Smoking (active and passive), N-acetyltransferase 2, and risk of breast cancer

Background: The relationship between smoking and breast cancer remains controversial. The study aim was to assess the relationship of passive and active smoking to breast cancer risk by N-acetyltransferase 2 (NAT2) phenotype, using a comprehensive assessment of both passive and active smoking. Methods: We undertook a population-based case–control study in Northeastern Ontario, Canada of 347 women diagnosed (2002–2004) with breast cancer and 775 population-based controls. The mailed study package included a questionnaire requesting information about established breast cancer risk factors, passive and active smoking, and a buccal swab for genetic analyses. Results: Among never-active smokers, a long duration of passive smoking was associated with an increased risk of breast cancer (odds ratio (OR) 1.86 (95% confidence interval (95% CI) 1.01–3.44) (test for trend (p = 0.07)); that risk was more elevated for NAT2 slow acetylators (OR 2.76, 95% CI 1.16–6.59) (and highest in extremely slow acetylators), but not elevated for NAT2 fast acetylators (OR 1.17, 95% CI 0.42–3.23). Among active smokers more than 20 pack-years of smoking was associated with an OR of 1.34 (95% CI 0.92-1.96); more elevated among NAT2 fast acetylators OR 1.93 (95% CI 1.01–3.69) but not elevated among NAT2 slow acetylators. Women who were NAT2 fast acetylators in the highest quartile for duration of active smoking had an OR of 2.74 (95% CI 1.42–5.27), with a significant test of trend (p = 0.005). Conclusions: These findings suggest that passive and active smoking may be related to breast cancer, and the effect may be differentially modified by NAT2 phenotype. Further research into the genetic modification of a breast cancer–smoking relationship may help to reconcile earlier discrepant findings.     

The changing incidence of human papillomavirus-associated oropharyngeal cancer using multiple imputation from 2000 to 2010 at a Comprehensive Cancer Centre

Introduction Human papillomavirus (HPV) is a risk and prognostic factor for oropharyngeal cancer (OPC). Determining whether the incidence of HPV-associated OPC is rising informs health policy. Methods HPV status was ascribed using p16 immunohistochemistry in 683/1474 OPC patients identified from the Princess Margaret Hospital's Cancer Registry (from 2000 to 2010). Missing p16 data was estimated using multiple (n = 100) imputation (MI) and validated using an independent OPC cohort (n = 214). Non-OPC head and neck squamous cell carcinoma (HNSCC) (n = 3262) were also used for time-trend comparison. Regression was used to compare HNSCC subsets and time-trends. The c-index was used to measure the predictive ability of MI. Results The incidence of OPC rose from 23.3% of all HNSCC in 2000 to 31.2% in 2010 (p = 0.002). In the subset of OPC tested for p16, there was no change in p16 positivity over time (p = 0.9). However, p16 testing became more frequent over time (p < 0.0001), but was nonetheless biased, favouring never-smokers [OR 1.87 (95% CI 1.29–2.70)] and tumors of the tonsil [OR 2.30 (1.52–3.47)] or base-of-tongue [OR 1.72 (1.10–2.70)]. These same factors were also associated with p16-positivity [ORs 3.22 (1.27–8.16), 7.26 (3.50–15.1), 5.83 (2.70–12.7), respectively]. Following MI and normalization, the proportion of OPC that was p16-associated rose from 39.8% in 2000 to 65.0% in 2010, p = 0.002, fully explaining the rise in OPC in our patient population. Conclusion The rise in HNSCC referrals seen from 2000 to 2010 at our institution was driven primarily by p16-associated OPC. MI was necessary to derive reliable conclusions when cases with missing data are considerable.     

