Comprehensive Case-control Study Research Articles

Colorectal cancer and associated genetic, lifestyle, cigarette, nargileh-hookah use and alcohol consumption risk factors: a comprehensive case-control study.

This study aimed to investigate the causes and risk factors of colorectal cancer (CRC) in a Turkish population, focusing on various modifiable and non-modifiable risk factors. A hospital-based case-control design was employed to compare individuals with CRC (cases) to individuals without CRC (controls). Male and female participants were recruited from the surgery, internal medicine, and out-patient departments. The study encompassed socio-demographic data, clinical information, radiological diagnoses, and biochemical measurements. Univariable and multivariable logistic regressions were used to determine associated risk factors of CRC. The study included 704 individuals with CRC and 704 controls. Significant socio-demographic disparities were observed between the groups, with over 30% of the cases having lower levels of education and income compared to the controls. Lifestyle factors such as obesity, higher rates of smoking (cigarettes and hookah) and alcohol consumption were more prevalent among cases than controls. Further significant associations were identified with intestinal inflammation, obesity, processed food consumption, and symptoms such as abdominal pain, cramps, diarrhea, constipation, blood in stool, bloating, irritable bowel syndrome, nausea/vomiting, anemia, stress, fatigue, weakness, and weight loss. Diet analysis revealed that individuals with CRC consumed more red meat, processed and fast foods along with less pulses and vegetables. Genetic predispositions and exposure to chemicals also correlated strongly with increased CRC risk. Multivariable regression analysis identified, nausea/vomiting, constipation, intestinal disease, genetics factor, hookah-nargileh use, history of any cancer, family history of bowel cancer, constipation, cigarette smoking, stress, milk-yogurt consumption, obesity and red meat consumption as significant determinants for CRC. CRC risk is influenced by dietary, lifestyle, and genetic factors. Awareness of hereditary risk and participation in screening are crucial. Lifestyle changes, such as avoiding smoking, hookah, and alcohol use, and adopting a healthy diet, are essential for prevention.

Assessing Colorectal Cancer Susceptibility in Kashmir, India: Insights from Xenobiotic Metabolism Gene Variants and Family Cancer History—A Comprehensive Case–Control Study

Assessing Colorectal Cancer Susceptibility in Kashmir, India: Insights from Xenobiotic Metabolism Gene Variants and Family Cancer History—A Comprehensive Case–Control Study

Comprehensive Case-Control Study of Protective and Risk Factors for Buruli Ulcer, Southeastern Australia.

To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.

Could oral hygiene prevent cases of at-home-acquired Legionnaires' disease? - Results of a comprehensive case-control study on infection sources, risk, and protective behaviors.

The "LeTriWa study" on community-acquired cases of Legionnaires' disease (LD) found that most cases likely acquired their infection at home (AHALD). However, which sources confer the infection is largely unknown. We therefore analyzed the data set from the LeTriWa study to find out if individual sources were associated with AHALD and if specific behavioral habits may increase or lower the risk for AHALD. During the study we had used two comparison groups: (i) controls matched for age group and hospital ("controls"), (ii) household members of cases with AHALD ("AHALD-HHM"). We inquired about exposure to water sources, such as showering or wearing dentures, as well as behavioral factors and habits related to oral hygiene. We took standardized household bathroom water and biofilm samples of both cases with AHALD and controls, and in addition from households of cases with AHALD only samples from suspect residential (non-)drinking water sources. We first conducted bivariate analyses for infection sources and behaviors, followed by multivariable analyses. There were 124 cases with AHALD, 217 controls and 59 AHALD-HHM. In bivariate analyses using controls for comparison, wearing dentures was the only variable significantly positively associated (odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.1-2.7, p-value = 0.02). Behavioral factors such as showering, letting water run before use and not being alcohol abstinent were significantly negatively associated, smoking was significantly positively associated. In a multivariable analysis, we identified good oral hygiene as a preventive factor for both denture wearers (OR = 0.33, 95% CI = 0.13-0.83, p-value = 0.02) and non-denture wearers (OR = 0.32, 95% CI = 0.10-1.04, p-value = 0.06). Analyses of comparisons with AHALD-HHM showed similar effects but lacked statistical power. We identified Legionella in 16 residential (non-)drinking water sources, one of which was a PCR-positive scratch sample of dentures. Wearing (inadequately cleaned) dentures or poor oral hygiene might confer an increased risk for AHALD, and oral hygiene may prevent AHALD. The hypothesis that Legionella in oral biofilm or dental plaque may be the cause of cases with AHALD should be examined further. If confirmed this may open new and simple avenues for the prevention of LD.

