Dietary intakes of carotenoids and other nutrients in the risk of nasopharyngeal carcinoma: a case–control study in Italy

Background:

Dietary habits have been related to the risk of nasopharyngeal carcinoma (NPC), but information on a wide range of macro- and micronutrients is still lacking, particularly for low-incidence countries.

Methods:

We conducted a hospital-based case–control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity of 18–76 years of age. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Nutrients intake was assessed through a validated food-frequency questionnaire. Adjusted odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression.

Results:

Dietary intake of carotenoids were inversely related to NPC risk, notably carotene (OR for highest vs lowest quartile=0.46; 95% CI: 0.26–0.79), α-carotene (OR=0.57; 95% CI: 0.33–0.97), and β-carotene (OR=0.42; 95% CI: 0.24–0.75). Increased NPC risk was observed for elevate cholesterol intake (OR=1.85; 95% CI: 1.12–3.05).

Conclusion:

Study findings suggest a protective effect of carotenoids against NPC in a low-risk population, adding further support to a possible beneficial role of a diet rich in fruits and vegetables in cancers of the head and neck.     

Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression

Background:

Glutathione S-transferase mu 3 (GSTM3) has been proven to be downregulated in renal cell carcinoma (RCC). We aimed to characterise the role of GSTM3 and its genetic predisposition on the occurrence and postoperative prognosis of RCC.

Methods:

The effect of GSTM3 on RCC aggressiveness was examined using transfection and silencing methods. Glutathione S-transferase mu 3 expression in renal tissues was examined by immunohistochemistry. The associations of rs1332018 (A-63C) and rs7483 (V224I) polymorphisms with RCC risk were examined using 400 RCC patients and 802 healthy controls. The factors contributing to postoperative disease-specific survival of RCC patients were evaluated using the Cox proportional hazard model.

Results:

Glutathione S-transferase mu 3 silencing increased the invasion and anchorage-independent growth of RCC cell lines. rs1332018 (AC+CC vs AA), which correlated with low expression of GSTM3 in kidney, was associated with RCC risk (odds ratio, 1.446; 95% confidence interval (CI), 1.111–1.882). rs1332018 variants and low GSTM3 expression significantly predicted unfavourable postoperative survivals of RCC patients (P<0.05). rs1332018 variants independently predicted a poor prognosis (hazard ratio, 2.119; 95% CI, 1.043–4.307).

Conclusion:

Glutathione S-transferase mu 3 may function as a tumour suppressor in RCC. rs1332018 genetic variants predispose the host to downregulating GSTM3 expression in kidney, facilitate carcinogenesis, and predict an unfavourable postoperative prognosis of RCC.     

Long-term dietary sodium,potassium and fluid intake; exploring potential novel risk factors for renal cell cancer in the Netherlands Cohort Study on diet and cancer

Background:

As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC.

Methods:

The Netherlands Cohort Study (NLCS) with case-cohort design included 120 852 participants aged 55–69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses.

Results:

Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02).

Conclusion:

Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.     

Sex and the clinical value of body mass index in patients with clear cell renal cell carcinoma

Background:

An increased body mass index (BMI) is significantly associated with favourable prognosis in renal cell carcinoma (RCC). This study investigated the associations among sex, BMI, and prognosis in clear cell RCC patients.

Methods:

We retrospectively analysed 435 patients with clear cell RCC who underwent a nephrectomy. The associations among sex, BMI, clinicopathologic factors, and cancer-specific survival (CSS) were analysed.

Results:

As a continuous variable, increased BMI was associated with higher CSS rate by univariate analysis in the whole population (hazard ratio, 0.888 per kg m^–2; 95% confidence interval, 0.803–0.982; P=0.021). A sub-population analysis by sex demonstrated that BMI was significantly associated with CSS in men (P=0.004) but not in women (P=0.725). Multivariate analysis revealed BMI to be an independent predictor of CSS in only men.

Conclusion:

Body mass index was significantly associated with clear cell RCC prognosis. However, the clinical value of BMI may be different between men and women.     

Cholecystectomy,gallstones, tonsillectomy,and pancreatic cancer risk: a population-based case-control study in minnesota

Background:

Associations between medical conditions and pancreatic cancer risk are controversial and are thus evaluated in a study conducted during 1994–1998 in Minnesota.

