FDG uptake, a surrogate of tumour hypoxia?

Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-D-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting

Reproductive and Hormonal Factors in Relation to Lung Cancer Among Nepali Women

Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.Background: Of the 1.8 million global incident lung cancer cases estimated in 2012, approximately 60% occurred in less developed regions. Prior studies suggest sex differences in lung cancer risk and a potential role for reproductive and hormonal factors in lung cancer among women. However, the majority of these studies were conducted in developed regions. No prior study has assessed these relationships among Nepali women. Methods: Using data from a hospital-based case-control study conducted in B. P. Koirala Memorial Cancer Hospital (Nepal, 2009–2012), relationships between reproductive and hormonal factors and lung cancer were examined among women aged 23–85 years. Lung cancer cases (n = 268) were frequency-matched to controls (n = 226) based on age (±5 years), ethnicity and residential area. The main exposures in this analysis included menopausal status, age at menarche, age at menopause, menstrual duration, gravidity, and age at first live-birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Results: Among postmenopausal women, those with a younger age at menopause (<45 years; 45–49 years) had an increased odds of lung cancer compared to those with an older (≥50 years) age at menopause [OR (95%CI): 2.14 (1.09, 4.17); OR (95% CI): 1.93 (1.07, 3.51)], after adjusting for age and cumulative active smoking years. No statistically significant associations were observed with the other reproductive and hormonal factors examined. Conclusion: These results suggest that Nepali women with prolonged exposure to endogenous ovarian hormones, via later age at menopause, may have a lower odds of lung cancer

Reproductive and Hormonal Factors in Relation to Lung Cancer Among Nepali Women

Background: Of the 1.8 million global incident lung cancer cases estimated in 2012, approximately 60% occurred in less developed regions. Prior studies suggest sex differences in lung cancer risk and a potential role for reproductive and hormonal factors in lung cancer among women. However, the majority of these studies were conducted in developed regions. No prior study has assessed these relationships among Nepali women.Methods: Using data from a hospital-based case-control study conducted in B. P. Koirala Memorial Cancer Hospital (Nepal, 2009–2012), relationships between reproductive and hormonal factors and lung cancer were examined among women aged 23–85 years. Lung cancer cases (n = 268) were frequency-matched to controls (n = 226) based on age (±5 years), ethnicity and residential area. The main exposures in this analysis included menopausal status, age at menarche, age at menopause, menstrual duration, gravidity, and age at first live-birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression.Results: Among postmenopausal women, those with a younger age at menopause (&lt;45 years; 45–49 years) had an increased odds of lung cancer compared to those with an older (≥50 years) age at menopause [OR (95%CI): 2.14 (1.09, 4.17); OR (95% CI): 1.93 (1.07, 3.51)], after adjusting for age and cumulative active smoking years. No statistically significant associations were observed with the other reproductive and hormonal factors examined.Conclusion: These results suggest that Nepali women with prolonged exposure to endogenous ovarian hormones, via later age at menopause, may have a lower odds of lung cancer

Three independently deleted regions at chromosome arm 16q in human prostate cancer: allelic loss at 16q24.1–q24.2 is associated with aggressive behaviour of the disease, recurrent growth, poor differentiation of the tumour and poor prognosis for the patient

Loss of heterozygosity at chromosome arm 16q is a frequent event in human prostate cancer. In this study, loss of heterozygosity at 16q was studied in 44 prostate cancer patients exhibiting various clinical features. Fifteen polymorphic polymerase chain reaction (PCR) markers were used to identify the separately deleted areas and the findings were compared with clinicopathological variables and 5-year survival of the patients. The results indicated that there are at least three independently deleted regions at 16q. Allelic losses at the central and distal areas were associated significantly with aggressive behaviour of the disease (16q24.1–q24.2, P< 0.01, and 16q24.3–qter, P< 0.05), and the central area of deletion was further significantly associated with poorly differentiated tumour cells (P< 0.05) and with recurrent (P< 0.01) growth of the tumour. During the follow-up period, 28% of the patients initially with M0 disease developed distant metastases. Of the patients showing allelic loss at 16q24.1–q24.2, distant metastasis were found in 45% during the 5-year follow-up period, and 31% of the patients showing loss at 16q21.1 also developed distant metastases. After the 5-year follow-up period, 14 (32%) of the patients remained alive, whereas 19 (43%) had died because of their prostate cancer. The overall survival rate of the patients showing allelic loss at 16q21.1 or 16q24.1–q24.2 was significantly lower than that of the patients with retained heterozygosity. © 1999 Cancer Research Campaig

Comprehensive resequence analysis of a 136 kb region of human chromosome 8q24 associated with prostate and colon cancers

Recently, genome-wide association studies have identified loci across a segment of chromosome 8q24 (128,100,000–128,700,000) associated with the risk of breast, colon and prostate cancers. At least three regions of 8q24 have been independently associated with prostate cancer risk; the most centromeric of which appears to be population specific. Haplotypes in two contiguous but independent loci, marked by rs6983267 and rs1447295, have been identified in the Cancer Genetic Markers of Susceptibility project (http://cgems.cancer.gov), which genotyped more than 5,000 prostate cancer cases and 5,000 controls of European origin. The rs6983267 locus is also strongly associated with colorectal cancer. To ascertain a comprehensive catalog of common single-nucleotide polymorphisms (SNPs) across the two regions, we conducted a resequence analysis of 136 kb (chr8: 128,473,000–128,609,802) using the Roche/454 next-generation sequencing technology in 39 prostate cancer cases and 40 controls of European origin. We have characterized a comprehensive catalog of common (MAF > 1%) SNPs within this region, including 442 novel SNPs and have determined the pattern of linkage disequilibrium across the region. Our study has generated a detailed map of genetic variation across the region, which should be useful for choosing SNPs for fine mapping of association signals in 8q24 and investigations of the functional consequences of select common variants

Imaging tumour hypoxia with positron emission tomography.

Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.Cancer Research UK (CRUK) funded the National Cancer Research Institute (NCRI) PET Research Working party to organise a meeting to discuss imaging cancer with hypoxia tracers and Positron Emission Tomography. IF was funded by CRUK and is also supported by the Chief Scientific Office. ALH is supported by CRUK and the Breast Cancer Research Foundation. RM is funded by NIHR Cambridge Biomedical Research Centre.This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2014610a.html