The impact of PSA and digital rectal examination on the risk of prostate cancer specific mortality in men with a PSA level <2.5 ng/ml

IntroductionIt is unknown whether a normal range, diagnostic serum prostate specific antigen (PSA) level's influence on prostate cancer specific mortality (PCSM) is dependent upon digital rectal examination (DRE) findings.MethodsBetween 2004 and 2007, 9081 men diagnosed with non-palpable (T1c, N = 1710) or palpable (T2–T4, N = 7371) and non-metastatic prostate cancer (PC) were identified from surveillance, epidemiology, and end results data, selected based on pre-treatment PSA < 2.5 ng/ml. A multivariable competing risks regression model evaluated whether DRE findings interacted with PSA level in predicting risk of PCSM.ResultsAfter median follow-up of 2.83 years, 118 of 548 deaths (21.5%) were due to PC. Increasing diagnostic PSA was associated with increased risk of PCSM (AHR = 3.52; 95% CI: 1.25–9.89; P = .017) in men with T1c, Gleason score 7–10 PC, but decreased PCSM risk (AHR = 0.66; 95% CI: 0.52–0.83; P < .001) for men with T2–T4 PC and any Gleason score.DiscussionFor men with diagnostic PSA level <2.5 ng/ml and palpable PC, risk of early PCSM increases by 34% for a 1 point decrease in PSA from 2. This suggests the existence of clinically detectable, low PSA secreting disease with an elevated risk of early PCSM, highlighting the importance of the DRE in men with PC and normal range, diagnostic PSA.     

MGMT Ile143Val polymorphism,dietary factors and the risk of breast,colorectal and prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study

O⁶-Methylguanine-DNA methyltransferase (MGMT) repairs DNA damage caused by alkylating agents including N-nitroso compounds from diet. MGMT Ile143Val polymorphism may lead to less DNA damage repair and increased cancer risk depending on the environmental exposures. We investigated interactions between dietary factors and the MGMT Ile143Val polymorphism in relation to breast, colorectal and prostate cancer risk. There were 276/1498, 273/2984 and 312/1486 cases/controls for the breast, colorectal and prostate cancer studies respectively; all nested within the EPIC-Norfolk study, a prospective cohort of approximately 25,000 men and women aged 40–79. Baseline 7-day food diary data were collected for dietary assessment. MGMT Ile143Val polymorphism was not overall associated with breast, colorectal and prostate cancer risk. There was a significant interaction between this polymorphism and intake of red and processed meat on colorectal cancer risk (P_interaction = 0.04) suggesting an increased risk among carriers of the variant genotype compared to the MGMT Ile143Ile common genotype. A lower colorectal cancer risk was seen with higher intake of vitamin E and carotene among the variant genotype group but not in the common genotype group (P_interaction = 0.009 and P_interaction = 0.005 for vitamin E and carotene, respectively). A higher prostate cancer risk was seen with higher alcohol intake among the variant genotype (OR = 2.08, 95% CI = 1.21–3.57, P_interaction = 0.0009) compared to the common genotype with lower alcohol intake. In this UK population, the MGMT Ile143Val polymorphism was not overall associated with breast, colorectal and prostate cancer risk. There was evidence for this polymorphism playing a role in modulating the risk of prostate cancer in presence of alcohol. For colorectal cancer, the MGMT Ile143Val polymorphism may confer increased or decreased risk depending on the dietary exposure.     

Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men

Background: Catechol-estrogen metabolites can induce carcinogenesis by acting as endogenous tumor initiators. Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is a main metabolic pathway of estrogen detoxification in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphisms and prostate cancer risk. Patients and methods: 129 patients with prostate cancer and 260 healthy controls were included in our study. A(TA)TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. Results: No significant differences were observed between the cancer group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P > 0.05). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA(7) vs TA(6)/TA(7) + TA(6)/TA(6)) (P = 0.18). In addition, no association was revealed between UGT1A1 genotype distribution and Gleason score (P = 0.55). Conclusion: Our data suggest that the TA repeat polymorphism of UGT1A1 gene does not seem to alter prostate cancer risk susceptibility in Caucasian men.     

