Obesity, body composition, and risk of renal cell cancer: a population-based case-control study.
Abstract: Aim of the study

This study assesses the role of body composition on renal cell carcinoma (RCC) among 335 cases and 337 controls in Florida and Georgia, 2003-2006.

Subjects and Methods

Cases were selected from participating hospitals and the Florida Cancer Data Registry. Controls were selected from the population using random-digit dialing, frequency-matched to cases by age, sex, and race. Cases and controls were assessed for body mass index (BMI), body fat percentage, and body fat distribution. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression.

Results

Among men, significant associations were observed between RCC and BMI > 40 (OR = 3.5; 95% CI: 1.2, 10.4), upper quartile waist-to-hip ratio (OR = 2.0; 95% CI: 1.0, 3.9), and upper quartile suprailiac skinfold thickness (OR = 2.1; 95% CI: 1.1, 3.9). Significant linear trends between RCC and body fat percentage were observed for men (p = 0.042) and women (p = 0.032). Among women, associations were stronger for upper quartile caloric intake (OR = 2.3; 95% CI: 1.2, 4.6) and upper quartile fat intake (OR = 2.7; 95% CI: 1.4, 5.2).

Conclusion

These findings confirm known associations between BMI and RCC and implicate the role of body fat percentage, central obesity, and diet in RCC etiology.

Keywords: body mass index, renal cell carcinoma, kidney cancer, obesity, skinfold thickness.
Article Type: Report
Subject: Body composition (Health aspects)
Body composition (Research)
Obesity (Complications and side effects)
Carcinoma, Renal cell (Risk factors)
Carcinoma, Renal cell (Diagnosis)
Carcinoma, Renal cell (Care and treatment)
Carcinoma, Renal cell (Research)
Authors: Asal, Nabih R.
Theis, Ryan P.
Grieb, Suzanne M. Dolwick
Burr, Deborah
Benardot, Dan
Siddiqui, Tariq
Pub Date: 01/01/2009
Publication: Name: International Journal of Health Science Publisher: Renaissance Medical Publishing Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 Renaissance Medical Publishing ISSN: 1791-4299
Issue: Date: Jan-March, 2009 Source Volume: 2 Source Issue: 1
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 203660862
Full Text: INTRODUCTION

Kidney and renal pelvis cancers account for nearly 4 percent of all new cancer cases in the United States, with 54,390 cases projected for the year 2008. (1,2) Over the past thirty years, kidney cancer incidence rates have nearly doubled--from 7.1 per 100,000 in 1975 to 13.3 per 100,000 in 2005. (1) Renal cell carcinoma (RCC) accounts for approximately 85 percent of all renal tumors. (3) Because genetic predispositions explain only 2 percent of RCC cases (3), incidence trends are likely due to environmental or lifestyle factors. The prevalence of obesity in particular has risen at a corresponding rate in the United States, from 13 percent of the population in 1960-1962 to 32 percent in 2001-2004 (4), implicating the role of population-level changes in body composition on trends in RCC incidence.

The positive association between obesity and risk of RCC has been established in the literature and recognized by the International Agency for Research on Cancer. (5,6) Initially, increased risks were observed only among women in studies using body mass index (BMI) as an obesity indicator. (7-10) A quantitative review of 22 cohort and case-control studies subsequently found equally strong associations between men and women, with a summary relative risk of 1.07 (95 percent CI: 1.05--1.09) per unit increase in BMI. (5)

Most studies of RCC and body composition have used BMI as an obesity indicator. (5) While BMI functions as an efficient measure of body composition in population samples, it remains an indirect indicator of body fat, which is presumably the etiologic factor in cancer development. To date, measures of body fat distribution in studies of RCC have been limited to waist circumference and waist-to-hip ratio (WHR). (11,12) We are not aware of any RCC studies using skinfold thickness as an adjunct measure of body fat distribution, nor of studies that assess body fat composition. Skinfold measurement is considered reliable for estimating peripheral adiposity (13), the influence of which can be compared against measures of central adiposity. Body fat composition as determined by bioelectrical impedance analysis (BIA) can complement BMI and body fat distribution measures. Recent studies using BIA have found increased risk of cancers of the breast (14,15), esophagus16, and rectum (17) with increasing body fat.

The present paper reports findings from a population-based case-control study of RCC in Florida and Georgia, evaluating the role of body composition using anthropometric and self-report measures. Study factors include height, weight, BMI, body fat composition, and body fat distribution measured at time of interview, as well as self-reported past weight. Measures of body fat distribution include hip and waist circumference, and skinfold thickness at the abdomen, triceps, suprailiac crest, and thigh.

SUBJECTS AND METHODS

Study Population

Ethical approval for this study was obtained from the institutional review boards of the University of Florida, the Florida Department of Health, Georgia State University, and Emory University Hospital. Cases with incident, histologically confirmed RCC were identified from records in three participating hospitals in North Florida and the Florida Cancer Data System registry. All white and African-American cases aged 20 years or older and diagnosed between January 1, 2000 and December 31, 2004 were considered for inclusion. Cases were excluded if their cancer was diagnosed in a transplant kidney or if they did not reside in Florida or Georgia. Among 459 living, eligible cases who could be contacted, 316 (69 percent) agreed to participate and were interviewed by trained personnel. An additional 15 cases were included from urology offices in North and Central Florida, and four from Emory University Hospital in Atlanta, producing a sample of 335 cases.