Type II diabetes and metabolic syndrome in relation to head and neck squamous cell carcinoma risk: A SEER-Medicare database study

BackgroundDiabetes and metabolic syndrome have been found to increase the risk of various cancers. Previous studies indicated that diabetes may increase the risk of head and neck squamous cell carcinoma (HNSCC). Metabolic syndrome has not been investigated as a risk factor. We tested whether type II diabetes or metabolic syndrome were associated with HNSCC using a very large database of medical administrative records, providing the ability to investigate relatively weak effects and stratify by subgroups.MethodsWe identified persons diagnosed with HNSCC between 1994 and 2007 in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We selected controls from a 5% sample of Medicare beneficiaries and frequency matched to cases on sex and duration of enrollment. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between type II diabetes/metabolic syndrome and HNSCC, adjusted for potential confounders, among 14,022 cases and 42,066 controls.ResultsWe observed a very weak inverse association between type II diabetes and HNSCC (OR = 0.92; 95% CI, 0.88–0.96) and a moderate inverse association for metabolic syndrome (OR = 0.81; 95% CI, 0.78–0.85). Associations were modified by tobacco use, with null results for type II diabetes among never users (OR = 1.00; 95% CI, 0.95–1.06) and inverse associations among ever users (OR = 0.80; 95% CI, 0.75–0.86).ConclusionsWe observed moderate inverse associations between metabolic syndrome and HNSCC and weak inverse associations between type II diabetes and HNSCC, which was contrary to the evidence to date. Inadequate control for confounding factors, such as overweight/obesity, may have influenced results.     

Maternal smoking during pregnancy and the risk of childhood brain tumors: Results from a Swedish cohort study

BackgroundTobacco metabolites and carcinogens can be found in placental and umbilical cord tissues of fetuses exposed to maternal smoking. However, studies regarding maternal smoking during pregnancy and childhood brain tumor (CBT) have shown inconsistent results.MethodsAll children born in Sweden between 1983 and 2010 and with information about maternal smoking during pregnancy, obtained from the Swedish Medical Birth Register, were included in this population based cohort study (n = 2,577,305). CBT cases were identified from the National Cancer Register. Cox regression models were used to estimate the effect of maternal smoking during pregnancy on the risk of CBTs.ResultsWe identified 1039 cases of CBT in the cohort. Overall, there was little or no effect of maternal smoking during pregnancy on the risk of CBTs. However, in analyses stratified by age at diagnosis and child’s sex, positive associations were found among 5–9 years old children. In this age interval, maternal smoking during pregnancy was associated with an increased risk of all CBTs combined only among male children (RR = 1.50, 95% CI 0.96–2.34), while for astrocytoma there was a positive association in both male (RR = 2.00, 95% CI 1.02–3.91) and female children (RR = 1.80, 95% CI 0.85–3.82).ConclusionResults from this large Swedish cohort study suggest that even though maternal smoking during pregnancy has a limited overall effect on CBTs, it may increase the risk of astrocytomas.     

Community-acquired infections and their association with myeloid malignancies

Introduction: Antigenic stimulation is a proposed aetiologic mechanism for many haematological malignancies. Limited evidence suggests that community-acquired infections may increase the risk of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). However, associations with other myeloid malignancies including chronic myeloid leukaemia (CML) and myeloproliferative neoplasms (MPNs) are unknown. Materials and methods: Using the Surveillance, Epidemiology and End Result (SEER)-Medicare database, fourteen community-acquired infections were compared between myeloid malignancy patients [AML (n = 8489), CML (n = 3626) diagnosed 1992–2005; MDS (n = 3072) and MPNs (n = 2001) diagnosed 2001–2005; and controls (200,000 for AML/CML and 97,681 for MDS/MPN]. Odds ratios (ORs) and 95% confidence intervals were adjusted for gender, age and year of selection excluding infections diagnosed in the 13-month period prior to selection to reduce reverse causality. Results: Risk of AML and MDS respectively, were significantly associated with respiratory tract infections, bronchitis (ORs 1.20 [95% CI: 1.14–1.26], 1.25 [95% CI: 1.16–1.36]), influenza (ORs 1.16 [95% CI: 1.07–1.25], 1.29 [95% CI: 1.16–1.44]), pharyngitis (ORs 1.13 [95% CI: 1.06–1.21], 1.22 [95% CI: 1.11–1.35]), pneumonia (ORs 1.28 [95% CI: 1.21–1.36], 1.52 [95% CI: 1.40–1.66]), sinusitis (ORs 1.23 [95% CI: 1.16–1.30], 1.25 [95% CI: 1.15–1.36]) as was cystitis (ORs 1.13 [95% CI: 1.07–1.18], 1.26 [95% CI: 1.17–1.36]). Cellulitis (OR 1.51 [95% CI: 1.39–1.64]), herpes zoster (OR 1.31 [95% CI: 1.14–1.50]) and gastroenteritis (OR 1.38 [95% CI: 1.17–1.64]) were more common in MDS patients than controls. For CML, associations were limited to bronchitis (OR 1.21 [95% CI: 1.12–1.31]), pneumonia (OR 1.49 [95% CI: 1.37–1.62]), sinusitis (OR 1.19 [95% CI: 1.09–1.29]) and cellulitis (OR 1.43 [95% CI: 1.32–1.55]) following Bonferroni correction. Only cellulitis (OR 1.34 [95% CI: 1.21–1.49]) remained significant in MPN patients. Many infections remained elevated when more than 6 years of preceding claims data were excluded. Discussion: Common community-acquired infections may be important in the malignant transformation of the myeloid lineage. Differences in the aetiology of classic MPNs and other myeloid malignancies require further exploration.     

HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese

Background: Chromosome 19q13.3 has been identified as one of the regions that associate with cancer risk in previous studies. Methods: We systematically examined the 70.772 kb region comprising four genes on chromosome 19q13.3 among Chinese using the haplotype-tagging SNP (htSNP) approach and the HapMap platform. The study involved 339 lung cancer cases and 358 non-cancer controls. Two htSNPs (rs1046282 and rs735482) captured most of the common haplotypes of CD3EA and the combined effects of sixteen htSNPs provided high coverage of common haplotypes of ERCC2, PPP1R13L, CD3EAP and ERCC1. Results: Both carriers of variant CC genotype [adjusted OR (95% CI) = 1.28 (1.02–1.60), P = 0.04] and variant C-allele among >20 years’ smokers [OR (95% CI) = 2.13 (1.24–3.67), P = 0.006] for CD3EAP rs735482 were at increased risk of lung cancer. Four haplotype blocks of strong linkage disequilibrium were identified. The haplotype ERCC2 rs3916874^G and rs238415^C [OR (95% CI) = 1.26 (1.02–1.57), P = 0.03] in block 1 and the haplotype PPP1R13L rs4803817^A, CD3EAP rs1046282^T, rs735482^C, ERCC1 rs3212980^A, rs3212964^G [OR (95% CI) = 3.56 (1.55–8.18), P = 0.005] in block 3 were associated with lung cancer risk. MDR (multifactor dimensionality reduction) analysis demonstrated the best significant model of two-attributes containing smoking duration and rs2298881 in ERCC1 (P = 0.004–0.005) and suggested that the effects of high-order interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could modulate lung cancer risk. Conclusions: HapMap-based study of 19q13.3 identified that genetic variation of CD3EAP and two loci were associated with lung cancer risk and interaction of smoking duration and genetic variants was the strongest predictor of lung cancer risk in a Chinese population.     

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.     

Plasma copeptin concentration and outcome after pediatric traumatic brain injury

Higher plasma copeptin level has been associated with poor outcomes of critical illness. The present study was undertaken to investigate the plasma copeptin concentrations in children with traumatic brain injury (TBI) and to analyze the correlation of copeptin with disease outcome. Plasma copeptin concentrations of 126 healthy children and 126 children with acute severe TBI were measured by enzyme-linked immunosorbent assay. Twenty-one patients (16.7%) died and 38 patients (30.2%) had an unfavorable outcome (Glasgow Outcome Scale score of 1–3) at 6 months. Plasma copeptin level was obviously higher in patients than in healthy children (46.2 ± 20.8 pmol/L vs. 9.6 ± 3.0 pmol/L, P < 0.001). Plasma copeptin level was identified as an independent predictor for 6-month mortality [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112–1.538, P = 0.005] and unfavorable outcome (OR 1.313, 95% CI 1.146–1.659, P = 0.003). The predictive value of copeptin was similar to that of Glasgow Coma Scale (GCS) score for 6-month mortality [area under curve (AUC) 0.832, 95% CI 0.755–0.892 vs. AUC 0.873, 95% CI 0.802–0.926, P = 0.412] and unfavorable outcome (AUC 0.863, 95% CI 0.790–0.918 vs. AUC 0.885, 95% CI 0.816–0.935, P = 0.596). Copeptin improved the AUC of GCS score for 6-month unfavorable outcome (AUC 0.929, 95% CI 0.869–0.967, P = 0.013), but not for 6-month mortality (AUC 0.887, 95% CI 0.818–0.936, P = 0.600). Thus, plasma copeptin level represents a novel biomarker for predicting 6-month clinical outcome in children with TBI.     

Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer

Methylating agents are involved in carcinogenesis, and the DNA repair protein O⁶-methylguanine-DNA methyltransferase (MGMT) removes methyl group from O⁶-methylguanine. Genetic variation in DNA repair genes has been shown to contribute to susceptibility to squamous cell carcinoma of the head and neck (SCCHN). We hypothesize that MGMT polymorphisms are associated with risk of SCCHN. In a hospital-based case–control study of 721 patients with SCCHN and 1234 cancer-free controls frequency-matched by age, sex and ethnicity, we genotyped four MGMT polymorphisms, two in exon 3, 16195C > T and 16286C > T and two in the promoter region, 45996G > T and 46346C > A. We found that none of these polymorphisms alone had a significant effect on risk of SCCHN. However, when these four polymorphisms were evaluated together by the number of putative risk genotypes (i.e. 16195CC, 16286CC, 45996GT + TT, and 46346CA + AA), a statistically significantly increased risk of SCCHN was associated with the combined genotypes with three to four risk genotypes, compared with those with zero to two risk genotypes (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) = 1.05–1.53). This increased risk was also more pronounced among young subjects (OR = 1.81; 95% CI = 1.11–2.96), men (OR = 1.24; 95% CI = 1.00–1.55), ever smokers (OR = 1.25; 95% = 1.01–1.56), ever drinkers (OR = 1.29; 95% CI = 1.04–1.60), patients with oropharyngeal cancer (OR = 1.45; 95% CI = 1.12–1.87), and oropharyngeal cancer with regional lymph node metastasis (OR = 1.52; 95% CI = 1.16–1.89). In conclusion, our results suggest that any one of MGMT variants may not have a substantial effect on SCCHN risk, but a joint effect of several MGMT variants may contribute to risk and progression of SCCHN, particularly for oropharyngeal cancer, in non-Hispanic whites.     

Potential role of selection bias in the association between childhood leukemia and residential magnetic fields exposure: A population-based assessment

PurposeData from the Northern California Childhood Leukemia Study (NCCLS) were used to assess whether selection bias may explain the association between residential magnetic fields (assessed by wire codes) and childhood leukemia as previously observed in case–control studies.MethodsWiring codes were calculated for participating cases, n = 310; and non-participating cases, n = 66; as well as for three control groups: first-choice participating, n = 174; first-choice non-participating, n = 252; and replacement (non-first choice participating controls), n = 220.ResultsParticipating controls tended to be of higher socioeconomic status than non-participating controls, and lower socioeconomic status was related to higher wire-codes. The odds ratio (OR) for developing childhood leukemia associated with high wire-codes was 1.18 (95% CI: 0.85, 1.64) when all cases were compared to all first-choice controls (participating and non-participating). The OR for developing childhood leukemia in the high current category was 1.43 (95% CI: 0.91, 2.26) when participating cases were compared to first-choice participating controls, but no associations were observed when participating cases were compared to non-participating controls (OR = 1.06, 95% CI: 0.71, 1.57) or to replacement controls (OR = 1.06, 95% CI: 0.71, 1.60).ConclusionsThe observed risk estimates vary by type of control group, and no statistically significant association between wire codes and childhood leukemia is observed in the California population participating in the NCCLS.     

Diabetes,physical activity and breast cancer among Hispanic women

Purpose: We assessed the association between diabetes and breast cancer and whether physical activity modified the effect of diabetes on breast cancer in Hispanic women. Methods: We used data from a case-control study of breast cancer among Hispanic women aged 30–79 conducted between 2003 and 2008 on the Texas–Mexico border. In-person interviews were completed with 190 incident breast cancer cases ascertained through surgeons and oncologists, and 979 controls who were designated as both high-risk (n = 511) and low-risk (N = 468) for breast cancer (with respective response rates of 97%, 83% and 74%). Results: After adjustment for menopausal status and mammography screening, there was no effect of diabetes on breast cancer risk (high-risk control group odds ratio [OR] 1.02, 95% confidence interval [CI] 0.71–1.48; low-risk control group OR 0.87, 0.58–1.30). Women who had a diabetes history and did not exercise were at no risk of breast cancer (OR 0.96, 95% CI 0.63–1.48) or a slightly reduced breast cancer risk (low-risk control group OR 0.72, 95% CI 0.46–1.15) depending on the control group used, while women with diabetes who did exercise had significantly reduced breast cancer risk (OR 0.41, 95% CI 0.21–0.83) regardless of the control group used (high-risk control group p-value for interaction = 0.013, low-risk control group p-value for interaction 0.183). Conclusions: Should other studies confirm our results, physical activity should be explored as a means of reducing breast cancer risk in diabetic women.     

