Recreational physical activity and epithelial ovarian cancer: a case-control study, systematic review, and meta-analysis.

It remains unclear whether physical activity is associated with epithelial ovarian cancer risk. We therefore examined the association between recreational physical activity and risk of ovarian cancer in a national population-based case-control study in Australia. We also systematically reviewed all the available evidence linking physical activity with ovarian cancer to provide the best summary estimate of the association. The case-control study included women ages 18 to 79 years with a new diagnosis of invasive (n=1,269) or borderline (n=311) epithelial ovarian cancer identified through a network of clinics, physicians, and state cancer registries throughout Australia. Controls (n=1,509) were randomly selected from the national electoral roll and were frequency matched to cases by age and state. For the systematic review, we identified eligible studies using Medline, the ISI Science Citation Index, and manual review of retrieved references, and included all case-control or cohort studies that permitted assessment of an association between physical activity (recreational/occupational/sedentary behavior) and histologically confirmed ovarian cancer. Meta-analysis was restricted to the subset of these studies that reported on recreational physical activity. In our case-control study, we observed weakly inverse or null associations between recreational physical activity and risk of epithelial ovarian cancer overall. There was no evidence that the effects varied by tumor behavior or histologic subtype. Twelve studies were included in the meta-analysis, which gave summary estimates of 0.79 (95% confidence interval, 0.70-0.85) for case-control studies and 0.81 (95% confidence interval, 0.57-1.17) for cohort studies for the risk of ovarian cancer associated with highest versus lowest levels of recreational physical activity. Thus, pooled results from observational studies suggest that a modest inverse association exists between level of recreational physical activity and the risk of ovarian cancer.     

Recreational physical activity and ovarian cancer in a population-based case-control study

Results from epidemiologic studies of physical activity and ovarian cancer have been inconsistent, with 2 prospective studies reporting a modest positive association. We evaluated this relationship in a population-based case-control study conducted in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. Community controls were selected randomly from lists of licensed drivers and Medicare recipients. Participation in moderate and vigorous recreational physical activity at age 12, age 20 and 5 years prior to diagnosis was assessed by telephone interview. Data were available for 327 cases and 3,129 controls. Results were adjusted for age, parity and other ovarian cancer risk factors. Total and vigorous physical activity were not associated with a substantial decrease in ovarian cancer risk at any age. The relative risk (RR) for women reporting > or = 7 vs. 0 hr/week of recent vigorous activity was 0.85 [95% confidence interval (CI) = 0.39-1.86; p for trend = 0.31]. When metabolic equivalent task (MET) hours of activity were estimated, only women in the highest category had any reduction in risk (RR for > 42 MET-hours/week at the reference age = 0.70; 95% CI = 0.36-1.35; p for trend = 0.41). Overall, our results provide only limited support for an inverse association between recreational physical activity and risk of ovarian cancer.     

Physical activity and risk of renal cell cancer

The relation between physical activity and renal cell cancer is unclear. High occupational physical activity has been associated with a decreased risk of renal cell cancer among men-but not among women-in two previous studies, while no association has been found for leisure time physical activity. Our aim was to investigate the association between occupational and leisure time physical activity in a prospective cohort of 17,241 Swedish twins. Information on physical activity and a wide range of potential confounding factors was obtained through a mailed questionnaire. During follow-up from 1967 through 1997 we identified 102 cases of renal cell cancer. We found no evidence of an inverse association between either occupational or leisure time physical activity and risk of renal cell cancer in this prospective cohort.     

Serum Folate Levels and Lung Cancer Risk: A Meta- Epidemiological Study of Population-based Case-Control Studies

Objective: While it has been claimed that lung cancer occurs due to epigenetic mechanisms, four systematic reviews were reported to investigate the association between serum folate levels and lung cancer risk. Considering some methodological problems founded in the systematic review, a meta-epidemiological study was conducted. Methods: The selection criteria of this study were defined that a case-control study was conducted to determine the risk of lung cancer occurrence according to the concentration of serum folate and its results showed odds ratio and its 95% confidence interval. Additional paper was explored from cited lists of 4 papers selected by previous systematic reviews. Random effect model was applied if I-squared value was over 50%. Results: For 5 case-control studies selected, the summary odds ratios (and their 95% confidence intervals) were 0.82 (0.74-0.90) in men, 0.70 (0.62-0.79) in former smokers, and 0.86 (0.75-1.00) in non-smokers. Conclusion: Higher foliate levels can decrease lung cancer risk in men and former smokers. Especially, the protective effect was highest in former smokers compared in non-smokers and current smokers. Based on these facts, folate fortification programs to reduce lung cancer risk would be focused on former smokers in men. And some epidemiological studies are needed to provide a hypothesis to explain the sex differences in the association between folate and lung cancer risk.     

