A prospective cohort study of cigarette smoking and the risk of endometrial cancer

Case-control studies have shown inverse associations between cigarette smoking and endometrial cancer risk. However, two small prospective cohort studies have not clearly supported an association. Moreover, quantitative measures of smoking have been examined infrequently. Our aim was to study the association between smoking and endometrial cancer risk in a large prospective cohort. We used proportional hazards models to estimate hazard ratios relating cigarette smoking to endometrial cancer risk among 70 591 women aged 40-59 years at recruitment into a randomised controlled trial of mammography screening for breast cancer. During an average of 10.6 years of follow-up (751 833 person-years), a total of 403 women were diagnosed with incident endometrial cancer. We found that a reduced endometrial cancer risk was evident only among women who currently smoked 20 cigarettes per day or more (hazard ratio=0.62, 95% CI=0.42-0.92, P for trend=0.03). There was some suggestion of an inverse association with smoking duration, but this was less clear. The association did not vary with menopausal status, relative body weight, or the use of hormone replacement therapy, but it appeared to be stronger among parous than nulliparous women. The underlying biological mechanisms of this association remain unclear.     

A prospective cohort study of cigarette smoking and pancreatic cancer in Japan

Objective: To examine the association of cigarette smoking with the risk of death from pancreatic cancer in a prospective cohort study. Methods: A total of 110,792 inhabitants, aged 40–79 years (46,465 men and 64,327 women), were enrolled from 1988 to 1990 and followed up for mortality to the end of 1997. At baseline a self-administered questionnaire was used to obtain information on cigarette smoking and other lifestyle factors. Results: During the follow-up period (mean ± SD: 8.1 ± 1.8 years), 225 deaths due to pancreatic cancer were identified. After adjustment for age, body mass index, history of diabetes mellitus, and gallbladder diseases, the relative risks (RRs) for current smokers were 1.6 (95% CI 0.95–2.6) in males, and 1.7 (95% CI: 0.84–3.3) in females. Men who smoked more than 40 cigarettes per day had a substantially higher risk of pancreatic cancer, with a RR of 3.3 (95% CI: 1.4–8.1). A significantly decreasing trend in risk with increasing years after smoking cessation was observed (trend p = 0.04) among male ex-smokers. The RRs were 0.85 (95% CI 0.36–2.0) and 0.85 (0.36–2.0) for those who had quit smoking for 10–19 and 20 years, respectively. Conclusions: Our cohort study confirmed that cigarette smoking was associated with an increased risk of death from pancreatic cancer.     

Prospective cohort study of cigarette smoking and colorectal cancer risk in women

Epidemiological studies have consistently found a positive association between cigarette smoking and risk of colorectal adenomas, so the absence of a clear association between smoking and colorectal cancer risk may seem paradoxical. However, if colorectal cancer develops only after an induction period of about 35 years, as has been proposed recently, then studies in which all subjects have fewer than about 35 years between smoking commencement and assessment of outcome would be unlikely to detect this association. Few studies have examined smoking of several decades' duration among women. Therefore, in the cohort study reported here, we used proportional hazards models to estimate hazard ratios relating cigarette smoking to colorectal cancer risk among 89,835 women aged 40-59 years at recruitment into the Canadian National Breast Screening Study, a randomized controlled trial of mammography screening for breast cancer. During an average 10.6 years of follow-up (936,433 person-years), a total of 527 women were diagnosed with incident colorectal cancer (363 colon and 164 rectal). We found that smoking was associated with increased risk of rectal cancer 30 years or more after commencement, and especially with smoking of 40 years' duration or longer (hazard ratio=3.14, 95% CI=1.33-7.42). There was little evidence for altered risk of colon cancer. These results, along with those of other recent studies, support the hypothesis that tobacco smoking is an initiator, rather than a promoter, of rectal cancer. However, the results do not support an association with colon cancer risk, even with smoking of very long duration and high intensity.     

Dietary fiber and colorectal cancer risk: the multiethnic cohort study

OBJECTIVE: To investigate the association of dietary fiber with colorectal cancer METHODS: A total of 85,903 men and 105,108 women completed a quantitative food frequency questionnaire in 1993-1996. A total of 1,138 men and 972 women were subsequently diagnosed with adenocarcinoma of the large bowel. Cox proportional hazards models were used to calculate multivariate adjusted relative risks (RR) and 95% confidence intervals (95% CI) for colorectal cancer. RESULTS: High consumers of dietary fiber were more active, less overweight, and less likely to be cigarette smokers than low consumers in both sexes. Fiber was inversely associated with colorectal cancer risk after adjustment for age and ethnicity in men (RR = 0.49; 95% CI, 0.41-0.60, highest vs. lowest quintile) and women (RR = 0.75; 95% CI, 0.61-0.92). After further adjustment for lifestyle and dietary factors, the inverse association remained significant in men (RR = 0.62; 95% CI, 0.48-0.79), but not in women (RR = 0.88; 95% CI, 0.67-1.14). Adjustment for the combination of replacement hormone use with either cigarette smoking or body mass index accounted for the lack of association with fiber in women. CONCLUSION: Dietary fiber was inversely associated with colorectal cancer risk in men, but its relation to replacement hormone use and other factors affected its inverse association in women.     

