rs1048943

This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.

A comprehensive meta-analysis of 50 case-control studies from the Indian subcontinent identified genetic variants modifying lung cancer risk, finding FDR-corrected associations for rs3547/XRCC1 (OR=1.83-2.72) and rs1048943/CYP1A1 (OR=2.07). The rs1048943/CYP1A1 variant showed strongest associations with adenocarcinoma (OR=3.38) and squamous cell carcinoma (OR=3.53) with significant effect modification by smoking status. Global meta-analysis confirmed rs1048943/CYP1A1 association across world populations (OR=1.22, p=0.01).

This case-control study examined the association between CYP1A1 gene polymorphisms and cervical cancer risk in 728 Chinese women (360 cases, 368 controls). The rs4646903 polymorphism showed significant association with increased cervical cancer risk (OR=1.45, 95% CI 1.20-1.95 for TC+CC vs TT genotypes). A significant SNP-SNP interaction was identified between rs4646903 and rs1048943 (P=0.0107), with subjects carrying TC/CC at rs4646903 and AG/GG at rs1048943 having the highest risk (OR=2.03, 95% CI 1.42-2.89).

A case-control study of 830 Korean breast cancer patients and 390 controls evaluating associations between genetic polymorphisms in estrogen receptor genes (ESR1, ESR2) and estrogen-metabolizing enzyme genes (CYP1A1, CYP1B1, COMT) with breast cancer risk. ESR1 rs2881766 (OR=1.40, p=0.02), rs2077647 (OR=1.37, p=0.02), rs926778 (OR=1.56, p≤0.01), and rs2273206 (OR=1.40, p=0.01) increased breast cancer risk, while rs3798377 (OR=0.76, p=0.05) decreased risk in overall patients. Associations varied substantially by age group and tumor subtype, with rs2881766 consistently increasing risk across all age groups except luminal B subtype.

Meta-analysis of 13 case-control studies (3,489 subjects) examining CYP1A1 and CYP11A1 polymorphisms in polycystic ovary syndrome (PCOS). CYP1A1 MspI (rs4646903) showed increased PCOS risk with RR=1.47 (95% CI: 1.11-1.94, p=0.008) in Caucasians, while CYP1A1 Ile462Val (rs1048943) showed no significant association (RR=1.40, p=0.159). CYP11A1 [TTTA]n repeat polymorphism was associated with increased risk (RR=1.16, p<0.001) in Caucasian populations.

This study examined PAH-related DNA adduct levels in 111 female never-smokers from Iran, evaluating 21 SNPs in 14 xenobiotic metabolism genes and 12 SNPs in 8 DNA repair genes. DNA adduct levels were significantly lower with NAT2 slow alleles (β=-0.24, p=0.01) and ERCC5 non-risk genotype (β=0.16, p=0.04), but higher with MPO risk alleles (β=0.21, p=0.01). The combination of phase I genes and measured NER capacity explained 17% more variation in adduct levels than environmental exposure alone (r²=0.24 vs 0.07), demonstrating the importance of genetic polymorphisms in PAH metabolism and DNA repair capacity.

A prospective pharmacogenetic study of 69 metastatic breast cancer patients treated with docetaxel plus capecitabine identified CYP1A1 rs1048943 A>G (Ile462Val) as significantly associated with progression-free survival (P=0.0003, HR=0.4 for GA/GG vs AA genotype). While 79 CYP450 SNPs were tested, only this single variant remained significant after Bonferroni correction and multivariate analysis (P=0.004).

Study of 314 German workers (218 bitumen-exposed, 96 non-exposed controls) examining how 18 SNPs in metabolizing enzyme genes modulate urinary PAH metabolites (1-OHP and OHPHE). The CYP1A1 3801T>C CC variant showed 58% higher OHPHE (P=0.051), GSTM1*1 carriers had 11% lower OHPHE (P=0.046), and NAT2*803GG showed 15-16% decrease in OHPHE (P=0.042). No SNPs reached significance for 1-OHP.

This family-based association study examined genetic variation in xenobiotic metabolism genes and clubfoot risk. In 1,776 individuals from 619 families, rs1048943/CYP1A1 showed significant altered transmission (p=0.003), and CYP1A2 variants demonstrated both maternal (rs11854147, p=0.03, RR=1.24) and fetal (rs2470890, p=0.01, RR=1.33) genotypic effects. A significant gene interaction was detected between rs105740/EPHX1 and rs1799929/NAT2 (p=0.007). The authors conclude that xenobiotic metabolism genes may contribute to clubfoot susceptibility, particularly in the context of maternal smoking exposure.

This comprehensive review examines genetic association studies on prostate cancer, discussing GWASs that have identified over 75 variants associated with PCa risk (as of February 2016), with major susceptibility regions at 8q24, 17q12, 17q24, 10q11, and 19q13. The paper also reviews candidate gene-based approaches targeting genes involved in androgen signaling, carcinogen metabolism, DNA repair, vitamin D signaling, inflammation, angiogenesis, and cellular adhesion, as well as regulatory RNA genes.

Population-based case-control study of 1,115 women examining GST and CYP polymorphisms in relation to non-Hodgkin lymphoma risk, with stratification by smoking status. Overall NHL risk was not significantly altered by variant polymorphisms, but increased risk of DLBCL in non-smokers was associated with GSTP1 variant G allele (OR=1.6, 95% CI: 1.0-2.3) and CYP1A1 variant G allele (OR=2.4; 95% CI: 1.0-5.7), while decreased risk was observed for CYP1B1 variant G allele (OR=0.6, 95% CI: 0.4-1.0).

Population-based case-control study (713 NHL cases, 1,700 controls) in Korea examining associations between drug-metabolizing gene polymorphisms and non-Hodgkin lymphoma risk. GSTP1 rs1695 AG/GG genotypes were associated with decreased NHL risk (OR=0.66-0.67), while CYP1A1 rs1048943 AG/GG genotypes were associated with increased NHL risk (OR=1.26-1.32). Smoking did not modify these associations.

A candidate gene association study of 6,752 women from the Study of Osteoporotic Fractures examined 31 polymorphisms in 18 candidate osteoporosis genes for associations with fracture risk and bone mineral density. ALOX15_G48924T (rs7220870) T/T genotype was associated with 33% higher hip fracture risk (HR=1.33, 95% CI 1.00-1.77); PRL_T228C (rs7739889) C alleles reduced nonvertebral fracture risk by ~20%; BMP2_A125611G (rs235764) G/G showed 51% higher vertebral fracture risk (OR=1.51, 95% CI 1.03-2.23); and MMP2_C595T (rs243865) T allele carriers had reduced vertebral fracture risk. No significant associations were found with total hip BMD.