Alcohol consumption and ankle-to-brachial index: results from the Cardiovascular Risk Survey

Background and Methodology

A low ankle-to-brachial index (ABI) is a strong correlate of cardiovascular disease and subsequent mortality. The relationship between ABI and alcohol consumption remains unclear. Data are from the Cardiovascular Risk Survey (CRS), a multiple-ethnic, community-based, cross-sectional study of 14 618 Chinese people (5 757 Hans, 4 767 Uygurs, and 4 094 Kazakhs) aged 35 years and over at baseline from Oct. 2007 to March 2010. The relationship between alcohol intake and ABI was determined by use of analysis of covariance and multivariable regressions.

Principal Findings

In men, alcohol consumption was significantly associated with ABI (P<0.001). After adjusted for the confounding factors, such as age, sex, ethnicity, body mass index, smoking, work stress, diabetes, and fasting blood glucose, the difference remained significant (P<0.001); either the unadjusted or multivariate-adjusted odds ratio (OR) for peripheral artery disease (PAD) was significantly higher in men who consumed >60.0 g/d [OR  = 3.857, (95% CI: 2.555–5.824); OR = 2.797, (95% CI: 1.106–3.129); OR = 2.878, (95% CI: 1.215–4.018); respectively] and was significantly lower in men who consumed 20.1–40.0 g/d [OR  = 0.330, (95% CI: 0.181–0.599); OR = 0.484, (95% CI: 0.065–0.894); OR = 0.478, (95% CI: 0.243–1.534); respectively] and 40.1–60.0 g/d [OR  = 0.306, (95% CI: 0.096–0.969); OR = 0.267, (95% CI: 0.087–0.886); OR = 0.203, (95% CI: 0.113–0.754); respectively] compared with never drinking, respectively (all P<0.01). Neither in unadjusted nor in multivariate-adjusted model was the association between ABI and alcohol consumption significant (all P>0.05) in women. Similarly, PAD was not correlated with alcohol intake in women (all P>0.05).

Conclusions/Significance

Our results indicated that in Chinese men, alcohol consumption was associated with peripheral artery disease, and consumption of less than 60 g/d had an inverse association with peripheral atherosclerosis whereas consumption of 60 g/d or more had a positive association.     

Association of mitochondrial DNA variations with lung cancer risk in a Han Chinese population from southwestern China

Mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage and mutation due to the high rate of reactive oxygen species (ROS) production and limited DNA-repair capacity in mitochondrial. Previous studies demonstrated that the increased mtDNA copy number for compensation for damage, which was associated with cigarette smoking, has been found to be associated with lung cancer risk among heavy smokers. Given that the common and “non-pathological” mtDNA variations determine differences in oxidative phosphorylation performance and ROS production, an important determinant of lung cancer risk, we hypothesize that the mtDNA variations may play roles in lung cancer risk. To test this hypothesis, we conducted a case-control study to compare the frequencies of mtDNA haplogroups and an 822 bp mtDNA deletion between 422 lung cancer patients and 504 controls. Multivariate logistic regression analysis revealed that haplogroups D and F were related to individual lung cancer resistance (OR = 0.465, 95%CI = 0.329–0.656, p<0.001; and OR = 0.622, 95%CI = 0.425–0.909, p = 0.014, respectively), while haplogroups G and M7 might be risk factors for lung cancer (OR = 3.924, 95%CI = 1.757–6.689, p<0.001; and OR = 2.037, 95%CI = 1.253–3.312, p = 0.004, respectively). Additionally, multivariate logistic regression analysis revealed that cigarette smoking was a risk factor for the 822 bp mtDNA deletion. Furthermore, the increased frequencies of the mtDNA deletion in male cigarette smoking subjects of combined cases and controls with haplogroup D indicated that the haplogroup D might be susceptible to DNA damage from external ROS caused by heavy cigarette smoking.     

Putative EPHX1 enzyme activity is related with risk of lung and upper aerodigestive tract cancers: a comprehensive meta-analysis

Background

EPHX1 is a key enzyme in metabolizing some exogenous carcinogens such as products of cigarette-smoking. Two functional polymorphisms in the EPHX1 gene, Tyr113His and His139Arg can alter the enzyme activity, suggesting their possible association with carcinogenesis risk, particularly of some tobacco-related cancers.

