Significant Increased Cancer Risk Research Articles

Appendix removal affects the subsequent cancer risk in Asian adults: A territory-wide population-based cohort study

Human appendix is critical for the maintenance of intestinal homeostasis. Appendicectomy has been the optimal treatment of acute appendicitis, yet the cancer incidence after appendix removal remains unclear. In this territory-wide retrospective cohort study, adult participants who underwent appendicectomy from 2000 to 2018 were retrieved from a population database (n = 43,983), while matched reference participants were retrieved as controls (n = 85,853). After appendicectomy, the overall cancer risk was significantly increased (subdistribution hazard ratio (SHR) = 1.124) compared to the non-appendicectomy group. Appendicectomy-treated males had higher cancer risk than males without appendicectomy (SHR = 1.197), while such difference was not observed in female participants. Significant increase in cancer risk was also observed in elder participants (age >60) with appendicectomy (SHR = 1.390). Appendicectomy was positively correlated with the risk of digestive tract and respiratory cancers including colon (SHR = 1.440), pancreas (SHR = 1.930), and trachea, bronchus, and lung (SHR = 1.394). In contrast, the risk of liver cancer was markedly decreased after appendicectomy (SHR = 0.713). In conclusion, we reported the association of appendicectomy with subsequent cancer incidence. These findings highlight the potential complication after appendix removal and the necessity of post-operative management to monitor and prevent long-term adverse events.

Assessing drinking water quality based on water quality indices, human health risk, and burden of disease attributable to heavy metals in rural communities of Yazd County, Iran, 2015–2021

The water quality indices, health risk, and burden of disease attributable to heavy metals in rural communities of Yazd County, Iran during 2015–2021 were studied. The drinking water quality index (DWQI) based on 27 parameters (including heavy metals) and heavy metal pollution index (HPI) were used for assessing drinking water quality. The health risk and burden of disease from heavy metals in drinking water were estimated in terms of hazard quotient (HQ), hazard index (HI), incremental lifetime cancer risk (ILCR), and disability-adjusted life year (DALY). Based on the DWQI scores by community, the drinking water quality in rural communities of Yazd County was characterized as good for 61 %, fair for 25 %, marginal for 2 %, and poor for 12 %. The distribution of the rural communities into the HPI categories was as follows: 43 % for excellent, 36 % for good, 14 % for poor, and 7 % for unsuitable. In about 20 % of the rural communities, the average HI level of heavy metals was higher than the boundary limit of one. The highest average HQ level at the county level was related to arsenic (As) to be 0.44. In all the communities, the total ILCR values of the heavy metals were in the category of significant increased cancer risk (10−6 to 10−4). At the county level, As and cadmium (Cd) exhibited the two highest cancer risk levels to be 1.96 × 10−4 and 1.87 × 10−4 for ILCR, respectively. The DALY rate (per 100,000 people) induced by exposure to the heavy metals via drinking water was 13.9, which was considered relatively high as compared to that of other drinking water pollutants obtained in the previous studies. The drinking water quality improvement through decreasing Cd and As levels below the standard values can drastically reduce the attributable burden of disease and promote the public health in the rural communities.

Risk of cancer with immunosuppressants compared to immunomodulators in multiple sclerosis: A nested case-control study within the French nationwide claims database.

The objective was to compare the risk of malignancies in real-world settings between exclusive immunosuppressant (IS) and immunomodulator (IM) use in multiple sclerosis (MS). A nested case-control study was designed within a new-user cohort of all patients with MS who initiated a first IM or IS between 2008 and 2014, and without cancer history, using the information of the SNDS nationwide French claims database. Incident cancer cases were matched with up to six controls on year of birth, sex, initiation date, and disease risk score of cancer. A conditional logistic regression (odds ratio [95% confidence interval]) was used to compare exclusive IS versus IM use during follow-up and according to three use durations. From 28 720 newly treated patients with MS, 407 incident cancers were observed during the follow-up with 2324 matched controls. A significant increase in cancer risk was observed for IS compared with IM (1.36 [1.05, 1.77]), with similar increases for the first 2 years of use but not for ≥2 years (1.06 [0.65, 1.75]). Similar increase was also observed for IS with indications other than MS (1.37 [1.04, 1.81]) but not for IS indicated only in MS (1.03 [0.45, 2.34]). Compared with IM, a 37% increase in cancer risk was observed for IS with indications other than MS and used for a short duration (≤2 years) but not for IS indicated only in MS. The absence of risk for prolonged exposure of IS with indications other than MS is not in favor of a causal relation with these drugs.