Postoperative plasma copeptin levels independently predict delirium and cognitive dysfunction after coronary artery bypass graft surgery

Copeptin can reflect individual's stress state and are correlated with poor outcome of critical illness. The occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD) is associated with worse outcome after coronary artery bypass graft (CABG) surgery. The present study aimed to investigate the ability of postoperative plasma copeptin level to predict POD and POCD in patients undergoing CABG surgery. Postoperative plasma copeptin levels of 108 patients were measured by an enzyme-linked immunosorbent assay. It was demonstrated that plasma copeptin levels were substantially higher in patients with POD than without POD (1.8 ± 0.6 ng/mL vs. 1.1 ± 0.3 ng/mL; P < 0.001) and in patients with POCD than without POCD (1.9 ± 0.6 ng/mL vs. 1.1 ± 0.4 ng/mL; P < 0.001). Plasma copeptin level and age were identified as independent predictors for POD [odds ratio (OR), 67.386; 95% confidence interval (CI), 12.031–377.426; P < 0.001 and OR, 1.202; 95% CI, 1.075–1.345; P = 0.001] and POCD (OR, 28.814; 95% CI, 7.131–116.425; P < 0.001 and OR, 1.151; 95% CI, 1.030–1.285; P = 0.003) using a multivariate analysis. For prediction of POD, the area under receiver operating characteristic curve (AUC) of the copeptin concentration (AUC, 0.883; 95% CI, 0.807–0.937) was markedly higher than that of age (AUC, 0.746; 95% CI, 0.653–0.825; P = 0.020). For prediction of POCD, the AUC of the copeptin concentration (AUC, 0.870; 95% CI, 0.792–0.927) was markedly higher than that of age (AUC, 0.735; 95% CI, 0.641–0.815; P = 0.043). Thus, postoperative plasma copeptin level may be a useful, complementary tool to predict POD and POCD in patients undergoing CABG surgery.     

Polymorphisms in NAT2 and GSTP1 are associated with survival in oral and oropharyngeal cancer

Introduction: Functional polymorphisms in drug metabolizing enzymes (DMEs) may be determinants of survival in oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods: OOSCC cases (N = 159) with a history of either tobacco or alcohol use were genotyped for polymorphisms in eight DMEs. Overall and disease-specific survival were analyzed using Kaplan–Meier plots and the log-rank test. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) in exploratory analyses of patient subgroups. Results: Kaplan–Meier analyses showed N-acteyltransferase-2 (NAT2) fast acetylators experienced a 19.7% higher 5-year survival rate than slow acetylators (P = 0.03) and this association was similar in oropharyngeal and oral cancer. After multiple adjustment, including tumor site and stage, the NAT2 fast acetylator phenotype was associated with improved overall survival (vs. slow acetylators) provided chemotherapy or radiation were not used (HR, 0.26; 95% CI, 0.10–0.66). However, NAT2 phenotype was unrelated to survival in patients treated with chemoradiotherapy (HR, 1.21; 95% CI, 0.54–2.73) or radiotherapy (HR, 0.67; 95% CI, 0.31–1.59) (P-for-NAT2/treatment-interaction = 0.04). Normal activity GSTP1 was associated with a 19.2% reduction in 5-year disease-specific survival relative to reduced activity GSTP1 (P = 0.04) but this association was not modified by treatment. Conclusions: Our results suggest that functional polymorphisms in NAT2 and GSTP1 are associated with OOSCC survival. Confirmation of these results in larger studies is required.     