Polymorphisms of glutathione-S-transferase M1 and T1 and prostate cancer risk in a Tunisian population

Several genes involved in the metabolism of carcinogenesis have been found to be polymorphic in the human population, and specific alleles are associated with increase risk of cancer of various sites. This study is focused on the polymorphic enzymes glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) that involved in the detoxification of many xenobiotics involved in the etiology of prostate cancer. Objective. To evaluate whether GSTM1 and/or GSTT1 contribute to prostate cancer (CaP) etiology, we studied 110 incident CaP cases and 122 controls. Results. The probability of having CaP was increased in men who had homozygous deleted (non-functional) genotypes at GSTT1 (OR = 2.17; 95% CI = 1–3.79) but not GSTM1 (OR = 0.89; 95% CI = 0.66–1.88). Hence, individuals lacking the GSTT1 gene are at approximately twofold higher risk of developing prostate cancer in comparison with individuals with at least one active allele in the GSTT1 locus. Conclusion. These results suggest that GSTT1 is associated with CaP risk. The effect of smoking associated with the GSTT10/0 genotype was not found to affect the risk of prostate cancer.     

Comparable amounts of sex steroids are made outside the gonads in men and women: Strong lesson for hormone therapy of prostate and breast cancer

The objective of this study was comparison of circulating androgens and their metabolites as well as estrogens measured for the first time by a validated mass spectrometry technology in 60–80-year-old men and women of comparable age.Castration in men (n = 34) reduces the total androgen pool by only about 60% as indicated by the decrease in the serum levels of the glucuronide metabolites of androgens compared to intact men (n = 1302). Such data are in agreement with the 50 to 75% decrease in intraprostatic dihydrotestosterone (DHT) concentration after castration. Most interestingly, the same amounts of androgens and estrogens are found in postmenopausal women (n = 369) and castrated men of comparable age.The most significant therapeutic implication of these findings is the absolute need to add a pure (nonsteroidal) antiandrogen to castration in men with prostate cancer in order to block the action of the 25 to 50% DHT left in the prostate after castration. Not adding an antiandrogen to castration in men treated for prostate cancer is equivalent to not prescribing a blocker of estrogens in women suffering from breast cancer because they are postmenopausal and have low circulating estradiol.     

Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio Ischaemic Heart Disease Risk Factor Study

ObjectivesZinc may play a role in the development of type 2 diabetes (T2D), because it is involved in antioxidant and anti-inflammatory activities. However, the role of zinc in the etiology of T2D has been poorly investigated. This study was conducted to study the association of serum zinc on T2D risk in middle-aged and older Finnish men.MethodsThis was a 20-year prospective follow-up study on 2220 Finnish men from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) who were 42 to 60 years old at baseline in 1984–1989. The main outcome was incident T2D. Serum zinc, body mass index (BMI), fasting blood glucose (FBG), serum insulin, C-reactive protein (CRP) and, in a subset of 751 participants, insulin-like growth factor-binding protein-1 (IGFBP-1), were measured. Also, the homeostatic model assessment (HOMA) was used to quantify insulin resistance (HOMA-IR), beta-cell function (HOMA-β) and insulin sensitivity (HOMA-IS).ResultsAt baseline, serum zinc was associated with higher BMI, serum insulin, HOMA-IR, HOMA-β and IGFBP-1 and lower HOMA-IS. During the average follow-up of 19.3 years, 416 men developed T2D. Men in the highest quartile of serum zinc had 60% higher risk (95% CI 20–113%; P-trend < 0.001) for incident T2D compared with the men in the lowest quartile, after multivariate adjustments. This association was attenuated after adjustment for BMI (HR = 1.39, 95% CI 1.04–1.85; P-trend = 0.013) or HOMA-IS (HR = 1.38, 95% CI 1.04–1.83; P-trend = 0.015), whereas adjustment for the other factors had only modest impact on the association.ConclusionHigher serum zinc was associated with higher risk of T2D; effects of zinc on BMI and insulin sensitivity may partly explain the association. Further prospective studies are warranted to confirm our results and explore potential mechanisms.     