Association between TERT rs2853669 polymorphism and cancer risk: A meta-analysis of 9,157 cases and 11,073 controls

BackgroundIt has been reported that the functional telomerase reverse transcriptase (TERT) rs2853669 polymorphism might contribute to different types of human cancer. However, the association of this mutation with cancer remains controversial. Here, we conducted a meta-analysis to characterize this relationship.Materials and methods/Main resultsA systematic search of studies on the association of TERT rs2853669 polymorphism with all types of cancer was conducted in PubMed, Embase and Cochrane Library. The summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used to pool the effect size in a fixed-effects model or a random-effects model where appropriate. A total of 13 articles and 15 case-control studies, including 9,157 cases and 11,073 controls, were included in this meta-analysis. Overall, the pooled results indicated that the rs2853669 polymorphism was significantly associated with increased cancer risk in a homozygote comparison model (CT vs. TT: OR = 1.085, 95% CI: 1.015–1.159, P = 0.016). In the stratified analyses, a significant increased cancer risk was observed in Asian, but not Caucasian patients. A subgroup analysis by cancer type also revealed a significant increase in the risk of lung cancer, but not breast cancer.ConclusionsThe results of this meta-analysis suggest that the TERT rs2853669 polymorphism is associated with a significantly increased risk of cancer, particularly lung cancer, in Asian populations.

Impact of LMP7 (rs2071543) gene polymorphism in increasing cancer risk: evidence from a meta-analysis and trial sequential analysis.

Genetic variant LMP7 (low molecular weight polypeptide 7) –145 C > A may influence the function of immune surveillance of an individual and lead to cancer development. Various studies have investigated the relevance of LMP7 –145 C > A gene polymorphism with cancer risk; but, their results are conflicting and inconsistent. To obtain a comprehensive conclusion, a meta-analysis was performed by including eight eligible published studies retrieved from PubMed (Medline), EMBASE and Google Scholar web search until December 2016. Individuals with AA genotype (AA vs CC: p = 0.001; OR = 2.602, 95% CI = 1.780 to 3.803) of LMP7 -145 C > A were found to have 2 folds higher risk of cancer than those with CC genotype. The recessive genetic model (AA vs AC + CC) also indicated that individuals with AA genotype have 2 folds higher cancer risk than AC and CC genotypes (p = 0.001; OR = 2.216, 95% CI = 1.525 to 3.221). Also, significant increased cancer risk was observed in Asians but not in Caucasians. No publication bias was observed during the analysis. Trial sequential analysis also strengthened our current findings. These results suggest that genetic variant LMP7–145 C > A has significant role in increasing cancer risk in overall and Asian population, and could be useful as a prognostic marker for early cancer predisposition.

PON1 L55M polymorphism might contribute to the risk of cancer.

The results involved in correlation of PON1 L55M polymorphism and cancer risk are still inconsistent and controversial. Therefore, we performed this comprehensive meta-analysis for the effects of PON1 L55M polymorphism and cancer risk. We carried out a database search in PubMed (Medline) and EMBASE covering all published articles. The strength of association between PON1 L55M polymorphism and cancer risk was estimated by pooled ORs with corresponding 95% confidence intervals (CI). Twenty-one independent case-control studies concerned with association between PON1 L55M polymorphism and cancer risk were finally included in this meta-analysis. We found that there was a statistical significance between PON1 L55M polymorphism and cancer risk (OR=1.21, 95% CI: 1.04-1.40). In stratified analyses by site of cancer, statistically significant increased breast cancer risk was found (OR=2.04, 95% CI: 1.29-3.21). In stratified analyses by ethnicity, statistically significant increased cancer risk was found in Caucasian populations (OR=1.25, 95% CI: 1.03-1.51). In stratified analyses by source of control, significant increased cancer risk was found in hospital-based studies (OR=1.26, 95% CI: 1.10-1.44). This meta-analysis suggested that PON1 L55M polymorphism might increase the risk of cancer.

