Odds ratios and relative risks approximate one another56
; some general comments about differences between the sexes can be made by evaluating aggregate studies that compare men and women. Figure 3 displays the relative risks/odds ratios of colon cancer for the most overweight category for 10 articles57,58,59,60,61,62,63,64,65,66
that compared men and women; a sign test showed that these studies found that obesity placed men more than women at an increased risk for colon cancer (p<0.025). Only one study, of Japanese subjects,59
showed women to be more at risk than men; the impact of ethnicity will be discussed in the last section of this review.
Figure 3Results of 10 studies57,58,59,60,61,62,63,64,65,66 that compared the relative risk/odd ratios (RR/OR) of colon cancer of the most obese men and women with normal weight men and women.
divided each of six sets of women and five sets of men into five BMI groups. The lowest group in each group was eliminated because its relative risk/odds ratio is always 1. Each of the six sets of women and five sets of men bears four BMI group specific, gender specific relative risks/odds ratios: there are 44 data points. Relative risks and odds ratios are calculated by taking their logarithms. The natural logarithm of relative risk/odds ratio is the dependent (or Y) variable. BMI group, female sex, and female sex × BMI group are independent (or X) variables. Multiple linear regression results are shown in table 1; variability of the three independent variables accounted for 57% of the variability in relative risk/odds ratios (p<0.0001). Each independent variable was statistically significant. No outliers were present; neither was there heterscedasticity or curvilinearity. Although a positive coefficient for female sex appears to imply that women have, in general, a greater relative risk of colon cancer, this is not true because the interaction variable (female sex × BMI group) shows that there are two regression equations. That there are two regression equations implies that the sexes differ as regards the relationship between obesity and colon cancer.
Table 1Results of multiple linear regression of the natural logarithm of relative risks/odds ratios of seven studies57,64,66,68,69,70,71 on body mass index (BMI) group, female sex, and the interaction of BMI group and female sex
The effect of obesity is more pronounced for men than women. Although for BMI group 2 the estimated relative risk/odds ratio was just slightly greater for women than for men, men had an increasingly greater relative risk/odds ratio than women for BMI groups 3, 4, and 5. As a person gains weight, there is a much more modest rise in colon cancer risk for women than there is for men.
If VAF is indeed an important factor, the difference between the sexes may exist because BMI is a better measure of VAF in men than in women.64,72,73
On the other hand, given the lack of an epidemiological connection between leptin and colon cancer in women, there may be real biological differences at work. Differences between men and women often relate to oestrogen; the two matters best explored in this regard are menopausal status and the use of oestrogenic hormones in postmenopausal women.
Conversion of androgens to oestrogens by adipose tissue is the prime source of extraglandular oestrogen in postmenopausal women; age and obesity increase circulating oestrogen levels.74,75,76
Oestrogen supplementation in men, but not women, increases insulin resistance; the higher the oestradiol/testosterone ratio, the greater are plasma glucose and insulin levels.77,78
If hyperinsulinaemia increases the risk of colon cancer, obesity induced hyperoestrogenaemia in men would be one reason why obesity in men causes an increased colon cancer risk; this theory is unsupported by epidemiology.
If hyperoestrogenaemia from obesity causes a greater colon cancer risk in men than in women, one might conclude that: (1) premenopausal women would be less affected by obesity than postmenopausal women because premenopausal women have ovarian oestrogen that might make any added oestrogen from obesity less important79
; and (2) hormone replacement therapy (HRT) in postmenopausal women would increase the risk of death from colon cancer. The two best studies that have assessed menopausal status and colon cancer risk have shown that conclusion (1) is false: Slattery and colleagues57
found that postmenopausal women who have a BMI >30 kg/m2
have 1.29 times the risk of women with a BMI <23 kg/m2
and, for premenopausal women, a ratio of 2.19; Terry and colleagues80
found that postmenopausal women who have a BMI >30 kg/m2
have 0.92 times the risk of women with a BMI <25 and, for premenopausal women, a ratio of 1.75. These findings are perplexing given that the menopause is associated with a redistribution of fat towards the abdomen.55,81
The latter conclusion is well supported by studies of age. In Sweden, obese women younger than 55 years, but not older, had a twofold increased colon cancer risk.82
Obesity conferred a twofold colon cancer risk for nurses aged 34–39 years33
but not for a group of women mostly over 65 years.83
The issue is not simple; Dutch women with an age at menarche above 13 years had an odds ratio of 0.51 (95% confidence interval 0.28–0.94) of those who had their first periods below age 14 years.84
In general, however, the consensus is that obesity may confer just as great an added colon cancer risk for women who are premenopausal as it does for men in general.85,86
As with most matters that concern HRT, the risks of colon cancer are best described as undecided. Although Calle and colleagues87
found that HRT reduced the risk of colon cancer, only seven of 14 studies cited in her table 6 bear an overall risk of 0.9 or less among those who received HRT. The confusion is perhaps better illustrated by the results of two studies on this issue displayed in table 2: the results of Slattery and colleagues57
lead one to believe that obesity and HFT together increase colon cancer risk; those of Lin and colleagues71
lead to the opposite conclusion.
Table 2Results of the study of Slattery and colleagues57 and Lin and colleagues71 evaluating the interaction of body mass index (BMI) and hormone replacement therapy (HRT) among postmenopausal women with regard to the risk of colon cancer