Is Coronavirus Infection Associated With Musculoskeletal Health Complaints? Results From a Comprehensive Case-Control Study.

Objective:This case-control study investigated the association between SARS-CoV-2 infection and musculoskeletal health complaints (MHC). The specific aims of the study were (1) to compare the 1-month prevalence of MHC among post-acute COVID-19 patients and participants who never tested positive for COVID-19 matched by the former group’s age and gender; (2) to identify the predictors of MHC among all participants, and (3) define the factors independently associated with MHC in post-acute COVID-19 patients.Methods and Analysis:The study was conducted in Bangladesh from February 24 to April 7, 2022. The face-to-face interview was taken using a paper-based semi-structured questionnaire. MHC was measured using the musculoskeletal subscale of subjective health complaints produced by Eriksen et al. Descriptive analysis was conducted to compute MHC prevalence and compare them across groups. Multiple logistic analyses were employed to identify MHC predictors for the participants.Results:The prevalence of MHC was 38.7%. Adjusted analysis suggested that the SARS-CoV-2 infection was independently associated with MHC (AOR = 3.248,95% CI = 2.307-4.571). Furthermore, unemployment (AOR = 4.156, 95% CI = 1.308-13.208), moderate illness (AOR = 2.947,95% CI = 1.216-7.144), treatment in hospitals’ general word (AOR = 4.388,95% CI = 1.878-10.254) and health complaints after COVID-19 (AOR = 4.796,95% CI = 2.196-10.472) were found to be the predictors of MHC among post-acute COVID-19 patients.Conclusion:Our study found a robust association between SARS-CoV-2 infection and MHC and recommends that healthcare authorities be prepared to deal with the high burden of MHC among post-acute COVID-19 patients.

Descriptive study of cattle and dog rabies cases in the Sheki-Zagatala region of Azerbaijan (2015–2016): Knowledge, attitudes, and practices of people towards rabies

Every year, rabies causes great damage to human health and the economy of countries around the world. This neurotropic and zoonotic viral disease is endemic to Azerbaijan. This study describes cattle and dog rabies cases identified between 2015 and 2016. In addition, a questionnaire was administered to 100 respondents comprised of case owners, and non-case animal owners, to assess knowledge, attitudes, and practices within this population. The study demonstrates a general lack of knowledge of rabies in the participating communities. The majority of respondents were familiar with rabies and understood that animal bites are a source of transmission. However, many respondents did not know that rabies is preventable and admitted not knowing additional routes of transmission. In addition, there was less perceived risk with contact with animal saliva. Despite free vaccinations in Azerbaijan, only 27 out of 45 dogs in this study were vaccinated. Although educational programming and preventive vaccination of dogs has been implemented, and significant progress has been made in the sphere of epidemiological surveillance and prevention, rabies cases remain problematic in the Sheki-Zagatala region. Regular educational programs for communities, strengthening of the existing vaccination programs, and a comprehensive epidemiological case-control study to identify the disease risk factors could help reduce the burden of rabies in Azerbaijan.

Heparanase (HPSE) gene polymorphism (rs12503843) contributes as a risk factor for hepatocellular carcinoma (HCC): a pilot study among Egyptian patients

BackgroundHeparanase activity was found to be included in human cancer development and growth. Heparanase (HPSE) gene single nucleotide polymorphisms (SNPs) have been found to be correlated with different human cancers. In the current study, we investigated whether HPSE SNPs were a hepatocellular carcinoma (HCC) risk factor by carrying out a comprehensive case-control pilot study. HPSE rs12331678 and rs12503843 were genotyped in 70 HCC-diagnosed patients and 30 healthy controls by modified amplification refractory mutation system (ARMS PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. ResultsHPSE rs12331678 distributions showed that there were no statistically significant differences between both cohorts either in genotypic or allelic distribution but there was a significant correlation between the rs12503843 (T allele) and the HCC risk in the whole samples (P = 0.042). No significant association was observed between the HPSE rs12331678 and rs12503843 gene polymorphisms and all clinicopathologic markers or with SNP stratification based on HCV carrier in HCC groups. ConclusionOur findings suggest for the first time the HPSE gene SNP characterization in HCC Egyptian patients, and our findings reveal there were associations between the HPSE rs12503843 (T allele) and the susceptibility to HCC.