SU‐F‐T‐505: A Novel Approach for Sparing Critical Organs at Risk for Cancer Patients Undergoing Radiation Oncology Treatments

Purpose:A major goal of an effective radiation treatment plan is to deliver the maximum dose to the tumor while minimizing radiation exposure to the surrounding normal structures. For example, due to the radiation exposure to neighboring critical structures during prostate cancer treatment, a significant increase in cancer risk was observed for the bladder (77%) and the rectum (105%) over the following decade. Consequently, an effective treatment plan necessitates limiting the exposure to such organs which can best be achieved by physically displacing the organ at‐risk. The goal of this study is to present a prototype for an organ re‐positioner device designed and fabricated to physically move the rectum away from the path of radiation beam during external beam and brachytherapy treatments. This device affords patient comfort and provides a fully controlled motion to safely relocate the rectum during treatment.Methods:The NiTi shape memory alloy was designed and optimized for manufacturing a rectal re‐positioner device through cooling and heating the core alloy for its shaping. This has been achieved through a prototyped custom designed electronic circuit in order to induce the reversible austenitic transformation and was tested rigorously to ensure the integrity of the actuated motion in displacement of the target anatomy.Results:The desirable NiTi shape‐setting was configured for easy insertion and based on anatomical constraint. When the final prototype was evaluated, accuracy and precision of the maximum displacement and temperature changes revealed that the device could safely be used within the target anatomy.Conclusion:The organ re‐positioner device is a promising tool that can be implemented in clinical setting. It provides a controlled and safe displacement of the delicate organ(s) at risk. The location of the organ being treated could also be identified using conventional onboard imaging devices or MV imaging available on‐board most modern clinical accelerators.

French nuclear power plants and childhood leukemia.

