Physical activity,diabetes, and thyroid cancer risk: a pooled analysis of five prospective studies

Purpose  

Although many studies have linked obesity with increased risk of thyroid cancer, few have investigated the role of obesity-related lifestyle characteristics and medical conditions in the etiology of this disease. We examined the associations of self-reported physical activity and diabetes history with thyroid cancer risk in a large pooled analysis of prospective cohort studies.     

Cigarette smoking and the risk of gastric cancer: a pooled analysis of two prospective studies in Japan

To examine the association between cigarette smoking and the risk of gastric cancer, we conducted a pooled analysis of 2 population-based prospective cohort studies in rural northern Japan. Cohort 1 included 9,980 men (>or=40 years old) and Cohort 2 included 19,412 men (40-64 years old). The subjects completed a self-administered questionnaire on cigarette smoking and other health habits. We identified 228 cases of gastric cancer among Cohort 1 subjects (9 years of follow-up with 74,073 person-years) and 223 among Cohort 2 subjects (7 years of follow-up with 141,675 person-years). From each cohort, we computed the relative risk (RR) and 95% confidence interval (CI) of gastric cancer associated with smoking using a Cox regression analysis and pooled these estimates to obtain summary measures. The pooled multivariate RRs (95% CIs) for current smokers and past smokers compared to subjects who had never smoked were 1.84 (1.39-2.43) and 1.77 (1.29-2.43), respectively. The higher number of cigarettes smoked per day among current smokers was associated with a linear increase in risk (trend p < 0.05). The significant increase in risk for past smokers remained for up to 14 years after cessation. An increased risk was noted for cancer of the antrum but not for cardia or body lesions. The risk was increased for both differentiated and nondifferentiated histologic subtypes. Our findings support the hypothesis that cigarette smoking is a risk factor for gastric cancer.     

Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies

The primary risk factor for bladder cancer is cigarette smoking. Using a combined analysis of 11 case-control studies, we have accurately measured the relationship between cigarette smoking and bladder cancer in men. Available smoking information on 2,600 male bladder cancer cases and 5,524 male controls included duration of smoking habit, number of cigarettes smoked per day and time since cessation of smoking habit for ex-smokers. There was a linear increasing risk of bladder cancer with increasing duration of smoking, ranging from an odds ratio (OR) of 1.96 after 20 years of smoking (95% confidence interval [CI] 1.48-2.61) to 5.57 after 60 years (CI 4.18-7.44). A dose relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15-20 cigarettes per day, OR = 4.50 (CI 3.81-5. 33), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% after 1-4 years, OR = 0.65 (0. 53-0.79), and was over 60% after 25 years of cessation, OR = 0.37 (0. 30-0.45). However, even after 25 years, the decrease in risk did not reach the level of the never-smokers, OR = 0.20. (0.17-0.24). The proportion of bladder cancer cases attributable to ever-smoking was 0.66 (0.61-0.70) for all men and 0.73 (0.66-0.79) for men younger than 60. These estimates are higher than previously calculated.     

Cigarette smoking, alcohol drinking and the risk of gallbladder cancer death: a prospective cohort study in Japan

Gallbladder cancer is a rare cancer with a poor prognosis, and few risk factors have been identified to date. This prospective study was conducted to evaluate the association of cigarette smoking and alcohol consumption with the risk of gallbladder cancer death. A baseline survey in 45 areas throughout Japan was conducted from 1988 to 1990 using a self-administered questionnaire, and a total of 113,496 participants (65,740 women) aged 40-89 years at entry were followed for 15 years. During the follow-up period, 165 gallbladder cancer deaths (95 women) were observed. Among women, the hazard ratio (HR) [95 percent confidence interval: 95% CI] of current smoker was 2.00 [0.91-4.42], when adjusted for age and drinking. There was no clear association between alcohol consumption and the risk. Among men, HR of current smoker was 2.27 [1.05-4.90]. HRs of those who smoked 21 cigarettes or more per day and those with 801-1,000 cigarette-years were 3.18 [1.18-8.53] and 3.44 [1.40-8.45], respectively, and positive linear associations were observed between that risk and the number of cigarettes per day (p for trend = 0.007) or "cigarette-years" (p for trend = 0.012). The alcohol dose was linearly associated with risk (p for trend = 0.004), where the HR among those who consumed 72.0 g or more of alcohol per day was 3.60 [1.29-9.85]. Among both men and women, cigarette smoking may elevate the risk of death from gallbladder cancer. Drinking may pose an elevated risk among men, but that seems to be less true among women.     

