Int. J. Cancer: 118, 1496–1500 (2006) ' 2005 Wiley-Liss, Inc.
Body size and composition and colon cancer risk in women Robert J. MacInnis1,2, Dallas R. English1,3,4, John L. Hopper3, Dorota M. Gertig3, Andrew M. Haydon4 and Graham G. Giles1,3,4* 1 Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia 2 School of Population Health, University of Melbourne, Melbourne, Australia 3 Centre for Genetic Epidemiology, University of Melbourne, Melbourne, Australia 4 Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia Studies of colon cancer risk in males have reported strong positive associations with obesity, particularly with central adiposity. The association has been weaker and less consistent for women. In a prospective cohort study of women, body measurements were taken directly; fat mass and fat-free mass being estimated by bioelectrical impedance analysis and central adiposity by waist circumference and waist-to-hip ratio (WHR). Among 24,072 women followed on average for 10.4 years, 212 colon cancers were ascertained via the population cancer registry. We reviewed medical records of all cases and classified them according to anatomic site and stage. The central adiposity measures of WHR (hazard ratio per 0.1 unit increase 5 1.31, 95% confidence interval (CI) 1.08– 1.58) and waist circumference (hazard ratio per 10 cm increase 5 1.14, 95% CI 1.02–1.28) were positively associated with colon cancer risk. There was little or no association between other anthropometric measures and risk of colon cancer. There was some evidence that the associations were stronger for proximal tumors, but no evidence that risk differed by stage for any of the anthropometric measures. Central adiposity appears to be associated with colon cancer risk in women. ' 2005 Wiley-Liss, Inc. Key words: colon cancer; anthropometry; bioelectrical impedance analysis; cohort study; Australia
Colon cancer is the second most common cancer of Australian women, the world standardised colon cancer incidence rate being 22.5 per 100,000, which is similar to estimates for North American white populations.1 Much international effort is being expended in the search for modifiable risk factors for colon cancer.2,3 In this regard, studies of colon cancer risk in males have reported strong positive associations with obesity, particularly with central adiposity.4 The association with body mass index (BMI) is less consistent and weaker for women,5–12 and 3 cohort studies of women that examined central adiposity found only weak associations.7,8,13 Two of these studies used self-reported measurements of waist and hip circumferences to estimate the waist-to-hip ratio (WHR),7,8 which may be inaccurate and imprecise and result in attenuation of any true association. To our knowledge, none have reported results using direct measures of overall adipose and nonadipose mass. It is also uncertain whether any association with elements of body size and composition might be limited to a particular tumor subsite or stage of disease. Cohort studies have reported mixed results when examining body size associations with proximal and distal colon cancer separately,5–7,9,14,15 while the results were uncertain from 1 cohort study that reported associations by stage of disease.14 Effect modification by menopausal status may also explain the inconsistent findings.6 We assessed the relationship between body size and composition and incidence of colon cancer in women in a prospective cohort study by using direct anthropometric measurements. These measures included waist and hip circumferences as well as estimates of nonadipose mass and adipose mass from bioelectrical impedance analysis. We also analysed risk by tumor stage and subsite. Publication of the International Union Against Cancer
Material and methods The cohort The Melbourne Collaborative Cohort Study (MCCS) is a prospective cohort study of 41,528 people (24,479 women) aged between 27 and 75 at baseline, 99.3% of whom were aged 40–69 at recruitment.16 Recruitment occurred between 1990 and 1994. The Cancer Council Victoria’s Human Research Ethics Committee approved the study protocol. Southern European migrants to Australia (including 3,008 Italian women and 2,461 Greek women) were deliberately recruited to extend the range of lifestyle exposures and to increase genetic variation. Subjects were recruited via the Electoral Rolls (registration to vote is compulsory for adults in Australia), advertisements and community announcements in local media (e.g., television, radio and newspapers). Comprehensive lists of Italian and Greek surnames were used to target southern European migrants in the phone book and Electoral Rolls. Subjects We recruited 24,479 women, of