Preventable lifestyle and eating habits associated with gastric adenocarcinoma: A case-control study.

Background: Besides the well-established risk factors for gastric adenocarcinoma (GaC), many other etiological factors remain largely unexplored. This large comprehensive case-control study aimed to investigate the preventable lifestyle and eating habits associated with GaC.Methods: Consecutive patients with primary microscopically-confirmed GaC diagnosed in 2016-2018 were matched by sex, age, height, and socioeconomic status at a 1:1 ratio with healthy controls. Association of GaC versus control with investigated factors was assessed using the multivariable-adjusted conditional logistic regression for paired samples.Results: Together 302 GaC patients and 302 healthy controls were investigated. Participants receiving higher education and those eating majorly vegetables had less frequently GaC. The majorly frying cooking habit was associated with a higher incidence of GaC. People complaining about poor sleep quality had more often GaC. The more often one smoked, the more often he/she had GaC. A higher frequency for having pickled food was associated with more frequent GaC, while having more frequently vegetables/fruit, beans, or kelps was associated with less often GaC. A greater preference for sour or bitter taste was associated with less frequent GaC. The frequencies of thin liquid intake after meal, swallowing hot food without adequate cooling, doing other things while eating, eating overnight food, and eating midnight snack were all positively associated with GaC, while going to bed regularly was associated with less often GaC.Conclusions: Education level, sleep quality, smoking, the frequencies of use of several foods and seasonings, the preference for specific tastes, and various eating and living habits were associated with GaC. The findings offer important hints for further prospective investigations and for easy effective GaC-preventative strategy-making.

BARD1 is A Low/Moderate Breast Cancer Risk Gene: Evidence Based on An Association Study of the Central European p.Q564X Recurrent Mutation.

In addition to several well-established breast cancer (BC) susceptibility genes, the contribution of other candidate genes to BC risk remains mostly undefined. BARD1 is a potentially predisposing BC gene, however, the rarity of its mutations and an insufficient family/study size have hampered corroboration and estimation of the associated cancer risks. To clarify the role of BARD1 mutations in BC predisposition, a comprehensive case-control association study of a recurring nonsense mutation c.1690C>T (p.Q564X) was performed, comprising ~14,000 unselected BC patients and ~5900 controls from Polish and Belarusian populations. For comparisons, two BARD1 variants of unknown significance were also genotyped. We detected the highest number of BARD1 variants in BC cases in any individual BARD1-specific study, including 38 p.Q564X mutations. The p.Q564X was associated with a moderately increased risk of BC (OR = 2.30, p = 0.04). The estimated risk was even higher for triple-negative BC and bilateral BC. As expected, the two tested variants of unknown significance did not show significant associations with BC risk. Our study provides substantial evidence for the association of a deleterious BARD1 mutation with BC as a low/moderate risk allele. The p.Q564X was shown to be a Central European recurrent mutation with potential relevance for future genetic testing.

The relationship between viral infection and nasal polyps:A Meta-analysis

Objective:The relationship between viral infection and the occurrence of nasal polyps was explored to help us understand the etiology and pathogenesis of nasal polyps, and to provide scientific basis for the prevention and treatment of nasal polyps through a Meta-analysis. Method:By searching Pubmed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database, and VIP Database, time starts from database building until January 1, 2018, a comprehensive case-control study on the relationship between human papillomavirus, Epstein-Barr virus (EBV), respiratory virus infection and nasal polyps published at home and abroad has been conducted. At the same time, relevant literature references have been included and the full texts have been obtained. Stata 12.0 analysis software was used to perform statistical processing on each original data.Odds ratios (OR) and their 95% confidence interval (CI) were adopted to assess the strength of association. Result:21 articles with 24 studies were included on the relationship between HPV, EBV, respiratory viral infection and nasal polyps. The Meta-analysis results showed that the OR of HPV infection and nasal polyps was 6.74, 95%CI was 2.50－18.20, P<0.001, the OR of EBV and nasal polyps was 5.15, 95%CI was 1.66－16.02, P=0.005, the OR of respiratory viruses and nasal polyps was 1.68, 95%CI was 0.93－3.03, P=0.087.There was no significant publication bias in all of the comparisons. Conclusion:HPV and EBV infection were closely associated with the nasal polyps. Respiratory viral infection was not associated with the nasal polyps. Viral infection may be one of the etiologies of nasal polyps. It plays an important role in the pathogenesis of nasal polyps. The prevention and treatment of the virus infection should be targeted at early intervention.