Consumption of fruits,vegetables, and seaweeds (sea vegetables) and pancreatic cancer risk: The Ohsaki Cohort Study

Studies on the effects of consumption of fruits, vegetables, and seaweeds on the incidence of pancreatic cancer are not conclusive. We examined the association (if any) between the consumption of fruits, vegetables, and seaweeds and the risk of pancreatic cancer in Japan. Data from 32,859 participants registered in the Ohsaki National Health Insurance Cohort Study who were 40–79 years old and free of cancer at baseline were analyzed. Consumption of fruits, vegetables, and seaweeds was assessed at baseline using a self-administered food frequency questionnaire (containing 40 items). Incidences of pancreatic cancer were identified by computer linkage with the Miyagi Prefectural Cancer Registry. During 11 years of follow-up, 137 pancreatic cancers (67 men and 70 women) were identified. The hazard ratios (95% confidence interval) of pancreatic cancer risk for the highest versus the lowest tertile were 0.82 (0.40–1.68, trend P = 0.57) in men and 0.64 (0.35–1.20, trend P = 0.22) in women for total consumption of fruits, 0.89 (0.46–1.73, trend P = 0.76) in men and 0.67 (0.33–1.35, trend P = 0.23) in women for total consumption of vegetables, and 0.92 (0.46–1.84, trend P = 0.81) in men for consumption of seaweeds (results for the consumption of seaweeds in women were not analyzed because of poor reliability), respectively. Total consumption of fruits, vegetables, and seaweeds was not associated with a reduced risk of pancreatic cancer.     

Cancer mortality and occupational exposure to aromatic amines and inhalable aerosols in rubber tire manufacturing in Poland

Aim: Most data on carcinogenic risk in the rubber industry are based on data from Western countries. This study assessed cancer risks in a retrospective cohort in a Polish tire manufacturing plant, relying on quantified exposure to inhalable aerosols and aromatic amines instead of job titles or external comparisons. Methods: Cumulative exposure for all exposures was assigned to cohort members based on estimates from a company-specific JEM. Cancer risks associated with cumulative exposure adjusted for co-exposures, gender and year of birth were calculated. Results: Exposure levels were higher for women than for men. Aromatic amine exposure was significantly associated with increased urinary bladder cancer risk (RR = 7.32–8.27), depending on exposure level, and prostate cancer at low levels only (RR = 5.86). In women, increased risks were found for all cancers (RR = 2.50) and of the digestive organs and peritoneum (RR = 4.54) at low level only, while an exposure-response association with breast cancer risk was found. Inhalable aerosol exposure was associated with cancers of the liver and intrahepatic bile ducts in a dose-dependent manner, while dose-dependent reduced risks were found for respiratory cancers (most notably the larynx) and cancer of the colon. Conclusions: Increased risks for specific cancer sites in this rubber plant were similar to Western Europe and the US. However, several cancer risks were gender-specific which could relate to higher exposure levels in women or to differences in exposures to chemicals not assessed in this study.     

Smoking and other risk factors for pancreatic cancer: A cohort study in men in Lithuania

Background: Cancer of the pancreas is a relatively rare, but highly fatal cancer worldwide. Cigarette smoking has been recognized as an important risk factor, but the relation to other potential determinants is still inconsistent. We investigated the association between different lifestyle, biological and anthropometric factors and the risk of pancreatic cancer in a prospective population-based cohort study from Kaunas, Lithuania. Methods: Our study included 7132 urban men initially free from any diagnosed cancer, followed for up to 30 years. 77 incident cases of pancreatic cancer were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Results: Compared to never smokers, current smokers had a significantly increased risk of pancreatic cancer, HR was 1.79 (95% CI 1.03–3.09) after adjustment for age, body mass index, education and alcohol consumption. Among smokers, a significant association with higher smoking intensity was shown (≥20 cigarettes/day: HR = 2.60; 95% CI 1.42–4.76, P_trend = 0.046). We also observed a significantly increased risk for ≥30 pack-years of smoking (HR = 2.24; 95% CI 1.12–4.49, P_trend = 0.16) and for age at starting smoking <18 years (HR = 2.29; 95% CI 1.11–4.70, P_trend = 0.43) as compared to never smokers. Alcohol consumption, body mass index and total cholesterol level were not significantly associated with pancreatic cancer. Conclusions: Smoking significantly increases pancreatic cancer incidence and its high prevalence in Lithuania may partly explain high incidence of the disease. No convincing evidence was found that alcohol consumption, body mass index or serum cholesterol level were associated with pancreatic cancer risk, although the assessment was limited by the lack of statistical power.     