Cyclin D1 G870A polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case–control study

Background: A common G to A polymorphism (G870A) in the splice donor region of exon 4 of cyclin D1 (CCND1) gene generates two mRNAs (cyclin D1a and D1b) through an alternative splicing at the site of this polymorphism. Cyclin D1a and b proteins differ in their COOH-terminus, a region involved in protein degradation. We examined the association between this CCDN1 genotype and the susceptibility to hepatocellular carcinoma (HCC) in a Turkish population. Methods: The genotype frequency of this polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. Hospital-based case–control study was designed consisting of 160 diagnosis subjects with hepatocellular carcinoma and 160 cancer-free control subjects matched on age, gender, smoking and alcohol status. Results: The allele frequencies of case subjects (A, 0.55; G, 0.45) were significantly different from those of control subjects (A, 0.42; G, 0.58) (p = 0.002). The odds ratios (ORs) for the CCND1 870 GA and AA genotypes when compared with the GG genotypes were 1.39 (95% confidence interval [CI] 0.82–2.36, p = 0.22) and 2.52 (95% CI 1.38–4.62, p = 0.003) respectively. The presence of at least one CCND1 870A allele was associated with increased risk for HCC (OR, 1.73; 95% CI, 1.06–2.82, p = 0.03). When combining the GG and GA genotypes as a reference genotype, we found that the OR for the AA genotype was 2.06 (95% CI 1.24–3.44, p = 0.006). Conclusion: Our results suggest that the CCND1 G870A single nucleotide polymorphism is associated with an increased risk of HCC in our Turkish population.     

Case-control study of birth characteristics and the risk of hepatoblastoma

Background: Hepatoblastoma is a malignant embryonal tumor typically diagnosed in children younger than five years of age. Little is known on hepatoblastoma etiology. Methods: We matched California Cancer Registry records of hepatoblastomas diagnosed in children younger than age 6 from 1988 to 2007 to birth records using a probabilistic record linkage program, yielding 261 cases. Controls (n = 218,277), frequency matched by birth year to all cancer cases in California for the same time period, were randomly selected from California birth records. We examined demographic and socioeconomic information, birth characteristics, pregnancy history, complications in pregnancy, labor and delivery, and abnormal conditions and clinical procedures relating to the newborn, with study data taken from birth certificates. Results: We observed increased risks for hepatoblastoma among children with low [1500–2499 g, Odds Ratio (OR) = 2.02, 95% confidence interval (CI) 1.29–3.15] and very low birthweight (<1500 g, OR = 15.4, 95% CI 10.7–22.3), preterm birth <33 weeks (OR = 7.27, 95% CI 5.00, 10.6), small size for gestational age (OR = 1.75, 95% CI 1.25–2.45), and with multiple birth pregnancies (OR = 2.52, 95% CI 1.54–4.14). We observed a number of pregnancy and labor complications to be related to hepatoblastoma, including preeclampsia, premature labor, fetal distress, and congenital anomalies. Conclusion: These findings confirm previously reported associations with low birthweight and preeclampsia. The relation with multiple birth pregnancies has been previously reported and may indicate a relation to infertility treatments.     

An updated meta-analysis on the association of TGF-β1 gene promoter -509C/T polymorphism with colorectal cancer risk

AimPublished data on the association between transforming growth factor-β1 (TGF-β1) gene promoter-509C/T polymorphism and colorectal cancer (CRC) risk are inconsistent and inconclusive. To derive a more precise estimation of this association, a meta-analysis was carried out.MethodsMeta-analysis was performed to evaluate reported studies of the relationship between TGF-β1 gene promoter-509C/T polymorphism and colorectal cancer risk using fixed-effects model and random-effects model.ResultsWe observed an increased colorectal cancer risk among subjects carrying TGF-β1 gene promoter-509CC + CT genotype (odds ratio (OR) = 1.18%, 95% confidence interval (95% CI): 1.06–1.32) using 4440/6785 cases/controls in total population. We observed an increased risk of the TGF-β1 gene promoter -509CC, CT and CC + CT polymorphisms for colorectal cancer in population-based study (OR = 1.36, 95% CI: 1.19–1.56, OR = 1.18, 95% CI: 1.03–1.34 and OR = 1.26, 95% CI: 1.12–1.43, respectively) in stratified analysis. We observed an increased colorectal risk among CC and CC + CT carriers in European and American population (OR = 1.22, 95% CI: 1.04–1.43 and OR = 1.18, 95% CI: 1.02–1.38, respectively). We also observed an increased risk of colon cancer among subjects carrying CC + CT genotype (OR = 1.31, 95% CI: 1.05–1.63).ConclusionsThe present meta-analysis results suggest that TGF-β1 gene promoter -509C allele variant is a possible risk factor for developing colorectal cancer. Recommendations for further studies include pooling of individual data to verify results from the study and to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental and lifestyle factors.     

