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A prospective study of body size and colon cancer mortality in Japan: The JACC Study


OBJECTIVE: To determine whether body size measurements are risk factors for colon cancer death among the Japanese.

DESIGN AND SUBJECTS: A nationwide prospective study, the Japan Collaborative Cohort (JACC) Study from 1988 to 1999. The present analysis included 43?171 men and 58?775 women aged 40–79?y who respond to a questionnaire on current weight and height, weight around 20?y of age, and other lifestyle factors. Body mass index (BMI) at baseline and 20?y of age (B-BMI and 20-BMI, respectively) were calculated.

RESULTS: We identified 127 deaths from colon cancer during the follow-up of 424?698 person-years among men and 122 deaths during the follow-up of 591?787 person-years among women. After adjustments for the lifestyle factors known to modify the risk of colon cancer, weight at baseline showed a significant positive association in women, while no such association was seen in men. There was also a significant trend of increasing risk with the increase in B-BMI among women. Women with B-BMI ≥28?kg/m2 had a relative risk (RR) of 3.41 (95% confidence interval (CI): 1.44–8.06) compared with those with BMI of 20–<22?kg/m2. 20-BMI also presented the same trend of increasing risk as B-BMI. Women with 20-BMI of <22 and B-BMI of >26?kg/m2, that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29–9.02) compared with those with 20-BMI of <22 and B-BMI of <22?kg/m2. There were no corresponding trends of colon cancer risk for B-BMI, 20-BMI, or BMI change among men.

CONCLUSIONS: These study data suggest that obesity and excessive weight gain are associated with the risk of colon cancer death in Japanese women but no such relationship was found in Japanese men.


Colon cancer is now the fourth leading cause of cancer death among men and the third among women in Japan. This malignancy has markedly increased since the end of World War II. The ratio of the age-adjusted rate (adjusted by the 1985 Japanese model population) in 1999 to that in 1960 was 4.1 (from 3.6 to 14.7 per 100?000 population) and 2.7 (from 3.6 to 9.8 per 100?000 population) among men and women, respectively.1 International comparison studies2 and observations3 of increased rates in subjects who migrate from low- to high-risk regions indicate that westernization or industrialization may lead to an increase in the rates of colon cancer. Although the precise causes of colon cancer remain unclear, various dietary components such as high consumption of red meat or animal fat, physical inactivity, and obesity have been studied as possible risk factors.4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27

Despite the number of prospective4,5,6,7,8,9,10,11,12,13,14,15,16,17,18 and case–control19,20,21,22,23,24,25,26,27 studies that have examined the association between body size and colon cancer in greater or lesser detail, the evidence of obesity as a risk factor is inconclusive. Several studies4,5,6,7,8,9,10,11,12,13,19,22,23,24 have found positive associations between body mass and risk of colon cancer in men, whereas most of the studies4,5,6,7,9,14,15,16,20,21,22,23,24,25,26 in women suggested either no association or only weakly positive associations. A few studies8,17 have shown that obesity is indeed related to colon cancer in women. Some studies20,26 found no association in either men or women, and one study18 reported that men who developed colon cancer weighed slightly less than those who did not. Height also appeared to be associated with an increased risk of colon cancer in some studies,11 but not all.25 Few studies, however, have been addressed the effect of body size on colon cancer risk among Asians, who are generally shorter and leaner than Occidentals among whom the incident and mortality rates of colon cancer are higher. Since the prevalence of obesity has gradually increased in Japan in recent years, it is important to characterize its role in colon cancer mortality.

To elucidate the effects of body size on the risk of colon cancer death among Japanese, we prospectively examined the associations of height, weight and body mass index (BMI) at baseline (B-BMI), BMI around age 20 (20-BMI), and BMI change with colon cancer among Japanese men and women, using nationally representative large-scale cohort data.