Physical activity and endometrial cancer risk, a systematic review of current evidence.

OBJECTIVE: To assess the epidemiologic evidence for the association between physical activity and endometrial cancer risk, taking into account the methodologic quality of each study. DESIGN: Systematic review, best evidence synthesis. DATA SOURCES: Studies were identified through a systematic review of literature available on PubMed through December 2006. REVIEW METHODS: We included cohort and case-control studies that assessed total and/or leisure time and/or occupational activities in relation to the incidence of endometrial cancer. The methodologic quality of the studies was assessed with a comprehensive scoring system. RESULTS: The included cohort (n = 7) and case-control (n = 13) studies consistently show that physical activity is associated with a decreased risk of endometrial cancer. The best evidence synthesis showed that the majority (80%) of 10 high-quality studies found risk reductions of >20%. Pooling of seven high-quality cohort studies that measured total, leisure time, or occupational activity showed a significantly decreased risk of endometrial cancer (summary estimate: OR, 0.77; 95% CI, 0.70-0.85) for the most active women. Case control studies with relatively unfavorable quality scores reported divergent risk estimates, between 2-fold decreased and 2-fold increased risk. Effect modification by body mass index or menopausal status was not consistently observed. Evidence for an effect of physical activity during childhood or adolescence was limited. CONCLUSIONS: Physical activity seems to be associated with a reduction in the risk of endometrial cancer, which is independent of body weight. Further studies, preferably prospective cohort studies, are needed to determine the magnitude of the risk reduction and to assess which aspects of physical activity contribute most strongly to the reduced risk and in which period of life physical activity is most effective.     

Physical activity and risk of ovarian cancer: a prospective cohort study in the United States.

Increased physical activity may lower the risk of ovarian cancer by reducing the frequency of ovulation, decreasing body fat, or diminishing chronic inflammation. Previous epidemiological studies examining the association between physical activity and risk of ovarian cancer have been inconsistent. We investigated the association of physical activity with ovarian cancer in a prospective cohort of 27,365 individuals from the Breast Cancer Detection Demonstration Project. During 227,045 person-years of follow-up, 121 cases of ovarian cancer were ascertained. Usual physical activity during the past year was assessed by a self-administered questionnaire. After adjusting for potential risk factors for ovarian cancer, the relative risks (95% confidence intervals) across increasing quintiles of total physical activity were 1.0, 0.73 (0.43-1.25), 0.84 (0.50-1.40), 0.56 (0.31-1.00), and 0.70 (0.41-1.21), respectively (P for trend = 0.13). In this prospective cohort study among U.S. women, we found no overall significant association between physical activity and risk of ovarian cancer, although the results are suggestive of an inverse association.     

Physical activity and pancreatic cancer risk: a systematic review

BACKGROUND: Physical activity has been associated with a lower risk for pancreatic cancer in several studies, but the overall epidemiologic evidence is not consistent. We therefore did a systematic review to evaluate the association between physical activity and pancreatic cancer risk. METHODS: We searched MEDLINE and EMBASE through April 2008 and examined the reference lists of the retrieved articles. We excluded studies that relied on job titles as surrogate measures for physical activity. We used a random-effects model to pool study-specific risk estimates comparing the highest versus the lowest category of physical activity. RESULTS: Total physical activity (occupational and leisure time) was not significantly associated with risk for pancreatic cancer [4 prospective studies; summary relative risk, 0.76, 95% confidence interval (95% CI), 0.53-1.09]. A decreased risk for pancreatic cancer was observed for occupational physical activity (3 prospective studies; relative risk, 0.75; 95% CI, 0.58-0.96) but not for leisure-time physical activity (14 prospective studies; relative risk, 0.94; 95% CI, 0.83-1.05). No association was found with light physical activity (2 prospective studies; relative risk, 1.01; 95% CI, 0.77-1.34), moderate physical activity (6 prospective studies; relative risk, 0.83; 95% CI, 0.58-1.18), or vigorous physical activity (7 prospective studies; relative risk, 0.94; 95% CI, 0.80-1.12). CONCLUSIONS: This systematic review does not provide strong evidence for an association between physical activity and risk for pancreatic cancer.     