Diet impacts mortality from cancer: results from the multiethnic cohort study

Purpose

Cancer is the second leading cause of death in the United States and mortality varies by ethnicity. The objective of this study was to examine the association between cancer mortality and dietary intake among a large multiethnic population.

Methods

A prospective cohort design was used to examine cancer mortality among 146,389 participants. Multiethnic cohort study participants represent five ethnic groups: African American, Native Hawaiian, Japanese American, Latino, and Caucasian. Hazard ratios for cancer mortality by intake levels of five food groups and discretionary fat were calculated using Cox proportional hazards models stratified by sex and ethnicity.

Results

There were a total of 2,028 male and 1,464 female fatal cancer cases at the end of follow-up. Among Japanese American men only, there was a significant protective effect seen in those reporting a high grain intake (HR = 0.49, 95 % CI 0.35–0.69); there was no effect of grain consumption in any other ethnic-sex group. There was no evidence that ethnicity modified associations between fruit, vegetable, meat, dairy, or discretionary fat intake and cancer mortality among men. Associations between food group consumption and risk for cancer mortality among women were similar across ethnic groups.

Conclusions

The considerable reduction in cancer risk associated with high grain consumption among a specific ethnic-sex group, Japanese American men, warrants further investigation. Additional research is needed to validate this observation and determine whether this was a chance finding, or possibly due to differential intake of specific grain subtypes, and/or related to a sex-specific cancer type.     

Associations of cigarette smoking and alcohol drinking with stomach cancer survival: A prospective patient cohort study in Japan

Cigarette smoking and alcohol drinking may affect the prognosis of stomach cancer, but evidence has been inconsistent. We investigated the associations between pretreatment smoking and alcohol drinking and the risk of all‐cause and stomach cancer death among 1,576 patients with histologically confirmed stomach cancer diagnosed during 1997–2010 at a single hospital in Japan. Histories of smoking and alcohol drinking were assessed using a self‐administered questionnaire. The patients were followed until December 31, 2013. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 9,625.1 person‐years, 670 all‐cause and 419 stomach cancer deaths were documented. Among the patients overall, ever‐drinking was significantly associated with an increased risk of all‐cause death (HR: 1.25; 95% CI: 1.03–1.51), but not stomach cancer death. Positive linear associations with the frequency of drinking (p_trend = 0.02) and the amount of alcohol consumed per day (p_trend = 0.03) were observed for the risk of all‐cause death. Ever‐smoking was not related to either the risk of all‐cause or stomach cancer death. Conversely, among the patients who underwent curative resection, a significant positive association was found between ever‐smoking and the risk of stomach cancer death (HR: 2.44; 95% CI: 1.17–5.08). A positive association was also found for earlier age at start of smoking (p_trend = 0.0046). Pretreatment smoking and alcohol drinking have significant effects on stomach cancer survival. Lifestyle adjustments throughout life may improve survival.     

The MTHFR C677T polymorphism and colorectal cancer: the multiethnic cohort study.

Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in the metabolism of folate, a nutrient that has been inversely related to colorectal cancer risk. The common C677T variant in the MTHFR gene results in a reduced activity of this enzyme, thereby increasing the availability of folate for the production of thymidylate and purine for DNA synthesis and repair. We investigated the association of the 677TT genotype with colorectal cancer in a case-control study of 822 cases and 2,021 controls nested within the Multiethnic Cohort Study. The Multiethnic Cohort Study is a large prospective study of men and women of Japanese, White, African American, Latino, and Native Hawaiian origin, residing in Hawaii and Los Angeles. After adjusting for covariates, we found an inverse association between colorectal cancer risk and the TT genotype, with odds ratios (OR; and 95% confidence intervals) for the CC, CT, and TT genotypes of 1.00, 1.01 (0.84-1.21), and 0.77 (0.58-1.03), respectively. This association was similar in both sexes, stronger at high levels of folate intake, and limited to light and nondrinkers (P for interaction with ethanol = 0.02). An analysis by subsite (rectum versus colon) and stage (regional/distant versus in situ/localized) showed that the inverse association with the TT genotype was limited to colon tumors, especially those diagnosed at an advanced stage. The OR for the TT versus CC genotype for early- and late-stage colon cancer was 0.88 (0.58-1.33) and 0.52 (0.32-0.85), respectively (P for difference in OR = 0.04). The frequency of the T allele was relatively low in African Americans (0.13) and Native Hawaiians (0.22), consistent with their greater likelihood of presenting at a late stage when diagnosed with colorectal cancer. This study corroborates previous findings of an inverse association of the MTHFR 677TT genotype with colorectal cancer, especially at high levels of folate and low levels of ethanol intake. It also suggests that this effect may be specific to advanced colon cancer.     

