We investigated the association between plasma 25(OH)D and the subsequent colorectal cancer incidence risk by a nested casecontrol study in The Japan Public Health Center-based Prospective Study, covering 375 newly diagnosed cases of colorectal cancer from 38 373 study subjects during a 11.5-year follow-up after blood collection. Two controls were matched per case on sex, age, study area, date of blood draw, and fasting time. In a conditional logistic regression model with matched pairs adjusted for smoking, alcohol consumption, body mass index, physical exercise, vitamin supplement use, and family history of colorectal cancer, plasma 25(OH)D was not significantly associated with colorectal cancer in men or in women. However, the lowest category of plasma 25(OH)D was associated with an elevated risk of rectal cancer in both men (odds ratio (OR), 4.6; 95% confidence interval (CI), 1.0 -20) and women (OR, 2.7, 95% CI, 0.94 -7.6), compared with the combined category of the other quartiles. Our results suggest that a low level of plasma 25(OH)D may increase the risk of rectal cancer. Ecologic studies have reported that sunlight or solar ultraviolet B exposure is inversely associated with the risk of colorectal cancer incidence and mortality in the United States (Grant and Garland, 2004;Giovannucci, 2005) and in Japan (Mizoue, 2004). This ultraviolet B is involved in the production of vitamin D from 7-dehydrocholesterol in the skin (Holick, 2004). Vitamin D, which is derived from skin and dietary products or supplemental sources, is catalysed to 25-hydroxyvitamin D in the liver, which is the most useful measure of vitamin D status (Hunter, 1998). The 25-hydroxyvitamin D re-enters the circulation and is converted in the kidney by 25-hydroxyvitamin D-1a-hydroxylate to 1,25-dihydroxyvitamin D, which regulates calcium metabolism through its interaction with its major target tissues, bone and intestine; 25-hydroxyvitamin D is also metabolised in colorectal mucosa for regulation of cellular growth.Several prospective studies reported that 25-hydroxyvitamin D in the blood was inversely associated with colorectal cancer risk (Garland et al, 1989;Braun et al, 1995;Wactawski-Wende et al, 2006), and especially distal colon and rectal cancer (Tangrea et al, 1997;Feskanich et al, 2004). One cohort was used to analyse a small number of cases (Garland et al, 1989;Braun et al, 1995), while others were from specific populations such as Finnish male smokers (Tangrea et al, 1997) and US nurses (Feskanich et al, 2004). Further confirmation is needed from general populations, especially with a different sunlight exposure and skin pigmentation reducing the cutaneous synthesis of vitamin D (Clemens et al, 1982;Matsuoka et al, 1991).We investigated the association between plasma 25-hydroxyvitamin D and the subsequent risk of colorectal cancer in a nested case -control study in a large general population cohort in Japan.
MATERIALS AND METHODSThe Japan Public Health Centre-based Prospective Study (JPHC study) is an ongoing cohort study inves...