The Association of Digit Ratio (2D : 4D) with Cancer: A Systematic Review and Meta-Analysis

Table 1

Characteristics of the included studies.

	Authors/country	Country	Sample size (s)	Major findings
	Prostate cancer
(1)	Mendes et al., 2016 [20]	Brazil	100 prostate cancer patients and 100 healthy individuals	Right and left 2D : 4D were lower in prostate cancer patients relative to controls; Dr-l was not different between groups; 2D : 4D did not correlate with Gleason score
(2)	Stolten et al., 2016 [26]	USA	452 prostate cancer patients	2D : 4D was not related to Gleason score, family history, or metastatic status
(3)	Garcia-Cruz et al., 2012 [24]	Spain	204 patients undergoing prostate biopsy	2D : 4D > 0.95 was related to neoplasia (OR = 4.4)
(4)	Waters et al., 2013 [25]	USA	238 prostate cancer patients	African-American men with prostate cancer were 3.70 times more likely to have low 2D : 4D than Caucasian men with prostate cancer; 2D : 4D was not related to presence of metastasis, Gleason score, family history, or age at diagnosis
(5)	Oh et al., 2012 [21]	Korea	770 consecutive men aged 40 years or older that presented with lower urinary tract symptoms	Right 2D : 4D < 0.95 was associated with higher cancer detection rate and greater core cancer volume and higher Gleason score
(6)	Muller et al., 2011 [19]	Australia	6258 men from community sample	2D : 4D was not associated with prostate cancer risk in all participants; There was a weak inverse association between 2D : 4D and risk of prostate cancer for age < 60
(7)	Rahman et al., 2011 [18]	UK	1524 prostate cancer cases and 3044 population-based controls	High right 2D : 4D was associated with lower prostate cancer risk
(8)	Jung et al., 2011 [22]	Korea	366 > 40 years old men with a PSA level ≤ 40 ng/ml presenting for lower urinary tract symptoms	Patients with 2D : 4D < 0.95 were more likely to have prostate cancer on biopsy
(9)	Salomao et al., 2014 [23]	Brazil	474 men > 40 years old: with prostate cancer (); high risk for prostate cancer (); and low risk for prostate cancer ()	2D : 4D was not different between the three groups
	Breast cancer
(10)	Hong et al., 2014 [27]	China	109 breast cancer patients and 109 controls	Right and left 2D : 4D was higher in patients than controls; Right and left 2D : 4D (but not Dr-l) correlated negatively with age at disease presentation
(11)	Muller et al., 2012 [28]	Australia	9044 women from community sample	Left 2D : 4D was positively and Dr-l was inversely associated with breast cancer risk; Right 2D : 4D was not related to breast cancer risk; Right 2D : 4D and Dr-l were inversely associated with age at breast cancer diagnosis
	Testicular cancer
(12)	Trabert et al., 2013 [29]^A	USA	246 testicular germ cell tumor patients and 236 controls	Right and left 2D : 4D and Dr-l were not associated with testicular germ cell tumor risk
(13)	Auger and Eustache, 2010 [30]^A	France	71 testicular cancer patients and 122 controls	2D : 4D and Dr-l were not different between the two groups
	Gastric cancer
(14)	Sheng et al., 2016 [32]^A	China	94 male patients with gastric cancer and 91 controls	Right and left 2D : 4Ds were lower in gastric cancer patients than controls; 2D : 4D ratio was not associated with tumor size, lymph node involvement or distant metastases, and age of onset
(15)	Hopp et al., 2013 [31]^A	Brazil	57 patients with gastric cancer and 59 controls	Left 2D : 4D was higher and Dr-l was lower in patients relative to controls; 2D : 4D did not correlate with cancer staging, tumor size, regional lymph node involvement, or distant metastases; Low Dr-l was associated with adenocarcinomas
	Oral cancer
(16)	Hopp and Jorge, 2011 [17]	Brazil	25 oral squamous cell carcinoma patients, 25 individuals with oral premalignant lesions, and 25 controls	2D : 4D was higher in males with oral squamous cell carcinoma than in males with oral premalignant lesions and controls
	Brain tumor
(17)	Bunevicius et al., 2016 [33]	Lithuania	85 primary brain tumor (glioma, meningioma, and pituitary adenoma) patients and 106 controls	Right and left 2D : 4D were lower in brain tumor patients relative to controls; In meningioma and glioma patients, age at presentation correlated negatively with left 2D : 4D and positively with Dr-l
	Cervical intraepithelial neoplasia
(18)	Brabin et al., 2008 [34]	United Kingdom	Human papillomavirus (HPV) negative, normal smear (); HPV-positive, normal smear (); cervical intraepithelial neoplasia (CIN) 1 (); CIN 2/3 ()	2D : 4D ratio was similar for HPV-positive and HPV-negative women with normal smear; Women with any degree of cervical dysplasia were significantly more likely to have a higher 2D : 4D when compared with HPV-negative women; There was nonsignificant trend for the association of higher 2D : 4D ratio with persistent HPV infection

^ACase-control studies included in the meta-analysis.