Cigarette smoking and the risk of thyroid cancer

Thyroid cancer, whose aetiology is largely uncertain, has been negatively associated with cigarette smoking in a number of studies, possibly consistent with the greater occurrence of the disease in women than in men. This association was explored in the context of a Canadian case-control study of thyroid cancer. Newly diagnosed cases were identified primarily through provincial cancer registries in Canada and controls were identified from the general population. Data were collected through mailed questionnaires, yielding 1224 cases and 2659 controls. Reduced risk was observed for ever/never cigarette smoking (risk ratio estimate (RR) of 0.71 (95% confidence interval (CI)=0.60-0.83) for females and 0.77 (95% CI=0.58-1.02)) for males. Dose-response effects were observed with duration, quantity smoked and pack-years of exposure, although there was no decreasing protective effect with the age started smoking or years since stopped smoking. There is evidence of reduced risk for all histological subgroups. The protective effect of smoking may be due to a number of different mechanisms, including an effect on thyroid stimulating hormone and on oestrogen metabolism.     

Cigarette smoking, N-acetyltransferase 2 genotypes, and breast cancer risk: pooled analysis and meta-analysis.

Approximately 10 years ago, it was noted that smoking increased risk of breast cancer among women with N-acetyltransferase 2 (NAT2) slow acetylation genotypes. This report was followed by a number of studies to address this question. We pooled data from 10 existing studies and also conducted a meta-analysis of 13 studies published from 1996 to October 2006 that were conducted among women, were published in English, and had adequate information on smoking and NAT2 genotyping. Raw data were requested from authors. Unconditional logistic regression was done for pooled analysis, and random effect models was done for meta-analysis. Study heterogeneity was assessed, and sensitivity tests were done when subgroups were excluded from the analysis. In the pooled analysis, there was a significant interaction between smoking, NAT2 genotype, and risk of breast cancer [pack-years (continuous variable, P(interaction) = 0.03)], with higher pack-years significantly associated with an increased risk of breast cancer among women with NAT2 slow genotypes (pooled analysis relative risk, 1.49; 95% confidence interval, 1.08-2.04). These findings were supported by the meta-analysis including all studies; pack-years were significantly associated with risk among slow acetylators in a dose-dependent fashion (meta-analysis relative risk, 1.44; 95% confidence interval, 1.23-1.68 for > or =20 pack-years versus never smokers), but not among rapid acetylators. Similar relationships were noted for smoking status (ever, never) and duration of smoking. Our results show that cigarette smoking is associated with an increase in breast cancer risk among women with NAT2 slow acetylation genotypes. Because slow NAT2 genotypes are present in 50% to 60% of Caucasian populations, smoking is likely to play an important role in breast cancer etiology.     

Cigarette smoking, alcohol consumption, and breast cancer risk

The effects of cigarette smoking and alcohol consumption on breast cancer risk were investigated in 276 primary, histologically confirmed breast cancer patients and 1,519 community-based comparison subjects identified in 1977 and 1978 in North Carolina. Data on both behaviors and other pertinent personal and medical characteristics were obtained by interview. Analytic methods included stratification and logistic regression. Among current cigarette smokers of 1-20 cigarettes per day and over 20 per day, the odds ratios (ORs) adjusted for age, race, alcohol consumption, estrogen use, and oral contraceptive use for breast cancer were 0.75 [95% confidence interval (CI) 0.52-1.09] and 0.57 (95% CI 0.30-1.08), respectively. A decrease in risk was not seen in former smokers. With respect to alcohol consumption, the adjusted OR for those having one drink or more per week compared to those having less than one was 1.45 (95% CI 0.99-2.12). If the comparison was ever versus never drinkers, the adjusted OR was 1.47 (95% CI 1.10-1.97); for current drinkers versus nondrinkers, the adjusted OR was 1.89 (95% CI 1.40-2.56). The ORs were adjusted for age, race, cigarette smoking, estrogen use, an oral contraceptive use. These data supports those reports showing an inverse association of cigarette smoking and a positive association of alcohol consumption with breast cancer risk.     

DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis

Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies. In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1-28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association was detected. The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years.     

Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies

Alcohol has been hypothesized to promote ovarian carcinogenesis by its potential to increase circulating levels of estrogen and other hormones; through its oxidation byproduct, acetaldehyde, which may act as a cocarcinogen; and by depletion of folate and other nutrients. Case-control and cohort studies have reported conflicting results relating alcohol intake to ovarian cancer risk. We conducted a pooled analysis of the primary data from ten prospective cohort studies. The analysis included 529 638 women among whom 2001 incident epithelial ovarian cases were documented. After study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then were pooled using a random effects model; no associations were observed for intakes of total alcohol (pooled multivariate RR=1.12, 95% CI 0.86-1.44 comparing > or =30 to 0 g day(-1) of alcohol) or alcohol from wine, beer or spirits and ovarian cancer risk. The association with alcohol consumption was not modified by oral contraceptive use, hormone replacement therapy, parity, menopausal status, folate intake, body mass index, or smoking. Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. This pooled analysis does not support an association between moderate alcohol intake and ovarian cancer risk.     

Cigarette smoking and breast cancer risk among young women (United States)

Objectives: To evaluate whether heavy cigarette smoking as a teenager or long-term smoking increases breast cancer risk or, alternatively, whether smoking acts as an anti-estrogen and reduces risk.Methods: Data from a multi-center, population-based, case-control study among women under age 55 were analyzed.Results: Among women under age 45, there was a modest inverse relation with current (OR=0.82, 95% CI=0.67, 1.01) but not past (OR=0.99, 95% CI=0.81, 1.21) smoking. Odds ratios were decreased for current smokers who began at an early age (0.59 for15, 95% CI=0.41, 0.85) or continued for long periods of time (0.70 for >21 years, 95% CI=0.52, 0.94). In subgroup analyses, reduced odds ratios were observed among current smokers who were ever users of oral contraceptives (0.79, 95% CI=0.63, 0.98), were in the lowest quartile of adult body size (0.53, 95% CI=0.34, 0.81), or never or infrequently drank alcohol (0.68, 95% CI=0.47, 0.98). Among women ages 45-54, there was little evidence for an association with smoking.Conclusions: These results suggest that breast cancer risk among women under age 45 may be reduced among current smokers who began smoking at an early age, or long-term smokers, but require confirmation from other studies.     

Cigarette smoking and risk of prostate cancer in the physicians' health study (United States)

To assess whether cigarette smoking is associated with prostate cancer incidence or mortality, we analyzed a large cohort of 22,071 men, aged 40-84 at baseline, in the Physicians' Health Study. During an average of 12.5 years of follow-up, we documented 996 cases of prostate cancer, including 113 fatal cases. Men were categorized according to smoking status, total pack-years smoked, and duration of smoking. We used Cox proportional hazard models to estimate the relative risks associated with smoking. Compared to never smokers, the age-adjusted relative risks (RR) of total prostate cancer were 1. 14 (95% confidence interval [CI] = 1.00-1.30) for past smokers, 1.10 (95% CI = 0.78-1.55) for current smokers of less than 20 cigarettes per day, and 1.10 (95% CI = 0.84-1.44) for current smokers of 20 or more cigarettes per day. Adjustment for body mass index, height, alcohol intake, and physical activity did not materially alter these findings. No significant association was observed in analyses of total pack-years smoked or duration of smoking. The results were similar for non-fatal and fatal prostate cancer. These data indicate no material association between cigarette smoking and prostate cancer incidence or mortality.     

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.     

Cigarette smoking and breast cancer risk: update of a prospective cohort study

SummaryIntroduction Ultrasound (US) preoperative examination of the axillary lymph nodes combined with the fine needle aspiration biopsy (FNAB) is often used in order to reduce the number of sentinel lymph node (SLN) biopsy procedures in clinically node negative breast cancer patients. The pathohistological characteristics of the ultrasonically negative axillary lymph nodes in clinically negative axillary lymph nodes are not known. The aim of our study was to compare the pathohistological characteristics of ultrasonically uninvolved axillary lymph nodes (US group) versus clinically uninvolved axillary lymph nodes (non-US group) in SLN biopsy candidates.Methods We included 658 patients after SLN biopsy; 286 patients in the US group and 372 in the non-US group. The pathohistological characteristics of axillary lymph nodes were evaluated by univariate analysis and logistic regression.Results In the univariate analysis, the proportion of macrometastastic SLN, total number of metastatic lymph nodes per patient, proportion of nonsentinel lymph node (NSLN) metastases and proportion of NSLN macrometastases were found to be lower in the US group compared to the non-US group. In the logistic regression model, only US of the axilla (p=0.010; OR: 0.57) and tumor size were significant predictors for the presence of SLN macrometastases or macrometastatic NSLN (p<0.001; OR: 0.23).Conclusion The patients with US negative axillary lymph nodes form a distinct subgroup of early breast cancer patients having a significantly lower tumor burden in the axillary lymph nodes compared to those with only clinically negative axillary lymph nodes.     

Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies

Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8-143.2) for SqCC, 111.3 (95% CI: 69.8-177.5) for SCLC and 21.9 (95% CI: 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5-124.6), 108.6 (95% CI: 50.7-232.8) and 16.8 (95% CI: 9.2-30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.     

Birth order and risk of childhood cancer: A pooled analysis from five US States

The causes of childhood cancers are largely unknown. Birth order has been used as a proxy for prenatal and postnatal exposures, such as frequency of infections and in utero hormone exposures. We investigated the association between birth order and childhood cancers in a pooled case‐control dataset. The subjects were drawn from population‐based registries of cancers and births in California, Minnesota, New York, Texas and Washington. We included 17,672 cases <15 years of age who were diagnosed from 1980 to 2004 and 57,966 randomly selected controls born 1970–2004, excluding children with Down syndrome. We calculated odds ratios and 95% confidence intervals using logistic regression, adjusted for sex, birth year, maternal race, maternal age, multiple birth, gestational age and birth weight. Overall, we found an inverse relationship between childhood cancer risk and birth order. For children in the fourth or higher birth order category compared to first‐born children, the adjusted OR was 0.87 (95% CI: 0.81, 0.93) for all cancers combined. When we examined risks by cancer type, a decreasing risk with increasing birth order was seen in the central nervous system tumors, neuroblastoma, bilateral retinoblastoma, Wilms tumor and rhabdomyosarcoma. We observed increased risks with increasing birth order for acute myeloid leukemia but a slight decrease in risk for acute lymphoid leukemia. These risk estimates were based on a very large sample size, which allowed us to examine rare cancer types with greater statistical power than in most previous studies, however the biologic mechanisms remain to be elucidated.     

Fruit and vegetable intake and gastric cancer risk in a large United States prospective cohort study

OBJECTIVE: Fruit and vegetable intake may protect against gastric cancer incidence. Results from case-control studies have indicated an inverse association, but results from cohort studies are inconsistent. METHODS: We prospectively investigated the association in 490,802 participants of the NIH-AARP Diet and Health Study using Cox proportional hazards models adjusted for gastric cancer risk factors. We present hazard ratios (HR) and 95% confidence intervals (CI) per increase of one daily serving per 1,000 calories. RESULTS: During 2,193,751 person years, 394 participants were diagnosed with incident gastric cancer. We observed no significant associations between total fruit and vegetable intake (1.01, 0.95-1.08), fruit intake (1.04, 0.95-1.14), or vegetable intake (0.98, 0.88-1.08) and gastric cancer risk. Results did not vary by sex or anatomic subsite (cardia versus non-cardia). All 13 botanical subgroups examined had no significant associations with either anatomic sub-site. CONCLUSION: We did not observe significant associations between overall fruit and vegetable intake and gastric cancer risk in this large prospective cohort study.     

Cigarette smoking, alcohol consumption and risk of breast cancer in young women

The possible association between cigarette smoking, alcohol consumption and the risk of development of breast cancer before the age of 45 was investigated by means of a population-based case-control study in Sweden and Norway. Information was obtained, by personal interview, from 422 (89.2%) of all eligible patients with breast cancer newly diagnosed between May 1984 and May 1985, and from 527 (80.6%) of all age-matched controls. The possible confounding effects of oral contraceptive (OC) use, education, and reproductive and several other factors were taken into account in multivariate analyses. No association was found between ever smoking (versus never smoking) and breast cancer (odds ratio 1.0; 95% confidence interval (CI) 0.8-1.3). Further, there was no relation between breast cancer and duration of smoking, age at start of regular smoking, length of time since the start of regular smoking, or number of cigarettes smoked per day. There was no significant interaction between smoking, use of OCs, parity, and breast cancer. A moderate or high current consumption of beer, wine, liquor or total alcohol did not increase the risk of breast cancer. An alcohol intake of 5 grams per day or more was associated with a decreased risk of breast cancer (odds ratio 0.6; 95% CI 0.4-0.9), but possible effects of a change in habits after diagnosis, of recall bias and of residual confounding, e.g. by dietary habits, need serious consideration.