Risk factor assessment for breast cancer in North Cyprus: a comprehensive case-control study of Turkish Cypriot women

Background/aim: This case-control study aims to assess the strength of associations between reproductive, lifestyle, sociodemographic, and dietary factors as well as other potential breast cancer risks and breast cancer (BC) in a North Cyprus population. Materials and methods: The study includes 408 BC patients and 412 age-matched controls recruited from Near East Hospital and Dr. Burhan Nalbantoglu State Hospital in North Cyprus. Information regarding clinical and epidemiological characteristics was collected through a standardized interview. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression before and after adjusting for the potential confounders. Results: In addition to various recognized BC risk factors, strong associations with BC were reported from women with fertility drugs used for >6 cycles (OR = 3.305, 95% CI 1.850–5.906, P < 0.001), depression (OR = 2.10, 95% CI 1.33–3.30, P < 0.001), exposure to radiation (OR = 1.74, 95% CI 1.02–2.98, P = 0.041), and excess consumption of oil (OR = 2.703, 95% CI 1.62–4.48, P < 0.001) and sugar (OR = 3.42, 95% CI 1.39–8.40, P = 0.007). Parental consanguinity (OR = 0.16, 96% CI 0.09–0.30, P < 0.001) and daily water intake of 1–2 L (OR = 0.36, 95% CI 0.19–0.66, P < 0.001) were strong protective factors. Conclusion: Our results demonstrate the presence of classical as well as several additional BC risks. The findings will be of great benefit in establishing adequate evidence-based awareness and preventative measures in the North Cyprus population.

Breakfast habits and its relationship to body mass index and cognitive function among final year medical students

Background: Balanced and healthy nutrition is needed in order to avert adverse effects of poor eating practices. Children and adults often miss breakfast due to many reasons including lack of time. Evidence indicates that breakfast consumption is more beneficial than skipping breakfast following a long overnight fast. Its effect on cognitive function is still under debate. Our aim was to conduct a preliminary study to investigate breakfast habits and its effect of certain aspects of cognition in medical students in a university in Colombo, Sri Lanka. Methods: This study was a descriptive cross-sectional study. We assessed breakfast eating practices of final year medical students. Self-administered and questionnaire and trail making test for visual attention, task switching, speed of processing, and executive functioning were used as study instruments. Results: Results of 121 students were analysed. 55.4% skipped breakfast at least a day. Of them, 21% had their breakfast ≤3 days a week. Majority consumes a local meal based on rice or wheat flour. Commonest reason for missing the morning meal was lack of time (n=53, 79.1%). There was no significant difference was found in mean BMI and trail making score between breakfast skippers and non-skippers. Conclusions: Skipping breakfast among final year medical students is common. Lack of time due to busy schedules is highlighted as a possible reason for this. Skipping breakfast did not affect some aspects of cognition and body mass index significantly. A more comprehensive case control study among medical students, exploring neuro cognitive function related to breakfast habits is worthwhile.

P720 Use of proton pump inhibitors associated with a markedly increased risk of microscopic colitis