10-Year risk of colorectal cancer: Development and validation of a prediction model in middle-aged Japanese men

Background: To estimate an individual's probability of developing colorectal cancer (CRC) may aid health professionals and individuals in improving lifestyle behaviors or deciding the screening regimens. As fewer studies on cancer risk prediction were seen so far, we initially developed an assessment tool with synthesizing key information from a variety of CRC risk factors through a large population-based cohort study. Method: The prediction model was derived from 28,115 men in the Japan Public Health Center-based (JPHC) Prospective Study Cohort II (follow-up: 1993–2005), with risk factors selected by Cox proportion hazard regression. 18,256 men in the JPHC Study Cohort I (follow-up: 1995–2005) were used to evaluate the model's performance. Results: 543 and 398 CRCs were diagnosed during the follow-up period in Cohorts II and I, respectively. The prediction model, including age, BMI, alcohol consumption, smoking status, and the daily physical activity level, showed modest discrimination ability for CRC (C = 0.70; 95% confidential interval, 0.68–0.72) in Cohort II and well calibrated in Cohort I (Hosmer–Lemeshow χ² = 14.2, P = 0.08). Conclusion: The 10-year CRC risk prediction model may be used to estimate CRC risk in Japanese men. It may also play a role in the promotion of CRC prevention strategies.     

Male infertility: Decreased levels of selenium,zinc and antioxidants

In this study, we aimed to compare the level of zinc, selenium, glutathione peroxidase activity and antioxidant status in following populations of men: severe inflammation in prostate (>10⁶ white blood cells in prostate secretion; n = 29), severe leukocytospermia, (>10⁶ white blood cells in semen; n = 31), mild inflammation, (0.2–1 M white blood cells in semen or prostate secretion; n = 24), non-inflammatory oligozoospermia (n = 32) and healthy controls (n = 27). Male partners of infertile couples had reduced level of antioxidative activity, selenium and zinc in their seminal plasma. Most importantly, reduced selenium levels were evident in all patient groups regardless of inflammation status. Therefore, these patients might gain some benefit from selenium supplementation.     

Significant association between hypolipoproteinemia(a) and lifetime risk of cancer: An autopsy study from a community-based Geriatric Hospital

BackgroundOur recent study showed that a low lipoproteinemia(a) [Lp(a)] level was a risk factor for cancer and all-cause deaths. The purpose of this study was to verify the role of the Lp(a) level on cancer among consecutive autopsy cases.MethodsThe subjects consisted of 1354 cases (775 men and 579 women). The average age at death was 79.9 years. Hypolipoproteinemia(a) was defined as an Lp(a) level of below 80 mg/L. Overall, 62.3% of the subjects had suffered from at least one to a maximum of five malignancies throughout their lives. The most frequent type of malignancy was gastric cancer, followed by leukemia, lung cancer, and colon cancer.ResultsThe cancer-bearing status decreased linearly according to the Lp(a) level in both men and women (P = 0.01 and P < 0.001, respectively). The median Lp(a) level was significantly lower among the cases with hepato-biliary–pancreatic cancers or hematopoietic malignancy, but was higher among cases with lung cancer, especially lung adenocarcinoma. Hypolipoproteinemia(a) was a significant risk factor for any origins of cancer, with an odds ratio of 1.94 (95% CI, 1.45–2.60; P < 0.001). It was also a risk factor for hepato-biliary cancers and leukemia, but it was a protective factor for lung cancer.ConclusionsOur findings suggested hypolipoproteinemia(a) would be a significant risk factor for cancer except lung cancer. This study complements our previous study showing that hypolipoproteinemia(a) would increase the lifetime risk of cancer other than lung cancer.     

