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Association between body mass index and risk of breast cancer in Tunisian women

BACKGROUND AND OBJECTIVES: The number of breast cancer in women has increased dramatically in Tunisia. The cause is perceived to stem from adaptation to a westernized life style which increases body mass index (BMI). This study aimed to investigate the association between BMI and breast cancer among Tunisian women. DESIGN AND SETTING: Hospital-based case control study of breast cancer patients seen between November 2006 and April 2009 at the University College Hospital Farhat Hached in Sousse, Tunisia. PATIENTS AND METHODS: Standardized questionnaires concerning BMI and other anthropometric data were completed on 400 breast cancer cases and 400 controls. The controls were frequency-matched to the cases by age. RESULTS: BMI at diagnosis was positively correlated with the risk of breast cancer among postmenopausal women (P<.001 for trend). When compared with women with a low BMI (<19), women with a BMI of 23-27 and 27-31 had a 1.7-fold (95% CI, 1.1-2.9) and 2.1-fold (95% CI, 1.1-3.9) increased risk of breast cancer, respectively, after adjustment for non-anthropometric risk factors. BMI at diagnosis was not related to the risk of breast cancer among premenopausal women. The odds ratios for premenopausal women with a BMI of 23-27 and 27-31 were 1.5 (95% CI, 0.8-2.8) and 1.3 (95% CI, 0.4-4.5), respectively. Furthermore, present BMI was not associated with breast cancer risk in either pre- and postmenopausal women. CONCLUSIONS: Weight control in obese women may be an effective measure of breast cancer prevention in postmenopausal women.

adipose tissue. 2 Conversely, the protective mechanism among premenopausal women is not well understood. 2 Although the association between high BMI and breast cancer risk is well established, the vast majority of studies have been conducted in Western countries. The aim of our study was to examine the relationship between anthropometric variables and risk of breast cancer in Tunisian women, where it seems that many women have a relatively high BMI. 20

METHODS
We performed a case-control study to determine the relationship between BMI and breast cancer risk among Tunisian women. All subjects were selected from University College Hospital (UCH) Farhat Hached Sousse in Tunisia. After hospital approvals were obtained, histologically confirmed breast cancer cases were ascertained from November 2006 to April 2009. Eligible cases included females aged 25-75 years.
During the study period, 400 eligible women participated in our study. We excluded subjects who had documented malignancy in other sites.
Controls were randomly selected from among noncancer patients who received medical care: 20% of the controls were admitted for ophthalmology problems; 12% for tooth extraction and for ear, nose, and throat conditions; 8% for stomach flu or other acute digestive infections; 17% for surgery (appendix, strangulated hernia, hemorrhoids, or other conditions); 9% for lower back pain and disk problems; 18% for diabetes; 11% for irregular heart rates and other acute circulatory conditions; 5% for acute urinary tract infection. A total of 98% (400/408) of the controls identified initially participated in the study. Selection of controls was restricted to patients whose current hospital admission was for a condition diagnosed within 1 year of the interview to reduce the proportion of controls who may have modified their habits as a result of having a chronic disease. Efforts were made to frequency match the cases and controls by age (within 5-year intervals). The study was approved by the ethics committee of UCH Farhat Hached Sousse in Tunisia and all participants provided informed consent.
A structured questionnaire was used to collect detailed information. Subjects were asked to complete the questionnaire under the guidance of medical students. Heights and weights at present and at the time of diagnosis were measured in the clinic by the physicians, while using a sliding rule fixed on the bathroom scale. All subjects, dressed in light clothing and without shoes, supported their heels on the plate, and the buttocks or back were in contact with the device. The subjects looked straight in front of them but did not touch the device by the back of the head. Heights and weights were measured, respectively, to the nearest 0.2 cm and to the nearest 0.3 kg. Questions were asked about other risk factors for breast cancer, including a family history of breast cancer, menopausal status, exercise habits, pregnancy history, and oral contraceptives use. Demographic data were also collected The BMI was calculated as weight (kg) divided by height squared (m 2 ). Quartile distributions were used to categorize BMI to facilitate comparisons: BMI <19, 19-23, 23-27, 27-31 and >31. Odds ratios (ORs) were used to measure the association between breast cancer risk and BMI. Logistic regression models gave the maximum likelihood estimates of OR with 95% confidence interval (CI). Data were stratified by menopausal status to replicate prior analyses performed in western studies. Comparisons were drawn within each group concerning odds ratios for BMI at the time of diagnosis, and BMI at present. Tests for trends were performed by entering categorical variables as continuous parameters in the model. We performed data analysis using SPSS version 10.0.

