Pre-diagnostic 25-hydroxyvitamin D levels and subsite-specific colorectal cancer risk: a nested case-control study from the Norwegian Women and Cancer Study (NOWAC)

Colorectal cancer (CRC), the third most common cancer globally, causes over 900 000 deaths annually. Although vitamin D is observed to have potential anti-carcinogenic properties, research findings on its preventable effect against CRC remain inconclusive. Notably, different subsites within the colon and rectum may be associated with distinct risk factors. While some studies have explored this relationship with circulating 25-hydroxyvitamin D (25(OH)D), the results remain contradictory. Our study employed a nested case-control design, involving 775 CRC cases matched with 775 cancer-free controls based on age, region of living and the time of blood sampling. The study was conducted within the Norwegian Women and Cancer post-genome cohort, which comprises approximately 50 000 women. We measured pre-diagnostic circulating plasma 25(OH)D status 5-13 years before diagnosis. Adjustment variables were based on self-administered questionnaires and included BMI, physical activity level, smoking, intake of processed meat, calcium, alcohol and fibre. An increase of 5 nmol/l in 25(OH)D reduced the risk of proximal colon cancer by 6 % (OR = 0·94, 95 % CI 0·89, 0·99). Furthermore, a sensitivity analysis revealed a 62 % increased risk among the women with 25(OH)D levels below 50 nmol/l compared with sufficient levels, ≥ 50 to < 75 nmol/l (OR = 1·62, 95 % CI 1·01, 2·61). No association was found with CRC, colon or distal colon cancer. We observed a subsite-specific association between 25(OH)D and CRC, highlighting the need for further investigation to elucidate the potential underlying mechanisms and clinical implications.