The Geocap Study described by Sermage-Faure et al. (2012) suggested to them “a possible excess risk of AL [childhood acute leukemia] in the close vicinity of French NPPs [nuclear power plants] in 2002–2007”. The abstract contains general results of two analyses: the nationwide Geocap case-control study showing the odds ratio of cancer incidence OR = 1.9 (1.0–3.3, 95% confidence interval [CI]) and a concomitant study with standardized incidence ratio (SIR) = 1.9 (1.0–3.2, 95% CI). However, we provide evidence that this hypothetical risk increase is likely a statistical fluctuation. In addition, the data are subject to confounding factors that were not addressed. The putative increase in leukemia risk therefore cannot be justifiably attributed to very small radiation doses associated with the operation of the NPPs. First, the authors have not one datum in Table 2 (Sermage-Faure et al. 2012) that shows a statistically significant increase in cancer risk, whether for children under 5 or under 15 years of age, in either the interval 1990–2001 or 2002–2007. Only by data dredging and subdividing the numbers into smaller time intervals and other discriminatory indices in Table 4 (Sermage-Faure et al. 2012), can they produce a few showing statistical significance. But then, the numbers of children included in each time interval are small. Second, the results in the abstract are based on only 14 cancer cases near 19 NPPs. Fourteen cases are too few for a clinically significant result. Fourteen cases near 19 NPPs are on average 0.7 cases per NPP. Third, neither any confounding factor nor individual history of the children (especially their migrations) was taken into consideration. These omissions and the mentioned small-sample-size-related statistical problems invalidate the claimed association of cancer risk with NPP proximity. Additional weak points of the analysis were diligently mentioned by the authors (Sermage-Faure et al. 2012). First, no correlation was found between cancer cases and radioactive releases from NPPs. Second, similar French investigations several years earlier failed to find an increase in risk (White-Koning et al. 2004; Evrard et al. 2006; Laurier et al. 2008). And the evaluation over a wider time period (1990–2007) did not show a statistically significant risk increase. Third, total accumulated doses over the time period 2002–2007 were in the range of microsieverts – several orders of magnitude lower than the variations in natural background radiation. Fourth, lower doses were received by children living up to 5 km from the NPP, where the risk was estimated to be higher, while no risk increase was found among children who received the highest doses. These four weaknesses alone should have been sufficient to invalidate any claimed association between NPP operation and cancer, without the three points raised in this Letter. One can add also that despite the authors’ reluctance to unambiguously relate the leukemia incidence to the NPP emissions, they nevertheless suggest that leukemia is a consequence of radiation exposure from NPP operation. We point out in the present Letter why this suggestion is not justified. Attribution of an excess risk of cancers to nearby NPPs is a well known practice, even though many independent studies, such as COMARE (2011), CANUPIS (Spycher et al. 2011) or RADICON (2013), have demonstrated no correlation between radiation exposures around NPPs and cancer incidence. Observed increases can be attributed to population mixing, as pointed out in the most recent extensive review of childhood leukemia around NPPs (Janiak 2014). The population mixing hypothesis considered involves “the influx of outside workers to rural regions where nuclear installations are being set up and where local people are not immune to pathogens brought along with the incomers” (Janiak 2014). The Geocap Study (Sermage-Faure et al. 2012) is one of many studies on cancer risk around NPPs. The presented conclusions implicitly blame NPP-related, low-dose-radiation exposures for increased cancer risk. The “call for investigation for potential risk factors related to the vicinity of NPP” (Sermage-Faure et al. 2012) should be seriously questioned because such studies will lack statistical power for demonstrating any change (increase or decrease) in risk. In addition, such studies can promote potentially-harmful radiophobia (Jaworowski 2010; Scott 2011; Orient 2014), thereby making it difficult to communicate accurate information to the public on the health effects of radiation exposure, especially in the event of an actual radiological emergency (Allison 2009; Sanders 2010). The previous version of this Letter was submitted to the International Journal of Cancer. In his reply, the Editor stated that our remarks would not interest the journal’s readers.

Prédisposition héréditaire aux cancers digestifs, mammaires, gynécologiques et gonadiques : état des lieux du syndrome de Peutz-Jeghers

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease due to mutations in the tumor suppressor gene STK11. PJS is characterized by periorificial hyperpigmented macules (lentiginosis) and hamartomatous polyposis. Polyps can be located anywhere in the gastrointestinal tract, but are preferably observed in the small bowel (70-90%), the colon (50%) and the stomach (25%). They tend to be cancerous in a particular sequence hamartoma-dysplasia-cancer. The diagnosis is often made in the first or second decade following the appearance of lentigines or upon the occurrence of complications due to polyps (obstruction, intussusception, occult bleeding responsible for anemia). Furthermore PJS is associated with a significant increase in cancer risk (relative risk of 89% over the life according to the most recent series). Digestive cancers are the more frequent with cumulative incidences of 55% for gastro-intestinal cancer (39% for colorectal cancer, 13% for small bowel cancer and between 11 and 36% for pancreatic cancer, respectively). There is also an increased risk of non digestive cancers. In particular the risk of breast cancer is similar to that of patients carrying deleterious BRCA1 or BRCA2 mutations (cumulative incidence of 45%). Gynecological and gonadal tumors are frequent as well and can be more (adenoma malignum) or less aggressive (ovarian sex cord tumors with annular tubules and testicular tumors with calcified Sertoli cells). Finally the frequency of lung cancer is moderatly increased. Recommendations for screening and management based on retrospective series in the literature have led to various strategies. The aim of this paper is to summarize the clinical and molecular diagnostic criteria of PJS as well as recommendations on screening strategies, management and monitoring.