whom 97 were excluded from analysis because they had colorectal cancer before baseline. A further 310 women were excluded because they did not have a complete set of valid measurements, leaving 24,072 women available for analysis. Measurements Height, weight and waist and hip circumferences were measured once at baseline attendance for each participant according to written protocols that were based on standard procedures.17 Weight was measured to 100 g using digital electronic scales, height to 1 mm using a stadiometer and waist and hip circumferences were measured to 1 mm using a 2-meter metal anthropometric tape. Bioelectrical impedance analysis was performed with a single frequency (50 kHz) electric current produced by a BIA101A RJL system analyzer (RJL systems, Detroit, MI). Resistance and reactance were measured with subjects in a supine position. Questionnaire measures At interview, questions were asked about conventional risk factors such as reproductive history, country of birth, diet, alcohol, physical activity and highest level of education. Additionally, Abbreviations: BMI, body mass index; CI, confidence interval; FFM, fat-free mass; HRT, hormone replacement therapy; IGF, insulin-like growth factors; MCCS, Melbourne Collaborative Cohort Study; WHR, waist-to-hip ratio. Grant sponsor: National Health and Medical Research Council; Grant numbers: 209057, 170215, 251533; Grant sponsor: VicHealth; Grant number: 1998-0406. *Correspondence to: Cancer Epidemiology Centre, The Cancer Council Victoria, 1 Rathdowne Street, Carlton South, VIC 3053, Australia. Fax: 161-3-9635-5330. E-mail:
[email protected] Received 10 June 2005; Accepted after revision 28 July 2005 DOI 10.1002/ijc.21508 Published online 26 September 2005 in Wiley InterScience (www.interscience. wiley.com).
FEMALE BODY COMPOSITION AND COLON CANCER
women were asked to report their use of hormone replacement therapy (HRT) and oral contraceptives. Age at menopause was determined by the age at which a woman’s periods had ceased naturally for at least the past 12 months (regardless of their use of HRT) or at which they had a bilateral oophorectomy (if this was the reason for cessation of periods). The remaining women who indicated having had a hysterectomy without bilateral oophorectomy were considered postmenopausal, with unknown age at menopause if their age at baseline was greater than 55 years (age at which natural menopause had occurred in 90 percent of the total cohort). Cohort follow-up and case ascertainment Addresses and vital status of the subjects were determined by record linkage to Electoral Rolls, Victorian death records, the National Death Index, from electronic phone books, and from responses to mailed questionnaires and newsletters. By 31 December 2003, 396 (1.6%) subjects had left Victoria and 1,069 (4.4%) had died. None of the participants whose deaths were identified through the National Death Index had colorectal cancer listed as a cause of death. All subjects gave written consent, allowing access to their medical records to confirm diagnoses. Cases were identified from notifications to the Victorian Cancer Registry of diagnoses of adenocarcinoma of the colon (International Classification of Diseases 9th revision rubric 153.0–153.4, 153.6–153.9 or 10th revision rubric C18.0, C18.2–C18.9). We reviewed medical records of all reported colorectal tumors and classified them according to anatomic site (subsite within the colon) and stage. Tumours arising in the caecum, ascending colon, hepatic flexure and transverse colon were defined as proximal, while tumors arising in the descending and sigmoid colons were defined as distal. Stage was categorized into 4 groups based on the American Joint Committee on Cancer (AJCC) staging system: stage I (T1–2, N0, M0), stage II (T3–4, N0, M0), stage III (Tany, N1–2, M0) and stage IV (Tany, Nany, M1). Statistical analysis Cox’s proportional hazards regression models, with age as the time axis,18 were used to estimate the hazard ratios associated with each anthropometric measure. Follow-up began at baseline and ended at diagnosis of colon cancer, rectal cancer or cancer of unknown primary site, death, the date last known to be in Victoria or 31 December 2003 (the date that ascertainment of colon cases by the Victorian Cancer Registry was complete), whichever came first. We performed additional analyses restricted to women who were postmenopausal at baseline attendance. The temporal nature of the associations with body size and composition was assessed by estimating the hazard ratio for each anthropometric measure as a function of years since menopause, using a time-varying covariate. We compared hazard ratios in 2 time-varying strata,