Background: Microscopic colitis (MC) is a chronic inflammatory bowel disease with unknown etiology. Proton pump inhibitor (PPI) use has been consistently linked to an increased risk of MC. The specific role of the different classes of PPI is unknown. Based on the nationwide Danish registries we explored the association between MC and use of PPI and in addition the effect of different classes of PPIs and dose-dependency. Secondly we explored the effect of concomitant use of PPI and NSAID. Methods: In a ten-year period (January 2004 to December 2013) we identified 10652 patients with a first-time recorded diagnosis of MC including 6254 (59%) with collagenous colitis (CC) and 4398 (41%) with lymphocytic colitis (LC). MC cases were identified via the Danish Pathology Registry. For each MC case, we sampled 10 population controls. Information on PPI use was obtained from the Danish Prescription Register. The analysis conformed to a case-control design, estimating the odds ratio (OR) for the association between PPI use and the risk MC using conditional logistic regression, while adjusting for potential confounders. Results: We found strong associations between current PPI use and both CC (adjusted OR [aOR] 8.75; 95% CI: 8.12–9.43) and LC (aOR 5.03; 95% CI: 4.61–5.49). This association was seen across all individual PPIs, however, the strongest association was seen with current use of lansoprazole, for both CC (aOR 20.10; 95% CI: 18.05–22.37) and LC (aOR 7.70; 95% CI: 6.79–8.73). When considering timing, ORs were highest for current use of PPI, while the association quickly diminished when considering recent or past exposure. When analyzing the prescribed strength of PPI, we found no apparent dose-response pattern. The use of NSAID was associated with a modest increased risk of CC (aOR 1.70; 95% CI: 1.55–1.87). However, the combination of NSAID and PPI and was associated with a higher risk for CC (aOR 9.72; 95% CI: 8.65–10.92) compared to the use of one of the drugs alone. Conclusions: In a large comprehensive case-control study based on nationwide Danish registries we found an increased risk of MC associated with the use of PPI and especially an increased risk with the use of lanzoprazole. The combination of NSAID and PPI and was associated with a high risk for CC.

Case-Control Pilot Study on Acute Diarrheal Disease in a Geographically Defined Pediatric Population in a Middle Income Country.

Introduction Acute diarrheal disease (ADD) is a common cause of morbidity and mortality in children under 5 years of age. Understanding of the etiology of ADD is lacking in most low and middle income countries because reference laboratories detect limited number of pathogens. The objective of this study was to determine the feasibility to conduct a comprehensive case-control study to survey diarrheal pathogens among children with and without moderate-to-severe ADD. Materials and Methods Microbiology and molecular-based techniques were used to detect viral, bacterial, and parasitic enteropathogens. The study was conducted in Bucaramanga, Colombia, after Institutional Review Board approval was obtained. Results Ninety children less than 5 years of age were recruited after a written informed consent was obtained from parents or guardians. Forty-five subjects served as cases with ADD and 45 as controls. Thirty-six subjects out of 90 (40.0%) were positive for at least one enteropathogen, that is, 20 (44.4%) cases and 16 (35.5%) controls. Conclusions The three most common enteric pathogens were enteroaggregative E. coli (10.0%), Norovirus (6.7%), and Salmonella spp. (5.6%). The E. coli pathogens were 18.8% of all infections making them the most frequent pathogens. Half of ADD cases were negative for any pathogens.

Investigating the Contribution of Peri-domestic Transmission to Risk of Zoonotic Malaria Infection in Humans.

BackgroundIn recent years, the primate malaria Plasmodium knowlesi has emerged in human populations throughout South East Asia, with the largest hotspot being in Sabah, Malaysian Borneo. Control efforts are hindered by limited knowledge of where and when people get exposed to mosquito vectors. It is assumed that exposure occurs primarily when people are working in forest areas, but the role of other potential exposure routes (including domestic or peri-domestic transmission) has not been thoroughly investigated.Methodology/Principal FindingsWe integrated entomological surveillance within a comprehensive case-control study occurring within a large hotspot of transmission in Sabah, Malaysia. Mosquitoes were collected at 28 pairs households composed of one where an occupant had a confirmed P. knowlesi infection within the preceding 3 weeks (“case”) and an associated “control” where no infection was reported. Human landing catches were conducted to measure the number and diversity of mosquitoes host seeking inside houses and in the surrounding peri-domestic (outdoors but around the household) areas. The predominant malaria vector species was Anopheles balabacensis, most of which were caught outdoors in the early evening (6pm - 9pm). It was significantly more abundant in the peri-domestic area than inside houses (5.5-fold), and also higher at case than control households (0.28±0.194 vs 0.17±0.127, p<0.001). Ten out of 641 An. balabacensis tested were positive for simian malaria parasites, but none for P. knowlesi.Conclusions/SignificanceThis study shows there is a possibility that humans can be exposed to P. knowlesi infection around their homes. The vector is highly exophagic and few were caught indoors indicating interventions using bednets inside households may have relatively little impact.

