BMJ  2005;331:882-883 (15 October), doi:10.1136/bmj.38572.440359.AE (published 26 September 2005)

Paper

Innate left handedness and risk of breast cancer: case-cohort study

¹ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, Netherlands

Introduction

Among the proposed origins of breast cancer are intrauterine influences, such as exposure to sex hormones.¹ Such exposure may also influence cerebral lateralisation, with hand preference being one of its manifestations. We know only of case-control studies on a putative common origin of left handedness and breast cancer, some of which show an association.² We assessed the association between handedness and incidence of breast cancer in a population based prospective cohort of healthy, middle aged women followed up for 16 years.

Participants, methods, and results

In a breast cancer screening study in Utrecht, the Netherlands, 12 178 women born between 1932 and 1941 and recruited between 1982 and 1985 (participation rate 40%) had baseline questionnaire data recorded about reproductive history, demography, lifestyle, and innate hand preference and had anthropometric measures taken. Linkage with the regional cancer registry provided data on all new cases of invasive breast cancer that occurred until 1 January 2000. Follow-up for adequate information about the person years lived for all 12 178 women would have been costly and time consuming, so we ascertained vital status until 1 January 2000 in a random selection of 1500 women and used their follow-up data to calculate person years lived in the 12 178 women. Exclusion of women with incomplete data left 1426 women; 55 women from the random sample and 371 from outside the random sample had breast cancer (incidence of breast cancer 2.5 per 1000 person years). We used Prentice's method for Cox regression as recommended by Barlow and colleagues³ for analysis with the statistical software SAS (version 8.2, SAS Institute, NC, USA) and a dedicated macro (http://lib.stat.cmu.edu/general/robphreg).

The random sample comprised 165 (11.6%) left handed women. Mean age at baseline was similar for left and non-left handed women (47.4 (range 41.6-53.1) and 47.0 (41.0-53.1) years respectively). These groups did not differ in anthropometry, socioeconomic status, smoking habits, family history of breast cancer, or reproductive history (except for parity—21.8% of left handed v 10.9% of non-left handed women were nulliparous).

The relative risk for breast cancer in left handed women compared with non-left handed women was 1.39 overall (table). The risk was 2.41 when the cancer was premenopausal (diagnosis before reported onset of menopause or, if menopausal data were unavailable, diagnosis at age < 51 years), but there was no excess risk for postmenopausal cancers (table)). Adjustment for risk factors hardly affected the overall association between left handedness and incidence of breast cancer. We found an excess risk for breast cancer in left handed women with a body mass index of 25 but not in those whose index was > 25 (P interaction 0.07), and in parous but not nulliparous women (P interaction 0.02).

View this table: [in this window] [in a new window]   Association between handedness and incidence of breast cancer in study participants followed up at 16 years

 

Comment

We found that left handed women are more than twice as likely to develop premenopausal breast cancer as non-left handed women. This risk is compatible with left handedness being a marker of constitutional risk rather than of environmental risk as with postmenopausal breast cancer.

Our findings among premenopausal women may be compatible with a stronger association in women with a normal body mass index, as high body mass index is a particular risk factor for postmenopausal breast cancer. However, our data did not allow for a robust analysis of this issue.

The origin of the association may lie in intrauterine exposure to steroid hormones, as supported by data showing a higher prevalence of left handedness in women with intrauterine exposure to diethylstilbestrol.⁴ Although the underlying mechanisms remain elusive, our results support the hypothesis that left handedness is related to increased risk of breast cancer.

What is already known on this topic High levels of sex hormone in utero may induce left handedness and may change breast tissue as a source for breast cancer Some case-control studies provide evidence for a relation between left handedness and increased breast cancer risk, but prospective evidence is lacking What this study adds Prospective data show an increased risk of premenopausal breast cancer among left handed women

---

This article was posted on bmj.com on 26 September 2005: http://bmj.com/cgi/doi/10.1136/bmj.38572.440359.AE

Contributors: All authors analysed and interpreted the data, critically revised the manuscript, and approved the final version. PAHvanN and PHMP conceived and designed the study. SGE, PAHvanN, and PHMP acquired the data. Bernard Slotboom and Bep Verkerk handled and processed the data. MKR, CSPMU, and DEG drafted the manuscript. CSPMU is the guarantor.