Association between the STK15 F31I Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 43,626 Subjects

The association between the Serine/threonine kinase 15 (STK15) F31I polymorphism (rs2273535) and cancer susceptibility remains controversial. To further investigate this potential relationship, we conducted a comprehensive meta-analysis of 27 published studies involving a total of 19,267 multiple cancer cases and 24,359 controls. Our results indicate statistical evidence of an association between the STK15 F31I polymorphism and the increased risk of overall cancer in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA, and A vs. T. In a stratified analysis by cancer type, there was an increased risk of breast cancer in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA, and A vs. T, as well as esophageal cancer in two genetic models: AA vs. TA+TT and AA vs. TA. In a stratified analysis by ethnicity, there was a significant increase in cancer risk among Asians, but not Caucasians, in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA and A vs. T. In addition, a stratified analysis by ethnicity in the breast cancer subgroup revealed a significant increase in cancer risk among Asians in two genetic models: AA vs. TA+TT and AA vs. TT, as well as among Caucasians in one genetic model: AA vs. TA. In summary, this meta-analysis demonstrates that the STK15 F31I polymorphism may be a risk factor for cancer.

Association between cytotoxic T lymphocyte antigen-4 +49A/G, −1722T/C, and −1661A/G polymorphisms and cancer risk: a meta-analysis

Cytotoxic T lymphocyte antigen-4 (CTLA-4), a key gene that contributes to the susceptibility and clinical course of cancer, is an important down-regulator of T cell activation and proliferation. The +49A/G polymorphism is commonly studied because of its association with cancer risks. However, other polymorphisms, such as -1722T/C and -1661A/G, have not been studied in detail. We performed a meta-analysis using 43 eligible case-control studies with a total of 19,089 patients and 21,388 controls to examine the association between CTLA-4 +49A/G, -1722T/C, and -1661A/G polymorphisms and cancer risk. We searched the PubMed and EMBASE databases for all articles published up to July 17, 2013. Individuals with the +49 A allele (AA/AG vs. GG, odds ratio (OR) = 1.21, 95% confidence interval (95% CI) = 1.16-1.27) and -1661 G allele (AG/GG vs. AA, OR = 1.52, 95% CI = 1.34-1.73) had increased cancer risk. However, no significant association between cancer risk and the -1722T/C polymorphism was found (CC/CT vs. TT, OR = 1.04, 95% CI = 0.92-1.16). In subgroup analysis for the +49A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.25, 95 % CI = 1.18-1.31), patients with breast cancer (OR = 1.28, 95% CI = 1.15-1.42), and patients with lung cancer (OR = 1.20, 95 % CI = 1.07-1.35). For the -1661A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.52, 95% CI = 1.34-1.73), patients with breast cancer (OR = 1.48, 95% CI = 1.07-2.03), and patients with oral cancer (OR = 3.16, 95% CI = 1.84-5.45). However, no significant increase in cancer risk was found in the subgroups for the -1722T/C polymorphism. In conclusion, the results suggest that +49A/G and -1661A/G polymorphisms in CTLA-4 are risk factors for cancers, whereas the -1722T/C polymorphism is not associated with an increased risk of cancer.

Observational studies on the risk of cancer associated with tumor necrosis factor inhibitors in rheumatoid arthritis: A review of their methodologies and results