A sample of population controls was identified using random-digit dialing (RDD)18, frequency-matched to cases by age (+/5 years), sex and race. Until an adequate sample of cases had been acquired, frequencies from Surveillance, Epidemiology, and End Results (SEER) data were used for matching. (19) During the final year of the study, random sampling of telephone lists specific to African-American households was used to supplement RDD and ensure an adequate sample of African-American controls. Respondents were eligible as controls if they met the matching criteria and reported no history of kidney disease. Among 801 eligible respondents who could be contacted by telephone, 337 (42 percent) participated as controls.

Measurements

Participants were interviewed in-person by personnel trained in epidemiologic interviewing, dietary assessment and anthropometry. Data was collected using a structured questionnaire, which assessed medical, occupational, and family histories, lifetime use of cigarettes, beverages and artificial sweeteners, and lifetime exposure to radiation, pesticides and environmental tobacco smoke. For cases, age at diagnosis was known and used as a reference for assessing all exposure histories, minimizing potential exposure misclassification. A 70-item Block food frequency questionnaire (20) was used to assess past nutritional intake for a single one-year period.

At time of interview, weight in kilograms and height in centimeters were taken without shoes. Weight was measured using a TANITA BF-350 Body Composition Analyzer/Scale (TANITA Corporation of America, Arlington Heights, IL.), and height using a GPM anthropometer (Siber Hegner, Zurich, Switzerland). Self-reported weight at age 20, age 40, age 60, and maximum lifetime weight were collected as part of the epidemiologic interview. Body mass index at time of interview was calculated by dividing weight in kilograms by height in meters squared. Classification of BMI used four groups derived from the obesity classification system of the World Health Organization (21): Normal = 18.5-24.9; Overweight = 2529.9; Obese =30-39.9; Extremely obese = > 40.

Body fat distribution was assessed at time of interview by waist and hip circumference in centimeters using a GPM measuring tape (Siber Hegner, Zurich, Switzerland) and skinfold thickness in millimeters at the triceps, abdomen, suprailiac crest and thigh using skinfold calipers (Holtain Ltd., Wales, UK). Three separate caliper readings were taken at each skinfold site, and an average of the three was calculated. Caliper measurements had an upper limit of 45 mm. Two additional skinfold measures were computed for "core" subcutaneous fat (abdomen + supraliliac) and at all four sites combined. To compare the influence of central and peripheral fat distribution, variables were calculated representing the percentage of each individual site within the overall measure. Body fat percentage at time of interview was measured using two methods: (1) foot-to-foot bioelectrical impedance (TANITA); and (2) four-site skinfold thickness measurements. Bioelectrical impedance could not be used on subjects with pacemakers or internal electronic devices, representing 6 percent of cases and 4 percent of controls. Sex-specific formulas for the estimation of body fat by skinfolds were taken from Golding et al. (1989). (22)

Statistical Methodology

Analyses of demographic factors between cases and controls employed the Pearson chi-square test for independence. Measures of relative risk were estimated by the odds ratio (OR) and 95 percent confidence interval (CI), using unconditional logistic regression. Potential confounders in the association between RCC and body composition included medical history, tobacco use, daily caloric intake, and daily fat intake. The influence of these factors was tested in models adjusted for age, race, smoking (pack-years), and BMI and stratified by sex. Subsequent models for the influence of body composition factors on RCC were controlled for age, sex, race, smoking (pack-years), education, daily caloric intake, and daily fat intake. Tests for trend employed the Wald chi-square statistic, computed for continuous variables within adjusted models. All tests for statistical significance were two-sided and evaluated a [+ or -] = 0.05. Statistical analyses were performed using SPSS 14.0 software (SPSS Inc., Chicago, IL.).

RESULTS

Demographic information was complete for all 335 cases and 337 controls (Table 1), except for one case who declined to report educational status. Cases and controls did not differ significantly with respect to sex, race, or annual household income. Although controls tended to be better educated than cases, this difference was not statistically significant (P = 0.16). The mean age among cases at time of interview was 66 years, while the mean age among controls was 62 years a difference that was statistically significant (P = 0.001). Cases were interviewed between 0.4 years and 6.3 years following diagnosis, with a mean diagnosis-to-study interval of 3.1 years.

Table 2 provides adjusted odds ratios for selected risk factors for RCC, stratified by sex. Notably, high levels of daily caloric and fat intake were positively associated with RCC among women, but not men. Conversely, pack-years of tobacco use produced a significant association with RCC for men (P = 0.008) but not for women. These three potential confounders were chosen as covariates in subsequent adjusted models.

Table 3 provides t-tests for the statistical difference in means between cases and controls on continuous body composition measures. Few measures of past weight collected by self-report were significantly different between cases and controls. Differences were generally stronger for relative than for absolute measures of obesity. The greatest differences were observed for measures of body fat percentage, whether by BIA or skinfold thickness. Body fat percentage calculated from skinfold thickness was consistently lower than that calculated from BIA, likely due to the proportion of subjects whose skinfold thickness exceeded the upper limit on one or more caliper measurements (22 percent). Mean body fat percentage by BIA was 35.6 percent among cases and 33.6 percent among controls (P = 0.006). Cases also had significantly greater mean values than controls for maximum lifetime BMI (P = 0.026), BMI at time of interview (P = 0.033), waist (cm) at time of interview (P = 0.031), WHR (P = 0.002), and skinfold thickness (mm) measured at the suprailiac crest (P = 0.020), thigh (P = 0.034), core (P = 0.018), and all four sites combined (P = 0.015).

