Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study

Background:

Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC).

Method:

We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment.

Results:

After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46–3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27–2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco–HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant.

Conclusion:

Our findings strongly implicate tobacco smoke as a causal factor of HCC development.     

Correlates of anti-EBV EBNA1 IgA positivity among unaffected relatives from nasopharyngeal carcinoma multiplex families

Background:

To determine whether non-viral nasopharyngeal carcinoma (NPC) risk factors might be associated with (and mediated through) Epstein–Barr virus (EBV) serological responses linked to NPC risk, we evaluated predictors of risk of anti-EBNA1 IgA seropositivity and other markers among unaffected relatives from a large NPC family study in Taiwan.

Methods:

Multivariate logistic regression conditioned on family was used to examine the associations between sociodemographic, dietary, lifestyle, and occupational variables and risk of anti-EBV EBNA1 IgA positivity, anti-VCA IgA, and anti-DNase positivity.

Results:

Among 2393 unaffected relatives from 319 multiplex families, 1180 (49.3%) were anti-EBV EBNA1 IgA seropositive. None of the associations with anti-EBNA1 IgA were statistically significant, except for being 31–50 years of age (vs <30, adjusted ORs 0.51–0.57). For one or more EBV serological markers, there were suggestive associations for older age, GuangDong firm salted fish, betel use, current alcohol use, and male gender.

Conclusion:

Overall, we found little evidence to suggest that non-viral NPC risk factors significantly alter EBV serological patterns, suggesting that non-viral NPC risk factors act through pathways independent of EBV serological responses.     

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case–control study

Background:

Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC.

Methods:

We conducted a case–control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview.

Results:

Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin.

Conclusion:

These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis.     

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.     

Cigarette smoking and risk of acoustic neuromas and pituitary tumours in the Million Women Study

Background:

The relationship between cigarette smoking and incidence of acoustic neuromas and pituitary tumours is uncertain.

Methods:

We examined the relation between smoking and risk of acoustic neuromas and pituitary tumours in a prospective study of 1.2 million middle-aged women in the United Kingdom.

Results:

Over 10.2 million person years of follow-up, 177 women were diagnosed with acoustic neuromas and 174 with pituitary tumours. Current smokers at recruitment were at significantly reduced risk of incident acoustic neuroma compared with never smokers (adjusted relative risk (RR)=0.41, 95% confidence interval (CI)=0.24–0.70, P=0.001). Past smokers did not have significantly different risk of acoustic neuroma than never smokers (RR=0.87, 95% CI=0.62–1.22, P=0.4). Smoking was not associated with incidence of pituitary tumours (RR in current vs never smokers=0.91, 95% CI=0.60–1.40, P=0.7).

Conclusion:

Women who smoke are at a significantly reduced risk of acoustic neuromas, but not of pituitary tumours, compared with never smokers. Acoustic neuromas are much rarer than the cancers that are increased among smokers.     

Clustering of health behaviours in adult survivors of childhood cancer and the general population

Background:

Little is known about engagement in multiple health behaviours in childhood cancer survivors.

Methods:

Using latent class analysis, we identified health behaviour patterns in 835 adult survivors of childhood cancer (age 20–35 years) and 1670 age- and sex-matched controls from the general population. Behaviour groups were determined from replies to questions on smoking, drinking, cannabis use, sporting activities, diet, sun protection and skin examination.

Results:

The model identified four health behaviour patterns: ‘risk-avoidance'', with a generally healthy behaviour; ‘moderate drinking'', with higher levels of sporting activities, but moderate alcohol-consumption; ‘risk-taking'', engaging in several risk behaviours; and ‘smoking'', smoking but not drinking. Similar proportions of survivors and controls fell into the ‘risk-avoiding'' (42% vs 44%) and the ‘risk-taking'' cluster (14% vs 12%), but more survivors were in the ‘moderate drinking'' (39% vs 28%) and fewer in the ‘smoking'' cluster (5% vs 16%). Determinants of health behaviour clusters were gender, migration background, income and therapy.

Conclusion:

A comparable proportion of childhood cancer survivors as in the general population engage in multiple health-compromising behaviours. Because of increased vulnerability of survivors, multiple risk behaviours should be addressed in targeted health interventions.     

Cigarette smoking,alcohol intake,and risk of glioma in the NIH-AARP Diet and Health Study

Background:

Although cigarette smoking and alcohol drinking increase the risk of several cancers and certain components of cigarette smoke and alcohol can penetrate the blood–brain barrier, it remains unclear whether these exposures influence the risk of glioma.

Methods:

We examined the associations between cigarette smoking, alcohol intake, and risk of glioma in the National Institutes of Health-AARP Diet and Health Study, a prospective study of 477 095 US men and women ages 50–71 years at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using models with age as the time metric and adjusted for sex, race/ethnicity, education, and marital status.