Association between ambient air pollution and breast cancer risk: The multiethnic cohort study

Previous studies using different exposure methods to assess air pollution and breast cancer risk among primarily whites have been inconclusive. Air pollutant exposures of particulate matter and oxides of nitrogen were estimated by kriging (NO_x, NO₂, PM₁₀, PM_2.5), land use regression (LUR, NO_x, NO₂) and California Line Source Dispersion model (CALINE4, NO_x, PM_2.5) for 57,589 females from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993–1996) through 2010. Cox proportional hazards models were used to examine the associations between time-varying air pollution and breast cancer incidence adjusting for confounding factors. Stratified analyses were conducted by race/ethnicity and distance to major roads. Among all women, breast cancer risk was positively but not significantly associated with NO_x (per 50 parts per billion [ppb]) and NO₂ (per 20 ppb) determined by kriging and LUR and with PM_2.5 and PM₁₀ (per 10 μg/m³) determined by kriging. However, among women who lived within 500 m of major roads, significantly increased risks were observed with NO_x (hazard ratio [HR] = 1.35, 95% confidence interval [95% CI]: 1.02–1.79), NO₂ (HR = 1.44, 95% CI: 1.04–1.99), PM₁₀ (HR = 1.29, 95% CI: 1.07–1.55) and PM_2.5 (HR = 1.85, 95% CI: 1.15–2.99) determined by kriging and NO_x (HR = 1.21, 95% CI:1.01–1.45) and NO₂ (HR = 1.26, 95% CI: 1.00–1.59) determined by LUR. No overall associations were observed with exposures assessed by CALINE4. Subgroup analyses suggested stronger associations of NO_x and NO₂ among African Americans and Japanese Americans. Further studies of multiethnic populations to confirm the effects of air pollution, particularly near-roadway exposures, on the risk of breast cancer is warranted.     

Fat and meat intake and prostate cancer risk: the multiethnic cohort study

Dietary fat and meat as potential risk factors for prostate cancer have been the focus of many epidemiologic investigations, and findings from recent studies in particular have been inconsistent. Therefore, we examined the association between these exposures and prostate cancer risk in the Multiethnic Cohort Study. The analyses included 82,483 men in Hawaii and Los Angeles aged >or=45, who completed a detailed quantitative food frequency questionnaire in 1993-1996. During the follow-up period of 8 years, a total of 4,404 incident cases, including 1,278 nonlocalized or high-grade cancer cases, were identified. Cox proportional hazard models were used to estimate relative risks of prostate cancer after adjustment for time on study, ethnicity, family history of prostate cancer, education, body mass index, smoking status and energy intake. Intake of different types of fat (total, saturated, monounsaturated or polyunsaturated), n-6 fatty acid, cholesterol, various meats, and fats from meat showed no association with overall prostate cancer risk or with nonlocalized or high-grade prostate cancer. Furthermore, we found little evidence of any relation of fat and meat intake with prostate cancer risk within any of the 4 racial/ethnic groups (African Americans, Japanese Americans, Latinos and Whites). There was a suggestion of a protective effect of n-3 fatty acid intake that was limited to Latinos and Whites. However, overall, our findings from a large cohort study of ethnically diverse population give no indication that intake of fat and meat substantially affects prostate cancer risk.     