Inhibitors of the inflammatory cytokine tumor necrosis factor (TNF) have proven to be highly effective in the treatment of various autoimmune conditions, including rheumatoid arthritis (RA). Indeed, according to several international guidelines that were based upon abundant evidence from therapeutic trials and clinical experience, these agents have come to be considered a cornerstone of therapy for RA patients with severe or refractory disease (1, 2) However, in addition to its central role in the immune driven systemic inflammation of RA, TNF is also important to immunologic surveillance. Because of the key role that the immune system plays in host defense, there is concern that therapy with TNF inhibitors (TNFi) might predispose patients to adverse effects related to impaired immunity, including an increased incidence of infections and/or cancer. Despite many years of clinical research and more than a decade since the introduction of TNF inhibitors into the clinic, there is disagreement about the potential association between use of these agents and malignancy. From a mechanistic standpoint, it could be hypothesized that inhibition of TNF could either enhance or inhibit cancer development (3–6). On the one hand, via mechanisms such as induction of apoptosis or suppressive effects on gene expression, TNF may suppress the development of certain tumors (5). Indeed, the name ‘TNF’, which was coined well before the role of this cytokine in inflammation and in numerous autoimmune diseases was known, reflects the observed inhibitory effects of this cytokine on certain tumors. Therefore, blockade of TNF may enhance the risk of cancer. In addition, TNF serves as a key element of the inflammatory response whose inhibition may increase the risk to various infections. This could potentially place the host at greater risk of cancers driven by chronic infections, particularly viral (7). By these mechanisms, inhibiting TNF might increase the risk of cancer. On the other hand, uncontrolled inflammation itself may also potentiate cancer (3, 4). Also, among the myriad activities of TNF is its profound effect on angiogenesis, which is critical to tumor growth, survival, and metastasis (3, 4). Therefore, potent anti-inflammatory treatments, such as TNFi, could decrease the risk of cancer through suppressing inflammation and reducing angiogenesis. This concept is supported by two lines of data. First, patients with higher levels of systemic inflammation, such as those with RA, are at a greater risk for developing lymphomas (8). Second, treatment with corticosteroids, which possess diverse anti-inflammatory properties, appear to be associated with a lesser risk of lymphoma development (9). Similar to the basic science suggesting that TNFi may increase or decrease the risk of cancer, randomized controlled trials do not provide definitive evidence about this relationship. Two recent meta-analyses found no clear evidence of increased cancer risk with the use of TNFi. (10, 11). One large meta-analysis that included only the monoclonal antibodies, infliximab and adalimumab, found an increased risk of cancer (12). A meta-analysis focused on etanercept suggested a trend toward an increased risk but the confidence interval spanned one for the primary analysis and secondary analyses did not all suggest increased cancer risk (13). Furthermore, a study of patients enrolled in adalimumab trials for early RA found no significant increase in cancer risk (14). While randomized controlled trials are the gold standard for efficacy, they may not provide the best information regarding a drug’s toxicity, owing to their relatively short duration and strict inclusion criteria that may exclude important at-risk groups (15). Epidemiologic studies of patients in typical care allows for analysis of more relevant subjects with a variety of comorbid conditions using concomitant treatments. With this background, we undertook a systematic review of epidemiologic studies of the relationship between TNFi and cancer. Prior reviews have examined this risk of cancer in RA (16). Whereas, this review focuses on both the methodologic attributes of studies examining TNFi and cancer, as well as their results. We did not attempt a meta-analysis because of the obvious methodological heterogeneity and opted to present the findings as a systematic review, as suggested by the Cochrane Collaboration (17).

P2-259 Cancer risk in children with birth defects: a longitudinal, population-based assessment among 2.7 million births

IntroductionThe published literature, to date, is largely inconclusive regarding cancer risk among children with birth defects. To improve knowledge of such risk, we studied population-based (statewide) birth cohorts from Arizona,...

The association between two polymorphisms in the TYMS gene and breast cancer risk: a meta-analysis