Physical activity, white blood cell count, and lung cancer risk in a prospective cohort study

Previous studies have suggested that physical activity may lower lung cancer risk. The association of physical activity with reduced chronic inflammation provides a potential mechanism, yet few studies have directly related inflammatory markers to cancer incidence. The relation among physical activity, inflammation, and lung cancer risk was evaluated in a prospective cohort of 4,831 subjects, 43 to 86 years of age, in Beaver Dam, Wisconsin. A total physical activity index was created by summing up kilocalories per week from sweat-inducing physical activities, city blocks walked, and flights of stairs climbed. Two inflammatory markers, WBC count and serum albumin, were measured at the baseline examination. During an average of 12.8 years of follow-up, 134 incident cases of lung cancer were diagnosed. After multivariable adjustment, participants in the highest tertile of total physical activity index had a 45% reduction in lung cancer risk compared with those in the lowest tertile (hazard ratio, 0.55; 95% confidence interval, 0.35-0.86). Participants with WBC counts in the upper tertile (>or=8 x 10(3)/microL) were 2.81 (95% confidence interval, 1.58-5.01) times as likely to develop lung cancer as those with counts in the lowest tertile (<6.4 x 10(3)/microL). Serum albumin was not related to lung cancer risk. There was no evidence that inflammation mediated the association between physical activity and lung cancer risk, as the physical activity risk estimates were essentially unchanged after adjustment for WBC count. Although the potential for residual confounding by smoking could not be eliminated, these data suggest that physical activity and WBC count are independent risk factors for lung cancer.     

Association of Physical Activity and Sedentary Behavior with Colorectal Cancer Risk in Moroccan Adults: A Large-Scale,Population-Based Case–Control Study

Background: Physical activity has been associated with a lower risk of colorectal cancer in studies mainly conducted in high-income countries, while sedentary behavior has been suggested to increase CRC risk. In this study, we aimed to investigate the role of physical activity and sedentary behavior on CRC risk in the Moroccan population. Methods: A case-control study was conducted involving 1516 case-control pairs, matched on age, sex and center in five university hospital centers. A structured questionnaire was used to collect information on socio-demographics, lifestyle habits, family history of CRC, and non-steroidal anti-inflammatory drug (NSAID) use. Information on physical activity and sedentary behavior were collected by the Global Physical Activity Questionnaire (GPAQ). For each activity (work, household, and recreational activities), a metabolic equivalent (MET) was calculated using GPAQ recommendations. Conditional logistic regression models were used to assess the association between physical activity, sedentary behavior and the risk of overall CRC, colon cancer, and rectal cancer taking into account other CRC risk factors. Results: High level of physical activity was associated with lower risk of rectal cancer, colon cancer, and overall CRC, the adjusted odds ratios (ORa) for the highest versus the lowest level of activity were 0.67 (95% CI: 0.54-0.82), 0.77 (95% CI: 0.62-0.96), and 0.72 (95% CI: 0.62-0.83), respectively. In contrast, sedentary behavior was positively associated with rectal cancer risk (ORa=1.19, 95% CI: 1.01-1.40), but was unrelated to colon cancer risk (ORa=1.02, 95% CI: 0.87-1.20). Conclusion: We found an inverse association between physical activity and CRC risk in the Moroccan population, and a positive association between sedentary behavior and rectal cancer risk. Considering that one-third of the total population studied had a sedentary lifestyle, these results may be used to improve strategies of public health suitable for Moroccan population.     