Racial/ethnic differences in colorectal cancer risk: the multiethnic cohort study

Incidence rates in the United States show clear racial/ethnic disparities for colorectal cancer. We examined the extent to which ethnic differences in risk factors could explain the age-adjusted variation in the risk of colorectal cancer, overall and by stage at diagnosis, among 165,711 African Americans, Japanese Americans, Latinos, Native Hawaiians and whites participating in the Multiethnic Cohort Study. Over a median follow-up period of 10.7 years, 2,564 incident cases of colorectal cancer were identified through surveillance, epidemiology and end result tumor registry linkages in Hawaii and California. Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for each ethnic group compared to whites. After accounting for known/suspected risk factors, Japanese Americans (men, RR = 1.27, 95% CI = 1.09-1.48; women, RR = 1.49, 95% CI = 1.24-1.78) and African American women (RR = 1.48, 95% CI = 1.23-1.79) remained at increased risk of colorectal cancer relative to whites; African American and Japanese American women were also at increased risk of advanced disease compared to whites. In site-specific analyses, after multivariable adjustment, African Americans (both sexes) and Japanese American women remained at increased risk for colon cancer, and Japanese Americans (both sexes) and Native Hawaiian men for rectal cancer compared to whites. The results of our study suggest that differences in the distribution of known/suspected risk factors account for only a modest proportion of the ethnic variation in colorectal cancer risk and that other factors, possibly including genetic susceptibility, are important contributors to the observed disparities in incidence.     

Type 2 diabetes and colorectal cancer survival: The multiethnic cohort

This analysis examined type 2 diabetes (T2D) as a predictor of colorectal cancer (CRC) survival within the Multiethnic Cohort Study. Registry linkages in Hawaii and California identified 5,284 incident CRC cases. After exclusion of cases with pre‐existing cancer diagnosis within 1 year and systemic disease, the analytic dataset had 3,913 cases with 1,800 all‐cause and 678 CRC‐specific deaths after a mean follow‐up of 9.3 ± 5.2 years. Among CRC cases, 707 were diagnosed with T2D 8.9 ± 5.3 years before CRC. Cox regression with age as time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for T2D status as predictor of CRC‐specific and all‐cause survival while adjusting for known confounders. Overall, CRC‐specific survival was not associated with pre‐existing T2D (HR = 0.84; 95% CI = 0.67–1.07). However, a significant interaction was seen for comorbidity (p_interaction = 0.03) with better survival among those without pre‐existing conditions (HR = 0.49; 95% CI = 0.25–0.96) while no association was seen in patients with comorbid conditions. All‐cause mortality was also not related to pre‐existing T2D (HR = 1.11; 95% CI = 0.98–1.27), but significantly elevated for individuals with T2D reporting comorbid conditions (HR = 1.36; 95% CI = 1.19–1.56). Stratification by T2D duration suggested higher CRC‐specific and all‐cause mortality among participants with a T2D history of ≥10 than <10 years. The findings were consistent across sex and ethnic subgroups. In contrast to previous reports, pre‐existing T2D had no influence on disease‐specific and all‐cause survival among CRC patients. Only participants with additional comorbidity and possibly those with long T2D duration experienced higher mortality related to T2D.     

Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast cancer risk: the multiethnic cohort.

Collective evidence suggests that the insulin-like growth factor (IGF) system plays a role in prostate and breast cancer risk. IGF-binding proteins (IGFBP) are the principal regulatory molecules that modulate IGF-I bioavailability in the circulation and tissues. To examine whether inherited differences in the IGFBP1 and IGFBP3 genes influence prostate and breast cancer susceptibility, we conducted two large population-based association studies of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites. To thoroughly assess the genetic variation across the two loci, we (a) sequenced the IGFBP1 and IGFBP3 exons in 95 aggressive prostate and 95 advanced breast cancer cases to ensure that we had identified all common missense variants and (b) characterized the linkage disequilibrium patterns and common haplotypes by genotyping 36 single nucleotide polymorphisms (SNP) spanning 71 kb across the loci ( approximately 20 kb upstream and approximately 40 kb downstream, respectively) in a panel of 349 control subjects of the five racial/ethnic groups. No new missense SNPs were found. We identified three regions of strong linkage disequilibrium and selected a subset of 23 tagging SNPs that could accurately predict both the common IGFBP1 and IGFBP3 haplotypes and the remaining 13 SNPs. We tested the association between IGFBP1 and IGFBP3 genotypes and haplotypes for their associations with prostate and breast cancer risk in two large case-control studies nested within the Multiethnic Cohort [prostate cases/controls = 2,320/2,290; breast cases (largely postmenopausal)/controls = 1,615/1,962]. We observed no strong associations between IGFBP1 and IGFBP3 genotypes or haplotypes with either prostate or breast cancer risk. Our results suggest that common genetic variation in the IGFBP1 and IGFBP3 genes do not substantially influence prostate and breast cancer susceptibility.     