Thymidylate synthase (TYMS), which catalyzes the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate, is a central enzyme in the folate metabolic pathway. Epidemiological studies have evaluated the association between TYMS gene polymorphisms and breast cancer susceptibility; however, the published data are still inconclusive. To derive a more precise assessment of this relationship, we performed a meta-analysis based on currently available data by searching PubMed, EMBASE databases, and the Cochrane Library. A total of 10 eligible studies were identified for the TYMS TSER polymorphism (six studies with 2,718 cases and 3,423 controls) and for the TYMS TS3'-UTR polymorphism (five studies with 1,969 cases and 2,290 controls). The overall odds ratio (OR) and the corresponding 95% confidence interval (CI) showed a statistical association between the TSER polymorphism and breast cancer risk under homozygote comparison (2R/2R vs. non-2R/non-2R; OR 1.25; 95% CI 1.04-1.50), allele contrast (2R vs. non-2R; OR 1.09; 95% CI 1.01-1.19) and the recessive model (OR 1.19; 95% CI 1.01-1.39). In the subgroup analysis by ethnicity, a statistically significant increase in cancer risk was found among Caucasians for homozygote comparison (OR 1.31; 95% CI 1.10-1.57), the allele contrast model (OR 1.12; 95% CI 1.02-1.23) and the dominant model (OR 1.40; 95% CI 1.00-1.95). For the TS3'-UTR polymorphism, significant effects were shown using the allele contrast model (OR 1.33; 95% CI 1.03-1.73). However, the TS3'-UTR polymorphism increased breast cancer risk among Asian women (del6 vs. ins6; OR 1.41; 95% CI 1.01-1.98) but not Caucasian women using the homozygote comparison. In conclusion, our meta-analysis suggests that the TSER polymorphism may increase susceptibility to breast cancer in the Caucasian population and the TS3'-UTR polymorphism may be a genetic determinant for developing breast cancer in the Asian population; therefore, ethnic background should be carefully considered in further studies.

Slowing the Increase in the Population Dose Resulting from CT Scans

The annual number of CT scans in the U.S. is now over 70 million. The concern is that organ doses from CT are typically far larger than those from conventional X-ray examinations, and there is epidemiological evidence of a small but significant increased cancer risk at typical CT doses. Because CT is a superb diagnostic tool and because individual CT risks are small, when a CT scan is clinically indicated, the CT benefit/risk balance is by far in the patient's favor. Nevertheless, CT should operate under the ALARA (As Low As Reasonably Achievable) principle, and opportunities exist to reduce the significant population dose associated with CT without compromising patient care. The first opportunity is to reduce the dose per scan, and improved technology has much potential here. The second opportunity is selective replacement of CT with other modalities, such as for many head and spinal examinations (with MRI), and for diagnosing appendicitis (selective use of ultrasound + CT). Finally, a fraction of CT scans could be avoided entirely, as indicated by CT decision rules: Clinical decision rules for CT use represent a powerful approach for slowing down the increase in CT use, because they have the potential to overcome some of the major factors that result in some CT scans being undertaken when they are potentially not clinically helpful. In the U.S. and potentially elsewhere, legislative approaches are a possible option, to improve quality control and reduce clinically unneeded CT use, and it is also possible that upcoming changes in heath care economics will tend to slow the increase in such CT use.

Genomic and gene expression signatures of radiation in medulloblastomas after low-dose irradiation in Ptch1 heterozygous mice

Accurate cancer risk assessment of low-dose radiation poses many challenges that are partly due to the inability to distinguish radiation-induced tumors from spontaneous ones. To elucidate characteristic features of radiation-induced tumors, we analyzed 163 medulloblastomas that developed either spontaneously or after X-ray irradiation at doses of 0.05-3 Gy in Ptch1 heterozygous mice. All spontaneous tumors showed loss of heterozygosity in broad regions on chromosome 13, with losses at all consecutive markers distal to Ptch1 locus (S-type). In contrast, all tumors that developed after 3 Gy irradiation exhibited interstitial losses around Ptch1 with distal markers retained (R-type). There was a clear dose-dependent increase in the proportion of R-type tumors within the intermediate dose range, indicating that the R-type change is a reliable radiation signature. Importantly, the incidence of R-type tumors increased significantly (P = 0.007) at a dose as low as 50 mGy. Integrated array-comparative genomic hybridization and expression microarray analyses demonstrated that expression levels of many genes around the Ptch1 locus faithfully reflected the signature-associated reduction in genomic copy number. Furthermore, 573 genes on other chromosomes were also expressed differently between S-type and R-type tumors. They include genes whose expression changes during early cerebellar development such as Plagl1 and Tgfb2, suggesting a recapitulation of gene subsets functioning at distinct developmental stages. These findings provide, for the first time, solid experimental evidence for a significant increase in cancer risk by low-dose radiation at diagnostic levels and imply that radiation-induced carcinogenesis accompanies both genomic and gene expression signatures.