Funding: This work was supported by the Dutch Cancer Society (grant UU-KC-85-13). The funding organisations had no role in any aspect of the study, the manuscript, or the decision to publish.

Competing interests: None declared.

Ethical approval: Not needed.

References

1. Trichopoulos D. Hypothesis: does breast-cancer originate in utero? Lancet 1990;335: 939-40.[CrossRef][Web of Science][Medline]
2. Titus-Ernstoff L, Newcomb PA, Egan KM, Baron JA, Greenberg ER, Trichopoulos D, et al. Left-handedness in relation to breast cancer risk in postmenopausal women. Epidemiology 2000;11: 181-4.[Medline]
3. Barlow WE, Ichikawa L, Rosner D, Izumi S. Analysis of case-cohort designs. J Clin Epidemiol 1999;52: 1165-72.[CrossRef][Web of Science][Medline]
4. Scheirs JGM,Vingerhoets AJJM. Handedness and other laterality indexes in women prenatally exposed to DES. J Clin Exp Neuropsychol 1995;17: 725-30.[Medline]

(Accepted 18 July 2005)

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    What's this?

Relevant Articles

Left handedness and breast cancer: Correlation is spurious

Adrian J Bloor
BMJ 2005 331: 1023-1024. [Extract] [Full Text]

Left handedness and breast cancer: Should left handed premenopausal women be screened?

Bettina Lieske
BMJ 2005 331: 1024. [Extract] [Full Text]

Left handed women are at higher risk of breast cancer
BMJ 2005 331: 0. [Full Text]

Related external webpages:

Paper plus

This article has been cited by other articles:

• Gardener, H, Munger, K, Chitnis, T, Spiegelman, D, Ascherio, A (2009). The relationship between handedness and risk of multiple sclerosis. Mult Scler 15: 587-592 [Abstract]  
• (2006). From the Library. Br J Ophthalmol 90: 126-126 [Full text]  
• (2005). Left-Handedness, Large Placenta, and Breast Cancer Risk. JWatch Women's Health 2005: 5-5 [Full text]  
• Lieske, B. (2005). Left handedness and breast cancer: Should left handed premenopausal women be screened?. BMJ 331: 1024-1024 [Full text]  
• Bloor, A. J (2005). Left handedness and breast cancer: Correlation is spurious. BMJ 331: 1023-1024 [Full text]  

Rapid Responses:

Read all Rapid Responses

More left handed relatives too?

Arunachalam, Kumar, et al.
bmj.com, 14 Oct 2005 [Full text]

Are epidemiologists missing the point?

Sabapathy P Balasubramanian
bmj.com, 15 Oct 2005 [Full text]

Re: Are epidemiologists missing the point?

Cuno S Uiterwaal, et al.
bmj.com, 16 Oct 2005 [Full text]

Innate left handedness and risk of breast cancer: a spurious correlation

Adrian J Bloor
bmj.com, 17 Oct 2005 [Full text]

Re: Innate left handedness and risk of breast cancer: a spurious correlation

Cuno S Uiterwaal, et al.
bmj.com, 18 Oct 2005 [Full text]

Screening for left-handed premenopausal women needed?

Bettina Lieske
bmj.com, 18 Oct 2005 [Full text]

Breast malhandling

A Sadnicka
bmj.com, 20 Oct 2005 [Full text]

Re: Screening for left-handed premenopausal women needed?

Cuno S Uiterwaal, et al.
bmj.com, 20 Oct 2005 [Full text]

On Human Laterality And Breast Cancer

Mr Ali I Malik, et al.
bmj.com, 20 Oct 2005 [Full text]

Re: Breast malhandling

Cuno S. Uiterwaal, et al.
bmj.com, 22 Oct 2005 [Full text]

Online poll

Find out more on doc2doc >>