Dietary factors and polymorphisms in vitamin D metabolism genes: the risk and prognosis of colorectal cancer in northeast China

Abstract

CYP24A1 and CYP27B1 are critical genes determining 1α,25(OH)2D3 concentration and impacting on carcinogenesis. A case–control study including 528 colorectal cancer (CRC) patients and 605 cancer-free controls and a follow-up study with 317 cases were conducted in northeast China. Genotypes were tested by TaqMan Genotyping Assays. Individuals carrying the GG genotype of CYP27B1 G > T (rs10877012) exhibited decreased CRC risk compared with those with the TT genotype (ORadjusted (ORadj) = 0.57, 95% Confidence Interval (CI) = 0.38–0.84). Compared with the TT genotype, a significant association between the CC genotype of CYP27B1 C > T (rs4646536) and a reduced risk of CRC was observed (ORadj = 0.59, 95% CI = 0.40–0.88). We also observed significant combined effects of the two polymorphisms in CYP27B1 with dietary factors, including the intake of cereals, overnight meal, allium vegetables, pork, canned fruit, and braised fish, on CRC risk. These associations remained significant after Bonferroni correction for multiple comparisons. The Hazard Ration (HR) of patients with the AA genotype (CYP24A1 A > G, rs4809957) was 2.38 (95% CI = 1.30–4.37) when compared with the GG genotype. Thus, our findings suggested that two polymorphisms in CYP27B1 are associated with CRC susceptibility. CYP24A1 A > G (rs4809957) polymorphism may lead to a worse prognosis of CRC.

Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment

“… Gene Polymorphism Study Main finding Ref. CYP27B1 rs10877012 (G > T); rs4646536 (C > T) A follow-up study with 528 CRC patients and 605 cancer-free controls Reduced CRC risk in GG carriers of rs10877012 and CC genotype of rs4646536; higher CRC risk in GT + TT carries of rs10877012 94 , 95 CYP27A1 rs4674343 (G > A); rs6436086 (T > C) 1260 men with prostate cancer and 1331 controls Positive association of rs4674343 and rs6436086 with prostate cancer risk 96 rs964293 10,835 postmenopausal women (5419 CRC cases and 5416 controls) Modify the association between combined oestrogen-progestogen hormone treatment and CRC incidence 97 rs6068816; rs2181874 426 NSCLC cases and 445 controls from China Reduction of NSCLC susceptibility by rs6068816 in both smokers and non-smokers; reduction of NSCLC risk in smokers with mutated homozygous rs6068816; increased NSCLC risk in those with mutated homozygous rs2181874 98 rs4809957 (A > G) 528 CRC cases and 605 cancer-free controls in northeast China Worse prognosis of CRC patients with CYP24A1 A>G (rs4809957) 94 rs2296241 582 ESCC patients and 569 controls in a Northern Chinese population Positive correlation between ESCC and rs2296241 99 GC rs12512631; rs2239182 3566 primary melanoma cases Longer cutaneous melanoma overall survival in those with rs12512631 and rs2239182 in GC 100 , 101 rs7041 426 NSCLC cases and 445 controls from China; 1777 breast cancer cases and 1839 controls Significant association of decreased NSCLC incidence with rs7041; increased risk of breast cancer in rs7041 TT genotype 98 , 102 rs4588 522 metastatic CRC patients Longer CRC patients over...…”

“…Another study which involved 3336 incident primary melanoma cases found that VDR single nucleotide polymorphisms (SNPs), rs1544410/Bsm I and rs731236/Taq I, significantly correlated with melanoma survival among subjects exposed to high UVB 117 . A case-control study including 528 CRC patients and 605 cancer-free controls and a follow-up study with 317 cases, which were conducted in northeast China, suggested that two polymorphisms in CYP27B1 (rs10877012 and rs4646536) are associated with decreased CRC risk while CYP24A1 (rs4809957) polymorphism might lead to a worse prognosis of CRC 94 . It was also reported that the CYP24A1 variant rs964293 modulated the association between combined oestrogen-progestogen (E+P) hormone therapy and CRC risk, suggesting the important role of CYP24A1 polymorphism in cancer progression 97 .…”

CYP27B1 Gene Polymorphism rs10877012 in Patients Diagnosed with Colorectal Cancer

“…It is worth mentioning that this latter study was performed in a population of northeast China, the wild-type genotype was TT where (in our study it was GG) [21]. To our knowledge, the two citied papers [20,21] are the only references in the PubMed database that directly associate rs10877012 to the development of CRC.…”

“…Comparison of GG vs. TT in the whole population: we obtained a 3.20-times (p = 0.002) higher risk of CRC, whereas for Vidigal et al's population the result was not statistically significant (p = 0.412) [20]. Another paper demonstrated that the GG genotype, compared to the TT genotype, diminished the risk of CRC (OR = 0.57; 95% CI 0.38-0.84; p = 0.005), which turned out to be only statistically significant in elderly people [21].…”

“…The reference allele is G, while the alternative allele is T. The minor allele frequency (MAF) oscillates around 27.83% (TopMed study, global population) [19]. Nevertheless, it has been linked directly to CRC occurrence [20,21], and also indirectly due to its influence on the level of 25(OH)D circulating in the blood [22,23]. However, others do not confirm this indirect association [24][25][26].…”