Methods:

Cases (n=215) were ascertained from hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic. Controls (n=676) were randomly selected from the general population and frequency matched to cases by age and sex. The history of medical conditions was gathered with a questionnaire during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression.

Results:

After adjustment for confounders, subjects who had cholecystectomy or gallstones experienced a significantly higher risk of pancreatic cancer than those who did not (OR (95% CI): 2.11 (1.32–3.35) for cholecystectomy and 1.97 (1.23–3.12) for gallstones), whereas opposite results were observed for tonsillectomy (0.67 (0.48–0.94)). Increased risk associated with cholecystectomy was the greatest when it occurred ⩽2 years before the cancer diagnosis (5.93 (2.36–15.7)) but remained statistically significant when that interval was ⩾20 years (2.27 (1.16–4.32)).

Conclusions:

Cholecystectomy, gallstones, and tonsillectomy were associated with an altered risk of pancreatic cancer. Our study suggests that cholecystectomy increased risk but reverse causality may partially account for high risk associated with recent cholecystectomy.     

Dietary intake of nitrate and nitrite and risk of renal cell carcinoma in the NIH-AARP Diet and Health Study

Background:

Nitrate and nitrite are present in many foods and are precursors of N-nitroso compounds, known animal carcinogens and potential human carcinogens. We prospectively investigated the association between nitrate and nitrite intake from dietary sources and risk of renal cell carcinoma (RCC) overall and clear cell and papillary histological subtypes in the NIH-AARP Diet and Health Study.

Methods:

Nitrate and nitrite intakes were estimated from a 124-item food frequency questionnaire. Over a mean follow-up of 9 years, we identified 1816 RCC cases (n=498, clear cell; n=115, papillary cell) among 491 841 participants. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

Individuals in the highest quintile of nitrite intake from animal sources compared with those in the lowest quintile, had an increased risk of total RCC and clear cell subtype (HR=1.28, 95% CI, 1.10–1.49 and HR=1.68, 95% CI, 1.25–2.27, respectively). Nitrite from processed meats and other animal sources were associated with increased clear cell adenocarcinoma risk (HR=1.33, 95% CI, 1.01–1.76 and HR=1.78, 95% CI, 1.34–2.36, respectively). We found no association for nitrite intake from plant sources or nitrate intake overall.

Conclusion:

Our findings suggest that nitrite from animal sources may increase the risk of RCC, particularly clear cell adenocarcinomas.     

The impact of aspirin,statins and ACE-inhibitors on the presentation of colorectal neoplasia in a colorectal cancer screening programme

Background:

There is increasing evidence that aspirin, statins and ACE-inhibitors can reduce the incidence of colorectal cancer. The aim of the present study was to assess the impact of these medications on an individual''s risk of advanced neoplasia in a colorectal cancer screening programme.

Methods:

A prospectively maintained database of the first round of screening in our geographical area was analysed. The outcome measure was advanced neoplasia (cancer or intermediate or high risk adenomata).

Results:

Of the 4188 individuals who underwent colonoscopy following a positive occult blood stool test, colorectal pathology was present in 3043(73%). Of the 3043 patients with colorectal pathology, 1704(56%) had advanced neoplasia. Patients with advanced neoplasia were more likely to be older (OR 1.38; 95% CI 1.19–1.59) and male (OR 1.66; 95% CI 1.43–1.94) (both P<0.001). In contrast, those on aspirin (OR 0.68; 95% CI 0.56–0.83), statins (OR 0.65; 95% CI 0.55–0.78) or ACE inhibitors (OR 0.71; 95% CI 0.57–0.89) were less likely to have advanced neoplasia at colonoscopy (all P<0.05).

Conclusion:

In patients undergoing colonoscopy following a positive occult blood stool test with documented evidence of aspirin, statin or ACE-inhibitor usage, advanced neoplasia is less likely, suggesting that the usage of these medications may have a chemopreventative effect.     

Skin cancers associated with autoimmune conditions among elderly adults

Background:

Immunosuppression is a risk factor for certain skin cancers. Autoimmune conditions can involve the skin, and may involve immunosuppressive therapies.