Acute myeloid leukemia incidence following radiation therapy for localized or locally advanced prostate adenocarcinoma

Introduction: The effect of radiation therapy on acute myeloid leukemia incidence among prostate cancer patients has not been sufficiently elucidated despite evidence that acute myeloid leukemia is a consequence of therapeutic radiation in other primary malignancies. Therefore, we investigated the effect of definitive therapy with radiation therapy (external beam radiation therapy [EBRT] or brachytherapy) on acute myeloid leukemia incidence in a population-based cohort of patients with localized or locally advanced prostate cancer. Methods: We utilized the Surveillance, Epidemiology, and End Results database to identify a cohort of men (n = 168,612) with newly diagnosed prostate adenocarcinoma between January 1988 and December 2003. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of acute myeloid leukemia incidence following definitive therapy with EBRT alone, brachytherapy alone, or surgery alone compared to no definitive therapy (i.e. no EBRT, brachytherapy, or surgery). Results: The cohort yielded 184 acute myeloid leukemia cases during 1,064,820 person-years of follow-up after prostate adenocarcinoma diagnosis. Patients treated with EBRT had a higher adjusted relative risk of developing acute myeloid leukemia than patients treated with brachytherapy or surgery when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR = 2.05, 95% CI 1.29, 3.26; brachytherapy: HR = 1.22, 95% CI 0.46, 3.22; surgery: HR = 1.24, 95% CI 0.77, 1.98). Conclusions: Our findings suggest that acute myeloid leukemia incidence is a greater concern for patients treated with EBRT than brachytherapy for localized or locally advanced prostate adenocarcinoma.     

Neural control of leg stiffness during hopping in boys and men

The purpose of the study was to investigate whether boys and men utilise different control strategies whilst hopping. Eleven boys (11–12 yr old) and ten men completed hopping at 1.5 Hz, 3.0 Hz and at their preferred frequency. A footswitch measured contact and flight times, from which leg stiffness was calculated. Simultaneously, surface electromyograms (EMGs) of selected lower limb muscles were recorded and quantified for each 30 ms period during the first 120 ms post-ground contact. At 1.5 Hz there were no differences between the groups in relative stiffness or muscle activity. At 3.0 Hz men had significantly shorter contact times (P = 0.013), longer flight times (P = 0.002), greater relative stiffness (P = 0.01) and significantly greater soleus (P = 0.012) and vastus lateralis (P < 0.001) activity during the initial 30 ms post-ground contact. At the preferred frequency men hopped significantly faster than the boys (P = 0.007), with greater leg stiffness (P < 0.01) and with more extensor activity in most time periods. Boys and men demonstrated similar control strategies when hopping at a slow frequency, but when hopping frequency increased men were able to better increase feedforward and reflex muscle activity to hop with greater relative stiffness.     

Cancer incidence in the AGRICAN cohort study (2005–2011)

BackgroundNumerous studies have been conducted among farmers, but very few of them have involved large prospective cohorts, and few have included a significant proportion of women and farm workers. Our aim was to compare cancer incidence in the cohort (overall, by sex, and by work on farm, occupational status and pesticide use) within the general population.MethodsMore than 180,000 participants in the AGRICAN cohort were matched to cancer registries to identify cancer cases diagnosed from enrolment (2005–2007) to 31st December 2011. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs).ResultsOver the period, 11,067 incident cancer cases were identified (7304 men and 3763 women). Overall cancer incidence did not differ between the cohort and the general population. Moreover, SIRs were significantly higher for prostate cancer (SIR = 1.07, 95%CI 1.03–1.11) and non-Hodgkin lymphoma (SIR = 1.09, 95%CI 1.01–1.18) among men, skin melanoma among women (SIR = 1.23, 95%CI 1.05–1.43) and multiple myeloma (men: SIR = 1.38, 95%CI 1.18–1.62; women: SIR = 1.26, 95%CI 1.02–1.54). In contrast, SIRs were lower for upper aerodigestive tract and respiratory cancers. Increase in risk was greater in male farm workers for prostate and lip cancer, in female farm workers for skin melanoma, and in male farm owners for multiple myeloma. Moreover, incidence of multiple myeloma and skin melanoma was higher among male and female pesticide users respectively.ConclusionWe found a decreased incidence for tobacco-related cancers and an increased incidence of prostate cancers, skin melanoma and multiple myeloma. Specific subgroups had a higher cancer incidence related to occupational status and pesticide use.     