Anti-Diabetic Medications Do Not Influence Risk of Lung Cancer in Patients with Diabetes Mellitus: a Systematic Review and Meta-analysis

Objectives: Several preclinical and observational studies have shown that anti-diabetic medications (ADMs) may modify the risk of lung cancer. We performed a systematic review and meta-analysis evaluating the effect of metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), and insulin on the risk of lung cancer in patients with diabetes mellitus (DM). Materials and Methods: We conducted a systematic search of Pubmed and Web of Science, up to August 20, 2013. We also searched the Conference Proceedings Citation Index (CPCI) andChina National Knowledge Infrastructure (CNKI) for abstracts from major meetings. Fixed or random effect pooled measures were selected based on heterogeneity among studies, which was evaluated using Q test and the I2 of Higgins and Thompson. Meta-regression was used to explore the sources of between-study heterogeneity. Publication bias was analyzed by Begg’s funnel plot and Egger’s regression test. Associations were assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 15 studies (11 cohort, 4 case-control) were included in this meta-analysis. In observational studies no significant association between metformin (n=11 studies; adjusted OR=0.99, 95%CI: 0.87-1.12), SUs (n=5 studies; adjusted OR=0.98, 95%CI: 0.79-1.22), or TZDs (n=7 studies; adjusted OR=0.92, 95%CI: 0.75-1.13), insulin (n=6 studies; adjusted OR=1.13, 95%CI: 0.79-1.62) use and risk of developing lung cancer was noted. There was considerable inherent heterogeneity between studies not explained by study design, setting, or location. Conclusions: Meta-analysis of existing studies does not support a protective or harmful association between ADMs use and risk of lung cancer in patients with DM. There wasconsiderable heterogeneity across studies, and future, well-designed, prospective studies would be required for better understanding of any association.     

Trace elements and cancer risk: a review of the epidemiologic evidence

Worldwide, there are more than 10 million new cancer cases each year, and cancer is the cause of approximately 12% of all deaths. Given this, a large number of epidemiologic studies have been undertaken to identify potential risk factors for cancer, amongst which the association with trace elements has received considerable attention. Trace elements, such as selenium, zinc, arsenic, cadmium, and nickel, are found naturally in the environment, and human exposure derives from a variety of sources, including air, drinking water, and food. Trace elements are of particular interest given that the levels of exposure to them are potentially modifiable. In this review, we focus largely on the association between each of the trace elements noted above and risk of cancers of the lung, breast, colorectum, prostate, urinary bladder, and stomach. Overall, the evidence currently available appears to support an inverse association between selenium exposure and prostate cancer risk, and possibly also a reduction in risk with respect to lung cancer, although additional prospective studies are needed. There is also limited evidence for an inverse association between zinc and breast cancer, and again, prospective studies are needed to confirm this. Most studies have reported no association between selenium and risk of breast, colorectal, and stomach cancer, and between zinc and prostate cancer risk. There is compelling evidence in support of positive associations between arsenic and risk of both lung and bladder cancers, and between cadmium and lung cancer risk.     

Modifiable Factors and Colon Cancer Risk in Thai Population

To demonstrate the possible impact of modifiable factors on colon cancer development in Thai population, we conducted this case-control study from June 2016 until June 2017. The study was conducted in 11 Thai provincial hospitals. The hospitals in this study were selected by stratification by regions. Patients included 504 ones who were newly diagnosed with colon cancer within 1 month. In the control group, 997 health individuals were enrolled. Both case and control were adjusted by age. The results of this study showed that age and socioeconomic factors were associated with colon cancer risk. In addition, it was found that family history of colon cancer had very high association with colon cancer risk. Behavioral factors, including smoking, inadequate physical exercise, and salty food consumption were associated with colon cancer. We detected no association between obesity, alcohol consumption, and colon cancer. The results suggested that colon cancer might have higher association with genetic factors than behavioral factors among Thai patients. Based on the results of this study, stop smoking and promote adequate physical activity are suggested to reduce the incidence of colon cancrr among Thai patients.     

The association between physical activity and renal cancer: systematic review and meta-analysis

Background:

Physical activity may decrease renal cancer risk by reducing obesity, blood pressure, insulin resistance, and lipid peroxidation. Despite plausible biologic mechanisms linking increased physical activity to decreased risk for renal cancer, few epidemiologic studies have been able to report a clear inverse association between physical activity and renal cancer, and no meta-analysis is available on the topic.

Methods:

We searched the literature using PubMed and Web of Knowledge to identify published non-ecologic epidemiologic studies quantifying the relationship between physical activity and renal cancer risk in individuals without a cancer history. Following the PRISMA guidelines, we conducted a systematic review and meta-analysis, including information from 19 studies based on a total of 2 327 322 subjects and 10 756 cases. The methodologic quality of the studies was examined using a comprehensive scoring system.