Results:

During a median 10.5 person-years of follow-up, 492 men and 212 women were diagnosed with first primary glioma. Among men, current, heavier smoking was associated with a reduced risk of glioma compared with never smoking, but this was based on only nine cases. No associations were observed between smoking behaviours and glioma risk in women. Greater alcohol consumption was associated with a decreased risk of glioma, particularly among men (>2 drinks per day vs <1 drink per week: HR=0.67, 95% CI=0.51–0.90).

Conclusion:

Smoking and alcohol drinking do not appear to increase the risk of glioma.     

Prognostic value of ABO blood group in southern Chinese patients with established nasopharyngeal carcinoma

Background:

ABO blood group is associated with aetiology of nasopharyngeal carcinoma (NPC); however, the effect of it on survival of patients diagnosed with NPC has not been explored.

Methods:

We retrospectively analysed two cohorts of southern Chinese patients with WHO histological type III: intensity-modulated radiotherapy (IMRT) cohort, 924 patients; and conventional radiotherapy (CRT) cohort, 1193 patients. Associations of ABO blood group with survival were estimated using Cox regression.

Results:

In IMRT cohort, we observed significant associations of blood type A with overall survival (OS) and distant metastasis-free survival (DMFS), compared with type O, after adjusting for prognostic factors. Compared with non-A blood types (B, AB, and O), type A patients had significantly lower OS and DMFS (adjusted hazard ratio (HR)=1.49, 95% CI 1.03–2.17, P=0.036; HR=1.68, 95% CI 1.13–2.51, P=0.011, respectively); similar results were obtained in CRT cohort. Subgroup analyses of the entire population showed that lower OS conferred by blood type A was not significantly modified by age, smoking status, drinking status, immunoglobulin A against Epstein–Barr virus viral capsid antigen (VCA-IgA) titre, or chemotherapy; however, lower OS was not observed in female patients or patients with early clinical stage disease.

Conclusion:

ABO blood group is associated with survival in NPC; patients with blood type A had significantly lower OS and DMFS than patients with non-A blood types.     

A prospective study of coffee intake and pancreatic cancer: results from the NIH-AARP Diet and Health Study

Background:

Evidence evaluating the association between type of coffee intake (caffeinated, decaffeinated) and risk of pancreatic cancer is limited.

Methods:

In the US NIH-AARP Diet and Health Study, we used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) for coffee intake and risk of pancreatic cancer among 457 366 US adults.

Results:

Over 4 155 256 person-years of follow-up, 1541 incident first primary pancreatic cancers occurred. Following detailed adjustment for tobacco smoking history, risk estimates for coffee drinking were not statistically significant; compared with never drinkers of coffee, the hazard ratios (95% CI) were 1.05 (0.85–1.30), 1.06 (0.86–1.31), 1.03 (0.85–1.25), 1.00 (0.79–1.25), and 1.24 (0.93–1.65) for <1, 1, 2–3, 4–5, and ≥6 cups per day, respectively (P-value for trend 0.46). The observed null association was consistent across all examined strata (sex, smoking status, coffee caffeination, and prevalent diabetes).

Conclusions:

In a prospective study of coffee intake with the largest number of pancreatic cancer cases to date, we did not observe an association between total, caffeinated, or decaffeinated coffee intake and pancreatic cancer.     

Flavonoid intake and risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study Cohort

Background:

Limited epidemiological studies show inverse associations between dietary flavonoid intake and pancreatic cancer risk, but results are inconsistent and are based on few cases. We examined the association between intake of flavonoids and pancreatic cancer risk in the large, prospective National Institutes of Health-AARP Diet and Health Study Cohort.

Methods:

During follow-up through 2006 (median follow-up 10.6 years), 2379 pancreatic cancer cases were identified. We used Cox proportional hazards modelling to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

We found no association between total flavonoid intake (Q5 vs Q1 HR=1.09, 95% CI: 0.96–1.24) or any flavonoid subtypes and pancreatic cancer risk. Significant interactions were not observed by age, sex, smoking status, BMI or diabetes.

Conclusion:

Our results do not support the hypothesis that flavonoids have a protective role in pancreatic cancer carcinogenesis.     

Heavy smoking and lung cancer: Are women at higher risk? Result of the ICARE study

Background:

Whether women are more or equally susceptible to the carcinogenic effects of cigarette smoke on the lungs compared with men is a matter of controversy. Using a large French population-based case–control study, we compared the lung cancer risk associated with cigarette smoking by gender.