Mortality and incidence of new primary cancers in men with prostate cancer: A Danish population-based cohort study

Background: Prostate cancer (PC) survivors may have an increased risk of new primary cancers (NPCs) due to shared risk factors or PC-directed treatments. Methods: Using Danish registries, we conducted a cohort study of men with (n = 30,220) and without PC (n = 151,100) (comparators), matched 1:5 on age and PC diagnosis/index date. We computed incidence rates of NPCs per 10,000 person years (PY) and associated 95% confidence intervals (CI), and used Cox proportional hazards regression to compute hazard ratios (HRs) and 95%CI, adjusting for comorbidities. In order to obviate any impact of shorter survival among prostate cancer patients, we censored comparator patients when the matched prostate cancer patient died or was censored. Results: Follow-up spanned 113,487 PY and 462,982 PY in the PC and comparison cohorts, respectively. 65% of the cohorts were aged >70 years at diagnosis. Among PC patients, 51% had distant/unspecified stage, and 63% had surgery as primary treatment. The PC cohort had lower incidence of NPCs than their comparators. The adjusted HR of NPC among men with PC versus the comparators was 0.84 (95%CI = 0.80, 0.88). Lowest HRs were among older men, those with distant stage, and were particularly evident for cancers of the brain, liver, pancreas, respiratory, upper gastrointestinal, and urinary systems. Conclusions: We find no evidence of an increased risk of NPCs among men with PC. The deficit of NPCs among men with PC may be a true effect but is more likely due to lower levels of risk factors (e.g., smoking) in PC patients versus comparators, clinical consideration of cancers at new organs as metastases rather than new primaries, or under-recording/under-reporting of NPCs among PC patients.     

Expression of IL-32 modulates NF-κB and p38 MAP kinase pathways in human esophageal cancer

BackgroundEsophageal cancer is the seventh leading cause of cancer death in males in USA, and there is a strong link has been demonstrated between inflammation and esophageal cancer, interleukin (IL)-32 is a recently described pro-inflammatory cytokine characterized by the induction of nuclear factor NF-κB activation, the p38MAPK also plays an important role in key cellular processes related to inflammation and cancer. We investigated whether the IL-32 expression may be involved in esophageal carcinogenesis through modulates the activity of NF-κB and p-p38 MAPK.MethodMalignant esophageal tissue and blood samples were obtained from 65 operated untreated patients, normal samples was obtained from 35 patients operated for other reasons as control. IL-32 expression visualized by immunohistochemistry, Real time RT–PCR for IL-32 mRNA expression, NF-κB phosphorylation and phosphorylated p38mapk were analyzed by immunoblotting, ELISA for further detection IL-32 and cytokines (TNF-α, IL-1β, IL-6 and IL-8) concentration in the patient’s sera.ResultsIL-32 expression was increased in immunohistochemical staining for malignant esophageal tissue and it’s correlated with the relative expression level of IL-32 mRNA P = 0.007, the P-NF-κB level elevated in tumor tissue compared with control and no difference in the total NF-κB level P = 0.003 while the IL-32 up-regulated the P-pNF-κB in the esophageal tumor P = 0.005. There is increase in p-p38MAPK activation underlying IL-32 expression in tumor P = 0.004, but no change in total p38 MAPK in malignant esophagus. The plasma level of IL-32 expression was increased in malignant esophageal patients P = 0.01, with increased in the levels of the cytokines TNF-α, IL-6, and IL-1β P<0.05.ConclusionsUnderstanding the pathway of IL-32 expression to stimulate the secretion cytokines via the activation of NF-κB and up-regulation of p-p38MAPK may or may not prove to be a therapeutic target, or a biomarker, and future studies will finally answer this hypothesis generated.     