Methods:

We conducted a population-based case–control study among elderly US adults using Surveillance, Epidemiology, and End Results-Medicare-linked data of 44 613 skin cancer cases and 178 452 frequency-matched controls. Medicare claims identified autoimmune conditions. Adjusted odds ratios (ORs) compared prevalence in cases and controls.

Results:

The most frequent autoimmune condition was rheumatoid arthritis (2.29%), which was associated with slightly increased risk of Merkel cell carcinoma (N=1977; OR (95%CI): 1.39 (1.10–1.74)). Risk of cutaneous non-Hodgkin''s lymphoma (N=2652) was increased with psoriasis (OR (95%CI): 3.20 (2.62–3.92)). Risk of Kaposi''s sarcoma (N=773) was elevated with ulcerative colitis (OR (95%CI): 2.76 (1.42–5.39)), and risk of other sarcomas (N=1324) was elevated with Graves disease (2.62 (1.30–5.31)).

Conclusions:

These findings suggest that immune disturbances in the skin, arising from autoimmune conditions or their treatment, promote development of skin cancer.     

The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records

Background:

The risk of cancer with hypercalcaemia in primary care is unknown.

Methods:

This was a cohort study using calcium results in patients aged ⩾40 years in a primary care electronic data set. Diagnoses of cancer in the following year were identified.

Results:

Participants (54 267) had calcium results: 1674 (3%) were ⩾2.6 mmol l⁻¹. Hypercalcaemia was strongly associated with cancer, especially in males: OR 2.92, 95% CI 2.17–3.93, P=<0.001; positive predictive value (PPV) 11.5% females: OR 1.86, 95% CI 1.39–2.50, P<0.001: PPV 4.1%.

Conclusions:

Hypercalcaemia is strongly associated with cancer in primary care, with men at most risk, despite hypercalcaemia being more common in women.     

The influence of cytokine gene polymorphisms on the risk of developing gastric cancer in patients with Helicobacter pylori infection

Background

Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population.

Patients and methods.

In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1β, IL-1ra, TNF-α, TLR-4) in all subjects.

Results

We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233–1.329) and for chronic gastritis 2.073 (95% CI: 1.005–4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583–9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583–3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626–3.139). Other alleles had OR less than 1.

Conclusions

We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation.     

Sex-specific exposure prevalence of established risk factors for oesophageal adenocarcinoma

Background:

There is an unexplained male predominance in the incidence of oesophageal adenocarcinoma, and the sex-specific distribution of its risk factors in the general population is not known.

Methods:

A random sample of Swedish citizens aged 40–79 years completed a questionnaire for assessment of the prevalence of five risk factors for oesophageal adenocarcinoma: reflux symptoms, body mass index, tobacco smoking habits, socioeconomic status, and use of non-steroidal anti-inflammatory drugs (NSAIDs). Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the association of these risk factors, separately and combined, with male sex, with women as reference.

Results:

Among 6969 invited people, 4906 (70.4%) completed the questionnaire. Adjusted prevalence estimates showed a negative association with male sex with regard to reflux disease (OR=0.70, 95% CI=0.58–0.84), whereas overweight (OR=1.98, 95% CI=1.72–2.27) and obesity (OR=1.22, 95% CI=1.01–1.47), previous smoking (OR=1.50, 95% CI=1.30–1.72), and no NSAID use (OR=1.35, 95% CI=1.15–1.49) were positively associated.

Conclusions:

Exposure to some but not all established risk factors for oesophageal adenocarcinoma seems to be more common in men than in women, but the differences are small and unlikely to explain the male predominance of this tumour.     

Dietary fat intake and risk of epithelial ovarian cancer by tumour histology

Background:

Studies of fat intake and epithelial ovarian cancer (EOC) risk have reported inconsistent findings, hence we hypothesised that associations may vary by histologic subtype.

Methods:

We evaluated fat intake in a New England case–control study including 1872 cases and 1978 population-based controls (1992–2008). Epithelial ovarian cancer risk factors and diet were assessed using a food frequency questionnaire at enrolment. Logistic regression was used to estimate associations between fat intake and EOC risk and polytomous logistic regression was used to test whether associations varied by histologic subtype.