Methodology/Principal Findings

A comprehensive systematic review and meta-analysis was performed of available studies on these two polymorphisms and cancer risk published up to November 2010, consisting of 84 studies (31144 cases and 42439 controls) for Tyr113His and 77 studies (28496 cases and 38506 controls) for His139Arg primarily focused on lung cancer, upper aerodigestive tract (UADT) cancers (including oral, pharynx, larynx and esophagus cancers), colorectal cancer or adenoma, bladder cancer and breast cancer. Results showed that Y113H low activity allele (H) was significantly associated with decreased risk of lung cancer (OR = 0.88, 95%CI = 0.80–0.96) and UADT cancers (OR = 0.86, 95%CI = 0.77–0.97) and H139R high activity allele (R) with increased risk of lung cancer (OR = 1.18, 95%CI = 1.04–1.33) but not of UADT cancers (OR = 1.05, 95%CI = 0.93–1.17). Pooled analysis of lung and UADT cancers revealed that low EPHX1 enzyme activity, predicted by the combination of Y113H and H139R showed decreased risk of these cancers (OR = 0.83, 95%CI = 0.75–0.93) whereas high EPHX1 activity increased risk of the cancers (OR = 1.20, 95%CI = 0.98–1.46). Furthermore, modest difference for the risk of lung and UADT cancers was found between cigarette smokers and nonsmokers both in single SNP analyses (low activity allele H: OR = 0.77/0.85 for smokers/nonsmokers; high activity allele R: OR = 1.20/1.09 for smokers/nonsmokers) and in combined double SNP analyses (putative low activity: OR = 0.73/0.88 for smokers/nonsmokers; putative high activity: OR = 1.02/0.93 for smokers/ nonsmokers).

Conclusions/Significance

Putative low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers, whereas putative high EPHX1 activity may have a harmful effect. Moreover, cigarette-smoking status may influence the association of EPHX1 enzyme activity and the related cancer risk.     

Chromosome 15q25 (CHRNA3-CHRNA5) variation impacts indirectly on lung cancer risk

Genetic variants at the 15q25 CHRNA5-CHRNA3 locus have been shown to influence lung cancer risk however there is controversy as to whether variants have a direct carcinogenic effect on lung cancer risk or impact indirectly through smoking behavior. We have performed a detailed analysis of the 15q25 risk variants rs12914385 and rs8042374 with smoking behavior and lung cancer risk in 4,343 lung cancer cases and 1,479 controls from the Genetic Lung Cancer Predisposition Study (GELCAPS). A strong association between rs12914385 and rs8042374, and lung cancer risk was shown, odds ratios (OR) were 1.44, (95% confidence interval (CI): 1.29–1.62, P = 3.69×10⁻¹⁰) and 1.35 (95% CI: 1.18–1.55, P = 9.99×10⁻⁶) respectively. Each copy of risk alleles at rs12914385 and rs8042374 was associated with increased cigarette consumption of 1.0 and 0.9 cigarettes per day (CPD) (P = 5.18×10⁻⁵ and P = 5.65×10⁻³). These genetically determined modest differences in smoking behavior can be shown to be sufficient to account for the 15q25 association with lung cancer risk. To further verify the indirect effect of 15q25 on the risk, we restricted our analysis of lung cancer risk to never-smokers and conducted a meta-analysis of previously published studies of lung cancer risk in never-smokers. Never-smoker studies published in English were ascertained from PubMed stipulating - lung cancer, risk, genome-wide association, candidate genes. Our study and five previously published studies provided data on 2,405 never-smoker lung cancer cases and 7,622 controls. In the pooled analysis no association has been found between the 15q25 variation and lung cancer risk (OR = 1.09, 95% CI: 0.94–1.28). This study affirms the 15q25 association with smoking and is consistent with an indirect link between genotype and lung cancer risk.     

The association between OGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis of 27 studies

Background

Numerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations.

