Functional polymorphism in manganese superoxide dismutase and antioxidant status: their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer.
OBJECTIVE
Manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, plays a key role in protecting cells from oxidative stress. Furthermore, the MnSOD rs4880 polymorphism is associated with enzyme activity. The authors evaluated the interaction between MnSOD genotypes and cervical carcinogenesis risk and the modulating effects of serum antioxidant nutrient status (beta-carotene, lycopene, zeaxanthin/lutein, retinol, alpha-tocopherol and gamma-tocopherol).


METHODS
Cases and controls for this study were recruited between June 2006 and July 2007 (263 controls, 84 cervical intraepithelial neoplasia (CIN), 94 CIN 2/3, and 99 cases of cervical cancer). The MnSOD polymorphism at rs4880T/C was examined using SNaPshot assays. Serum antioxidant vitamin concentrations were measured by reverse-phase gradient high-pressure liquid chromatography. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated after adjusting for age, menopause, parity, oral contraceptive use, smoking and alcohol consumption.


RESULTS
No association was found between the MnSOD rs4880 polymorphism and cervical cancer. However, genotypes significantly modified the risk of cervical cancer in association with the serum statuses of micronutrients (P(interaction)<0.05 for beta-carotene, lycopene, zeaxanthin/lutein, alpha-tocopherol, and gamma-tocopherol). Decreased CIN1 risk in association with the MnSOD rs4880 variant genotype was also observed particularly for subjects with higher beta-carotene and gamma-tocopherol levels. Similar results were observed for lycopene and alpha-tocopherol in relation to the risk of CIN2/3.


CONCLUSIONS
Our findings suggest that a higher antioxidant micronutrients status may decrease the risk of CIN and cervical cancer and modify the effect of the MnSOD polymorphism on disease risk.
Tong
Seo-Yun
SY
Department of Obstetrics and Gynecology, East-West Neo Medical Center, Kyung Hee University, #149 Sangil-Dong, Gangdong-Gu, Seoul 134-890, Republic of Korea.
Lee
Jong-Min
JM
Song
Eun-Seop
ES
Lee
Kwang-Beom
KB
Kim
Mi-Kyung
MK
Lee
Jae-Kwan
JK
Son
Sung-Kyong
SK
Lee
Jung-Pil
JP
Kim
Jae-Hoon
JH
Kwon
Yong-Il
YI
D000328:Adult; D002338:Carotenoids / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D024505:Tocopherols / Q000097:blood*; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000201:enzymology* / Q000235:genetics
D002338:Carotenoids; D013482:Superoxide Dismutase; D024505:Tocopherols