nach oben

Erschienen in:

01.01.2011 | Original paper

Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12

verfasst von: Seo-yun Tong, Mi Kyung Kim, Jae Kwan Lee, Jong Min Lee, Sang Woon Choi, Simonetta Friso, Eun-Seop Song, Kwang Beom Lee, Jung Pil Lee

Erschienen in: Cancer Causes & Control | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Objective

We evaluated associations between folate, vitamin B12, and the methylenetetrahydrofolate reductase (MTHFR) gene, and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer.

Methods

This multicenter case–control study enrolled 927 Korean women (440 controls, 165 patients with CIN 1, 167 patients with CIN 2/3, and 155 patients with cervical cancer, aged 20–75 years).

Results

Patients with cervical cancer had significantly lower median serum folate and vitamin B12 concentrations vs. controls. Higher serum folate was significantly associated with lower cervical cancer risk (p for linear trend = 0.0058) with a trend for a lower CIN risk after multivariate adjustment. Low folate and the MTHFR 677 C > T variant were associated with a higher risk for CIN2/3 and cervical cancer vs. wild-type or heterozygous genotypes with high folate [OR, 2.39 (1.18–4.85) and 3.19 (1.43–7.13)]. Low vitamin B12 and the MTHFR 677 C > T variant also were associated with a higher risk for CIN 2/3 and cervical cancers [OR, 2.52 (1.17–5.42) and 2.40 (1–5.73)] vs. wild-type or heterozygous status with high vitamin levels.

Conclusion

Serum folate concentration is inversely associated with the risk of cervical cancer, and the MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status.

Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer 37(8):S4–66

Shin HR, Park S, Hwang SY et al (2008) Trends in cervical cancer mortality in Korea 1993–2002: corrected mortality using national death certification data and national cancer incidence data. Int J Cancer 122(2):393–397CrossRefPubMed

Walboomers JMM, Jacobs MV, Manos MM et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189(1):12–19CrossRefPubMed

Kjellberg L, Hallmans G, Ahren AM et al (2000) Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection. Br J Cancer 82(7):1332–1338CrossRefPubMed

Josefsson AM, Magnusson PK, Ylitalo N et al (2000) Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study. Lancet 355(9222):2189–2193CrossRefPubMed

Powers HJ (2005) Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer. J Nutr 135(12 Suppl):2960S–2966SPubMed

Piyathilake CJ, Henao OL, Macaluso M et al (2004) Folate is associated with the natural history of high-risk human papillomaviruses. Cancer Res 64(23):8788–8793CrossRefPubMed

Hernandez BY, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT (2003) Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12. Cancer Causes Control 14(9):859–870CrossRefPubMed

Goodman MT, McDuffie K, Hernandez B et al (2001) Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia. Cancer Epidemiol Biomark Prev 10(12):1275–1280

10.

Butterworth CE Jr, Hatch KD, Macaluso M et al (1992) Folate deficiency and cervical dysplasia. Jama 267(4):528–533CrossRefPubMed

11.

Flatley JE, McNeir K, Balasubramani L et al (2009) Folate status and aberrant DNA methylation are associated with HPV infection and cervical pathogenesis. Cancer Epidemiol Biomark Prev 18(10):2782–2789CrossRef

12.

Shikany JM, Heimburger DC, Piyathilake CJ, Desmond RA, Greene PG (2004) Effect of folic acid fortification of foods on folate intake in female smokers with cervical dysplasia. Nutrition 20(5):409–414CrossRefPubMed

13.

Duhr A, Galan P, Hercberg S (1991) Folate status and the immune system. Prog Food Nutr Sci 15:43–60

14.

Sedjo RL, Fowler BM, Schneider A, Henning SM, Hatch K, Giuliano AR (2003) Folate, vitamin B12, and homocysteine status. Findings of no relation between human papillomavirus persistence and cervical dysplasia. Nutrition 19(6):497–502CrossRefPubMed

15.

Shannon J, Thomas DB, Ray RM et al (2002) Dietary risk factors for invasive and in situ cervical carcinomas in Bangkok, Thailand. Cancer Causes Control 13(8):691–699CrossRefPubMed

16.

Alberg AJ, Selhub J, Shah KV, Viscidi RP, Comstock GW, Helzlsouer KJ (2000) The risk of cervical cancer in relation to serum concentrations of folate, vitamin B12, and homocysteine. Cancer Epidemiol Biomark Prev 9(7):761–764

17.

Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Selhub J (2000) Case-control study of plasma folate, homocysteine, vitamin B(12), and cysteine as markers of cervical dysplasia. Cancer 89(2):376–382CrossRefPubMed

18.

Bailey LB, Gregory JF III (1999) Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr 129(5):919–922PubMed

19.

Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G (1988) Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 43:414–421PubMed

20.

Jones PA, Laird PW (1999) Cancer epigenetics comes of age. Nat Genet 21:163–167CrossRefPubMed

21.

Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3(6):415–428PubMed

22.

Frosst P, Blom HJ, Milos R et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113CrossRefPubMed

23.

Goyette P, Sumner JS, Milos R et al (1994) Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet 7(2):195–200CrossRefPubMed

24.

van der Put NM, Gabreels F, Stevens EM et al (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 62:1044–1051CrossRefPubMed

25.

Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M (1999) Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol Biomark Prev 8(6):513–518

26.