Adjusted odds ratios for height, weight, and relative weight are presented on Table 4. No significant differences between cases and controls were observed for measured height in centimeters or self-reported weight in kilograms at ages 20, 40, or 60 (results not shown). Measures of BMI were significantly associated with RCC among men, but not women. Men in the category of "extreme obesity" (BMI > 40) at time of interview were 3.5 times more likely to have RCC than those in a healthy BMI range. Maximum lifetime BMI was also significantly associated with RCC among men, with an odds ratio of 7.3 for extreme obesity compared with healthy BMI. These results should be carefully interpreted, given the wide confidence intervals that result from low cell counts in certain BMI categories.

Table 5 presents adjusted odds ratios for RCC by sex for body fat percentage at time of interview using both BIA and skinfold thickness methods. Body fat percentage by BIA produced significant tests for trend for both men (P = 0.042) and women (P = 0.032), although when the variable was treated as categorical, significant risk increases were not observed for men. Body fat percentage by skinfold thickness was significantly associated with RCC in men, with those in the highest quartile having a risk of RCC 2.5 times greater than those in the lowest quartile. Among women, body fat percentage by BIA proved to be the better predictor of RCC, with those in the highest quartile being nearly twice as likely to have RCC as those in the lowest quartile. Within the entire sample, having a body fat percentage of 40 percent or greater increased risk for RCC by 73 percent (OR = 1.73; 95% CI: 1.16, 2.57) (not shown in table). Men and women have different standards for what is considered a healthy range of body fat percentage (22), with higher allowed values for women than men. However, we considered a 40 percent threshold adequately high for observing increased risks in both sexs in non-stratified analyses. Correspondingly, when this analysis was stratified by sex, this threshold imposed a greater risk on men (OR = 2.92) than women (OR = 1.44).

Table 6 provides adjusted odds ratios for RCC by sex for selected body fat distribution measures. Among men, being in the highest quartile of waist circumference distribution produced a marginally significant 60 percent risk increase. Waist-to-hip ratio proved a more sensitive predictor of RCC risk among men, with those in the highest quartile being twice as likely to have RCC as those in the lowest quartile. When treated as a dichotomous variable for the entire sample (results not in table), WHR of 1.00 or greater increased risk of RCC by 60 percent (OR = 1.60; 95% CI: 1.03, 2.49). Most skinfold thickness measurements were not associated with RCC for either sex, whether treated as absolute or relative to the total of all four sites. Only results for suprailiac crest skinfolds are shown on the table. Abdominal skinfold thickness alone was not associated with RCC in men or women. However, among men, those in the highest quartile of suprailiac crest skinfold thickness had an odds ratio of 2.1 compared with those in the lowest quartile (P = 0.007). Core skinfold thickness (abdomen + suprailiac crest) was also associated with RCC among men (P = 0.036), although the association was weaker than for suprailiac crest alone--an expected result when combining a significant factor with a non-significant factor in the same measure.

All tests for the influence of lifetime weight gain on risk of RCC produced non-significant results, whether treated as absolute or relative weight. Gain in BMI from age 20 to maximum lifetime weight produced a marginally significant linear trend among men (P = 0.085), although when the variable was treated as categorical no significant associations were observed. To test whether possible cancer-related weight loss among cases was producing underestimated associations between RCC and body composition, we also assessed the influence of weight and BMI loss from maximum lifetime weight to time of interview. No significant differences were observed between cases and controls for either absolute or relative weight loss.

Lastly, race-stratified analyses were performed on body composition measures to determine whether RCC risk increases varied between whites and African-Americans. Among whites, significant RCC risk increases were observed for being obese (BMI > 30) at time of interview (OR = 1.7; 95% CI: 1.0, 2.7) and at maximum lifetime weight (OR = 2.1; 95% CI: 1.1, 4.0), and for being in the highest quartiles of body fat percentage (OR = 2.3; 95% CI: 1.2, 4.2) and core skinfold thickness (OR = 1.8; 95% CI: 1.1, 3.1). The sample of African-American participants (n = 144) was not large enough to detect associations between RCC and most body composition factors. However, among African-Americans, those in the highest quartile of waist-to-hip circumference had a marginally significant odds ratio of 3.0 (95% CI: 0.9, 10.1) compared with those in the lowest quartile, and a significant linear trend (P = 0.033).

DISCUSSION

The present study found recent BMI to be significantly associated with RCC among men, but not women--a finding that conflicts with other studies reporting significant risk increases for both sexs. (5,11) Most case-control studies of RCC have assessed BMI using self-reported height and weight, rather than anthropometric measures. (8-10, 23-31) Among these studies, reported odds ratios for the highest quartile of recent BMI range from 1.2 to 2.7 among women and from 1.3 to 3.3 among men. Recently, a population-based case-control study in Canada assessed odds ratios of RCC for clinical obesity (defined as BMI > 30), using the same standards as those in the present paper. (31) Use of this reference system makes findings more comparable among studies and facilitates the application of research findings to the practice of health promotion.

Because measures of current or recent BMI are proximal to diagnosis among cases, they are generally considered as indicators of past body composition, which is likely the more relevant factor. The present study found no associations between RCC and self-reported past obesity (with the exception of maximum lifetime weight and BMI), while the literature reports inconsistent findings on past weight (8,10,24,27,32,33) and weight gain. (24,28,30) However, two studies have found that BMI at age 20 was associated with increased risk for RCC among both women and men. (8,24) Cohort studies have also shown that past levels of obesity 34-37 and change in BMI since age 20 (38) are associated with risk for RCC.