Methods

We searched publications from MEDLINE and EMBASE which were assessing the associations between OGG1 Ser326Cys polymorphism and lung cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We used genotype based mRNA expression data from HapMap for SNP rs1052133 in normal cell lines among 270 subjects with four different ethnicities.

Results

The results showed that individuals carrying the Cys/Cys genotype did not have significantly increased risk for lung cancer (OR = 1.15, 95% CI = 0.98–1.36) when compared with the Ser/Ser genotype; similarly, no significant association was found in recessive, dominant or heterozygous co-dominant model (Ser/Cys vs. Cys/Cys). However, markedly increased risks were found in relatively large sample size (Ser/Ser vs. Cys/Cys: OR = 1.29, 95% CI = 1.13–1.48, and recessive model: OR = 1.19, 95% CI = 1.07–1.32). As to histological types, we found the Cys/Cys was associated with adenocarcinoma risk (Ser/Ser vs. Cys/Cys: OR = 1.32, 95% CI = 1.12–1.56; Ser/Cys vs. Cys/Cys: OR = 1.19, 95% CI = 1.04–1.37, and recessive model OR = 1.23, 95% CI = 1.08–1.40). No significant difference of OGG1 mRNA expression was found among genotypes between different ethnicities.

Conclusions

Despite some limitations, this meta-analysis established solid statistical evidence for an association between the OGG1 Cys/Cys genotype and lung cancer risk, particularly for studies with large sample size and adenocarcinoma, but this association warrants additional validation in larger and well designed studies.     

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru

Background

Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use.

Methodology and Results

A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions.

Conclusions

Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.     

Association of MDM2 SNP309 Variation with Lung Cancer Risk: Evidence from 7196 Cases and 8456 Controls

Background

Evidence suggests that MDM2 T309G polymorphism may be a risk factor for several cancers. Increasing investigations have been conducted on the association of MDM2 T309G polymorphisms with lung cancer risk and have yielded conflicting results. Previous meta-analyses on this issue have reported inconclusive data. The aim of the present study was to derive a more precise estimation of the relationship.

Methods and Findings

Updated meta-analyses examining the association between MDM2 T309G polymorphism and lung cancer risk were performed. Separate analyses on ethnicity, smoking status, histological types and gender as well as source of controls were also implemented. Eligible studies were identified for the period up to Feb 2012. Lastly, ten publications including eleven case-control studies were selected for analysis. The overall data failed to indicate a significant association between MDM2 T309G polymorphism and lung cancer risk (GG vs TT OR = 1.14; 95%CI = 0.95−1.37; dominant model: OR = 1.05; 95%CI = 0.92−1.19; recessive model: OR = 1.12; 95%CI = 0.99−1.27). In a subgroup analysis by smoking status, increased lung cancer risk was shown among never-smokers (GG vs TT: OR = 1.76; 95%CI = 1.36−2.29; dominant model: OR = 1.48; 95%CI = 1.22−1.81; recessive model: OR = 1.37; 95%CI = 1.11−1.69). In subgroup analysis by gender, elevated risk was presented among women under a recessive model (OR = 1.29; 95%CI = 1.04−1.59). In the subgroup analysis by ethnicity, histological types and source of controls, no marked associations were observed.

Conclusions

Compared to the previous meta-analyses, the results of this study confirmed that MDM2 T309G polymorphism might be a risk factor for lung cancer among never-smokers. However, the data failed to suggest a marked association between the G allele of MDM2 T309G and lung cancer risk among Asians. More interestingly, subgroup analysis by gender indicated that homozygous GG alleles might raise lung cancer risk among females.     

A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies

Background

MicroRNAs (miRNAs) negatively regulate the gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between single nucleotide polymorphism (SNP) in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies.