STK15 rs2273535 polymorphism and cancer risk: A meta-analysis of 74,896 subjects

Background: It has been suggested that the serine/threonine kinase 15 (STK15) T91A rs2273535 polymorphism is associated with susceptibility to cancer. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. Methods: PubMed was searched to select studies. Case–control studies containing available genotype frequencies of the STK15 rs2273535 polymorphism were chosen, and the odds ratio (OR) with its 95% confidence interval (CI) was utilized to assess the strength of association. Results: 52 studies – including 34,057 cases and 40,839 controls – were identified. A significant effect of the STK15 rs2273535 polymorphism on cancer risk was found (AA vs. TT: OR = 1.13, 95%CI = 1.01–1.26, P_{heterogeneity} < 0.001; AA vs. TA/TT: OR = 1.12, 95%CI = 1.02–1.22, P_{heterogeneity} < 0.001; TA/AA vs. TT: OR = 1.06, 95%CI = 1.01–1.12, P_{heterogeneity} < 0.001). Stratified analysis by cancer type revealed that the STK rs2273535 polymorphism may contribute to the risk of breast cancer (AA vs. TT: OR = 1.21, 95%CI = 1.01–1.44, P_{heterogeneity} = 0.002), colorectal cancer (AA vs. TA/TT: OR = 1.24, 95%CI = 1.05–1.47, P_{heterogeneity} = 0.124), and esophageal cancer (AA vs. TA/TT: OR = 1.19, 95%CI = 1.02–1.39, P_{heterogeneity} = 0.148). Further subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians (AA vs. TA/TT: OR = 1.20, 95%CI = 1.05–1.37, P_{heterogeneity} = 0.004). Conclusion: This meta-analysis suggests that the STK15 rs2273535 polymorphism is a candidate gene polymorphism for cancer susceptibility, especially in Asian populations.     

Polymorphisms of tumor-related genes IL-10, PSCA,MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population

BackgroundGastric cancer is the fourth most common cancer in the world. Environmental and genetic factors both play critical roles in the etiology of gastric cancer. Hundreds of SNPs have been identified to have association with the risk of gastric cancer in many races. In this study, 25 SNPs in genes for IL-10, IL-1B, MTRR, TNF-а, PSCA, PLCE1 and NOC3L were analyzed to further evaluate their associations with gastric cancer susceptibility in the Chinese Han population.MethodsTwo hundred and seventy nine gastric cancer patients and 296 healthy controls were recruited in this study. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Data management and statistical analyses were conducted by Sequenom Typer 4.0 Software and Pearson's χ² test.ResultsOne protective allele and three risk alleles for gastric cancer patients were found in this study. The allele “G” of rs1801394 in MTRR showed an association with a decreased risk of gastric cancer: odds ratio (OR) = 0.74, 95% confidence interval (95% CI) = 0.57–0.97, P = 0.030 in the additive model; OR = 0.495, 95% CI = 0.26–0.95, P = 0.034 in the recessive model. The other three SNPs, the allele “C” of rs1800871 in IL10 (OR = 1.33, 95% CI = 1.04–1.90; P = 0.026 in the additive model; OR = 1.46, 95% CI = 1.04–2.06; P = 0.030 in the recessive model), the allele “A” of rs2976391 in PSCA (OR = 1.30, 95% CI = 1.01–1.66; P = 0.041 in the additive model and OR = 1.48, 95% CI = 1.04–2.11, P = 0.028 in the recessive model), and the allele “G” of rs17109928 in NOC3L gene (OR = 1.34, 95% CI = 1.01–1.78; P = 0.042 by additive model analysis; OR = 1.47, 95% CI = 1.04–2.07, P = 0.028 by dominant model analysis), showed an association with an increased risk of gastric cancer.ConclusionsThese results indicate the importance of four gastric cancer susceptibility polymorphisms of IL-10, NOC3L, PSCA and MTRR in the Chinese Han population, which could be used in the determination of gastric cancer risk in clinical practice.