Paneth Cell in Adenomas of the Distal Colorectum Is Inversely Associated with Synchronous Advanced Adenoma and Carcinoma.

Recent studies have linked appearance of Paneth cells in colorectal adenomas to adenoma burden and male gender. However, the clinical importance of Paneth cells’ associations with synchronous advanced adenoma (AA) and colorectal carcinoma (CRC) is currently unclear. We performed a comprehensive case-control study using 1,900 colorectal adenomas including 785 from females, and 1,115 from males. We prospectively reviewed and recorded Paneth cell status in the colorectal adenomas consecutively collected between February 2014 and June 2015. Multivariable logistic regression analyses revealed that, in contrast to the adenomas without Paneth cells, the Paneth cell-containing adenomas at distal colorectum were inversely associated with presence of a synchronous AA or CRC (odds ratio [OR] 0.39, P = 0.046), whereas no statistical significance was reached for Paneth cell-containing proximal colorectal adenomas (P = 0.33). Synchronous AA and CRC were significantly associated with older age (60 + versus <60 years, OR 1.60, P = 0.002), male gender (OR 1.42, P = 0.021), and a history of AA or CRC (OR 2.31, P < 0.001). However, synchronous CRC was not associated with Paneth cell status, or a history of AA or CRC. Paneth cell presence in the adenomas of distal colorectum may be a negative indicator for synchronous AA and CRC, and seems to warrant further studies.

Prevalence of theHOXB13 G84E germline mutation in British men and correlation with prostate cancer risk, tumour characteristics and clinical outcomes

A rare recurrent missense variant in HOXB13 (rs138213197/G84E) was recently reported to be associated with hereditary prostate cancer. Population-based studies have established that, since the frequency of this single-nucleotide polymorphism (SNP) varies between geographic regions, the associated proportion of prostate cancer (PrCa) risk contribution is also highly variable by country. This is the largest comprehensive case-control study assessing the prevalence of the HOXB13 G84E variant to date and is the first in the UK population. We genotyped 8652 men diagnosed with PrCa within the UK Genetic Prostate Cancer Study (UKGPCS) and 5252 healthy men from the UK ProtecT study. HOXB13 G84E was identified in 0.5% of the healthy controls and 1.5% of the PrCa cases, and it was associated with a 2.93-fold increased risk of PrCa [95% confidence interval (CI) 1.94-4.59; P = 6.27 × 10(-8)]. The risk was even higher among men with family history of PrCa [odds ratio (OR) = 4.53, 95% CI 2.86-7.34; P = 3.1 × 10(-8)] and in young-onset PrCa (diagnosed up to the age of 55 years; OR = 3.11, 95% CI 1.98-5.00; P = 6.1 × 10(-7)). There was no significant association between Gleason Score, presenting prostate specific antigen, tumour-node-metastasis (TNM) stage or NCCN risk group and carrier status. HOXB13 G84E was not associated with overall or cancer-specific survival. We found that the polygenic PrCa risk score (PR score), calculated using the 71 known single-nucleotide polymorphisms (SNPs) associated with PrCa and the HOXB13 G84E variant act multiplicatively on PrCa risk. Based on the estimated prevalence and risk, this rare variant explains ∼1% of the familial risk of PrCa in the UK population. The clinical importance of HOXB13 G84E in PrCa management has not been established. This variant was found to have no effect on prognostic implications but could be used for stratifying screening, by identifying men at high risk. Prostate Testing for Cancer and Treatment (ProtecT): NCT02044172. Epidemiology and Molecular Genetics Studies (UKGPCS): NCT01737242.