Subjects and methods

JACC study

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk, the JACC Study (sponsored by the Ministry of Education, Culture, Sports, Science, and Technology of Japan), is a nationwide multicenter collaborative study to prospectively evaluate various risks or preventive factors as they relate to cancer mortality and incidence. Study methods and ethical issues have been described in detail elsewhere.27 Briefly, our study was initiated in 1988, and enrollment was continued until the end of 1990. Subjects were followed until the end of 1999 unless they had moved out of the study areas. A total of 45 municipalities were involved in this prospective study, including six cities (35% of the cohort population) and 34 towns and five villages (65%). These municipalities were selected from seven out of eight districts in Japan, thus covering almost the entire country. Enrollment was based on the participants in general health checkups periodically provided by these municipalities. We enrolled 127?477 apparently healthy inhabitants of these areas who had completed the questionnaire. Two strategies were applied to obtain informed consent for participation: in the majority of study areas. In some areas consent was obtained by signing the cover page of the questionnaire. In others, it was obtained at the group level by explaining the aim and confidentiality of the data to leaders of the community. Of 127?477 participants enrolled, 110?792 (46?465 men and 64?327 women) aged 40–79?y were followed up for mortality to the end of 1999.

The Ethics Committee of Fujita Health University approved this investigation.

Present study subjects

Of 110?792 subjects enrolled, we excluded from analysis 1258 with a history of any cancers at baseline, 6070 of unknown height, and 4393 of unknown weight. We also excluded subjects with extreme height (<120?cm or ≥200?cm: 47 subjects), weight (<30?kg or ≥120?kg: 27 subjects), or calculated BMI (<15?kg/m2 or ≥45?kg/m2: 201 subjects). To minimize confounding the data by undiagnosed diseases, we further excluded 933 subjects who had less than 1 year of follow-up time. Therefore, 43?171 men and 58?775 women were finally enrolled in the present study. In another analysis of the effects of BMI around aged 20?y and BMI change on colon cancer risk, we further excluded 27?483 subjects of unknown weight around 20?y of age, 65 extremely under- or overweight subjects (<30?kg or ≥120?kg), and 143 subjects with extreme calculated 20-BMI (<15?kg/m2 or ≥45?kg/m2). This left 31?585 men and 42?735 women eligible for the second analysis.

Data collection

A self-administrated questionnaire was used to assess baseline characteristics of the participants. It covered medical history and included lifestyle-related items such as diet, physical activity, drinking and smoking, and family history of several medical conditions including cancer. In the questionnaire, weight in kilograms and height in centimeters were entered by participants after the words ‘Current weight and height’ and ‘Weight around 20?y of age’. BMI at baseline was computed as current weight in kilograms divided by current height in square meters. 20-BMI was also computed as weight around 20?y of age in kilograms divided by current height in square meters.

Follow-up and identification of colon cancer cases

Our primary end points were death from any causes or 31 December 1999 (censored). Those who had moved away were also treated as censored. The mean follow-up period was 10.0?y (9.8?y for men and 10.1?y for women).

The vital status of subjects was checked annually in each study area by reviewing their population register sheets from the Ministry of Public Management, Home Affairs, Post and Telecommunications. For the deceased, causes of death were determined by death certificates available from the Ministry of Health, Labor and Welfare and coded according to the ninth revision of International Classification of Diseases (ICD-9) by the end of 1994 and according to ICD-10 from 1995. Colon cancer cases were defined by 153.0–153.9 (ICD-9) or C18.0–C18.9 (ICD-10). Certification of vital status was believed to be accurate because of the firmly established population registration system in Japan.

Statistical analysis

In the present study, variables of interest are current weight and height, B-BMI, 20-BMI, and BMI change. Tertiles of weight and height were defined separately for men and women from the distribution of total study subjects. BMI categories were defined as follows: <20.0, 20.0–<22.0, 22.0–<24.0, 24.0–<26.0, 26.0–<28.0, ≥28.0?kg/m2 to enable a detailed examination of the association of BMI and colon cancer mortality. In the analysis of BMI change, these six categories were combined into three (<22.0, 22.0–<26.0, ≥26.0), and the subjects were divided into nine groups of B-BMI/20-BMI combinations.

For each participant, the person-years of follow-up were calculated from the date of filling out the baseline questionnaire to death, moving away from the community, or the end of 1999, whichever occurred first. We used Cox proportional hazards modeling to compute relative risks (RRs), adjusting for age at enrollment. In another multivariate analysis, further adjustments were made to smoking status (never, past, current), alcohol drinking habit (none, past, present), exercise (≥5, 3–4, 1–2 hours per week, seldom), green leafy vegetable intake (3–7, 1–2 days per week, seldom), meat intake (3–7, 1–2 days per week, seldom), and family history of colon cancer. These variables were assessed by the baseline questionnaire and were selected as covariates because they were known or suspected to modify the risk of colon cancer. In the analysis, all variables were entered as dummy variables except for age at enrollment. Tests for trends were performed by modeling the categories of variable of interest as equally spaced ordinal variable.