Toffoli G, Gafa R, Russo A et al (2003) Methylenetetrahydrofolate reductase 677 C->T polymorphism and risk of proximal colon cancer in north Italy. Clin Cancer Res 9(2):743–748PubMed

27.

Ma J, Stampfer MJ, Giovannucci E et al (1997) Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 57(6):1098–1102PubMed

28.

Levine AJ, Figueiredo JC, Lee W et al (2010) Genetic variability in the MTHFR gene and colorectal cancer risk using the colorectal cancer family registry. Cancer Epidemiol Biomark Prev 19(1):89–100CrossRef

29.

Piyathilake CJ, Macaluso M, Johanning GL, Whiteside M, Heimburger DC, Giuliano A (2000) Methylenetetrahydrofolate reductase (MTHFR) polymorphism increases the risk of cervical intraepithelial neoplasia. Anticancer Res 20:1751–1757PubMed

30.

Rao GG, Kurien A, Gossett D, Griffith WF, Coleman RL, Muller CY (2006) A case-control study of methylenetetrahydrofolate reductase polymorphisms in cervical carcinogenesis. Gynecol Oncol 101(2):250–254CrossRefPubMed

31.

Zoodsma M, Nolte IM, Schipper M et al (2005) Methylenetetrahydrofolate reductase (MTHFR) and susceptibility for (pre)neoplastic cervical disease. Hum Genet 116(4):247–254CrossRefPubMed

32.

Sull JW, Jee SH, Yi S et al (2004) The effect of methylenetetrahydrofolate reductase polymorphism C677T on cervical cancer in Korean women. Gynecol Oncol 95(3):557–563CrossRefPubMed

33.

Lambropoulos AF, Agorastos T, Foka ZJ et al (2003) Methylenetetrahydrofolate reductase polymorphism C677T is not associated to the risk of cervical dysplasia. Cancer Lett 191(2):187–191CrossRefPubMed

34.

Henao OL, Piyathilake CJ, Waterbort JW et al (2005) Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3. Int J Cancer 113:991–997CrossRefPubMed

35.

Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ, for the A-SCC (2002) 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 287(16):2120–2129CrossRefPubMed

36.

Kim YO, Kim MK, Lee S-A, Yoon YM, Sasaki S (2009) A study testing the usefulness of a dish-based food-frequency questionnaire developed for epidemiological studies in Korea. Br J Nutr 101(8):1218–1227CrossRefPubMed

37.

Cody RP, Smith JK (1997) Multiple-regression analysis. Applied statistics and the SAS programming language, 4th edn. Upper Saddle River, NJ, Prentice Hall, pp 235–247

38.

Hosmer DW, Lemeshow S (2000) Applied logistic regression. John Wiley and Sons, NYCrossRef

39.

Kim HJ, Kim MK, Kim JU, Ha HY, Choi BY (2010) Major determinants of serum homocysteine concentrations in a Korean population. J Korean Med Sci 25(4):509–516CrossRefPubMed

40.

Kim YI (2004) Folate, colorectal carcinogenesis, and DNA methylation: lessons from animal studies. Environ Mol Mutagen 44(1):10–25CrossRefPubMed

41.

Ulrich CM, Potter JD (2007) Folate and cancer-timing is everything. JAMA 297(21):2408–2409CrossRefPubMed

42.

Gerhard DS, Nguyen LT, Zhang ZY, Borecki IB, Coleman BI, Rader JS (2003) A relationship between methylenetetrahydrofolate reductase variants and the development of invasive cervical cancer. Gynecol Oncol 90(3):560–565CrossRefPubMed

43.

von der Porten AE, Gregory JF III, Toth JP, Cerda JJ, Curry SH, Bailey LB (1992) In vivo folate kinetics during chronic supplementation of human subjects with deuterium-labeled folic acid. J Nutr 122(6):1293–1299

44.

Hatzis C, Bertsias G, Linardakis M, Scott J, Kafatos A (2006) Dietary and other lifestyle correlates of serum folate concentrations in a healthy adult population in Crete, Greece: a cross-sectional study. Nutr J 5(1):5CrossRefPubMed

45.

Galloway M, Rushworth L (2003) Red cell or serum folate? Results from the National Pathology Alliance benchmarking review. J Clin Pathol 56:924–926CrossRefPubMed

Titel: Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12
verfasst von: Seo-yun Tong
Mi Kyung Kim
Jae Kwan Lee
Jong Min Lee
Sang Woon Choi
Simonetta Friso
Eun-Seop Song
Kwang Beom Lee
Jung Pil Lee
Publikationsdatum: 01.01.2011
Verlag: Springer Netherlands
Erschienen in: Cancer Causes & Control / Ausgabe 1/2011
Print ISSN: 0957-5243
Elektronische ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-010-9675-6

Neu im Fachgebiet Onkologie

Hodgkin Lymphom: BrECADD-Regime übertrifft die Erwartungen

05.06.2024 ASCO 2024 Kongressbericht

Das Kombinationsregime BrECADD mit Brentuximab vedotin ermöglichte in der Studie HD21 beim fortgeschrittenen klassischen Hodgkin-Lymphom eine unerwartet hohe progressionsfreie Überlebensrate von 94,3% nach vier Jahren. Gleichzeitig war das Regime besser tolerabel als der bisherige Standard eBEACOPP.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12