Research has suggested a number of potential mechanisms explaining the association between obesity and risk of RCC. These include: (1) metabolic syndrome39; (2) hormonal influences (28); (3) associations between obesity and hypertension (40); (4) use of amphetamines or diuretics (30); (5) dietary factors (24,40); and (6) lipid peroxidation. (41) Of these, investigations into metabolic syndrome and diet have produced promising leads in understanding how obesity relates to RCC etiology. Metabolic syndrome results when excess weight increases circulating levels of free fatty acids and peptide hormones, leading to insulin resistance and compensatory hyperinsulinaemia. (39) Carcinogenesis may result because insulin and insulin-like growth factor 1 promote cellular proliferation and inhibit apoptosis in many tissue types. Increased WHR is believed to be associated with these changes (12), and waist circumference may function as a reliable indicator of metabolic changes that is less invasive than sampling blood serum. This study found positive associations between WHR and RCC, particularly among men and African-Americans. Central subcutaneous fat, as measured by skinfold thickness at the suprailiac crest, was also associated with RCC among men in this study. This represents the first known investigation of associations between skinfold thickness and RCC.

Among women, this study's results for dietary factors were stronger than results for body composition factors. Controlling for BMI, daily caloric and fat intake were both significantly associated with RCC in women. Elevated cholesterol and lipid levels that are associated with obesity may support tumor development and progression by an inhibitory effect on immune cells. (40) Asal et al. (1988) suggested that diets high in fat lead to arterionephrosclerosis, which in combination with cholesterol deposits in the renal tubules may enhance the development of renal cancer. (24) Further research is warranted to determine whether dietary factors explain links between obesity and RCC, or whether dietary and body composition factors independently increase risk for RCC, allowing for expected interactions between diet and obesity.

A number of limitations should be acknowledged when interpreting the results of this study. Among cases, the average time from diagnosis to follow-up was 3 years, leading to potential survivor bias in which excluded deceased cases had significantly different rates of exposure than those included in the sample. Yu et al. (1991) reported that obese patients diagnosed with RCC may have a better prognosis than non-obese RCC patients. (42) Interviewed cases in the present study may therefore have been more obese than those who did not survive long enough to participate, resulting in over-estimates of population risk ratios. The correspondence of our findings with those of prospective studies that avoid such biases (34-38), suggests that survivor bias was not likely. This study's low response rates for both cases (69 percent) and controls (42 percent) suggest that selection biases may have been present. While the low participation rate among controls is of concern, it should be noted that differences in education and income--cited among those factors typically differing as a result of this participation bias (43)--were not significantly different between cases and controls. Despite efforts to frequency match controls by age (+/- 5 years), controls were significantly younger than cases. This discrepancy occurred as a result of obtaining initial matching frequencies from SEER data, which represent national cancer statistics, while the case sample for this study was limited geographically to North Florida and Georgia.

It has been found that obese subjects are more likely to under-report while underweight subjects are more likely to over-report their body weight. (44) This may lead some investigators using self-report measures of obesity to report no association with renal cell cancer, when in fact a real association exists (Type II error). Evidence for the association between obesity and RCC should therefore be considered stronger when obesity indicators are based on anthropometric measures. In the present study, anthropometric measures of obesity revealed generally stronger associations than self-report measures, which are subject to recall errors. However, it should be noted that skinfold thickness measurements are subject to high inter-rater variability. (22) Bioelectric impedance analysis was considered the more reliable measure of body fat percentage.

This study adds to present epidemiologic findings that high BMI is a risk factor for renal cell cancer, although the lack of association among women conflicts with reports in the literature. It is likely that BMI functions as an indirect indicator of some other obesity-related variable, such as body fat percentage or body fat distribution, both of which were assessed in the present study. Body fat percentage proved to be a significant predictor of RCC among both men and women, while WHR and suprailiac skinfold thickness predicted RCC among men. Our findings provide tentative evidence for metabolic syndrome and diet as potential mechanisms explaining the link between obesity and RCC. Subsequent studies of body composition and RCC would benefit from a more comprehensive anthropometric assessment of obesity, evaluating the relative impact of absolute and relative weight, body fat percentage, and body fat distribution.

Acknowledgements

This research was supported by a Research Scholar grant from American Cancer Society (TURSG-02-068-01-PBP). Additionally, the authors would like to thank the research assistants who participated in this project for their effort in soliciting cases and controls and conducting interviews.

Conflict of interest: None

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Nabih R. Asal, Ryan P. Theis, Suzanne M. Dolwick Grieb, Deborah Burr, Dan Benardot, Tariq Siddiqui Department of Epidemiology and Biostatistics, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA

Corresponding author: Nabih R. Asal, Ph.D. College of Public Health and Health Professions, University of Florida, P.O. Box 100231, Gainesville, FL 32610-0231, Phone: (352) 273-5363, Fax: (352) 263-5365,

E-mail: asal@phhp.ufl.edu
TABLE 1--Demographic characteristics of renal cell carcinoma cases and
population controls, Florida and Georgia, 2003-2006

                             Cases (n = 335)    Controls (n = 337)

                               No.      %          No.      %

Age at interview
20-39 years                      3     0.9          20     5.9
40-59 years                     88    26.3         102    30.3
60-79 years                    203    60.6         179    53.1
80 + years                      41    12.2          36    10.7