All data were analyzed using SAS (Statistical Analysis System) software. The 95% confidence intervals (CIs) were presented for all RRs. All P-values were based on two-sided tests, and P<0.05 was considered statistically significant.


We identified 127 deaths from colon cancer during the follow-up of 424?698 person-years among men and 122 deaths during the follow-up of 591?787 person-years among women.

The associations of weight and height at baseline with colon cancer death risk by gender are presented in Tables 1 and 2. In multivariate analysis, weight at baseline showed a significant positive association in women, while no corresponding association was seen in men. We compared RRs among the nine categories of weight/height combinations to assess the effects of weight and height. Among men, the tallest were likely to show elevated RR at each stratum of weight, but no significant association was seen. RRs in light (<49.0?kg) and tall (≥153.1?cm) women were significantly higher (RR 3.48, 95% CI 1.27–9.50) than in women who were light and short (<149.0?cm). Women who were heavy (≥55.1?kg) and short, and those who were heavy and medium height (149.0–<153.1?cm) had multivariate-adjusted RRs of 3.24 (95% CI 1.30–8.08) and 3.45 (95% CI 1.54–7.71), respectively, compared with light and short women. However, the RR for tall and heavy women was 1.27 (95% CI 0.46–3.53).

Table 1 Adjusted relative risk (RR) for colon cancer death by weight and height at baseline among men, JACC study, 1988–1999
Table 2 Adjusted RR for colon cancer death by weight and height at baseline among women, JACC study, 1988–1999

The relations between B-BMI and BMI in young adults (20-BMI), and colon cancer death risk by gender are shown in Table 3. Among men, those with B-BMI of <20.0 had a significantly lower RR (0.44, 95% CI 0.21–0.93) than those with BMI of 20–<22. 20-BMI in men also showed no association with risk. In contrast, there was a significant trend of increasing risk with the increase in B-BMI among women. The strongest association was for the highest category (B-BMI ≥28) (RR 3.41, 95% CI 1.44–8.06). 20-BMI of women also presented the same trend of increasing risk as B-BMI. 20-BMI was significantly correlated with B-BMI among both men and women (Pearson r=0.52, P<0.0001, and r=0.45, P<0.0001, respectively).

Table 3 Adjusted RR for colon cancer death by BMI at baseline and around age 20 by gender, JACC study, 1988–1999

We compared RRs among the nine categories of 20-BMI/B-BMI combinations to assess the effects of 20-BMI and B-BMI, and the effect of BMI change (Table 4). When the subjects with low 20-BMI (<22.0) and low B-BMI (<22.0) were referenced, no association was seen in men by multivariate analysis, whereas the RR of women with medium 20-BMI (22–<26) and B-BMI (22–<26) was 2.01 (95% CI 1.02–3.97), and those with high 20-BMI (≥26) and B-BMI (≥26) was 3.33 (95% CI 1.46–7.63). We also found that women with low 20-BMI and high B-BMI, that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29–9.02).

Table 4 Adjusted RR for colon cancer death in nine groups according to BMI at baseline and around age 20 by gender, JACC study, 1988–1999


In Japan, the incidence and mortality rate of colon cancer are much lower than that in Western countries. This difference may be attributed in part to the fact that both Japanese men and women are generally shorter and lighter than Occidentals. Therefore, we examined whether BMI exhibited a positive association with colon cancer in such a low-risk population, as had been observed in some Western countries. Interestingly, in the Japanese population, BMI at entry into the study was strongly predictive of colon cancer over the almost 10-year follow-up period only among women but not among men.

Among prospective studies,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18 at least six4,5,6,7,8,9 included both men and women and presented separate estimates of RR of obesity for colon cancer. All six studies showed positive associations in men, but only two6,8 reported positive associations in women. As for the role of obesity in the etiology of colon cancer, Giovanucci28 has proposed that obesity results in insulin resistance, and that the resulting prolonged elevated insulin levels may increase colon cancer risk by acting as a tumor growth promoter or mitogen. Mckeown-Eyssen29 also suggested that the serum levels of glucose and triglycerides, which tend to be higher in obese people, may affect the fecal bile acids that have been implicated in the pathogenesis of colon cancer.