Research and development round-up: February 2009

Low to moderate alcohol consumption among women is associated with a statistically significant increase in cancer risk and may account for nearly 13% of the cancers of the breast, liver, rectum, and upper aerodigestive tract combined, according to a report.

Association of CYP1A1 Msp1 polymorphism with tobacco-related risk of gallbladder cancer in a north Indian population

Polymorphisms in the gene encoding the metabolic enzyme cytochrome P450 1A1 (CYP1A1) might contribute to the variability in individual susceptibility to gallbladder cancer (GBC). This study comprised 142 consecutive cases of proven GBC and 171 healthy participants of similar ethnicity. CYP1A1 6235 T/C transition was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The CC genotype of CYP1A1 was significantly associated with a risk of GBC [odds ratio (OR) 2.3, 95% confidence interval (CI)=1.1-4.5, P=0.026], and the age- and sex-adjusted OR was 2.0. The CYP1A1 C allele frequency was also higher in GBC patients (OR 1.4, 95% CI=1.0-2.0, P=0.039). After sex stratification, the TC genotype and C allele were significantly higher in men and conferred a risk for GBC (OR 4.2, 95% CI=1.8-9.7, P=0.001; OR 2.2, CI=1.3-3.7, P=0.005). In addition, the TC genotype and C allele frequencies were significantly higher in GBC patients without associated gallstones (OR 2.4, 95% CI=1.2-4.7, P=0.011; OR 1.6, CI=1.0-2.4, P=0.023). The usage of tobacco (smoking or nonsmoking) by GBC patients showed a significant increase in cancer risk with the TC genotype (OR 4.1, 95% CI=1.3-11.9, P=0.012). It seems that the higher risk of the TC genotype in men may be related to tobacco usage.

Family History of Cancer Among Children With Brain Tumors

The occurrence of brain tumors in children has been anecdotally associated with an increased cancer incidence among relatives. This study rigorously reviewed the epidemiologic literature regarding family history of cancer in children with brain tumors. Six case-control and 10 cohort studies remained after applying stringent inclusion criteria. Most studies found no significant increase in cancer risk among relatives of childhood brain tumor patients. Those associations that were detected were often of borderline significance or demonstrated wide confidence intervals. There is limited evidence that a family history of cancer is more common among families of childhood brain tumor patients.

CYP1A1 Msp1 T/C Polymorphism in Esophageal Cancer: No Association and Risk Modulation

Phase I enzyme CYP1A1 metabolizes environmental carcinogens and a Msp1 T/C functional polymorphism in 3'UTR in its gene has been reported to influence the inducibilty of the enzyme. There are controversies regarding association of the polymorphism with risk of esophageal cancer in Chinese and Caucasian populations. Moreover, no study has been done in Indian populations. The present study was aimed to explore the associations of CYP1A1 3'UTR polymorphism with clinical phenotypes and environmental interaction in esophageal cancer from North Indian population. A total of age- and gender-matched 161 cases and 201 healthy controls were used to genotype the CYP1A1 3'UTR polymorphism by PCR-EFLP methodology. None of the CYP1A1 genotypes and alleles was significantly associated with risk of esophageal cancer, even after adjusting for age and sex. After stratifying the genotypes according to disease characteristics such as tumor histology, location, and lymph nodes, individuals with TT genotype were at high risk for developing tumor in the upper third location (OR: 2.2, 95% CI: 0.81-6.2, p = 0.11). Interaction of tobacco usage (smoking or nonsmoking) and presence of occupational exposure in esophageal cancer patients did not show significant increase in cancer risk with CYP1A1 genotypes. However, in patients with alcohol habits, TT genotype showed a higher risk, which was not significant (OR: 2.5, 95% CI: 0.61-10.6, p = 0.19). In conclusion, CYP1A1 genotype did not influence the susceptibility of developing esophageal cancer. The presence of variant CYP1A1 genotypes together with environmental exposures also did not modulate the cancer risk.