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based,propensity score analysis

BackgroundThis study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.MethodsData on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.ResultsAfter adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.ConclusionsThese findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.     

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.     

Prolonged breastfeeding reduces risk of breast cancer in Sri Lankan women: A case–control study

Goal: To assess the association between duration of breastfeeding and the risk of breast cancer in Sri Lankan women. Methods: We conducted a case–control study in women aged 30–64 years in selected health care facilities in the Western province. A total of 100 recent cases of breast cancer (histologically confirmed) and 203 controls (age and parity matched) were included. Detailed information regarding breastfeeding, menstruation, reproductive factors, passive smoking and other confounders was collected using a structured questionnaire. Adjusted odds ratios and 95% confidence intervals were calculated using multiple logistic regressions. Principle results: Multivariate analysis found that those women who breastfed for ≥24 months during lifetime had significantly lower risk of breast cancer than those who breastfed for less than 24 months (OR = 0.40; 95%CI = 0.22, 0.73). Compared to 0–11 months of lifetime breastfeeding, there was a 66.3% reduction in breast cancer risk in women who breastfed for 12–23 months, 87.4% reduction in 24–35 months and 94% reduction in 36–47 months categories. The mean duration of breastfeeding per child for ≥12 months was also associated with reduced risk of breast cancer (OR = 0.52; 95%CI = 0.28, 0.94). The significant factors associated with increased risk of breast cancer were: post-menopausal women (OR = 1.74; 95%CI = 1.01, 3.01); having an abortion in the past (OR = 3.42; 95%CI = 1.75, 6.66) and exposure to passive smoking (OR = 2.96, 95%CI = 1.53, 5.75). Major conclusions: Prolonged breastfeeding significantly reduces the risk of breast cancer and this protective effect was supported by a dose–response relationship. Risk due to passive smoking should be emphasized in anti-smoking programmes.     

Tobacco and alcohol as risk factors for oesophageal cancer in a high incidence area in South Africa

BackgroundThe Eastern Cape Province of South Africa, which includes the former Transkei has high rates of squamous cell oesophageal cancer (OC), thought to be caused mainly by nutritional deficiencies and fungal contamination of staple maize. A hospital-based case-control study was conducted at three of the major referral hospitals in this region to measure, among other suspected risk factors, the relative importance of tobacco smoking and alcohol consumption for the disease in this population.MethodsIncident cases (n = 670) of OC and controls (n = 1188) were interviewed using a structured questionnaire which included questions on tobacco and alcohol-related consumption. Odds ratios (ORs) with 95% confidence intervals for each of the risk factors were calculated using unconditional multiple logistic regression models.ResultsA monotonic dose-response was observed across the categories of each tobacco-related variable in both sexes. Males and females currently smoking a total of >14 g of tobacco per day were observed to have over 4-times the odds of developing OC (males OR = 4.36, 95% CI 2.24–8.48; females OR = 4.56, 95% CI 1.46–14.30), with pipe smoking showing the strongest effect. Similar trends were observed for the alcohol-related variables. The quantity of ethanol consumed was the most important factor in OC development rather than any individual type of alcoholic beverage, especially in smokers. Males and females consuming >53 g of ethanol per day had approximately 5-times greater odds in comparison to non-drinkers (males OR = 4.72, 95% CI 2.64–8.41; females OR = 5.24, 95% CI 3.34–8.23) and 8.5 greater odds in those who smoked >14 g tobacco daily. The attributable fractions for smoking and alcohol consumption were 58% and 48% respectively, 64% for both factors combined.ConclusionTobacco and alcohol use are major risk factors for OC development in this region.ImpactThis study provides evidence for further reinforcement of cessation of smoking and alcohol consumption to curb OC development.