Sex
Female                         154    46.0         161    47.8
Male                           181    54.0         176    52.2

Race
White                          262    78.2         266    79.4
African-American                73    21.8          71    21.1

Education
Less than high school           41    12.3          28     8.3
High school diploma            184    55.1         183    54.3
Bachelor's or higher           109    32.6         126    37.4

Annual household income
Less than $15,000               38    11.3          45    13.4
$15,000-$24,999                 60    17.9          52    15.4
$25,000-$49,999                107    31.9          98    29.1
$50,000 and higher             111    33.1         130    38.6
Not reported                    19     5.7          12     3.6

TABLE 2--Adjusted odds ratios for selected risk factors for renal cell
carcinoma, by sex

                                                 Men

                           Cases (%)   Controls (%)   AOR (a)   95% CI
Medical history
Hypertension               104 (59%)     89 (51%)       1.1    0.7, 1.7
Kidney infections           16 (9%)       7 (4%)        2.1    0.8, 5.4
Kidney stones              44 (25%)      31 (18%)       1.5    0.9, 2.6
Diuretics (b)              51 (29%)      32 (19%)       1.4    0.8, 2.5

Tobacco use (x)
Never-smokers              57 (32%)      57 (32%)       1.0
Less than 5 PY              12 (7%)      31 (18%)       0.4    0.2, 0.9
5 to < 10 PY                11 (6%)      12 (7%)        0.9    0.3, 2.1
10 to < 20 PY              21 (12%)      15 (9%)        1.4    0.6, 3.0
20 or more PY              80 (44%)      61 (35%)       1.3    0.8, 2.1

Daily caloric intake (d)
1st quartile               46 (25%)      43 (25%)       1.0
2nd quartile               52 (29%)      36 (21%)       1.2    0.7, 2.3
3rd quartile               34 (19%)      54 (31%)       0.6    0.3, 1.1
4th quartile               49 (27%)      39 (23%)       1.3    0.7, 2.4

Daily fat intake (g) (e)
1st quartile               45 (25%)      43 (25%)       1.0
2nd quartile               46 (25%)      42 (24%)       0.9    0.5, 1.8
3rd quartile               41 (23%)      47 (27%)       0.8    0.4, 1.6
4th quartile               49 (27%)      40 (23%)       1.2    0.6, 2.3

                                                 Women

                           Cases (%)   Controls (%)   AOR (a)   95% CI
Medical history
Hypertension               80 (53%)      70 (44%)       1.3    0.8, 2.0
Kidney infections          40 (27%)      20 (13%)       2.5    1.4, 4.7
Kidney stones              18 (12%)      12 (8%)        1.7    0.8, 3.8
Diuretics (b)              49 (33%)      37 (24%)        1     0.6, 1.9

Tobacco use (c)
Never-smokers              73 (47%)      78 (48%)       1.0
Less than 5 PY             18 (12%)      18 (11%)       1.1    0.5, 2.3
5 to < 10 PY                3 (2%)       12 (8%)        0.3    0.1, 1.1
10 to < 20 PY               12 (8%)      18 (11%)       0.8    0.4, 1.8
20 or more PY              48 (31%)      35 (22%)       1.4    0.8, 2.4

Daily caloric intake (d)
1st quartile               33 (22%)      45 (28%)       1.0
2nd quartile               34 (23%)      44 (27%)       1.1    0.6, 2.0
3rd quartile               38 (25%)      40 (25%)       1.4    0.7, 2.6
4th quartile               46 (31%)      32 (20%)       2.3    1.2, 4.6

Daily fat intake (g) (e)
1st quartile               27 (18%)      51 (32%)       1.0
2nd quartile               40 (27%)      38 (24%)        2     1.0, 3.8
3rd quartile               38 (25%)      40 (25%)       1.8    0.9, 3.4
4th quartile               46 (31%)      32 (20%)       2.7    1.4, 5.2

(a) Adjusted for age, race, smoking (lifetime pack-years), and BMI

(b) Daily diuretic use for one year or longer; adjusted for age, race,
smoking (lifetime pack-years), BMI, and history of hypertension

(c) Wald x2 test for trend:  Men, P = 0.008; Women, P = 0.639

(d) Wald x2 test for trend:  Men, P = 0.697; Women, P = 0.027
    Quartile distributions:  Men: (1) [less than or equal to] 1430;
                                  (2) 1431 - 1872;
                                  (3) 1873 - 2291;
                                  (4) [greater than or equal to] 2292
                             Women: (1) [less than or equal to] 1199;
                                  (2) 1200 - 1528;
                                  (3) 1529 - 2031;
                                  (4) [greater than or equal to] 2032
(e) Wald x2 test for trend:  Men, P = 0.957; Women, P = 0.006
    Quartile distributions   Men: (1) [less than or equal to] 54.64;
                                  (2) 54.65 - 74.49;
                                  (3) 74.50 - 101.29;
                                  (4) [greater than or equal to] 101.30
                             Women: (1) [less than or equal to] 43.14;
                                  (2) 43.15 - 61.14;
                                  (3) 61.15 - 84.44;
                                  (4) [greater than or equal to] 84.45

TABLE 3--Differences in means between renal cell carcinoma cases and
controls on continuous body composition measures

                                               Cases (n = 335)