Methods:

The study included 2276 male and 650 female cases and 2780 male and 775 female controls. Lifetime smoking exposure was represented by the comprehensive smoking index (CSI), which combines the duration, intensity and time since cessation of smoking habits. The analysis was conducted among the ever smokers. All of the models were adjusted for age, department (a regional administrative unit), education and occupational exposures.

Results:

Overall, we found that the lung cancer risk was similar among men and women. However, we found that women had a two-fold greater risk associated with a one-unit increase in CSI than men of developing either small cell carcinoma (OR=15.9, 95% confidence interval (95% CI) 7.6, 33.3 and 6.6, 95% CI 5.1, 8.5, respectively; P<0.05) or squamous cell carcinoma (OR=13.1, 95% CI 6.3, 27.3 and 6.1, 95% CI 5.0, 7.3, respectively; P<0.05). The association was similar between men and women for adenocarcinoma.

Conclusion:

Our findings suggest that heavy smoking might confer to women a higher risk of lung cancer as compared with men.     

The interaction between smoking status and highly active antiretroviral therapy (HAART) use on the risk of Kaposi's sarcoma (KS) in a cohort of HIV-infected men

Background:

Although the independent effects of smoking status and HAART are reported as lower risks against KS, their combined effects have not been explored. We examined whether there is an interaction between smoking status and HAART use on the risk of KS development in an on-going US cohort of HIV-infected men.

Methods:

Cox proportional hazards regression was used to analyse a total sample of 2736 participants of the Multicenter AIDS Cohort Study (MACS).

Results:

We identified 530 incident KS cases with a total follow-up time of 26 594 person-years (incidence rate: 2.00 out of 100 person-years). Current smoking status and HAART use were independently associated with a lower risk of KS development (hazard ratio – HR=0.56, 95% CI: 0.35–0.90, P=0.02 and HR=0.27, 95% CI: 0.16–0.48, P<0.0001, respectively). There was no evidence of multiplicative interaction between current smoking status and HAART use on KS risk (HR=2.14, 95% CI: 0.97–4.73, P_interaction=0.06). Lower effect of smoking was only present among those not on HAART (HR=0.57, 95% CI: 0.35–0.92, P=0.02).

Conclusion:

The inverse association of cigarette smoking on KS risk may be limited to those not on HAART. The biological mechanism of smoking in KS carcinogenesis should be elucidated.     

Men with cancer change their health behaviour: a prospective study from the Danish diet, cancer and health study

Background:

Health behaviour changes may improve the quality of life and survival among cancer survivors. We prospectively examined changes in health behaviour among and between men with prostate cancer (PC), men with cancers other than PC and cancer-free men.

Methods:

We analysed data for 20 914 men (50–65 years), 426 with cancer, and 20 488 persons who were cancer-free between baseline (1993–1997) and follow-up (2000–2002) in multiple linear regression models to determine differences in changes in body mass index (BMI) and in alcohol and tobacco consumption.

Results

Body mass index and tobacco and alcohol consumption decreased significantly (P<0.001) between baseline and follow-up among both men with cancer and cancer-free men. Men with cancers other than PC significantly decreased their BMI (β=−058; 95% confidence interval (CI): −0.77, −0.40) and tobacco consumption (β=−1.36; 95% CI: −2.22, −0.49) compared with cancer-free men and were significantly more likely to quit smoking and lose weight.

Conclusion:

Men with cancers other than PC decreased their tobacco consumption and BMI significantly more than cancer-free men. Men with cancer do change their health behaviour; clinicians should take this into account in planning follow-up care for cancer survivors.     

Prognostic impact of family history in southern Chinese patients with undifferentiated nasopharyngeal carcinoma

Background:

Family history of cancer is associated with developing nasopharyngeal carcinoma (NPC); however, the impact of it on survival among established NPC patients remains unknown.

Methods:

We retrospectively analysed 1773 southern Chinese patients. Associations between a first-degree family history of NPC and overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated by Cox regression.

Results:

Among 1773 patients, 207 (11.7%) reported a first-degree family history of NPC. Compared with patients without a family history, the adjusted hazard ratios among those with it were 0.60 (95% confidence interval (CI), 0.37–0.98; P=0.040) for OS, 0.52 (95% CI, 0.24–1.12; P=0.096) for LRFS and 0.51 (95% CI, 0.27–0.97; P=0.040) for DMFS. There were trends for improving OS, LRFS and DMFS with increasing number of affected relatives (P_trend: 0.050, 0.114 and 0.044, respectively). But no significant benefits of family history in second- or third-degree relatives were observed. In subgroup analysis, we observed the effects of family history with restriction to male patients and those of advanced stage and treated with conventional radiotherapy and addition of chemotherapy.

Conclusion:

A first-degree family history of NPC is associated with improved survival of patients.     

Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study

Background:

Smokers with low body mass index (BMI) may be more susceptible to lung cancer.

