A case-control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma

ackground Low mitochondrial DNA (mtDNA) copy number is a common feature of renal cell carcinoma (RCC), and may influence tumor development. Results from a recent case-control study suggest that low mtDNA copy number in peripheral blood may be a marker for increased RCC risk. In an attempt to replicate that finding, we measured mtDNA copy number in peripheral blood DNA from a U.S. population-based case-control study of RCC. Methodology/Principal Findings Relative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay using DNA extracted from peripheral whole blood. Cases (n = 603) had significantly lower mtDNA copy number than controls (n = 603; medians 0.85, 0.91 respectively; P = 0.0001). In multiple logistic regression analyses, the lowest quartile of mtDNA copy number was associated with a 60% increase in RCC risk relative to the highest quartile (OR = 1.6, 95% CI = 1.1\u20132.2; Ptrend = 0.009). This association remained in analyses restricted to cases treated by surgery alone (OR Q1 = 1.4, 95% CI = 1.0\u20132.1) and to localized tumors (2.0, 1.3\u20132.8). Conclusions/Significance Our findings from this investigation, to our knowledge the largest of its kind, offer important confirmatory evidence that low mtDNA copy number is associated with increased RCC risk. Additional research is needed to assess whether the association is replicable in prospective studies

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Risk of renal cell carcinoma in relation to blood telomere length in a population-based case-control study

BACKGROUND: There are few known risk factors for renal cell carcinoma (RCC). Two small hospital-based case-control studies suggested an association between short blood telomere length (TL) and increased RCC risk. METHODS: We conducted a large population-based case-control study in two metropolitan regions of the United States comparing relative TL in DNA derived from peripheral blood samples from 891 RCC cases and 894 controls. Odds ratios and 95% confidence intervals were estimated using unconditional logistic regression in both unadjusted and adjusted models. RESULTS: Median TL was 0.85 for both cases and controls (P=0.40), and no differences in RCC risk by quartiles of TL were observed. Results of analyses stratified by age, sex, race, tumour stage, and time from RCC diagnosis to blood collection were similarly null. In multivariate analyses among controls, increasing age and history of hypertension were associated with shorter TL (P<0.001 and P=0.07, respectively), and African Americans had longer TL than Caucasians (P<0.001). CONCLUSION: These data do not support the hypothesis that blood TL is associated with RCC. This population-based case-control study is, to our knowledge, the largest investigation to date of TL and RC

Weather and the risk of sudden infant death syndrome: the effect of wind

STUDY OBJECTIVE—To examine and identify relations between sudden infant death syndrome (SIDS) and wind, particularly the föhn wind, in Christchurch, New Zealand.
DESIGN—A retrospective epidemiological study combining details of regional hourly meteorological variables and reported SIDS cases.
SETTING—Christchurch, New Zealand, between 1968 and 1997( )inclusively.
PARTICIPANTS—All 646 infants reported as dying from SIDS within the greater Christchurch region.
MAIN RESULTS—Analysis of 1968-1989 data revealed nine wind variables significantly related to SIDS. When compared with corresponding variables calculated over the 1990-1997 period, only the northerly wind on the day of death and the southerly wind three days before a SIDS death had estimated associations with similar effect size and sign. However, both these variables had confidence intervals that included unity.
CONCLUSIONS—No evidence was found to suspect that föhn winds influenced SIDS occurrence. The relations identified between SIDS incidence and wind, after controlling for the effects of temperature and trend, were tenuous and relatively small. More data are necessary to substantiate whether northerly winds on the day of death or southerly winds occurring three days before a death are truly associated with SIDS. It seems that wind has little, if any effect on SIDS incidence in Christchurch.


Keywords: sudden infant death syndrome; weather; föhn win

Social work ethics: Professional codes in Australia and the United States

This article compares and contrasts two main areas of the Australian and US codes of ethics for social workers. These have been selected for comparison because recent revisions in their provisions about dual relationships and con.dentiality raise challenging questions about acceptable practice standards

An investigation of risk factors for renal cell carcinoma by histologic subtype in two case-control studies

To investigate whether renal cell carcinoma (RCC) histologic subtypes possess different etiologies, we conducted analyses of established RCC risk factors by subtype (clear cell, papillary and chromophobe) in two case-control studies conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097 cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of total) and 917 European cases (84%) through a central slide review conducted by a single pathologist. For the remaining cases, histology was abstracted from the original diagnostic pathology report. Case-only analyses were performed to compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype differences by age, sex and race. Case-control analyses were performed to compute subtype-specific ORs for other risk factors using polytomous regression. In case-only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1-1.4 per 10-year increase), less likely to be female (OR = 0.5, 95% CI = 0.4-0.8) and more likely to be black (OR = 2.6, 95% CI = 1.8-3.9) as compared to clear cell cases (N = 1,524). In case-control analyses, BMI was associated with clear cell (OR = 1.2, 95% CI = 1.1-1.3 per 5 kg/m2 increase) and chromophobe RCC (N = 80; OR = 1.2, 95% CI = 1.1-1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0-1.2; test versus clear cell, p = 0.006). No subtype differences were observed for associations with smoking, hypertension or family history of kidney cancer. Our findings support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity-RCC association differs by histology. Copyright \ua9 2013 UICC