Although the reasons for the gender difference in previous studies,4,5,7,9 that is, that the association between increased BMI and colon cancer risk is stronger in men than in women, are not completely understood, the male tendency toward central adiposity and higher insulin levels may play a significant role. Another potential explanation for the weak or no association between BMI and colon cancer in women seen in previous studies4,5,7,9,14,15,20,21,22,23,24,26 may be the possible protective effects of estrogen. Estrogen replacement therapy appears to reduce colon cancer mortality.30 In postmenopausal women, the conversion of androgens to estrogens by adipose tissue is thought to be the primary source of extra-ovarian estrogen production, and circulating bio-available estrogen increases with age and excess body fat.31,32 In contrast, elevated estrogen levels as a consequence of obesity in men seems to lead to increased insulin resistance and elevated insulin.33

Why did our Japanese population study show a positive association between BMI and colon cancer shown in women but not in men? Both Japanese men and women have lower BMI than Occidentals (mean BMI at baseline in our study; men: 22.7?kg/m2, women: 22.9?kg/m2), possibly explaining our results. Since the degree of central or abdominal adiposity is low in Japanese men, the carcinogenetic effects of insulin resistance and hyperinsulinemia on colon cancer is considered to be weaker among them than among Occidental men. It is also supposed that the protective effect of extra-ovarian estrogen by body fat is weaker in Japanese women than in Occidental women. Recently, it was reported that obesity was associated with an increased risk of colon cancer in premenopausal but not postmenopausal Occidental women.17 One hypothesis to explain this observation is that obesity increases risk through hyperinsulinemia; however, high estrogen levels associated with obesity in postmenopausal women may have a countering influence. The opposing influences of insulin and estrogen appear to approximately cancel each other out. In our study, however, a positive association of obesity with colon cancer risk was observed even among women aged 55?y or older, suggesting that the adverse influence of obesity on hyperinsulinemia may predominate.

In our study, in agreement with others,34 the positive association of colon cancer risk with high BMI around age 20 seemed impressive in women but it may have been affected by inaccuracy in recalling weight. It may be also explained in part by the effect of B-BMI because 20-BMI is correlated with B-BMI. However, in fact, obesity has been shown to be associated with the risk of colorectal polyps.11 Therefore, our data support the possibility that high BMI and/or factors related to positive energy balance in early life may act on the later as well as earlier stages of colon carcinogenesis.

We also found that women with low 20-BMI and high B-BMI had a high RR of 3.41 (95% CI 1.29–9.02) compared to those with low 20-BMI and low B-BMI. This result suggests that excessive BMI change, that is, high adult weight gain, is associated with a significant increase in the risk of colon cancer among women. For most women, weight gains occur during pregnancy and menopause, which are the very periods when women experience the major biological effects of hormonal changes. Possibly the time and/or age of weight gain may be critical in elucidating the association between weight change and colon cancer risk. The various effects of the time and/or age of weight change needs further investigation.

It was suggested that tall people among both men and women seemed to be at elevated risk of colon cancer even in the Japanese population which is shorter, although this association was not significant, and the underlying mechanism is unknown. Adult height may be a proxy of positive energy balance during childhood, and inadequate nutritional intake in early life will stunt overall growth and organ cellularity in particular.35 Height also correlated closely with the total length of the human colon,36 and the greater number of stem cells in tall people could increase their exposure to potential carcinogens.

The strengths of our study include its prospective design and large size. We could analyze both men and women by similar methods and were able to control for a large number of other potential risk factors. Limitations of the present study also warrant discussion. First, since our results were based on mortality data, they reflect the potential effects of body size not only on colon cancer incidence but also on survival or both. A second limitation is the reliance on self-reported measurements of weight and height. It is well known that self-reported current weight and height, and past weight are influenced by factors such as gender and obesity. However, many studies37,38,39 have reported that they were accurate enough to use in an epidemiologic study. Third, we have no information on colon cancer screening. If lean individuals are more likely to get colon cancer screening, they would be expected to have more diagnosed polyps and fewer invasive cancers. This potential bias could not be verified since we did not collect any information during follow-up about the subjects’ screening participation. Fourth, we could not analyze by subsite of colon cancer because subsite data were not available.