Methods:

We prospectively examined the association between baseline BMI and lung cancer risk in the Singapore Chinese Health Study, a cohort of 63 257 Chinese enrolled between 1993 and 1998.

Results:

After adjustment for smoking intensity and duration, BMI was inversely associated with risk of lung cancer among current smokers (P for trend=0.0004). Current smokers at different dosage of smoking with low BMI had significantly higher risk for lung cancer than those with high BMI. Hazard ratios (95% confidence intervals) of lung cancer for heavy smokers with BMI of ⩾28, 24–<28, 20–<24, and <20 kg m⁻² were 6.37 (2.10–19.30), 9.01 (5.04–16.10), 8.53 (6.35–11.5), and 11.12 (6.60–18.70), respectively, as compared with nonsmokers. BMI had no modifying effects on lung cancer risk among nonsmokers and former smokers.

Conclusion:

Smokers with lower BMI may experience an enhanced risk of lung cancer. The findings have significant public-health implication given the increase in smoking prevalence in developing countries, where people still have relatively low BMI.     

Smoking cessation and lung cancer risk in an Asian population: Findings from the Singapore Chinese Health Study

Background:

Smoking cessation is an important strategy for reducing the harmful effects of tobacco, particularly in the prevention of lung cancer; however, prospective data on the impact of smoking cessation on lung cancer risk in Asian populations are limited.

Methods:

We studied a population-based cohort of Chinese men and women aged 45–74 years – participants of the Singapore Chinese Health Study. Information on smoking, lifestyle and dietary habits was collected at the time of recruitment in 1993–1998; and smoking status was assessed again at a second interview in 1999–2004 (mean interval 5.8 years). Participants were followed up to 31 December 2007, and incident cases of lung cancer were ascertained by linkage with population-wide registries.

Results:

Among 45 900 participants, there were 463 incident cases of lung cancer. Relative to current smokers, those who quit smoking subsequent to baseline assessment had a 28% decrease in the risk of lung cancer (adjusted hazard ratio (HR) 0.72; 95% CI (95% confidence interval): 0.53–0.98). The risk was less than half in ex-smokers who had quit before the first interview and maintained their status (HR 0.42; 95% CI: 0.32–0.56).

Conclusions:

Reduction in lung cancer incidence with smoking cessation in Asian populations is substantial and can be observed within a few years after quitting.     

Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort

Background:

Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics.

Methods:

We conducted a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n=565 cases). Multivariable conditional logistic regression models were used to estimate associations.

Results:

We observed no association between IGF-I and EOC overall or by tumour characteristics.

Conclusions:

In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.     

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.     

Predictive value of miR-9 as a potential biomarker for nasopharyngeal carcinoma metastasis

Background:

Nasopharyngeal carcinoma (NPC) has a distinctive geographic distribution and is characterised by its strong tendency of metastasis. We aimed to examine the microRNA (miRNA) expression profiles in plasma samples of NPC patients to explore their clinical significance in disease development and progression.

Methods:

This study was divided into four steps: (1) confirmation of differentially expressed miRNAs using microarray analysis and quantitative PCR validation; (2) comparison of plasma miR-9 levels during NPC progression; (3) evaluation of the predictive performance of plasma miR-9 as a biomarker for NPC metastasis; and (4) comparison of plasma miR-9 levels between pre- and post-treatment samples.

Results:

Plasma microarray profiling identified 33 differentially expressed miRNAs between NPC patients and healthy volunteers. The significantly declined level of miR-9 in NPC patients was confirmed through two-stage validation. The low level of plasma miR-9 was significantly correlated with worse lymphatic invasion and advanced TNM stage. The plasma miR-9 could distinguish locoregional from metastatic NPC cases with a high sensitivity and specificity. Furthermore, the plasma miR-9 level was significantly elevated in post-treatment plasma compared with those pre-treatment samples.

Conclusion:

Our study reports that plasma miR-9 may serve as a useful biomarker to predict NPC metastasis and to monitor tumour dynamics.     

Mammographic density and its interaction with other breast cancer risk factors in an Asian population

Background:

Joint effects of mammographic density and other risk factors on breast cancer risk remain unclear.

Methods:

From The Singapore Breast Screening Project, we selected 491 cases and 982 controls. Mammographic density was measured quantitatively. Data analysis was by conditional logistic regression.

Results:

Density was a significant risk factor, adjusting for other factors. Density of 76–100% had an odds ratio of 5.54 (95% CI 2.38–12.90) compared with 0–10%. Density had significant interactions with body mass index and oral contraceptive use (P=0.02).

Conclusions:

Percent density increases breast cancer risk in addition to effects of other risk factors, and modifies the effects of BMI and OCs.