                                              No.          Mean

Height (cm)                                   335         167.48

Weight (kg)
Age 20                                        334          66.07
Age 40                                        331          76.58
Age 60                                        244          80.68
Maximum lifetime (a)                          334          95.22
Time of interview (a)                         335          87.74
Gain age 20 to maximum lifetime               333          29.18
Loss from maximum to time of interview        334           7.47

BMI
Age 20 (a)                                    334          23.44
Age 40                                        331          27.17
Age 60                                        244          28.82
Maximum lifetime (b)                          334          33.74
Time of interview (b)                         335          30.97
Gain age 20 to maximum lifetime               333           10.3
Loss from maximum to time of interview        334           2.78

Waist (cm) (b)                                334         105.84
Hip (cm)                                      333         113.67
Waist/Hip (c)                                 333           0.93

Skinfold thickness (mm)
Abdomen (a)                                   330           30.2
Suprailiac (b)                                333          23.38
Triceps                                       331          23.77
Thigh (b)                                     328          27.86
Core (Abdomen + Suprailiac) (b)               330          53.69
Total (all 4 sites) (b)                       322         105.62
Core/Total                                    322          0.509

Bodyfat percentage (%)
Bioelectrical impedance method (c)            315          35.63
Skinfold thickness method (c)                 322          29.61

                                              Controls (n = 337)

                                              No.          Mean

Height (cm)                                   336         168.04

Weight (kg)
Age 20                                        335          64.57
Age 40                                        316          75.21
Age 60                                        211          79.77
Maximum lifetime (a)                          337          91.59
Time of interview (a)                         335          84.55
Gain age 20 to maximum lifetime               335          26.82
Loss from maximum to time of interview        335           6.93

BMI
Age 20 (a)                                    334          22.83
Age 40                                        315          26.52
Age 60                                        211          28.39
Maximum lifetime (b)                          336          32.39
Time of interview (b)                         335          29.86
Gain age 20 to maximum lifetime               334           9.48
Loss from maximum to time of interview        335           2.53

Waist (cm) (b)                                336         101.57
Hip (cm)                                      336         111.43
Waist/Hip (c)                                 336          0.908

Skinfold thickness (mm)
Abdomen (a)                                   334          28.78
Suprailiac (b)                                335          21.69
Triceps                                       336          22.99
Thigh (b)                                     332          26.08
Core (Abdomen + Suprailiac) (b)               334          50.46
Total (all 4 sites) (b)                       330          99.39
Core/Total                                    330          0.509

Bodyfat percentage (%)
Bioelectrical impedance method (c)            324          33.55
Skinfold thickness method (c)                 330          28.10

                                           T-test for difference

                                          t-statistic    P value

Height (cm)                                  0.741         0.459

Weight (kg)
Age 20                                      -1.313         0.189
Age 40                                      -0.905         0.366
Age 60                                      -0.577         0.564
Maximum lifetime (a)                        -1.893         0.059
Time of interview (a)                       -1.925         0.055
Gain age 20 to maximum lifetime             -1.548         0.122
Loss from maximum to time of interview       -0.59         0.556

BMI
Age 20 (a)                                  -1.748         0.081
Age 40                                      -1.403         0.161
Age 60                                      -0.894         0.372
Maximum lifetime (b)                        -2.229         0.026
Time of interview (b)                       -2.133         0.033
Gain age 20 to maximum lifetime             -1.553         0.121
Loss from maximum to time of interview      -0.736         0.462

Waist (cm) (b)                              -2.161         0.031
Hip (cm)                                    -1.153         0.249
Waist/Hip (c)                               -3.055         0.002

Skinfold thickness (mm)
Abdomen (a)                                 -1.921         0.055
Suprailiac (b)                              -2.323          0.02
Triceps                                     -1.124         0.262
Thigh (b)                                   -2.126         0.034
Core (Abdomen + Suprailiac) (b)             -2.365         0.018
Total (all 4 sites) (b)                     -2.435         0.015
Core/Total                                   0.000         1.000

Bodyfat percentage (%)
Bioelectrical impedance method (c)          -2.751         0.006
Skinfold thickness method (c)               -2.960         0.003

(a) P < 0.10, (b) P < 0.05, (c) P < 0.01

TABLE 4--Adjusted odds ratios for renal cell carcinoma by sex: height,
weight, and body mass index (BMI)

                                                 Men

                                Cases     Controls   AOR (a)   95% CI
                                 (%)        (%)

Height at interview (cm) (b)
1st quartile                   48 (27%)   40 (23%)     1.0
2nd quartile                   52 (29%)   37 (21%)     1.4    0.7, 2.6
3rd quartile                   41 (23%)   49 (28%)     0.8    0.4, 1.5
4th quartile                   40 (22%)   49 (28%)     0.7    0.4, 1.3

Weight at interview (kg) (c)
1st quartile                   42 (23%)   46 (26%)     1.0
2nd quartile                   46 (25%)   42 (24%)     1.1    0.6, 2.1
3rd quartile                   45 (25%)   44 (25%)     1.2    0.6, 2.1
4th quartile                   48 (27%)   42 (24%)     1.3    0.7, 2.5

BMI at interview (d)
18.5-24.9                      20 (11%)   29 (17%)     1.0
25.0-29.9                      69 (38%)   72 (42%)     1.2    0.6, 2.5
30.0-39.9                      75 (41%)   62 (36%)     1.7    0.8, 3.4
40.0 or greater                17 (9%)     8 (5%)      3.5    1.2, 10.4