In conclusion, there was a significant and positive association between BMI and colon cancer death in Japanese women but not in men. This association in women could be extended to lower BMI levels than that in Western populations. We also found that both obesity in early life and gains in adult body mass are predictors of colon cancer risk. The increased prevalence of obesity in Japan in recent years may bode ill for future trends in colon cancer incidence and mortality. The results of our study also suggested that the avoidance of excessive weight gain during adult life, that is, weight control may reduce colon cancer risk.


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We express their sincere appreciation to Dr K Aoki, Professor Emeritus, Nagoya University School of Medicine and the former chairman of the JACC Study Group, and also to Dr H Sugano, the former Director of the Cancer Institute of the Japanese Foundation for Cancer Research, who greatly contributed to the initiation of the study.

The present members of the JACC Study and their affiliations are as follows: Dr A Tamakoshi (present chairman of the study group), Nagoya University Graduate School of Medicine; Dr M Mori, Sapporo Medical University School of Medicine; Dr Y Motohashi, Akita University School of Medicine; Dr I Tsuji, Tohoku University Graduate School of Medicine; Dr Y Nakamura, Jichi Medical School; Dr H Iso, Institute of Community Medicine, University of Tsukuba; Dr H Mikami, Chiba Cancer Center; Dr Y Inaba, Juntendo University School of Medicine; Dr Y Hoshiyama, Showa University School of Medicine; Dr H Suzuki, Niigata University Graduate School of Medical and Dental Sciences; Dr H Shimizu, Gifu University School of Medicine; Dr H Toyoshima, Nagoya University Graduate School of Medicine; Dr S Tokudome, Nagoya City University Graduate School of Medical Sciences; Dr Y Ito, Fujita Health University School of Health Sciences; Dr S Hashimoto, Fujita Health University School of Medicine; Dr S Kikuchi, Aichi Medical University School of Medicine; Dr A Koizumi, Graduate School of Medicine and Faculty of Medicine, Kyoto University; Dr T Kawamura, Kyoto University Center for Student Health; Dr Y Watanabe and Dr T Miki, Kyoto Prefectural University of Medicine Graduate School of Medical Science; Dr C Date, Faculty of Human Environmental Sciences, Mukogawa Women's University; Dr K Sakata, Wakayama Medical University; Dr T Nose, Tottori University Faculty of Medicine; Dr N Hayakawa, Research Institute for Radiation Biology and Medicine, Hiroshima University; Dr T Yoshimura, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan; Dr K Fukuda, Kurume University School of Medicine; Dr N Okamoto, Kanagawa Cancer Center; Dr H Shio, Moriyama Municipal Hospital; Dr Y Ohno (former chairman of the study group), Asahi Rosai Hospital; Dr T Kitagawa, Cancer Institute of the Japanese Foundation for Cancer Research; Dr T Kuroki, Gifu University; and Dr K Tajima, Aichi Cancer Center Research Institute.

The past investigators of the study group were listed in Ohno et al27 except for the following seven members (affiliations are those at the time they participated in the study): Dr T Shimamoto, Institute of Community Medicine, University of Tsukuba; Dr H Tanaka, Medical Research Institute, Tokyo Medical and Dental University; Dr S Hisamichi, Tohoku University Graduate School of Medicine; Dr M Nakao, Kyoto Prefectural University of Medicine; Dr T Suzuki, Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases; Dr T Hashimoto, Wakayama Medical University; and Dr T Ishibashi, Asama General Hospital.

This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas (2) (No. 14031222) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The JACC Study has also been supported by Grants-in-Aid for Scientific Research from the same ministry (Nos. 61010076, 62010074, 63010074, 1010068, 2151065, 3151064, 4151063, 5151069, 6279102, and 11181101).

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Tamakoshi, K., Wakai, K., Kojima, M. et al. A prospective study of body size and colon cancer mortality in Japan: The JACC Study. Int J Obes 28, 551–558 (2004).

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  • body size
  • body mass index
  • weight change
  • colon cancer
  • cohort study

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