Results:

We observed a decreased risk of EOC when comparing the highest vs lowest quartiles of intake of omega-3 (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.66–0.96, P-trend=0.01) and omega-6 (OR=0.77, 95% CI 0.64–0.94, P-trend=0.02) and an increased risk with high consumption of trans fat (OR=1.30, 95% CI 1.08–1.57, P-trend=0.002). There was no significant heterogeneity by tumour histologic subtype; however, we observed a strong decreased risk for endometrioid invasive tumours with high intake of omega-3 (quartile (Q) 4 vs Q1, OR=0.58, 95% CI 0.41–0.82, P-trend=0.003).

Conclusions:

These findings suggest that higher intake of omega-3 may be protective for EOC overall and endometrioid tumours in particular, whereas greater consumption of trans fat may increase risk of EOC overall.     

Risk of bladder cancer in renal transplant recipients: a meta-analysis

Background:

Renal transplantation has been associated with a significantly increased risk of developing cancers during long-term follow-up, but for bladder cancer, this risk is less clear. We therefore performed a meta-analysis to determine whether bladder cancer risk in renal transplant recipients was increased.

Methods:

Eligible studies were identified through searches of PubMed and other public resources. Random-effects meta-analyses were used to pool overall estimates for standardised incidence ratios (SIRs). Heterogeneity test, sensitivity analysis, and assessment of publishing bias were also performed.

Results:

We identified a 3.18-fold higher SIR (95% confidence intervals (CI): 1.34–7.53, P=0.008) of bladder cancer in patients following renal transplantation compared with the general population, based on data from 79 988 patients with a total follow-up of 308 458 patient-years. When stratified by ethnicity, the SIRs for bladder cancer were 2.00 (95% CI: 1.51–2.65, P=0.001) and 14.74 (95% CI: 3.66–59.35, P<0.001) between European and Asian renal transplant recipients, respectively.

Conclusions:

Our study demonstrated that the risk of developing bladder cancer in transplant populations was increased. Such association suggests that physicians should be more vigilant in checking for bladder cancer in transplantation recipient population.     

Validation of the pre-treatment neutrophil–lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients

Background:

The neutrophil–lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Several studies suggest a negative impact of increased NLR for patient''s survival in different types of cancer. However, previous findings from small-scale studies revealed conflicting results about its prognostic significance with regard to different clinical end points in non-metastatic renal cell carcinoma (RCC) patients. Therefore, the aim of our study was the validation of the prognostic significance of NLR in a large cohort of RCC patients.

Methods:

Data from 678 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single centre, were evaluated retrospectively. Cancer-specific, metastasis-free, as well as overall survival (OS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of NLR, multivariate Cox regression models were applied for all three different end points. Influence of the NLR on the predictive accuracy of the Leibovich prognosis score was determined by Harrell''s concordance index.

Results:

Multivariate analysis identified increased NLR as an independent prognostic factor for overall (hazard ratio (HR)=1.59, 95% confidence interval (CI)=1.10–2.31, P=0.014), but not for cancer-specific (HR=1.59, 95% CI=0.84–2.99, P=0.148), nor for metastasis-free survival (HR=1.39, 95% CI=0.85–2.28, P=0.184). The estimated concordance index was 0.79 using the Leibovich risk score and 0.81 when NLR was added.

Conclusion:

Regarding patients'' OS, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. Adding the NLR to well-established prognostic models such as the Leibovich prognosis score might improve their predictive ability.     

High plasma fibrinogen level represents an independent negative prognostic factor regarding cancer-specific,metastasis-free,as well as overall survival in a European cohort of non-metastatic renal cell carcinoma patients

Background:

In recent years, plasma fibrinogen has been ascribed an important role in the pathophysiology of tumour cell invasion and metastases. A relatively small-scale study has indicated that plasma fibrinogen levels may serve as a prognostic factor for predicting clinical outcomes in non-metastatic renal cell carcinoma (RCC) patients.

Methods:

Data from 994 consecutive non-metastatic RCC patients, operated between 2000 and 2010 at a single, tertiary academic centre, were evaluated. Analyses of plasma fibrinogen levels were performed one day before the surgical interventions. Patients were categorised using a cut-off value of 466 mg dl⁻¹ according to a calculation by receiver-operating curve analysis. Cancer-specific (CSS), metastasis-free (MFS), as well as overall survival (OS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, a multivariable Cox regression model was performed for all three different endpoints.

