The

new england journal

medicine

n engl j med

370;10

nejm.org

march

2014

974

mutations in 192 Chinese patients with primary

ovarian insufficiency did not identify a mutation

DMC1

We suggest that mutations in genes encoding

proteins that regulate meiosis can result in auto-

somal recessive primary ovarian insufficiency in

humans, although our findings await confirma-

tion by independent groups. However, our results

are consistent with the finding that

Hfm1-

defi-

cient mice are infertile.

Further investigation of

HFM1

in larger series of women with primary

ovarian insufficiency and in infertile men is

warranted.

Jian Wang, M.S.

Boston Children’s Hospital

Boston, MA

Wenxiang Zhang, M.D.

Hong Jiang, M.D., Ph.D.

105th Hospital of People’s Liberation Army

Hefei, China

jiangh105@sina.com

Bai-Lin Wu, M.Med., Ph.D.

Fudan University

Shanghai, China

bai-lin.wu@childrens.harvard.edu

for the Primary Ovarian Insufficiency Collaboration

Supported by grants from the Ministry of Science and Technol-

ogy of China (2010CB529601, 2013CB945404), the Science and

Technology Council of Shanghai (09JC1402400), and a Fudan

Scholar Award from Fudan University (all to Dr. Wu).

Disclosure forms provided by the authors are available with

the full text of this letter at NEJM.org. A complete list of mem-

bers of the Primary Ovarian Insufficiency Collaboration is pro-

vided in the Supplementary Appendix.

De Vos M, Devroey P, Fauser BC. Primary ovarian insuffi-

ciency. Lancet 2010;376:911-21.

Nelson LM. Primary ovarian insufficiency. N Engl J Med 2009;

360:606-14.

Mandon-Pépin B, Touraine P, Kuttenn F, et al. Genetic inves-

tigation of four meiotic genes in women with premature ovarian

failure. Eur J Endocrinol 2008;158:107-15.

Wang H, Sun M, Qin Y, Xia T, Ma J, Chen ZJ. Mutations in

DMC1 are not responsible for premature ovarian failure in Chi-

nese women. Reprod Biomed Online 2013;26:175-8.

Guiraldelli MF, Eyster C, Wilkerson JL, Dresser ME, Pezza

RJ. Mouse HFM1/Mer3 is required for crossover formation and

complete synapsis of homologous chromosomes during meiosis.

PLoS Genet 2013;9(3):e1003383.

DOI: 10.1056/NEJMc1310150

Cancer Risk among Children Born after Assisted Conception

To the Editor:

Williams et al. (Nov. 7 issue)

reported no increase in the overall cancer risk

among British children born after assisted con-

ception. However, the study has several limita-

tions that deserve attention because the conclu-

sions are important to both future research and

the health of children born after assisted con-

ception.

The correctness of deterministic linkages de-

pends on the completeness of the data and may

vary according to age, with lower rates of link-

age for children 1 to 9 years of age.

Conse-

quently, it is possible that records were missed

or misclassified, leading to an underreporting of

the accuracy of the linkage. The authors found

overall cancer risks that were similar to those

reported in other studies, with considerable over-

lap in confidence intervals, but the studies they

refer to have indeed found a significant excess

risk. We found that the risk of early-onset acute

lymphoblastic leukemia was 2.5 times as high

among children born after assisted conception,

and the same assessment was reported in a re-

cent meta-analysis.

Our study emphasizes that

age at onset of cancer should be taken into con-

sideration and that cancers with differing causes

should not be lumped into one category.

Anastasia N. Iliadou, Ph.D.

Karolinska Institutet

Stockholm, Sweden

anastasia.nyman@ki.se

Eleni Petridou, M.D., Ph.D.

University of Athens

Athens, Greece

Hans-Olov Adami, M.D., Ph.D.

Karolinska Institutet

Stockholm, Sweden

No potential conflict of interest relevant to this letter was re-

ported.

Williams CL, Bunch KJ, Stiller CA, et al. Cancer risk among

children born after assisted conception. N Engl J Med 2013;369:

1819-27.

Li B, Quan HD, Fong A, Lu MS. Assessing record linkage

between health care and Vital Statistics databases using deter-

ministic methods. BMC Health Serv Res 2006;6:48.

Petridou ET, Sergentanis TN, Panagopoulou P, et al. In vitro

fertilization and risk of childhood leukemia in Greece and

Sweden. Pediatr Blood Cancer 2012;58:930-6.

Hargreave M, Jensen A, Toender A, Andersen KK, Kjaer SK.

Fertility treatment and childhood cancer risk: a systematic meta-

analysis. Fertil Steril 2013;100:150-61.

Adami H-O, Hunter D, Trichopoulos D, eds. Textbook of can-

cer epidemiology. 2nd ed. New York: Oxford University Press, 2008.

DOI: 10.1056/NEJMc1315232

The New England Journal of Medicine

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