Results:

Comparing high vs low levels of physical activity, we observed an inverse association between physical activity and renal cancer risk (summary relative risk (RR) from random-effects meta-analysis=0.88; 95% confidence interval (CI)=0.79–0.97). Summarising risk estimates from high-quality studies strengthened the inverse association between physical activity and renal cancer risk (RR=0.78; 95% CI=0.66–0.92). Effect modification by adiposity, hypertension, type 2 diabetes, smoking, gender, or geographic region was not observed.

Conclusion:

Our comprehensive meta-analysis provides strong support for an inverse relation of physical activity to renal cancer risk. Future high-quality studies are required to discern which specific types, intensities, frequencies, and durations of physical activity are needed for renal cancer risk reduction.     

Obesity, diet and risk of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) represents a group of heterogeneous diseases that significantly vary in their causes, molecular profiles, and natural progression. In 2007, there will be approximately 59,000 newly diagnosed NHL cases in the United States and over 300,000 cases worldwide. Although new therapeutic regimens are minimizing the number of deaths related to NHL, causes for the majority of lymphomas remain undetermined. Recent studies suggest that dietary factors may contribute to the rising rates of NHL. This review will summarize epidemiologic reports that have studied the relationship between obesity, physical activity, and diet and risk of NHL. Based on a number of case-control and prospective cohort studies, overweight/obesity probably increases the risk of NHL, whereas moderate physical activity may reduce risk. Several studies support an inverse association between intakes of vegetables and NHL risk, particularly for the consumption of cruciferous vegetables. This may relate to the induction of apoptosis and growth arrest in preneoplastic and neoplastic cells, two important actions of isothiocyanates found in cruciferous vegetables. Studies also suggest that fish intake may be inversely associated with risk of NHL, although findings have not been entirely consistent. This may relate to the high organochlorine content in some fish that could override a protective effect. High consumption of fats, meat, and dairy products also may increase lymphoma risk. The accumulated scientific evidence concerning the associations between obesity, diet, and NHL suggests several identified modifiable risk factors that might be recommended to decrease lymphoma risk.     

Exercise and nutrition interventions in advanced lung cancer: a systematic review

In this systematic review, we sought to evaluate the effect of physical activity or nutrition interventions (or both) in adults with advanced non-small-cell lung cancer (nsclc).

Methods

A systematic search for relevant clinical trials was conducted in 6 electronic databases, by hand searching, and by contacting key investigators. No limits were placed on study language. Information about recruitment rates, protocol adherence, patient-reported and clinical outcome measures, and study conclusions was extracted. Methodologic quality and risk of bias in each study was assessed using validated tools.

Main Results

Six papers detailing five studies involving 203 participants met the inclusion criteria. Two of the studies were single-cohort physical activity studies (54 participants), and three were controlled nutrition studies (149 participants). All were conducted in an outpatient setting. None of the included studies combined physical activity with nutrition interventions.

Conclusions

Our systematic review suggests that exercise and nutrition interventions are not harmful and may have beneficial effects on unintentional weight loss, physical strength, and functional performance in patients with advanced nsclc. However, the observed improvements must be interpreted with caution, because findings were not consistent across the included studies. Moreover, the included studies were small and at significant risk of bias.More research is required to ascertain the optimal physical activity and nutrition interventions in advanced inoperable nsclc. Specifically, the potential benefits of combining physical activity with nutrition counselling have yet to be adequately explored in this population.     

Risk factors for breast cancer: epidemiological evidence from Japanese studies

Although our understanding of the etiology of breast cancer has improved, many well-known risk factors are not modifiable and present knowledge has proved insufficient to allow the disease to be overcome. Indeed, incidence and mortality among Japanese women have increased over the past three decades. Here, we review epidemiological evidence from our cohort and case-control studies among Japanese women in comparison with other published findings. Our studies confirm the important role of established factors derived primarily from Western populations, such as menstrual and reproductive factors, anthropometric factors, physical activity, and alcohol intake, in the development of breast cancer. In addition, we provide further evidence to better understand the role of traditional Japanese foods in the etiology of breast cancer. Our cohort study found that a higher intake of isoflavone and higher levels of plasma genistein, but not daidzein, were associated with a decreased risk of breast cancer. Our case-control studies reveal a dose-response pattern for these compounds; specifically, decreased risk as women move from "no" to "moderate" intake and leveling off thereafter. In addition, gene-environment interactions have been revealed in the effects of isoflavones. The evidence reviewed suggests that isoflavone has a protective effect against breast cancer in Asian populations. Conversely, our cohort study did not observe an inverse association between breast cancer risk and the intake of green tea and/or the plasma level of tea polyphenols, but we did find an association between increased risk and active and passive smoking. In conclusion, based on current knowledge, primary prevention according to individual lifestyle modification should focus on alcohol intake, weight control, physical activity, and tobacco smoking.     

