DIP (rs28360071) II genotype (p = 0.002) and I allele (odds ratio is 0.54-0.89) (p = 0.004), intron7 DIP (rs28360017) II genotype (p = 0.003) and I allele (odds ratio 0.68 [0.53-0.88]) (p = 0.004), and G-652T (rs2075685) genotype (p = 0.044) and the T allele (odds ratio 1.35 [1.03-1.77]) (p = 0.032). In combining data into haploviews, the DDGG allele combination had an odds ratio of 0.12 (0.04-0.39) (p= 0.029) and the IIGT combination an odds ratio of 3.08 (1.25-7.55) (p = 0.01) for cervical cancer.Conclusion: Our results suggested that homozygous 'I' and 'T' genotypes in certain XRCC4 sequences may be associated with the development of cervical cancer and so may be a useful biomarker to predict cervical cancer susceptibility.

Breath carbon monoxide concentration in cigarette and bidi smokers in India.

OBJECTIVE: To measure and compare the breath carbon monoxide (CO) levels in cigarette and bidi smokers in India. METHODS: Breath CO was measured in 389 smokers (241 cigarette smokers,148 bidi smokers) using portable breath CO analyser (Bedfont-England, Smokelyzer). Tobacco contents and length of single stick of different brands of cigarette and bidi were also measured. RESULTS: Their mean age was 38.7 +/- 13.4 years. The average duration of smoking was 18.2 +/- 13.0 years. Average breath CO levels were 15.6 +/- 7.0 ppm in smokers and 4.07 +/- 1.16 ppm in non-smokers. Average breath CO level was significantly higher in bidi smokers (18.9 +/- 7.7 ppm) compared to cigarette smokers (13.6 +/- 5.8 ppm) when total consumption of cigarette/bidi was more than five pack-years (p = 0.002). Average tobacco weight of bidi (216.8 mg) was significantly less than cigarette (696 mg). CONCLUSIONS: Bidi is equally or more harmful than cigarette smoking. One bidi may be considered to one cigarette for calculating "pack-years" of smoking.