Maximum weight (kg) (e)
1st quartile                   43 (24%)   40 (23%)     1.0
2nd quartile                   44 (24%)   51 (29%)     0.8    0.5, 1.5
3rd quartile                   41 (23%)   45 (26%)     0.8    0.4, 1.5
4th quartile                   53 (29%)   40 (23%      1.3    0.7, 2.5

Maximum BMI (f)
18.5-24.9                       3 (2%)    14 (8%)      1.0
25.0-29.9                      53 (30%)   55 (33%)     4.3    1.1, 16.8
30.0-39.9                      96 (54%)   82 (49%)     5.4    1.4, 20.7
40.0 or greater                27 (15%)   17 (10%)     7.3    1.7, 31.5

                                                 Women

                                Cases     Controls   AOR (a)   95% CI
                                 (%)        (%)

Height at interview (cm) (b)
1st quartile                   39 (25%)   39 (24%)     1.0
2nd quartile                   35 (23%)   44 (27%)     0.9    0.4, 1.6
3rd quartile                   42 (27%)   37 (23%)     1.3    0.7, 2.5
4th quartile                   38 (25%)   41 (26%)     1.0    0.5, 2.0

Weight at interview (kg) (c)
1st quartile                   31 (20%)   47 (29%)     1.0
2nd quartile                   42 (27%)   37 (23%)     1.6    0.8, 3.1
3rd quartile                   37 (24%)   42 (26%)     1.3    0.7, 2.6
4th quartile                   44 (29%)   35 (22%)     2.0    1.0, 4.0

BMI at interview (d)
18.5-24.9                      30 (20%)   41 (26%)     1.0
25.0-29.9                      49 (32%)   51 (32%)     1.2    0.6, 2.3
30.0-39.9                      60 (39%)   49 (31%)     1.6    0.8, 3.0
40.0 or greater                14 (9%)    17 (11%)     1.2    0.5, 2.8

Maximum weight (kg) (e)
1st quartile                   31 (20%)   46 (29%)     1.0
2nd quartile                   39 (26%)   38 (24%)     1.4    0.7, 2.6
3rd quartile                   43 (28%)   36 (22%)     1.7    0.9, 3.2
4th quartile                   40 (26%)   41 (26%)     1.6    0.8, 3.1

Maximum BMI (f)
18.5-24.9                      16 (11%)   26 (16%)     1.0
25.0-29.9                      35 (23%)   45 (28%)     1.1    0.5, 2.3
30.0-39.9                      75 (50%)   61 (38%)     1.8    0.9, 3.8
40.0 or greater                25 (17%)   28 (18%)     1.4    0.6, 3.2

(a) Adjusted model controlled for age, race, smoking (lifetime
pack-years), daily caloric intake, daily fat intake, and education

(b) Wald x2 test for trend: Men, P = 0.092; Women, P = 0.653
    Quartile distributions: Men: (1)[less than or equal to] 170.2 cm;
                            (2) 170.3 cm - 174.3 cm;
                            (3) 174.4 cm - 178.4 cm;
                            (4) [greater than or equal to] 178.5 cm
                            Women: (1)[less than or equal to] 156.6 cm;
                            (2) 156.6 cm - 160.6 cm;
                            (3) 160.7 cm - 164.7 cm;
                            (4) [greater than or equal to] 164.8 cm

(c) Wald x2 test for trend: Men, P = 0.118; Women, P = 0.146
    Quartile distributions: Men: (1)[less than or equal to] 78.39 kg;
                            (2) 78.40 kg - 89.39 kg;
                            (3) 89.40 kg - 103.19 kg;
                            (4) [greater than or equal to] 103.20 kg
                            Women: (1)[less than or equal to] 65.59 kg;
                            (2) 65.60 kg - 76.39 kg;
                            (3) 76.40 kg - 88.79 kg;
                            (4) [greater than or equal to] 88.80 kg
(d) Wald x2 test for trend: Men, P = 0.028; Women, P = 0.295

(e) Wald x2 test for trend: Men, P = 0.043; Women, P = 0.425
    Quartile distributions  Men: (1)[less than or equal to] 83.90 kg;
                            (2) 83.91 kg - 97.06 kg;
                            (3) 97.07 kg - 111.12 kg;
                            (4) [greater than or equal to] 111.13 kg
                            Women: (1)[less than or equal to] 70.75 kg;
                            (2) 70.76 kg - 80.73 kg;
                            (3) 80.74 kg - 94.79 kg;
                            (4) [greater than or equal to] 94.80 kg
(f) Wald x2 test for trend: Men, P = 0.012; Women, P = 0.643

TABLE 5--Adjusted odds ratios for renal cell carcinoma by sex: body
fat composition at time of interview

                                          Men

Body fat method     Cases (%)    Controls (%)    AOR (a)     95% CI

Bioimpedance (b)
1st quartile        37 (22%)       45 (27%)        1.0
2nd quartile        45 (27%)       40 (24%)        1.2      0.7, 2.4
3rd quartile        40 (24%)       42 (25%)        1.0      0.6, 2.0
4th quartile        46 (27%)       39 (24%)        1.3      0.7, 2.5

Skinfolds '(c)
1st quartile        36 (21%)       49 (29%)        1.0
2nd quartile        42 (25%)       44 (26%)        1.4      0.7, 2.5
3rd quartile        37 (22%)       49 (29%)        0.9      0.5, 1.8
4th quartile        56 (33%)       30 (17%)        2.5      1.3, 4.7