Tobacco smoking and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population

BACKGROUND: It is unclear whether tobacco smoking is related to colorectal cancer risk in Japan. We evaluated the association among the Japanese population based on a systematic review of epidemiologic evidence. METHODS: Original data were obtained from searches of MEDLINE using PubMed, complemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. RESULTS: A total of six cohort studies and 15 case-control studies were thus identified. A substantial degree of heterogeneity was observed in the association between smoking and colon cancer; most case-control studies published before 1994 reported an inverse association, whereas studies conducted over the last decade did not find any significant association. Recent cohort studies have shown a non-significant 20-40% increase in colon cancer risk associated with current smoking. Several recent case-control studies and some cohort studies have identified a weak to strong positive association between smoking and rectal cancer. CONCLUSION: We conclude that tobacco smoking possibly increases the risk of colorectal cancer among the Japanese population. More specifically, tobacco smoking may possibly increase the risk of rectal cancer; however, epidemiologic evidence is still insufficient to demonstrate any clear association with colon cancer.     

Physical activity, water intake and risk of colorectal cancer in Taiwan: a hospital-based case-control study.

The age-adjusted mortality rates of colorectal cancer have been rising in Taiwan over the past 2 decades, and colorectal cancer is now the third leading cause of cancer mortality in the country. We conducted a hospital-based case-control study to clarify the nature of the association between physical activity, water intake and colorectal-cancer risk in Taiwan. A total of 163 subjects (aged 33-80 years) with histologically confirmed primary colorectal cancer and 163 hospital controls were enrolled during 1992. Dietary intake, physical activity and other lifestyle activities were assessed using a comprehensive food-frequency and lifestyle-activity questionnaire. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic-regression analysis. A strong inverse dose-response relation between increased water intake and rectal cancer was found among men after adjustment for other risk factors (p for trend = 0.0005). The OR for rectal cancer among men in the highest tertile of water intake was 0.08 (95% CI, 0.02-0.35) compared with that among men in the lowest tertile (OR = 1). Similar but not significant trends were seen among women (p = 0.29). The OR for colon cancer among men with active leisure-time physical activity was 0.19 (95% CI, 0.05-0.77) times that among sedentary men (p for trend = 0.03). However, physical activity was not associated with colon-cancer risk among women (p = 0.48). No differences in the amount of water intake were found related to level of physical activity. These findings add to the evidence that leisure-time activity may reduce colon-cancer risk, not only in high-risk but also in low-risk populations, and support the potential beneficial effect of increased water intake in reducing colorectal-cancer risk.     

Tobacco smoking and lung cancer risk: an evaluation based on a systematic review of epidemiological evidence among the Japanese population

BACKGROUND: Although tobacco smoking is the best established risk factor for lung cancer, the association is not as strong among Japanese as among Western populations. It would be of value, therefore, to quantify that association in Japan based on a systematic review of epidemiological evidence for the primary prevention of lung cancer. METHODS: Original data were obtained from MEDLINE searches using PubMed, supplemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of the association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer. A meta-analysis was also conducted to estimate the summary measure of those associations. RESULTS: A total of 8 cohort studies and 14 case-control studies were identified, almost all of which consistently showed a strong association of current smoking with the risk of lung cancer. The summary relative risk for current smokers versus never smokers was estimated as 4.39 (95% confidence interval 3.92-4.92) for men and 2.79 (95% confidence interval 2.44-3.20) for women. Cohort studies and case-control studies gave reasonably consistent summary measures. The summary relative risks were 11.7 and 2.30 for squamous cell carcinoma and adenocarcinoma, respectively, in men, and were 11.3 and 1.37 correspondingly in women. CONCLUSION: There is convincing evidence that tobacco smoking strongly increases the risk of lung cancer in the Japanese population, with the relative risk for current smokers compared with never smokers measuring around 4.4 for men and 2.8 for women.