Role of mtDNA Haplogroups in the Prevalence of Knee Osteoarthritis in a Southern Chinese Population

Mitochondrial DNA (mtDNA) has been implicated in various human degenerative diseases. However, the role of mtDNA in Osteoarthritis (OA) is less known. To investigate whether mtDNA haplogroups contribute to the prevalence of knee OA, we have carried out a comprehensive case-control study on 187 knee OA patients and 420 geographically matched controls in southern China. OA patients were classified on the Kellgren/Lawrence scale from two to four for the disease severity study and the data were analyzed by adjusting for age and sex. We found that patients with haplogroup G (OR = 3.834; 95% CI 1.139, 12.908; p = 0.03) and T16362C (OR = 1.715; 95% CI 1.174, 2.506; p = 0.005) exhibited an increased risk of OA occurrence. Furthermore, patients carrying haplogroup G had a higher severity progression of knee OA (OR = 10.870; 95% CI 1.307, 90.909; p = 0.007). On the other hand, people with haplogroup B/B4 (OR = 0.503; 95% CI 0.283, 0.893; p = 0.019)/(OR = 0.483; 95% CI 0.245, 0.954; p = 0.036) were less susceptible for OA occurrence. Interestingly, we found OA patients also exhibited a general increase in mtDNA content. Our study indicates that the mtDNA haplogroup plays a role in modulating OA development.

Abstract 2610: Association of polymorphisms and haplotypes in the insulin-like growth factor 1 receptor (IGF1R) gene with breast cancer in Korean women

Abstract Abstract The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase growth factor receptor that plays important roles in numerous cellular functions and signal transduction pathways. IGF1R may also play a role in the initiation and progression of breast cancer. However, studies of common variation in the IGF1R gene, involved in steroid hormone and IGF-1 metabolism, have yet to provide convincing evidence that such variants predict breast cancer risk. We genotyped 384 tagging single nucleotide polymorphisms (SNPs) in 1026 cases of breast cancer and 392 age-matched control in a population of Korean women. Of the 384 SNPs, fifty one SNPs in the IGF1R gene were examined for association with breast cancer in the study. All the SNPs investigated were in Hardy-Weinberg equilibrium. These SNPs tested were significantly associated with breast cancer risk, after correction for multiple comparisons stratified by adjusting for age at diagnosis, BMI, age at menarche, and age at first parturition. Among 51 IGF1R SNPs, three intron located SNPs (rs8032477, rs11635251, and rs12916884) with homozygous genotype (variant genotype) had increased risk of breast cancer (OR(CI 95%): 0.66(0.44-0.99), 0.54(0.37-0.80), and 0.59(0.37-0.94)). Seven of the 51 IGF1R SNPs were in LD and in one haplotype block, and were likely to be associated with breast cancer risk. Overall, this comprehensive case-control study found statistically significant associations between breast cancer risk and polymorphisms in IGF1R gene. Taking the status of the IGF1R polymorphism into consideration, our results may help in improving the ability to develop effective treatment modalities for those conditions in which IGF1R is involved. To the best of our knowledge, this study is the first to demonstrate the association between IGF1R polymorphisms with the risk of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2610. doi:1538-7445.AM2012-2610

Cancer type-specific modulation of mitochondrial haplogroups in breast, colorectal and thyroid cancer

BackgroundMitochondrial DNA (mtDNA) haplogroups and single nucleotide polymorphisms (mtSNP) have been shown to play a role in various human conditions including aging and some neurodegenerative diseases, metabolic diseases and cancer.MethodsTo investigate whether mtDNA haplogroups contribute to the occurrence of cancer in a specific Chinese population, we have carried out a comprehensive case-control study of mtDNA from large cohorts of patients with three common cancer types, namely, colorectal cancer (n = 108), thyroid cancer (n = 100) and breast cancer (n = 104), in Wenzhou, a southern Chinese city in the Zhejiang Province.ResultsWe found that patients with mtDNA haplogroup M exhibited an increased risk of breast cancer occurrence [OR = 1.77; 95% CI (1.03-3.07); P = 0.040], and that this risk was even more pronounced in a sub-haplogroup of M, D5 [OR = 3.11; 95%CI (1.07-9.06); p = 0.030]. In spite of this, in patients with breast cancer, haplogroup M was decreased in the metastatic group. On the other hand, our results also showed that haplogroup D4a was associated with an increased risk of thyroid cancer [OR = 3.00; 95%CI (1.09-8.29); p = 0.028]. However, no significant correlation has been detected between any mtDNA haplogroups and colorectal cancer occurrence.ConclusionOur investigation indicates that mitochondrial haplogroups could have a tissue-specific, population-specific and stage-specific role in modulating cancer development.