Methodology/Principal Findings

An updated meta-analysis based on 15 independent case-control studies consisting of 4999 cancer patients and 7606 controls was performed to address this association. It was found that miR-196a2 polymorphism significantly elevated the risks of digestive system cancers (CT vs. TT, OR = 1.25, 95% CI = 1.07–1.45; CC vs. TT, OR = 1.38, 95% CI = 1.13–1.67; CC/CT vs. TT, OR = 1.29, 95% CI = 1.10–1.50; CC vs. CT/TT, OR = 1.14, 95% CI = 1.01–1.30; C vs. T, OR = 1.15, 95% CI = 1.05–1.26). We also found that variant in miR-196a2 increased the susceptibility of colorectal cancer (CRC) (CT vs. TT, OR = 1.23, 95% CI = 1.04–1.44; CC vs. TT, OR = 1.32, 95% CI = 1.08–1.61; CC/CT vs. TT, OR = 1.25, 95% CI = 1.07–1.46; C vs. T, OR = 1.15, 95% CI = 1.05–1.28), while the association in recessive model (CC vs. CT/TT, OR = 1.16, 95% CI = 0.98–1.38) showed a marginal significance. Additionally, significant association between miR-196a2 polymorphism and increased risk of hepatocellular cancer (HCC) was detected. By stratifying tumors on the basis of site of origin, source of controls, ethnicity and allele frequency in controls, elevated cancer risks were observed.

Conclusion/Significance

Our findings suggest the significant association between miR-196a2 polymorphism and increased susceptibility of digestive system cancers, especially of CRC, HCC and Asians. Besides, C allele may contribute to increased digestive cancer risks.     

Prostate cancer postoperative nomogram scores and obesity

Purpose

Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms'' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity.

Methods

We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP) in southern California from 2000 to 2008. Progression-free probabilities (PFPs) were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs).

Results

In the present study, aggressive prostate cancer (Gleason ≥7), but not advanced stage, was associated with obesity (p = 0.01). After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28–0.90) and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01–1.50) and Gleason >7 (OR = 1.45; 95% CI = 1.11–1.90).

Conclusion

Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making.     

Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies

Background

MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results.

Methodology/Principal Findings

We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR = 1.18, 95% CI = 1.03–1.34, P<0.001 for heterogeneity test). In the stratified analyses, we observed that the CC genotype might modulate breast cancer risk (OR = 1.11, 95%CI = 1.01–1.23, P _{heterogeneity} = 0.210) and lung cancer risk (OR = 1.25, 95%CI = 1.06–1.46, P _{heterogeneity} = 0.958), comparing with the TC/TT genotype. Moreover, a significantly increased risk was found among Asian populations in a dominant model (TC/CC versus TT, OR = 1.24, 95% CI = 1.07–1.43, P _{heterogeneity} = 0.006).

Conclusions

These findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers.     

The effect of hOGG1 Ser326Cys polymorphism on cancer risk: evidence from a meta-analysis

Background

Human oxoguanine glycosylase 1 (hOGG1) in base excision repair (BER) pathway plays a vital role in DNA repair. Numerous epidemiological studies have evaluated the association between hOGG1 Ser326Cys polymorphism and the risk of cancer. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the association, we conducted a meta-analysis.

Methodology/Principal Findings

A comprehensive search was conducted to identify the eligible studies of hOGG1 Ser326Cys polymorphism and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. We found that the hOGG1 Ser326Cys polymorphism was significantly associated with overall cancer risk (Cys/Cys vs. Ser/Ser: OR = 1.19, 95%CI = 1.09–1.30, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.16, 95%CI = 1.08–1.26, P<0.001). Moreover, in subgroup analyses by cancer types, the stronger significant association between hOGG1 Ser326Cys polymorphism and lung cancer risk was found (Cys/Cys vs. Ser/Ser: OR = 1.29, 95%CI = 1.16–1.44, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.22, 95%CI = 1.12–1.33, P<0.001). The significant effects of hOGG1 Ser326Cys polymorphism on colorectal, breast, bladder, prostate, esophageal, and gastric cancer were not detected. In addition, in subgroup analyses by ethnicities, we found that the hOGG1 Ser326Cys polymorphism was associated with overall cancer risk in Asians (Cys/Cys vs. Ser/Ser: OR = 1.21, 95%CI = 1.10–1.33, P<0.001).