Alcohol consumption and endometrial cancer risk: the multiethnic cohort

The role of alcohol intake in the etiology of endometrial cancer is unclear. We examined the impact of alcohol intake on endometrial cancer risk among 41,574 postmenopausal African-American, Japanese-American, Latina, Native-Hawaiian and White women recruited to the prospective Multiethnic Cohort Study in 1993-1996. During an average of 8.3 years of follow-up, 324 incident invasive endometrial cancer cases were identified among these women. Data on alcohol intake and endometrial cancer risk factors were obtained from the baseline questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with alcohol intake were estimated using log-linear (Cox) proportional hazard models stratified by age, year of recruitment, ethnicity and study center, and adjusted for several confounding factors. Increased alcohol consumption was associated with increased risk (p trend = 0.013). Compared to nondrinkers, women consuming >or=2 drinks/day had a multivariate RR of 2.01 (95% CI: 1.30, 3.11). There was no increase in risk associated with <1 drink/day (RR = 1.01; 95% CI: 0.77, 1.33) and 1 to <2 drinks/day (RR = 1.09; 95% CI: 0.62, 1.93). There was no clear effect modification by body mass index, postmenopausal hormone use, parity, oral contraceptive use or smoking status, though our power to detect such interactions was limited. Our results suggest that only alcohol consumption equivalent to 2 or more drinks per day increases risk of endometrial cancer in postmenopausal women.     

The effect of secondhand smoke exposure on the association between active cigarette smoking and colorectal cancer

Background  

Studies published prior to 1980 failed to find an association between smoking and colorectal cancer, while subsequent studies reported an association after accounting for a three to four decade initiation period. The aims of this study were to determine the effect of accounting for secondhand smoke (SHS) exposure on the association between smoking and colorectal cancer and to determine the association between SHS and colorectal cancer.     

The association between smoking cessation before and after diagnosis and non-muscle-invasive bladder cancer recurrence: a prospective cohort study

Background

Smoking is a major risk factor for bladder cancer, but the relationship between smoking cessation after initial treatment and bladder cancer recurrence has been investigated less frequently and not prospectively yet.

Methods

722 non-muscle-invasive bladder cancer (NMIBC) patients (pTa, pT1, and CIS) from the prospective Bladder Cancer Prognosis Programme (BCPP) cohort, selected in the UK between 2005 and 2011, provided complete data on smoking behavior before and up to 5 years after diagnosis. The impact of smoking behavior on NMIBC recurrence was explored by multivariable Cox regression models investigating time-to-first NMIBC recurrence.

Results

Over a median follow-up period of 4.21 years, 403 pathologically confirmed NMIBC recurrences occurred in 210 patients. Only 25 current smokers at diagnosis quit smoking (14%) during follow-up and smoking cessation after diagnosis did not decrease risk of recurrence compared to continuing smokers (p?=?0.352).

Conclusions

Although quitting smoking after diagnosis might reduce the risk of recurrence based on retrospective evidence, this is not confirmed in this prospective study because the number of NMIBC patients quitting smoking before their first recurrence was too low. Nevertheless, this indicates an important role for urologists and other health care professionals in promoting smoking cessation in NMIBC.

     

A large-scale cohort study on risk factors for primary liver cancer, with special reference to the role of cigarette smoking

A large-scale cohort study in Japan (1966–1982) on life styles and primary liver cancer in men (123 out of 1709273 person-years) revealed a close association with cigarette smoking comparable to that for lung cancer, the relative risk (r.r.) for those smoking 1–29 and 30 or more cigarettes daily being 3.09 (1.78–5.35), 6.83 (3.56–13.10) for liver cancer, and 4.45 (3.77–5.25), 6.80 (5.51–8.41) for lung cancer, respectively. For liver cirrhosis, daily cigarette smoking was of less importance compared to daily alcohol drinking, r.r.=1.17 (1.00–1.36) and 1.82 (1.63–2.04). However, for liver cancer, the risk from daily cigarette smoking was much higher than from daily alcohol drinking, r.r=3.14 (1.82–5.42) and 1.89 (1.40–2.55). The risk of liver cancer among the liver cirrhosis cases was therefore calculated as 2.67 (1.49–4.79) for daily cigarette smokers and 1.00 (0.72–1.38) for daily alcohol drinkers. These results must be of special importance in interpreting the reason for the increasing, unique mortality trend of liver cancer in men in recent years in Japan.     

Bladder cancer and cigarette smoking in males: a case-control study

Cigarette consumption was compared between 355 males with cancer of the lower urinary tract and 276 male hospital controls. Both duration of smoking and average daily consumption of cigarettes showed a dose-response relationship with risks of developing bladder cancer. Quitting smoking seems to have a protective role, whereas higher relative risks are associated with an early age at start of smoking. The use of a filter seems to have a weak protective effect.