Results:

High plasma fibrinogen levels were associated with various well-established prognostic factors, including age, advanced tumour stage, tumour grade and histologic tumour necrosis (all P<0.05). Furthermore, in multivariable analysis, a high plasma fibrinogen level was statistically significantly associated with a poor outcome for patients'' CSS (hazard ratio (HR): 2.47, 95% confidence interval (CI): 1.49–4.11, P<0.001), MFS (HR: 2.15, 95% CI: 1.44–3.22, P<0.001) and OS (HR: 2.48, 95% CI: 1.80–3.40, P<0.001).

Conclusion:

A high plasma fibrinogen level seems to represent a strong and independent negative prognostic factor regarding CSS, MFS and OS in non-metastatic RCC patients. Thus, this easily determinable laboratory value should be considered as an additional prognostic factor for RCC patients'' individual risk assessment.     

Brain metastasis in renal cancer patients: metastatic pattern,tumour-associated macrophages and chemokine/chemoreceptor expression

Background:

The mechanisms of brain metastasis in renal cell cancer (RCC) patients are poorly understood. Chemokine and chemokine receptor expression may contribute to the predilection of RCC for brain metastasis by recruitment of monocytes/macrophages and by control or induction of vascular permeability of the blood–brain barrier.

Methods:

Frequency and patterns of brain metastasis were determined in 246 patients with metastatic RCC at autopsy. Expression of CXCR4, CCL7 (MCP-3), CCR2 and CD68⁺ tumour-associated macrophages (TAMs) were analysed in a separate series of 333 primary RCC and in 48 brain metastases using immunohistochemistry.

Results:

Fifteen percent of 246 patients with metastasising RCC had brain metastasis. High CXCR4 expression levels were found in primary RCC and brain metastases (85.7% and 91.7%, respectively). CCR2 (52.1%) and CCL7 expression (75%) in cancer cells of brain metastases was more frequent compared with primary tumours (15.5% and 16.7%, respectively; P<0.0001 each). The density of CD68⁺ TAMs was similar in primary RCC and brain metastases. However, TAMs were more frequently CCR2-positive in brain metastases than in primary RCC (P<0.001).

Conclusion:

Our data demonstrate that the monocyte-specific chemokine CCL7 and its receptor CCR2 are expressed in tumour cells of RCC. We conclude that monocyte recruitment by CCR2 contributes to brain metastasis of RCC.     

Cardiovascular sequelae in long-term survivors of young peoples' cancer: a linked cohort study

Background:

We aimed to define the incidence and risk of cardiovascular late effects (LEs) identified from inpatient hospital episode statistics (HES) among long-term survivors of cancer in young people by age at diagnosis (0–14 and 15–29 years).

Methods:

Records from the Yorkshire Specialist Register of Cancer in Children and Young People (1991–2006) were linked to inpatient HES data (1996–2011) to assess rates of cardiovascular LEs. Rates were compared with the general population in Yorkshire using age–sex-matched HES records for the entire region.

Results:

Of 3247 survivors of cancer, 3.6% had at least one cardiovascular LE. Overall, cardiovascular hospitalisations for the childhood cohort were threefold higher compared with the general population, but did not differ for young adults. For young adults, increased rates were limited to pericardial disease, cardiomyopathy and heart failure, pulmonary heart disease, hypertension and conduction disorders.

Conclusions:

Survivors of childhood and young adult cancer remain at increased risk of cardiovascular LEs compared with the general population.     

Smoking and adult glioma: a population-based case-control study in China

Background

Smoking increases the risk of numerous cancers; however, an association of smoking with adult gliomas has not been found in a population.

Methods

This case-control study included 4556 glioma cases (ICD-9 code 191.0–191.9) aged ≥30 years and 9112 controls from a national survey of smoking and mortality in China in 1989–1991. Controls from 325 255 surviving spouses of all-cause deaths were randomly assigned to cases in each of 103 areas according to sex and age groups at a ratio of 2:1. Smoking information was ascertained retrospectively by interviewing surviving spouses.