                                          Women

Body fat method     Cases (%)    Controls (%)    AOR (a)     95% CI

Bioimpedance (b)
1st quartile        28 (19%)       48 (30%)        1.0
2nd quartile        38 (26%)       36 (23%)        1.8      0.9, 3.5
3rd quartile        39 (27%)       39 (25%)        1.6      0.8, 3.1
4th quartile        42 (29%)       35 (22%)        1.9      1.0, 3.7

Skinfolds (c)
1st quartile        33 (22%)       44 (28%)        1.0
2nd quartile        35 (23%)       42 (27%)        1.0      0.5, 1.9
3rd quartile        40 (26%)       38 (24%)        1.3      0.7, 2.5
4th quartile        43 (29%)       34 (22%)        1.5      0.8, 2.9

(a) Adjusted model controlled for age, race, smoking (lifetime
pack-years), daily caloric intake, daily fat intake, and education

(b) Wald x2 test for trend:  Men, P = 0.042; Women, P = 0.032
    Quartile categories:     Men: (1) [less than or equal to] 24.29%;
                             (2) 24.30% - 29.04%;
                             (3) 29.05% - 33.99%;
                             (4) [greater than or equal to] 34.00%
                             Women: (1) [less than or equal to] 35.69%;
                             (2) 35.70% - 40.79%;
                             (3) 40.80% - 45.99%;
                             (4) [greater than or equal to] 46.00%
(c) Wald x2 test for trend:  Men, P = 0.047; Women, P = 0.089
    Quartile categories:     Men: (1) [less than or equal to] 22.64%;
                             (2) 22.65% - 26.30%;
                             (3) 26.31% - 30.07%;
                             (4) [greater than or equal to] 30.08%
                             Women: (1) [less than or equal to] 28.21%;
                             (2) 28.22% - 32.30%;
                             (3) 32.31% - 35.72%;
                             (4) [greater than or equal to] 35.73%

TABLE 6--Adjusted odds ratios for renal cell carcinoma by sex: body
fat distribution

                                               Men

                      Cases (%)    Controls (%)    AOR (a)     95% CI
Waist (cm) (b)
1st quartile          42 (23%)       46 (26%)        1.0
2nd quartile          46 (25%)       43 (25%)        1.1      0.6, 2.1
3rd quartile          38 (21%)       52 (30%)        0.8      0.4, 1.4
4th quartile          55 (30%)       34 (19%)        1.6      0.9, 3.1

Waist/Hip ratio (c)
1st quartile          34 (19%)       53 (30%)        1.0
2nd quartile          41 (23%)       49 (28%)        1.4      0.7, 2.6
3rd quartile          53 (29%)       36 (21%)        2.5      1.3, 4.8
4th quartile          52 (29%)       37 (21%)        2.0      1.0, 3.9

Suprailiac crest
skinfold (mm) (d)
1st quartile          42 (23%)       46 (26%)        1.0
2nd quartile          44 (24%)       44 (25%)        1.2      0.6, 2.1
3rd quartile          39 (22%)       51 (29%)        0.9      0.5, 1.7
4th quartile          55 (31%)       33 (19%)        2.1      1.1, 3.9

                                             Women

                      Cases (%)    Controls (%)    AOR (a)     95% CI
Waist (cm) (b)
1st quartile          31 (20%)       47 (29%)        1.0
2nd quartile          40 (26%)       37 (23%)        1.6      0.8, 3.1
3rd quartile          41 (27%)       40 (25%)        1.5      0.7, 2.9
4th quartile          41 (27%)       37 (23%)        1.5      0.7, 2.8

Waist/Hip ratio (c)
1st quartile          34 (22%)       44 (27%)        1.0
2nd quartile          33 (22%)       45 (28%)        0.9      0.5, 1.8
3rd quartile          39 (26%)       41 (26%)        1.2      0.6, 2.3
4th quartile          47 (31%)       31 (19%)        1.7      0.8, 3.4

Suprailiac crest
skinfold (mm) (d)
1st quartile          36 (24%)       42 (26%)        1.0
2nd quartile          36 (25%)       43 (27%)        1.0      0.5, 1.9
3rd quartile          39 (26%)       40 (25%)        1.2      0.6, 2.3
4th quartile          42 (28%)       36 (22%)        1.3      0.7, 2.5

(a) Adjusted model controlled for age, race, smoking (lifetime
pack-years), daily caloric intake, daily fat intake, and education

(b) Wald x2 test for trend: Men, P = 0.211; Women, P = 0.305
    Quartile categories     Men: (1) [less than or equal to] 96.99 cm;
                            (2) 97.00 cm - 104.99 cm;
                            (3) 105.00 cm - 115.07 cm;
                            (4) [greater than or equal to] 115.08 cm
                            Women: (1)[less than or equal to] 86.34 cm;
                            (2) 86.35 cm - 96.99 cm;
                            (3) 97.00 cm - 107.52 cm;
                            (4) [greater than or equal to] 107.53 cm
(c) Wald x2 test for trend: Men, P = 0.052; Women, P = 0.147
    Quartile categories     Men: (1) [less than or equal to] 0.921;
                            (2) 0.922 - 0.962;
                            (3) 0.963 - 1.007;
                            (4) [greater than or equal to] 1.008
                            Women: (1) [less than or equal to] 0.816;
                            (2) 0.817 - 0.865;
                            (3) 0.866 - 0.915;
                            (4) [greater than or equal to] 0.916
(d) Wald x2 test for trend: Men, P = 0.007; Women, P = 0.426
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