Conclusions

This meta-analysis showed that hOGG1 326Cys allele might be a low-penetrant risk factor for lung cancer.     

Ethnicity and cutaneous melanoma in the city of Sao Paulo, Brazil: a case-control study

Background

Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil.

Methodology/Principal Findings

We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe—Spain (OR = 3.01, 95% CI: 1.03–8.77), Italy (OR = 3.47, 95% CI: 1.41–8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05–8.93), or ≥2 European countries (OR = 2.82, 95% CI: 1.06–7.47); eye color—light brown (OR = 1.99, 95% CI: 1.14–3.84) and green/blue (OR = 4.62; 95% CI 2.22–9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21–6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03–9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03–3.19).

Conclusions

Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants.     

Smoking and COX-2 functional polymorphisms interact to increase the risk of gastric cardia adenocarcinoma in Chinese population

Background

Over-expression and increased activity of cyclooxygenase (COX)-2 induced by smoking has been implicated in the development of cancer. This study aimed to explore the interaction between smoking and functional polymorphisms of COX-2 in modulation of gastric cardia adenocarcinoma (GCA) risk.

Methods and Findings

Three COX-2 polymorphisms, including –1195G>A (rs689466), –765G>C (rs20417), and 587Gly>Arg (rs3218625), were genotyped in 357 GCA patients and 985 controls. In the multivariate logistic regression analysis, we found that the –1195AA, –765GC, and 587Arg/Arg genotypes were associated with increased risk of GCA (OR = 1.50, 95% CI = 1.05–2.13; OR = 2.06, 95% CI = 1.29–3.29 and OR = 1.67, 95% CI = 1.04–2.66, respectively). Haplotype association analysis showed that compared with G₋₁₁₉₅-G₋₇₆₅- G_Gly587Arg, the A₋₁₁₉₅-C₋₇₆₅-A_Gly587Arg conferred an increased risk of GCA (OR = 2.49, 95% CI = 1.54–4.01). Moreover, significant multiplicative interactions were observed between smoking and these three polymorphisms of –1195G>A, –765G>C, and 587Gly>Arg, even after correction by false discovery rate (FDR) method for multiple comparisons (FDR-P _interaction = 0.006, 5.239×10⁻⁴ and 0.017, respectively). Similarly, haplotypes incorporating these three polymorphisms also showed significant interaction with smoking in the development of GCA (P for multiplicative interaction = 2.65×10⁻⁶).

Conclusion

These findings indicated that the functional polymorphisms of COX-2, in interaction with smoking, may play a substantial role in the development of GCA.     

Impact of meat consumption, preparation, and mutagens on aggressive prostate cancer

Background

The association between meat consumption and prostate cancer remains unclear, perhaps reflecting heterogeneity in the types of tumors studied and the method of meat preparation—which can impact the production of carcinogens.

Methods

We address both issues in this case-control study focused on aggressive prostate cancer (470 cases and 512 controls), where men reported not only their meat intake but also their meat preparation and doneness level on a semi-quantitative food-frequency questionnaire. Associations between overall and grilled meat consumption, doneness level, ensuing carcinogens and aggressive prostate cancer were assessed using multivariate logistic regression.

Results

Higher consumption of any ground beef or processed meats were positively associated with aggressive prostate cancer, with ground beef showing the strongest association (OR = 2.30, 95% CI:1.39–3.81; P-trend = 0.002). This association primarily reflected intake of grilled or barbequed meat, with more well-done meat conferring a higher risk of aggressive prostate cancer. Comparing high and low consumptions of well/very well cooked ground beef to no consumption gave OR''s of 2.04 (95% CI:1.41–2.96) and 1.51 (95% CI:1.06–2.14), respectively. In contrast, consumption of rare/medium cooked ground beef was not associated with aggressive prostate cancer. Looking at meat mutagens produced by cooking at high temperatures, we detected an increased risk with 2-amino-3,8-Dimethylimidazo-[4,5-f]Quinolaxine (MelQx) and 2-amino-3,4,8-trimethylimidazo(4,5-f)qunioxaline (DiMelQx), when comparing the highest to lowest quartiles of intake: OR = 1.69 (95% CI:1.08–2.64;P-trend = 0.02) and OR = 1.53 (95% CI:1.00–2.35; P-trend = 0.005), respectively.