Results

After adjustment for confounders, smoking increased the risk of glioma deaths by 11% (odds ratio [OR] = 1.11; 95% confidence interval [CI]: 1.03–1.21). Compared with non-smokers; the increased risk was 9% (OR = 1.09; 95% CI: 0.99–1.20) in men and 16% (OR = 1.16; 95% CI: 1.00–1.36) in women. The risk increased with age and doses. For individuals aged ≥50 years, smoking was associated with higher risk of glioma death by 25% (OR = 1.25; 95% CI: 1.15–1.38); this increased risk for smokers who smoked ≥20 cigarettes daily for ≥30 years was 53% (OR = 1.53; 95% CI: 1.34–1.74). There were similar findings in both men and women and with either pathology-based or non–pathology-based comparisons.

Conclusions

This study indicates that smoking is associated with glioma deaths in the Chinese population. Long-term heavy smoking could be a factor for risk stratification in individuals attending brain tumor clinics.     

Quantitative assessment of the influence of EPHX1 gene polymorphisms and cancer risk: a meta-analysis with 94,213 subjects

Purpose

Previous studies investigating the association between EPHX1 polymorphisms (Tyr113His and His139Arg) and cancer risk have yielded inconsistent results. This meta-analysis was performed to derive a more precise estimation of relationship between two EPHX1 polymorphisms and risk of different types of cancer.

Methods

Data were extracted from relevant studies detected by a systematic literature search. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association between EPHX1 polymorphisms and cancer risk.

Results

This meta-analysis carefully collected 99 studies on these two polymorphisms and cancer risk published up to March 2014, consisting of 45 studies (20,091 cases and 27,396 controls) for Tyr113His and 54 studies (19,437 cases and 27,289 controls) for His139Arg. The results in overall population did not show any significant association between these two polymorphisms and cancer risk for all genetic models. However, EPHX1 Tyr113His homozygote individuals have a significantly increased risk of cancer among Asians (homozygote model: OR =1.46, 95% CI=1.05–2.03; recessive model: OR =1.39, 95% CI =1.10–1.76) and mixed population (homozygote model: OR =1.17, 95% CI =1.02–1.34; recessive model: OR =1.17, 95% CI =1.02–1.33), but not Caucasians.

Conclusion

His/His genotype of EPHX1 Tyr113His polymorphism is a risk factor for developing caner for Asian and mixed population, while no evidence was found for the association between the EPHX1 His139Arg polymorphism and increased cancer risk.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-014-0082-9) contains supplementary material, which is available to authorized users.     

The NQO1 polymorphism C609T (Pro187Ser) and cancer susceptibility: a comprehensive meta-analysis

Background:

Evidence is increasingly emerging about multiple roles for the NAD(P)H quinone oxidoreductase 1 enzyme in cancer. The C609T (rs1800566, Pro187Ser) null polymorphism of the NQO1 gene contributes significantly to the variation in enzymatic activity across different populations. NQO1 C609T polymorphism was thoroughly investigated with respect to cancer susceptibility. The results were inconsistent partly due to low sample sizes. The aim of the present work was to perform a meta-analysis to assess association for all common cancer sites separately and in combination.

Methods:

Our meta-analysis involved 92 studies including 21 178 cases and 25 157 controls. Statistical analysis involved individual cancer sites and the combined cancer risk. Association was tested under different genetic models.

Results:

We found a statistically significant association between the variant T allele and overall cancer risk in the worldwide population (for the TT vs CC model, OR=1.18 (1.07–1.31), P=0.002, I²=36%). Stratified analysis revealed that this association was largely attributed to the Caucasian ethnicity (for the TT vs CC model, OR=1.28 (1.12–1.46), P=0.0002, I²=1%). Stratification by tumour site showed significant association for bladder cancer in the worldwide population (for the TT vs CC model, OR=1.70 (1.17–2.46), P=0.005, I²=0%), and in the Asian population (for the TT vs CC model, 1.48 (1.14–1.93), P=0.003, I²=16%). Positive association was also found for gastric cancer in the worldwide population under the dominant model (OR=1.34 (1.09–1.65), P=0.006, I²=15%).

Conclusion:

Our results indicate that the C609T polymorphism of the NQO1 gene is an important genetic risk factor in cancer.