RESULTS
The distribution of the selected characteristics of breast cancer cases and controls is presented in Table 1. The mean age for cases (48.9 years) and for controls (49 years) was comparable. Cases and controls had a difference in family history of breast cancer (P=.02). The analysis was adjusted for family history of breast cancer but not for other factors, because there were no significant differences in age, previous oral contraceptive pill use, education level, or number of pregnancies. Among postmenopausal women, the BMI at diagnosis was positively associated with the risk of breast cancer (P<.001 for trend). The odds ratios for breast cancer increased with increasing BMI (>23, 1.74; >27, 2.08; >31, 3.81 after adjusting for non-anthropometric risk factors) ( Table 2). BMI at diagnosis, however, was not related to the risk of breast cancer among premenopausal women (>23, 1.52; >27, 1.33 after adjusting for non-anthropometric risk factors) ( Table 2). Present BMI was not associated with breast cancer risk among either pre-and postmenopausal women (Table 3).

DISCUSSION
Overweight and obesity are common health conditions and their prevalence is increasing globally. The World Health Organization recently called for the continuous monitoring of BMI to assess the trends in obesity in populations across time. 21 It is well known that excess weight is associated with an increased incidence of particular diseases and certain cancers such as di- gestive cancer and those associations of excess weight with overweight and obesity-related morbidity may differ among racial and ethnic groups. 22 This hospitalbased case control study found that the risk of developing breast cancer increased with BMI at the time of diagnosis in postmenopausal women (P<.001 for trend). BMI at diagnosis, however, was not related to the risk of breast cancer among premenopausal women. Furthermore, present BMI was not associated with a breast cancer risk among either pre-or postmenopausal women. The poor association between present BMI and breast cancer may be due to multiple factors, including the effect of chemotherapy, radiotherapy and surgery on appetite, and changes in lifestyle after diagnosis. Appetite changes from psychological effects on discovery of the disease may also contribute. We could not assess the effect of different factors on BMI for cases and controls, but the association between BMI at diagnosis for pre-and postmenopausal women had already fulfilled our requirement.
Our results are consistent with many previous studies 13,16,17,[23][24][25][26] which state that there is a positive correlation between BMI and risk of breast cancer in postmenopausal women. Among premenopausal women, the results were also consistent with some studies. 9,17,27 However, other studies found that a greater BMI is protective in premenopausal women. 3,15,17,28,29 Some researchers proposed that the incidence of breast cancer might be related to the number of years of obesity instead of only pre-or postmenopausal status. One study found that the risk of breast cancer in postmenopausal women increased with maximal lifetime BMI. 30 In premenopausal women, the result was exactly opposite. Therefore, it seems that the duration of obesity does not correlate well with the risk of breast cancer in all women, but only in a subgroup of postmenopausal women. 30 The association between BMI and the risk of breast cancer in premenopausal women is still unclear, and this  controversial issue should be subjected to further investigation. Weight gain and obesity are not only risk factors for breast cancer, but also contribute to the diagnosis process. A study from Geneva Cancer Registry, Switzerland compared diagnostic characteristics of obese with nonobese breast cancer patients. The findings showed that obese patients presented significantly more often with advanced stage disease, experienced more surgical delay and prolonged hospital stay after surgery. The authors speculated that the more advanced stage at diagnosis could be due to the larger breast size of obese women, with more fatty tissue, which can lead to difficulties in palpating the primary tumor and the axillary lymph nodes. Also, obese women may be more reluctant to undergo physical examination because of embarrassment about their weight. They suggest there is a need to educate women and doctors that self-examination and clinical examination may be less reliable in obese women, and to think of strategies to prevent advanced disease at diagnosis for this growing group of patients. 31 Previous studies have found an association between BMI and breast cancer risk among postmenopausal women who are not using hormonal replacement therapy. In fact, the cohort study of Lahmann et al., 32 reported that overall obesity and weight gain were positively associated with a risk of breast cancer and the percentage of body fat appeared to be a stronger predictor of breast cancer than BMI. This is particularly apparent among non-hormonal replacement therapy users, which is in line with the theory that increased exposure to higher biologically available estrogens among overweight postmenopausal elevates the risk of breast cancer. The authors noted that menopausal hormone use is a strong independent risk factor, more so in lean than in overweight women. 32 The strength of this study relates to the fact that heights and weights at diagnosis were measured in the clinic by the physicians rather than relying on self-reported weights and heights by the cases and controls. Anthropometric studies usually rely on self-reported measures and the evidence suggests that obese women tend to underestimate their weight gain as compared with lean adolescents. 33 In interpreting the results from our current study, several potential limitations need to be considered. A potential concern is the study sample size that is relatively small, particularly after stratification by menopausal status. Another potential limitation of our study concerns use of hospital-based cases and controls. While every effort was made to include all cases admitted to the study hospitals, we did not attempt to ascertain breast cancer patients who may not have come to this hospital. Therefore, the generalizability of our results may be limited because of the hospital-based study design. To avoid selection bias, controls were selected from among those women admitted to the study hospital, but controls were admitted for noncancerous conditions.
In summary, this study found that high BMI at diagnosis was positively correlated with an increased risk of breast cancer in postmenopausal Tunisian women. A significant dose-response relationship between BMI at diagnosis and breast cancer was also demonstrated. This indicates that weight control may be an effective measure for breast cancer prevention in postmenopausal women. The results also enhance our understanding of the pathogenesis of breast cancer in postmenopausal women and emphasize the need for research to clearly define the underlying mechanisms.