Discussion

Higher intake of well-done grilled or barbequed red meat and ensuing carcinogens could increase the risk of aggressive prostate cancer.     

Shortened telomere length is associated with increased risk of cancer: a meta-analysis

Background

Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting.

Methods

A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. Heterogeneity among studies and their publication bias were further assessed by the χ²-based Q statistic test and Egger''s test, respectively.

Results

The results showed that shorter telomeres were significantly associated with cancer risk (OR = 1.35, 95% CI = 1.14–1.60), compared with longer telomeres. In the stratified analysis by tumor type, the association remained significant in subgroups of bladder cancer (OR = 1.84, 95% CI = 1.38–2.44), lung cancer (OR = 2.39, 95% CI = 1.18–4.88), smoking-related cancers (OR = 2.25, 95% CI = 1.83–2.78), cancers in the digestive system (OR = 1.69, 95% CI = 1.53–1.87) and the urogenital system (OR = 1.73, 95% CI = 1.12–2.67). Furthermore, the results also indicated that the association between the relative telomere length and overall cancer risk was statistically significant in studies of Caucasian subjects, Asian subjects, retrospective designs, hospital-based controls and smaller sample sizes. Funnel plot and Egger''s test suggested that there was no publication bias in the current meta-analysis (P = 0.532).

Conclusions

The results of this meta-analysis suggest that the presence of shortened telomeres may be a marker for susceptibility to human cancer, but single larger, well-design prospective studies are warranted to confirm these findings.     

An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis

Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR) for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25–2.74). The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI:2.37–4.15), and for those with affected father 2.35 times (CI:2.02–2.72). The pooled estimate of RR for two or more affected first-degree family members relative to no history in father and in brother is 4.39 (CI:2.61–7.39). First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR:2.87, CI:2.21–3.74), than in men aged 65 and older (RR:1.92, CI:1.49–2.47), p for interaction = 0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI:55.6–63.5%) for men at all ages, 65.2% (CI:57.7–71.4%) for men younger than 65 and 47.9% (CI:37.1–56.8%) for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI:65.4–85.0%) of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect-modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65).     

Is There Evidence for Aetiologically Distinct Subgroups of Idiopathic Congenital Talipes Equinovarus? A Case-Only Study and Pedigree Analysis

Background

Idiopathic congenital talipes equinovarus (CTEV) is a common developmental foot disorder, the aetiology of which remains largely unknown. Some aspects of the epidemiology suggest the possibility of aetiologically distinct subgroups. Previous studies consider CTEV as a homogenous entity which may conceal risk factors in particular subgroups. We investigate evidence for aetiologically distinct subgroups of CTEV.

Methods

Parents of 785 probands completed a postal questionnaire. Family pedigrees were compiled by telephone. Case-only analysis was used to investigate interactions between risk factors and sex of the proband, CTEV laterality and CTEV family history.

Results

The male∶female ratio was 2.3∶1, 58% of probands were affected bilaterally and 11% had a first-second degree family history. There were modest interactions between family history and twin births (multivariate case - only odds ratio [ORca] = 3.87, 95%CI 1.19–12.62) and family history and maternal use of folic acid supplements in early pregnancy (ORca = 0.62, 95%CI 0.38–1.01); and between sex of the proband and maternal alcohol consumption during pregnancy (female, positive history and alcohol consumed: ORca = 0.33, 95%CI 0.12–0.89). Previous reports of an interaction between maternal smoking and family history were not confirmed. Relatives of female probands were affected more often than relatives of male probands.

Conclusions

These results provide tentative evidence for aetiologically distinct CTEV subgroups. They support the ‘Carter effect’, suggesting CTEV develops though a multifactorial threshold model with females requiring a higher risk factor ‘load’, and suggest areas where future aetiological investigation might focus. Large multi-centre studies are needed to further advance understanding of this common condition.     

Polymorphisms on 8q24 are associated with lung cancer risk and survival in han chinese

Chromosome 8q24 is commonly amplified in many types of cancer, particularly lung cancer. Polymorphisms in this region are associated with risk of different cancers. To investigate the relationship between three single nucleotide polymorphisms (SNPs) (rs1447295, rs16901979 and rs6983267) on 8q24 and lung cancer risk, we conducted an association study in two Han Chinese populations: one population was from Zhejiang Province (576 case patients and 576 control subjects), whereas the other was from Fujian Province (576 case patients and 576 control subjects). We found that rs6983267 was significantly associated with an increased risk of lung cancer in both populations. Compared with the TT genotype, the GG genotype was associated with a significant 1.555-fold increased risk of lung cancer [95% confidence interval (CI) 1.218–1.986, P = 4.0×10⁻⁴]. This effect was more pronounced in never-smokers [odds ratio (OR) = 2.366, 95% CI 1.605–3.488, P = 1.4×10⁻⁵]. Analyses stratified by histology revealed that rs6983267 GG genotype was most associated with patients with other histological types (OR = 3.012, 95% CI 1.675–5.417, P = 2.3×10⁻⁴). The AA genotype of rs1447295 was associated with increased risk for adenocarcinoma compared with the CC genotype (OR = 2.260, 95% CI 1.174–4.353, P = 0.015). Furthermore, the GG genotype of rs6983267 was associated with worse survival in the Zhejiang population (hazard ratio (HR) = 1.646, 95% CI 1.099–2.464, P = 0.016). No association was observed for rs16901979. These results suggest that genetic variations on 8q24 may play significant roles in the development and progression of lung cancer.     

Genetic variants of TSLP and asthma in an admixed urban population

Background

Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations.

Objectives

To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population.

Methodology and Main Results

Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR) = 1.50; 95% confidence interval (95% CI): 1.09–2.05, p = 0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR = 2.00, 95% CI: 1.04–3.83, p = 0.04) but not significant in never-smokers (OR = 1.34; 95% CI: 0.93–1.94, p = 0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR = 1.58, 95% CI: 1.10–2.27, p = 0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR = 1.15, 95% CI: 1.07–1.23, p = 0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR = 1.21, 95% CI: 1.08–1.34, p = 0.003; never-smokers: OR = 1.06, 95% CI: 0.94–1.17, p = 0.33).

Conclusions

Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction.     

Social, clinical and microbiological differential characteristics of tuberculosis among immigrants in Spain

Background

To identify the differential tuberculosis (TB) characteristics within the immigrant population with respect to natives in Spain.

Methodology/Principal Findings

A prospective cohort study design was implemented to examine the TB cases diagnosed and starting standard antituberculous treatment in Spain, between January 1st 2006 and March 31st 2007. A logistic regression analysis was performed to determine differential characteristics. 1,490 patients were included in the study population, 1,048 natives and 442 (29.7%) immigrants. According to the multivariate analysis, the following variables were significantly associated with immigrant TB cases: younger age (OR = 3.79; CI:2.16–6.62), living in group situation (OR = 7.61; CI:3.38–12.12), lower frequency of disabled (OR:0.08; CI:0.02–0.26) and retired (OR:0.21; CI:0.09–0.48) employment status, lower frequency of pulmonary disease presentation (OR = 0.47; CI:0.24–0.92), primary or emergency care admission (OR = 1.80; CI:1.05–3.06 and OR = 2.16; CI:1.36–3.45), drug resistance (OR = 1.86; CI:1.01–3.46), treatment default (OR:2.12; CI:1.18–3.81), lower frequency of alcohol and cigarette consumption (OR = 2.10; CI:1.42–3.11 and OR = 2.85; CI:2.10–3.87 respectively), more directly observed treatment (OR = 1.68; CI:1.04–2.69), and poor understanding of TB disease and its treatment (OR = 3.11; CI:1.86–5.20). The low percentage of primary MDR-TB in the native population (0.1% vs. 2.2% of immigrants) should be noted.

Conclusions/Significance

The differences show the need to introduce specific strategies in the management of TB within the immigrant population, including the improvement of social and work conditions.